During production from oil wells, the deposition of asphalteneand wax at surface facilities and porous media is one of the majoroperational challenges. The crude oil production rate is significantlyreduced due to asphaltene deposition inside the reservoir. In addition,the deposition of these solids inside the surface facilities is costlyto oil companies. In this study, the efficiency of different solventsin dissolving asphaltene and wax was investigated through static anddynamic tests. The analysis of solid deposits from the surface chokeof one of the Iranian carbonate oil fields showed that they consistedof 41.3 wt % asphaltene, and the balance was predominantly wax. Inaddition, the asphaltenes obtained from the surface choke solid depositshad a more complex structure than that of asphaltenes extracted fromthe crude oil itself. The static tests showed that xylene, toluene,gasoline, kerosene, and gas condensate had the highest efficienciesin dissolving solid deposits; conversely, diesel had a negative impacton dissolving solid deposits. Static tests on pure asphaltene showedthat, among the tested solvents, gas condensate and diesel had a negativeeffect on the solubility of asphaltene. The dynamic core floodingresults showed that asphaltene deposition inside the cores reducedthe permeability by 79–91%. Among the tested solvents, xylene,gasoline, and kerosene resulted in the highest efficacy in restoringthe damaged permeability, and higher efficiency was obtained withan equivalent solvent injection rate of 1 bbl/min versus 3 bbl/min. Asphaltenes are possible deposits inside the reservoir, nearthe wellbore region, inside the tubing string, and at the surfacefacilities; however, wax is rarely deposited inside the reservoirand near the wellbore region as it usually deposits in downstreamsections from tubing to surface facilities.18 Permeabilityreduction is the significant consequence of asphaltene and wax depositioninside the reservoir, which results in a considerable decline in productionrate.21Crude oil is a mixtureof various quantities and forms of organiccomponents such as resin, wax, and asphaltene. Asphaltene is the heaviestand most polar compound of crude oil.25 Solvent wash is one of the most common asphaltene and wax removalmethods, where the injected solvent redissolves these deposits fora while. Different solvents derived from renewable sources, aromaticand aliphatic solvents, cosolvents, and polymeric dispersants haverecently been used for asphaltene and wax removal.28 Although manysolvents have been used for this purpose, understating the natureof the deposits and then selecting the best solvent are of great importance.Asphaltene and wax removal from surface facilitiesand reservoirsis of great economic interest to production companies. The commonlypracticed methods are mechanical, chemical, and thermal treatments.1.1The “X”oil field in southern Iran has been producing nearly 15 000bbl/day; however, the production rate has recently declined to about6000 bbl/day. The primary reason for this decline is due to the depositionof organic compounds, mainly asphaltene and wax. The results of statictests in various wells showed an abnormally high-pressure drop inthe reservoir due to discontinuity in the flow regime because of permeabilityblockage. In addition, the well test results show a positive skineffect near the wellbore region. These two results prove that reservoiris damaged because of the deposition of these organic compounds. Inaddition, it was observed during workover activities that the downholetools face some restrictions in reaching the bottom of the well, whichis due to the deposition of organic compounds in the well column.Moreover, the deposition of these organic compounds is observed atthe surface facilities.22.1Table S1. In addition, the total dissolved solids (TDSs) of the formationbrine were about 200 000 ppmThe efficiency of solventsin dissolving the solid deposits was investigated using aliphaticand aromatic solvents such as xylene, toluene, gasoline, kerosene,gas condensate, and diesel. Crude oil and formation brine were collectedfrom the Sarvak formation in one of the Iranian carbonate oil fields.In addition, cyclohexane was used for measuring the base permeability.The API of the crude oil used in this study was about 32.8. The SARAanalysis of the crude oil was as follows: 68.7% saturate, 24.9% aromatics,5.5% resin, and 0.9% asphaltene. The colloidal instability index (CII)is a measure of asphaltene stability determination 1, where 2.2Figure S1a.The used carbonatecore samples in this study were taken from outcrops of the Sarvakformation, and rock properties were determined using X-ray diffraction(XRD) analysis and ζ-potential measurements. A D8 Bruker XRD(made by Germany) was used for determining the XRD pattern of therock sample. The XRD analysis of the carbonate sample showed thatit is mainly composed of dolomite. The XRD pattern of the carbonatecore sample is shown in Vt is theviscosity of the suspending liquid, Dt represents the dielectric constant, EM corresponds to the electrophoreticmobility, and ζ is the ζ-potential.29 A sample of 0.3 g dolomite rock powder was combined with100 mL of distilled water that contained the appropriate electrolyteat 25 ± 2 °C for 48 h to determine a point of zero charge(PZC = 6.7). The ζ-potential values versus pH are shown in Figure S1b.A microprocessor-equipped SZ-100  zeta-meterwas employed for streaming potential measurements. Utilizing the Smoluchowskiformula as shown by 2.330 The schematic diagram of the extraction process schematicallyby the modified IP-143 (ASTM D6560) procedure is shown in Figure S2.In this study, solid deposits are divided into four parts, includingasphaltene extracted from crude oil (AECO), wax extracted from crudeoil (WECO), solid deposits accumulated behind the surface choke (SC),and asphaltene extracted from SC (AESC). The accumulation of theseSCs has reduced the oil flow rate significantly. These solid depositsare mainly composed of asphaltene and wax, as explained in the followingsections. First, the oil and heptane in a volume ratio of 1–40were stirred for 24 h to precipitate the asphaltene and wax. Then,the heptane and crude oil solution was strained through the Whatmanfilter paper. In the next step, precipitated solid deposits were washedwith hot heptane to separate the asphaltene and wax.2.4Table S2.As mentioned before,the used carbonate core samples in this investigation were taken fromoutcrops of the Sarvak formation. The porosity of samples was measuredusing a helium porosity setup (Fars EOR Tech), and the absolute permeabilitywas measured using a GasPerm (Fars EOR Tech) setup. The porosity ofsamples was between 11 and 16%, and the permeability of samples wasbetween 5.83 and 11.83 mD. The diameter of core samples was 1.9 cm,while the length of samples was between 6.73 and 6.80 cm. The physicalproperties of the core samples utilized in this study are presentedin 2.5V = Q/A. Then, a back-calculationwas made using the calculated velocity, and the injection rate tothe cores was calculated in terms of cm3/min. Solvent injectionto the reservoir is carried out using coiled tubing, where a standardinjection rate of 1–3 bbl/min could be applied. Thus, in thisstudy, the minimum and the maximum injection rates of 1 and 3 bbl/minwere considered accordingly. The summary of calculated injection ratesfor each core sample is presented in Table S3.In order to investigate the effect of injectionrate on the efficiency of solvents, the constant injection rate couldnot be used for all of the cores because the porosity and length ofeach core were different. Thus, the concept of fluid velocity insideporous media was utilized. In this method, the actual velocity ofthe fluid inside the reservoir was calculated as 2.6The static bottle testswere carried out using solid deposits collected from the surface choke.In these experiments, 1 g of solid deposits was weighted and pouredinto a beaker. After that, different volumes (10–100 mL) ofsolvents  were added to the beaker. Then, a different retention timeof 1–10 days was applied to solvents, and solutions were filteredafterward. Finally, the weight of solids deposited on the filter paperwas measured, and the efficiency of each solvent was calculated.2.7Figure S3.31 The coreflood setup used in these experiments consists of two HPLC pumps,three accumulators, a differential pressure measurement, a core holder,an oven for providing constant heat, a hand pump for proving confiningpressure, and a backpressure regulator. The differential pressurewas recorded during the experiments, and the permeability was calculatedusing K is in mD, q is in cm3/min, A is in cm2, μ is in cP, ΔP is in kPa, and L is in cm34(i)Core samples were cleaned, dried,and vacuumed for about 24 h.(ii)Each core was saturated with formationbrine at 2000 psi for about 7 days.(iii)A total of 5 PVs of formation brinewas injected into the core.(iv)Injection of cyclohexane to the coreand measuring the initial permeability at the connate water saturation.In this step, 20 PVs were injected to determine cyclohexane permeability.(v)Injection of crude oilinto the cores.In this step, 20 PVs of crude oil were injected into the cores.(vi)A total of 20 PVs ofcyclohexanewas injected, and the cyclohexane permeability was measured. The calculatedpermeability in this section depicts the damaged permeability dueto asphaltene deposition inside the cores.(vii)Different solvents, including xylene,kerosene, and gasoline, and their mixture with gas condensate wereprepared. A 50–50% volumetric ratio was used to prepare themixed solvents. Then, each solvent was injected into the core withthe calculated injection rates. The retention time of 1–3 dayswas applied depending on the definition of each test.(viii)A total of 20 PVs of cyclohexanewas injected, and the cyclohexane permeability was measured. The calculatedpermeability in this section depicts the improved permeability bysolvent injection.The dynamictests were carried out using the core flood setup shown in Figure S4. It is worth mentioning that the reason for cyclohexanein this study is that this pure hydrocarbon does not affect in situasphaltenes by causing extra deposition or dissolving. Therefore,it could be used as a reference case for comparison during floodingexperiments.It is worth mentioning that the reservoir conditionswere applied in these experiments, where a temperature of 80 °C,a backpressure of 4000 psi, and a confining pressure of 4500 psi wereused in all experiments. The summary of the procedure of core floodexperiments conducted in this study is shown in 2.8–1 on a Perkin Elmer RX1 infrared(IR) spectrophotometer utilizing KBr pellet methods. The spectra wereinterpreted by IR-Pal V2.0 FT-IR spectra analysis software (Dr. Wolfvan Heeswijk) and previous research.The extracted mixtures were evaluated using FT-IR analysis between400 and 4000 cm33.1Initially, 20 g of solid deposits taken from behind the surfacechoke was measured, and the asphaltene content was determined. Thisexperiment was repeated three times, and finally, the asphaltene contentof the solid deposits was measured by averaging the results. 3.2In this section, different static bottletests were performed, and the efficiency of each solvent in dissolving1 g of solid deposits  was determined. 3.2.136Among the tested solvents, the maximum efficiencywas for xylene,toluene, gasoline, kerosene, and gas condensate. All of the testedsolvents (except diesel) responded well by increasing the solventvolume from 10 to 100 mL. The lowest efficiency of each solvent wasachieved when 10 mL of the solvent was used, and the efficiency reachedthe maximum value when the solvent volume increased to 100 mL. Theefficiency of 94.3, 92.1, 79.9, 40.9, and 28.5% was achieved for xylene,toluene, gasoline, kerosene, and gas condensate, respectively, whenthe volume of 100 mL was used for each solvent. On the other hand,the efficiency of diesel was zero with all of the tested volumes.The weight of solid deposits increased when the diesel volume wasincreased, resulting in negative diesel performance. The weight of1 g of solid deposits increased to 1.235, 1.273, 1.334, and 1.407g after adding 10, 20, 50, and 100 mL of diesel, respectively.39 The experiments’ results confirmed these solvents’applicability in dissolving organic deposits. On the other hand, gasoline,diesel, gas condensates, and kerosene are aliphatic solvents. Thealiphatic solvents are good candidates for dissolving paraffinic depositssuch as wax; however, they are ineffective for asphaltene removal.43 Among the tested aliphatic solvents in this study, gasoline showedbetter results than the others. Gasoline is mainly composed of aliphatics;however, some impurities (mainly aromatics) are added to its compositionto increase the octane number. These aromatic components in gasolinegive unique gasoline characteristics in dissolving the asphaltenedeposits. Kerosene and gas condensates are hydrocarbon-based aliphatics,which are relatively purer than gasoline in terms of added aromatics.Thus, they are less effective than gasoline in dissolving solid deposits.On the other hand, diesel is known to be the heaviest aliphatic, witha significant number of impurities in its composition.46 The presence of these impurities results in the formation of newbonds between diesel molecules and asphaltene deposits, resultingin the increase of the weight of asphaltene deposits and giving negativeefficiency to diesel.Xylene and toluene are potent aromatic solvents for dissolvingorganic compounds, especially asphaltene; however, toluene is lesseffective than xylene. These solvents can dissolve a significant fractionof asphaltene even at low volumes.3.2.2Aromatic solvents such as xylene and toluene are known to be veryeffective in removing asphaltene deposits; however, safety issuesand their high price are significant obstacles to be considered. Therole of aliphatic solvents such as gasoline, gas condensates, andkerosene as cheaper, widely available, and less risky solvents todissolve solid deposits is important. Thus, static tests using theabovementioned aliphatic solvents were performed, and the efficiencyof each solvent in dissolving 1 g of solid deposits was determinedaccordingly, as presented in 51The static test results showed that all three testedsolvents areaffected by the retention time and the solvent volume. Increasingthe retention time from 1 to 10 days and the volume of solvent from20 to 100 mL increased the efficiency of solvents. The best performanceof each solvent was achieved when a retention time of 10 days anda volume of 100 mL were used, where this value was 83.1, 42.9, and31.7% for gasoline, kerosene, and gas condensate, respectively. Aswas expected, the presence of aromatics in the gasoline content increasedthe solubility of solid deposits compared to the other two solvents.These findings are in good agreement with the results in the literature.3.2.3Due to the availability of aliphatic solvents and the toxic natureof the aromatic solvents, the efficiency of mixed solvents preparedby different proportions of these mixtures in dissolving solid depositswas examined. In the first part, different volumetric ratios of xyleneand gas condensate were mixed, and the efficiency of the mixed solventwas investigated, as shown in 43 In addition, mixed solvents preparedwith gasoline and gas condensate were also more affected by the volumeof the gasoline than retention time, as shown in As shown in 3.2.4In this part, pure asphaltene was extractedfrom solid deposits using the previous method. Then, the efficiencyof different aromatic and aliphatic solvents in dissolving 1 g ofasphaltene was determined at a retention time of 7 days, and the resultsare presented in 43 In addition, asphaltene is a polar compound of crude oil with ahigh affinity for adsorption. –1, respectively, due to creating new hydrogen bonds between asphalteneand diesel molecules for asphaltene+diesel. The higher peak intensityand peak area in the FT-IR spectrum correspond to the greater concentrationand stronger bonded, respectively.54 These hydrogen bonds are owing to partial negative and positivecharges (δ– and δ+) of oxygenand nitrogen atoms that are present in asphaltene molecules with hydrogenatoms of diesel molecules. In other words, the attachment of dieseland gas condensate to the asphaltene molecules is due to the creationof new hydrogen bonds that result from the electronegative oxygenand nitrogen atoms of asphaltene with hydrogen atoms of diesel andgas condensate. Thus, the adsorption of diesel and gas condensateincreases the weight of asphaltene. Consequently, the dissolving efficiencyof gas condensate and diesel becomes negative, as observed in thisstudy.Aliphatic solvents are not potentially perfect solventsfor dissolvingasphaltene. Instead, they perform well in dissolving wax.3.33.3.1n-heptane injection and then permeabilitywas measured. The results showed that 79–91% of the permeabilitywas reduced by asphaltene deposition during crude and n-heptane injection.This damage to the core is because of asphaltene deposition insidethe cores, as no wax is deposited at this condition. The WAT of thecrude oil used in this study is about 64 °C, suggesting thatno wax is deposited at 80 °C.The permeability measurement results showed that asphaltene depositioncould cause severe damage to the permeability of cores. In these experiments,20 PVs of crude oil were injected into the core samples and then followedby 20 PVs of 57 The reservoir cores used in this study are slightly tight in termsof permeability (5.83–11.83 mD). On the other hand, the asphaltenecontent of the crude oil used was about 0.9 wt %. Since the asphaltenecontent of the crude oil is relatively low and the cores’ permeabilityis very low, it may suggest that pore blocking is the dominant mechanismof permeability reduction in these experiments. Surface adsorption of asphalteneand pore blocking are the two major mechanisms of permeability reductionby asphaltene deposition. Based on results from ζ-potentialtests, the surface charge of dolomite rock is positive when pH isunder 6.7 (PZC). Moreover, crude oil is an acidic mixture due to thepresence of a large number of fatty acids. Hence, the charge of therock surface is positive in such an environment. On the other side,asphaltene particles of this specific crude oil have an overall negativecharge due to the presence of O–H and N–H bonds in theirstructures based on FT-IR results. The adsorption mechanism is directlyrelated to the asphaltene content of the crude and surface chargeof dolomite rock, where the asphaltene particles are gradually formedasphaltene layers and deposited into the rock surface due to the gravityof opposite charges, causing a reduction in the permeability. Furthermore,asphaltene particles are very heavy and polar and prefer to stickonto the rock surface (solid surface) instead of dispersing into theliquid phase (oleic or aqueous phases) when conditions become thermodynamicallyunstable for them. On the other hand, pore blocking occurs when asphalteneparticles are connected and form a bridge on the pore diameter, increasingthe rate of asphaltene accumulation and reducing the core permeability.3.3.2Initially, three experiments were performedto determine the adequate retention time on the efficiency of theinjected solvents. After asphaltene deposition inside the cores andmeasuring the damaged permeability by cyclohexane, xylene with a lowflow rate was injected into the cores and then different retentiontimes of 1, 2, and 3 days were applied at reservoir conditions (4000psi and 80 °C). Finally, the permeability affected by the solventswas measured using cyclohexane, as presented in The permeability results showed that solvent injectionto damagedcores effectively improves permeability. The permeability measurementresults showed that increasing the retention time from 1 to 2 dayswas very effective in improving the permeability; however, furtherincreasing the time to 3 days had minimal effect on the efficiency.The minimum efficiency of 32.06% was achieved after 1 day, and itincreased to 37.56 and 38.95% by increasing the retention time to2 and 3 days. Increasing the retention time provides more time forxylene to interact with the asphaltene particles. Thus, permeabilityincreases with retention time; however, this increase is not significantat some point. Hence, the retention time of 2 days was selected asthe optimum retention time of solvents in the following experiments.3.3.3The mechanism that reduces the permeabilityof the core sample must be clarified to find a suitable remedy. Hence,in the first step, the interactions between asphaltene and rock mustbe evaluated using FT-IR analysis and ζ-potential measurementsfor asphaltene and rock, respectively.–1) than that of AECO (3431 cm–1) correspond to the more concentration and stronger hydrogen-bonded,respectively.59 Hence, functional groups addedto the asphaltene structure are not soluble by normal heptane notonly for the formation of π–π stacking, charge-transferinteractions, multiple forces, and van der Waals interaction but alsothe stronger and more hydrogen bonds are formed in AESC.60 The IR spectrum at 1800 cm–1 corresponds to the C=O stretch of R–CO–Cl thatnever exists in the AECO and WECO structures.31 It shows that after well stimulation by HCl, residual Cl– ions from stimulation operation can enter the asphaltene structureduring the production. This hypothesis is confirmed by the presenceof a more intense peak at 550 cm–1 in the AESC thanthat of 545 cm–1 in AECO, attributed to the C–Clstretch of R–Cl in alkyl halides. The four unique peaks  in the AECO IR spectrumindicate the presence of phosphine and phosphonic acid functionalgroups that never exist in the AECO and WECO structures.52According to As mentioned before, the asphaltene samples obtainedfrom soliddeposits before the choke have a much more complicated structure thanthe asphaltene sample extracted from crude oil. This complicated processmay be due to the simultaneous precipitation of asphaltene and waxfrom the bottom hole to the surface by a drop in pressure and temperature,well stimulation operation, and the addition of some acidic componentsof crude oil to the solid deposits. In conclusion, this phenomenonindicates that the remedies for removing the solid deposits in theannulus, choke, and pipelines must be stronger than that of bottom-holeasphaltene or precipitated asphaltene in the reservoir.In theseexperiments, xylene, kerosene, and gasoline, as the mostwidely available aromatic and aliphatic solvents, were used to retrievethe damaged permeability due to asphaltene deposition in cores. Inaddition, the equivalent injection rates of 1 and 3 bbl/min were usedto investigate the effect of injection rate on solvent performance.The retention time, pressure, and temperature of 2 days, 4000 psi,and 80 °C, respectively, were used constantly.The experimentalresults showed that permeability is reduced becauseof asphaltene deposition inside the cores and some fraction of lostpermeability is recoverable by solvent injection, as presented in 3.3.4In this section, the effects of mixed solvents in retrieving thedamaged permeability were investigated. In this regard, differentsolvents were prepared by 50 vol % of xylene, kerosene, and gasolineand 50 vol % of gas condensate. Each solvent was injected by equivalentflow rates of 1 and 3 bbl/min. In addition, a retention time of 2days, a pressure of 4000 psi, and a temperature of 80 °C wereapplied accordingly. The injected solvents were able to recover some fractionof damagedpermeability. Among the tested solvents, a mixture of xylene/gas condensateperformed better than a mixture of gasoline/gas condensate and kerosene/gascondensate. In addition, solvents with an injection rate of 1 bbl/minperformed better than those of 3 bbl/min. The effective contact ofsolvents with the deposited asphaltene decreases with increasing injectionrate, thus decreasing the effectiveness of the solvent in dissolvingthe deposited asphaltene. Another observation from the results isthat the efficiency of mixed solvents is significantly lower thanthat of pure solvents alone. It seems that adding gas condensate tosolvents lowered the efficiency of solvents. For instance, xylenewith an injection rate of 1 bbl/min resulted in an efficiency of 37.56%,and the value was decreased to 29.68% when a mixture of gas condensateand xylene was used. The same behavior is observed for the other solventsas well. The static tests showed that gas condensate did not affectasphaltene and could only dissolve wax. In addition, the WAT of thecrude oil used in this study is about 64 °C, whereas the operatingtemperature is 80 °C. This suggests that only asphaltene is depositedinside the pores, and no wax is deposited. Thus, not only the injectionof a mixture of solvents with gas condensate has no additional effecton improving the permeability but it also hinders the solvents’efficiency. The volume of solvents is decreased when mixed with gas condensate; thus, the efficiencyis reduced as a result of these experiments.4The experimental investigationsyielded several quantitative andqualitative assertions about solvent use in reversing permeabilitydamage and removing deposited solids in oil well settings. The asphaltenesamples obtained from solid deposits behind the surface of the chokehave a much more complicated structure than that of the asphaltenesample extracted from crude oil. Moreover, based on the WAT of thecrude oil (64 °C) and the reservoir temperature (∼80 °C),it is deemed that only asphaltene deposition occurs inside the reservoir,while wax deposition occurs inside the tubing string and at the surfacefacilities. Hence, the screening of the solvents should be in a wayto address these issues, wherein the remedies for removing the soliddeposits in the annulus, choke, and pipelines must be stronger thanbottom-hole asphaltene or precipitated asphaltene in the reservoir.The static tests showed that xylene, toluene, gasoline, kerosene,and gas condensate could dissolve solid deposits to some extent; however,diesel and gas condensate were ineffective in dissolving the soliddeposits due to the formation of new bonds that increase the weightof asphaltene. Increasing the retention time and volume of solventduring static tests effectively increased solvents’ efficiencyin dissolving solid deposits and asphaltene, but the magnitude ofthe effects was solvent-dependent. In the core flooding experiments,to reverse the 79–91% of core permeability loss by asphaltenedeposition, the maximum efficiency (obtained at 1 bbl/min rather than3 bbl/min) of xylene, gasoline, and kerosene to restore the damagepermeability was 37.56, 25.14, and 17.80%, respectively.Forcleaning the surface facilities and tubing string, where asphalteneand wax depositions exist, solvents alone or their mixture with gascondensate could be very effective in dissolving the solid deposits.For this purpose, xylene, toluene, gasoline, and kerosene performedvery well in dissolving the solid deposits. In addition, gas condensateand xylene mixture, as well as mixtures of gas condensate and gasoline,resulted in reasonable efficiency in dissolving the solid deposits.In contrast, for the permeability reduction inside the porous mediaof the reservoir because of asphaltene deposition and in the absenceof wax deposition, the selection of suitable solvents is slightlydifferent. Xylene, gasoline, and kerosene effectively dissolved asphalteneand restored the damaged permeability due to asphaltene deposition.


The aim of this study was to systematically review the efficacy and safety of parecoxib and flurbiprofen axetil for perioperative analgesia in children through Bayesian network meta-analysis.We systematically searched PubMed, Embase, Cochrane Library, Web of Science, Sinomed, CNKI, VIP, and Wanfang Data databases on 18 July 2022 to obtain randomized controlled trials comparing perioperative parecoxib or flurbiprofen with placebo or standard treatment for pediatric analgesia. The outcomes were the postoperative pain score and the incidence of adverse events. The Gemtc package of R-4.0.3 and Stata 17.0 were used for Bayesian network meta-analysis.We retrieved 942 articles and 49 randomized controlled trials involving 3,657 patients who met the inclusion criteria. Compared with children who received placebo treatment, those who received flurbiprofen axetil had lower pain sores at each time point within 24 h postoperatively, and those who received parecoxib had lower pain sores at each time point within 12 h postoperatively. Compared with children who received tramadol treatment, both the children who received flurbiprofen axetil or parecoxib had lower pain scores at 8 h postoperatively. The ranking results demonstrated that flurbiprofen axetil had significant superiority in reducing pain scores at 2, 4, and 12 h postoperatively, and parecoxib had significant superiority in reducing pain scores at 0, 0.5, 1, 6, 8, and 24 h postoperatively. In terms of safety, compared with children who received placebo, those who received flurbiprofen axetil or parecoxib had a lower incidence of total adverse events and postoperative agitation. Compared with tramadol, flurbiprofen axetil and parecoxib both significantly reduced the incidence of total adverse events and postoperative nausea and vomiting. Compared with flurbiprofen axetil or fentanyl, parecoxib significantly reduced the incidence of postoperative nausea and vomiting. The ranking results showed that parecoxib was advantageous in decreasing the incidence of total adverse events and postoperative nausea and vomiting.Flurbiprofen axetil was most effective at reducing pain scores at 2, 4, and 12 h postoperatively. Parecoxib had an advantage in terms of reducing pain scores at 0, 0.5, 1, 6, 8, and 24 h postoperatively, as well as the incidence of total adverse events and postoperative nausea and vomiting.https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=348886, PROSPERO (CRD42022348886). Nearly half of the children still report moderate to severe pain during postoperative hospitalization . The resThere are limited options for analgesics for children. Ethical constraints in pediatric clinical trials have led to inadequate clinical evidence for many analgesics in children compared with adults, and the labels of most analgesics clearly state that they are not recommended for children . Opioidsin vivo  inhibitor. Owing to the novel drug carrier system of lipid microspheres, flurbiprofen axetil can be targeted to inflammatory sites and surgical incisions and control the release of the encapsulated drug for a longer-lasting effect . Flurbipin vivo . Parecoxin vivo .Clinical evidence for the use of parecoxib and flurbiprofen ester for perioperative analgesia in children has emerged as multimodal analgesia regimens and is increasingly advocated. However, only one meta-analysis published in 2015 systematically evaluated the effect of perioperative parecoxib on postoperative pain in children, demonstrating that, compared with placebo, parecoxib reduced pain scores and the incidence of adverse events . The effThis network meta-analysis was registered at PROSPERO (CRD42022348886), and the work was conducted following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) Statement. We systematically searched PubMed, Embase, Cochrane Library, Web of Science, Sinomed, CNKI, VIP, and Wanfang Data databases on 18 July 2022, using “parecoxib,” “flurbiprofen axetil,” “child, preschool,” “adolescent,” “postoperative period,” “perioperative period,” “intraoperative period,” “preoperative period,” “surgical procedures,” “operative,” and “general surgery” as keywords and MeSH terms combined with Boolean operators. The search equations can be scrutinized in The included studies were limited to those published in English or Chinese. The participants were children or adolescents (younger than 18 years) who underwent elective surgery with general anesthesia. The study groups received parecoxib or flurbiprofen axetil, and the control groups received placebo or standard treatment (fentanyl or tramadol) for perioperative analgesia. The outcomes evaluated were postoperative pain at 0, 0.5, 1, 2, 4, 6, 8, 12, and 24 h and the incidence of total adverse events, nausea and vomiting, and agitation. We excluded guidelines, reviews, comments, conference abstracts without full text and nonrandomized controlled studies.Two reviewers extracted the data independently. Disagreements were resolved by consensus through discussion and consultation with a third reviewer. The name of the first author, year of publication, sample size, patient age, surgery type, study design, and outcome measures were extracted from each study. In multi-arm trials, we only extracted the data from the arm related to our research.The quality of the included articles was evaluated by two reviewers using the Cochrane risk-of-bias tool for randomized controlled trials (RCTs) in the following domains: random sequence generation, concealment of allocation sequence, blinding of patients or outcome assessors, incomplete outcome data, selective reporting, and other types of bias. Disagreements were resolved through discussion or by the third reviewer. The risk of bias in each RCT was graded as high, low, or unclear.I2 and of >50% indicated significant heterogeneity. We used the node-splitting analysis to evaluate the inconsistency between the direct and indirect comparisons. If the P-value was >0.05, it indicated that direct and indirect comparisons tended to be consistent. We used random-effect consistency models within a Bayesian framework. The potential scale reduction factor proposed by Brooks et al. was used to diagnose the convergence degree of the model, and if the value tended to 1, the convergence was good  was used as the treatment effect estimator for continuous variables, while for dichotomous variables, it was the odds ratio. An MD of <0 indicated that the experimental group had a smaller value. The 95% CIs that did not include 0 were considered to show a significant difference between the two groups, which were compared. The odds ratio of <1 indicated that the incidence in the experimental group was lower. The 95% CIs that did not include 1 were considered to show a significant difference between the two groups. Global heterogeneity was assessed by was good . We plotWe retrieved 942 articles, and after the duplicates were removed, 437 articles were screened through titles and abstracts, and the full texts of 167 articles were retrieved to assess eligibility. A total of 49 RCTs involving 3,657 patients were included in the final analysis –67. The The characteristics of the included studies are shown in The quality assessment results of the included RCTs are summarized in A total of 9 RCTs reported pain scores at postoperative 0 and 0.5 h and 8 direct comparisons were established in the network model; 27 trials reported pain scores at postoperative 1 h and 10 direct comparisons were established in the network model; 30 trials reported pain scores at postoperative 2 h and 10 direct comparisons were established in the network model; 31 trials reported pain scores at postoperative 4 h and 10 direct comparisons were established in the network model; 17 trials reported pain scores at postoperative 6 h and 10 direct comparisons were established in the network model; 28 trials reported pain scores at postoperative 8 h and 9 direct comparisons were established in the network model; 28 trials reported pain scores at postoperative 12 h and 8 direct comparisons were established in the network model; and 26 trials reported pain scores at postoperative 24 h and 9 direct comparisons were established in the network model .At postoperative 0 h, flurbiprofen axetil and tramadol reduced the pain scores compared with placebo . At postA total of 40 RCTs reported the incidence of total adverse events and 10 direct comparisons were established in the network model; 34 trials reported the incidence of postoperative nausea and vomiting and 10 direct comparisons were established in the network model; and 13 trials reported the incidence of postoperative agitation and 7 direct comparisons were established in the network model .Compared with the placebo group, flurbiprofen axetil and parecoxib reduced the incidence of total adverse events and postoperative agitation . CompareAcross all outcomes, the assessment of inconsistency always supported the assumption of consistency between direct and indirect evidence. The results of the node splitting models are shown in Our analysis included 49 RCTs with 3,657 children aged 6 months to 14 years, and the aim of this study was to systematically evaluate the efficacy and safety of parecoxib and flurbiprofen axteil in perioperative analgesia in children using a Bayesian network meta-analysis. The results demonstrated that the pain scores of the flurbiprofen axetil group were significantly lower than those in the placebo group at all time points in the 24-h postoperative period, and the pain scores at all time points during the 12-h postoperative period of the parecoxib group were significantly lower than those in the placebo group. From the potential rankings, flurbiprofen axetil was superior to other drugs in reducing pain scores at 2, 4, and 12 h postoperatively, while parecoxib had some advantages in reducing pain scores at 0, 0.5, 1, 6, 8, and 24 h postoperatively.50 for COX-2 for at least 12 h, and the area under the valdecoxib concentration-time curve was similar to that in adults (40 mg)  . A popul (40 mg) . In chil (40 mg) . TherefoIn a previous network meta-analysis, parecoxib for analgesia after tonsillectomy in children was found to be better than fentanyl, and flurbiprofen axetil was superior to tramadol , but it In terms of safety, compared with children who received placebo, those who received flurbiprofen axetil or parecoxib had a lower incidence of total adverse events and postoperative agitation. Compared with tramadol, flurbiprofen axetil and parecoxib both significantly reduced the incidence of total adverse events and postoperative nausea and vomiting. Compared with flurbiprofen axetil or fentanyl, parecoxib significantly reduced the incidence of postoperative nausea and vomiting. The ranking results showed that parecoxib was more advantageous in decreasing the incidence of total adverse events and postoperative nausea and vomiting.Because few adverse events were reported in the included trials, such as respiratory depression, pruritus, headache, dizziness, and urinary retention, only total adverse events, postoperative nausea and vomiting, and agitation were analyzed in this study because of insufficient data. A multicenter retrospective study involving 3,542 patients found that postoperative administration of parecoxib resulted in a 0.2% incidence of adverse events, primarily hypotension, nausea, vomiting, pruritus, and rash . AnotherThere were a few limitations to this study. First, the included trials were associated with high risks of bias because most of them only mentioned “random” without specifying the method of generating the random sequence or describing the allocation concealment in detail. Second, most studies only recorded pain scores within the first 24 h after surgery, paying little attention to 48 or 72 h. Furthermore, we did not analyze other outcomes, such as opioid consumption or proportions of patients requiring rescue analgesia, which may have more clinical implications. Third, data on direct head-to-head comparisons of flurbiprofen axteil and parecoxib within the network were insufficient. Finally, there were some differences between studies in the type of surgery, perioperative care protocol, study drug dose, and timing of administration, which could explain the heterogeneity in our results.Based on the available clinical evidence, our network meta-analysis reached the following conclusions. Perioperative administration of flurbiprofen axetil and parecoxib were both effective in reducing postoperative pain scores and total adverse events compared with placebo. Flurbiprofen axetil and parecoxib also caused fewer total adverse events and postoperative nausea and vomiting compared with tramadol. Flurbiprofen axetil was most effective at reducing pain scores at 2, 4, and 12 h postoperatively. Parecoxib had an advantage in terms of reducing pain scores at 0, 0.5, 1, 6, 8, and 24 h postoperatively, as well as reducing the incidence of total adverse events and postoperative nausea and vomiting.The original contributions presented in the study are included in the article/XiC helped with study design, the selection of included articles, data extraction, quality assessment, data analysis and interpretation, and writing the manuscript. PC and QH helped with the study design, selection of included articles, data extraction, quality assessment, data analysis and interpretation, and the final review. XiaC, MH, and KT helped with the study design and the final review. All authors contributed to the article and approved the submitted version.


BackgroundBinge eating disorder (BED) is a condition characterized by episodes of consuming large amounts of food and feeling a lack of control over eating behavior. Stress, anxiety, and depression are risk factors for developing BED, which may be particularly relevant for medical students who experience high levels of academic pressure and stress. This study aims to investigate the prevalence of binge eating behaviors among medical students, as well as the types of negative emotions that are most strongly associated with binge eating.MethodologyThis cross-sectional study employed convenience sampling and included 332 medical students from Almaarefa University in Riyadh, Saudi Arabia. All medical students of all academic levels were eligible to participate in this study. Students from other colleges such as pharmacy students or students from other universities were excluded from this study. The research questionnaire collected information about negative emotions, BMI, number of meals, consumption of fast food, overeating behavior, and relevant demographic data. Descriptive and inferential statistics were used to analyze the data using SPSS Statistics version 26 .ResultsThe descriptive analysis showed that the majority of students reported consuming two meals per day and having snacks twice a day. Fast food consumption was reported by 58.1% of students. The study found that negative emotions such as stress, depression, and loneliness were significantly associated with binge eating behavior and had an impact on weight and BMI. The findings suggest the need for interventions to address negative emotions and promote healthy eating habits among medical students.ConclusionThe study concludes that negative emotions such as stress, aggression, and boredom are significantly associated with binge eating behaviors among medical students. Depression, disappointment, and thoughts about difficult tasks were linked to detrimental effects on BMI and weight loss. Binge eating disorder (BED) is a condition in which individuals experience episodes of eating large amounts of food and feel a lack of control over their eating behavior . A meta-Medical students commonly experience a variety of stressors, as it has been reported that the high incidence of anxiety, stress, and depression among medical students is mainly attributed to academic pressure, familial expectations, and fear of entering the medical field -6. OtherThe high prevalence of FEDs in medical students highlights the need for better prevention and treatment programs. Studies have shown that early detection during the premedical years may be vital, and prevention programs targeting medical students have shown positive results . The relStudy groupThis cross-sectional study employed convenience sampling and included 332 medical students from Almaarefa University in Riyadh, Saudi Arabia. The participant interviews for this research took place between July 14, 2023, and July 24, 2023. All medical students of all academic levels were eligible to participate in this study. Students from other colleges such as pharmacy students or students from other universities were excluded from this study.Data collection methodThe data collection tool used in this study was a questionnaire that was specifically designed to gather information on negative emotions, such as stress, anxiety, and depression, as well as BMI, number of meals per day, consumption of fast food, overeating, and demographic data. The questionnaire was developed by the researchers for the purpose of this study and has not been previously validated or tested for reliability. A pilot test of the questionnaire was conducted with a small group of participants (n=10) to identify any potential issues with the questions or response options. The face validity of the specially designed questionnaire used in this study was established by a team of experts in the field from Almaarefa University. These experts reviewed the questionnaire to ensure that the questions appeared to measure what they were intended to measure and were relevant to the study objectives. The team of experts evaluated the questionnaire for its clarity, appropriateness, and relevance to the target population. In this study, the questionnaire was self-reported, meaning that participants themselves filled out the questionnaire either in a paper-based format or through an online questionnaire. They were provided with instructions to answer all questions as accurately and honestly as possible. The questionnaire consisted of multiple-choice and open-ended questions. The questionnaire used in this study was administered in English as all the targeted participants, who were medical students in the college, were proficient in English. Therefore, there was no need for translation as English was already understood by the target population. It should be noted that an Arabic version of the questionnaire was also available upon request. This option was provided to accommodate participants who preferred or required the questionnaire in Arabic.BMIThe WHO BMI classification  is a sysThese categories were used in the research to classify participants' BMI measurements and analyze the distribution of BMI within the sample population.Ethical considerationEthical approval of the study was obtained from the Institutional Review Board of Almaarefa University with the research project number IRB23-062. Written consent was taken from each participant before collecting any data. Additionally, the data was stored securely with professional data collectors and was only accessible to authorized personnel. Identifiable information, such as names and contact information, was not included in this research.Statistical analysisThe data was cleared, coded, and entered using SPSS Statistics version 26  Descriptive statistics were used to summarize the data, including frequencies and percentages. To assess the relationships between variables, inferential statistics was used, including t-tests, chi-square tests, and correlation analyses. The level of statistical significance was set at a p-value of <0.05, indicating that a result is considered statistically significant if the p-value is less than 0.05. Data was transformed to enhance the interpretability of results. Frequency distribution rendered cumulative percentages to delineate the demographic features, the causes of binge eating, and eating habits. ANOVA appraised the relationship of the dependent variable (eating habits) with the independent variables (different negative emotions that were relieved). A two-tailed t-test was employed to analyze the effect of negative emotion-linked eating (NELE) on BMI and weight. The calculation of sample size was based on the following considerations: Z = standard normal distribution value at 95% confidence level = 1.96 and margin of error (d) = 5%.Participant’s characteristicsThe descriptive analysis of the study variables is summarized in Table The mean number of meals consumed per day was calculated as 2.27 (SD=0.85), whereas the mean number of snacks consumed per day was calculated as 1.98 (SD=1.174)  participants belonged to level 1, 5.4% (N=18) in level 2, 4.8% (N=16) in level 3, 10.5% (N=35) in level 4, 5.1% (N=17) in level 5, 12% (N=40) in level 6, 6% (N=20) in level 7, 13.3% (N=44) in level 8, 16 % (N=53) in level 9, 10.2% (N=34) in level 10, 4.2% (N=14) in level 11, 6.6% (N=22) in level 12, 3.6% (N=12) in level 13, and 3.6% (N=12) in level 14  preferred eating during times of stress, aggression, and boredom, and 51.2% (N=170) during loneliness. Regarding binge eating, 19.5% (N=65) reported eating during overwhelming situations, 28% (N=93) revealed during times of great stress, 28.91% (N=96) claimed binge eating when they feel depressed, 6.92% (N=23) students reported during times of disappointment, and 51% (N=170) students shared that loneliness triggers them to eat , depression (p<0.013*), a feeling of disappointment (p<0.003*), a feeling of loneliness (p<0.023*), and dissatisfaction toward eaten food (p<0.009*) Table .Impact of NELE on weightThe impact of NELE on weight is as follows: stress (p=0.003), depression (p=0.000), disappointment (p=0.001), loneliness p=0.015), and thought of a strenuous task (p=0.001) , feeling of being overwhelmed (p=0.001), depression (p=0.000), thought of a strenuous task (p=0.000), disappointment (p=0.000), stress (p=0.002), and loneliness (p=0.023) Table .This study aims to investigate the prevalence of binge eating behaviors among medical students, as well as the types of negative emotions that are most strongly associated with binge eating. In this study, the majority of medical students had a BMI within the normal range. This finding is consistent with a study conducted in Saudi Arabia, which reported that only 23% of medical students were overweight, while the majority had a normal BMI . SimilarFood consumption and preferencesOur study reveals that approximately half of the medical students surveyed consume only two meals per day. In contrast, a study conducted in Egypt found that over half of the medical students consumed three meals per day . The majEmotional influences on weight and BMIWhen under stress, agitated, or bored, more than two-thirds of our subjects chose to eat. It is obvious that medical students' eating habits are influenced by their emotions. This implies that tension, hostility, and boredom rule medical students' lives, or we may attribute these findings to the demanding lifestyle that each medical student leads. It may be inferred from our study's finding that half of the participants eat alone and that students spend the majority of their time alone studying or reading. Pertaining to binge eating, a fifth of the participants in our study admitted to eating during stressful situations, while a third admitted to eating when they were depressed. Half of the individuals said that feeling lonely led them to eat. In our study, depression, the idea of a difficult task, and disappointment were all substantially connected to the detrimental effects of eating on BMI, which were subsequently followed by feelings of overwhelm, stress, and loneliness. The influence of unpleasant emotions associated with eating on weight loss revealed a substantial correlation with depressive symptoms, disappointment, and thoughts of difficult tasks, followed by stress and loneliness. These results support another Saudi Arabian research which also found that individuals tend to lose weight while under stress . These fPotential implicationsThe findings of this study highlight the need for further exploration of the relationship between binge eating behaviors, negative emotions, and the socioeconomic and cultural factors specific to medical students. Understanding these associations can have potential implications for the development of targeted interventions and support programs to address and prevent binge eating disorders among medical students. Targeted interventions may include psychoeducation and awareness campaigns, screening and early intervention, counseling and support services, and nutritional guidance. By implementing these targeted interventions, medical schools and institutions can create a supportive environment that addresses the unique challenges faced by medical students, promotes mental well-being, and helps prevent and manage binge eating disorders.LimitationsOne limitation of this study is that the sample size and characteristics may not accurately represent all medical students or the general population. Another limitation is the use of self-reported data, which introduces the possibility of recall and social desirability biases. The cross-sectional design of the study makes it challenging to establish causal relationships, highlighting the need for longitudinal data. Additionally, the self-reported height and weight measurements may have led to misclassification of BMI. It is also important to note that the scale used to measure binge eating behaviors and negative emotions in the present study was not validated. The lack of validation introduces the possibility of measurement error and questions the reliability and accuracy of the results obtained from the scale. Considering these limitations, caution is advised when interpreting the findings, and future research should address these issues for a more comprehensive understanding of the topic.In conclusion, the study highlights the prevalence of binge eating behaviors among medical students, as well as the types of negative emotions such as stress, aggression, and boredom, which are significantly associated with binge eating. These negative effects were then followed by feelings of being overwhelmed, stressed, and lonely. Half of the students said that they ate when they felt lonely. Depression, thoughts about difficult tasks, and disappointment were all found to be significantly linked to the detrimental effects of eating on BMI. Students who experience these negative emotions have a significant impact on their ability to lose weight. In other words, negative emotions can be a barrier to weight loss.Due to the dearth of research on the epidemiology of binge eating in the region, it is often challenging to explain the variations in binge eating prevalence rates, as well as the kinds of negative emotions experienced by medical students living in the Kingdom of Saudi Arabia or the Middle East. Further research is needed to establish the relationship between binge eating and negative emotions, targeting a larger sample size.


Background: A major worry of juvenile penile LS is potential malignant degeneration to spinocellular carcinoma (SCC) in adulthood. LS is characterized by increased CD8+ and CD57+ cells, dermal sclerosis, epidermal atrophy, and hyperkeratosis. p53 and Ki67 are reliable premalignant markers. Our aim was to define the LS immunohistochemical profile of foreskin in children, focusing on tissue immune response and cell proliferation. Methods: Thirty specimens of foreskins removed from pediatric patients during circumcision were included: six from ritual operation (A), twelve from phimosis (B), and twelve from phimosis with LS (C). Formalin-fixed paraffin-embedded sections were stained for histomorphology and immunohistochemistry. A quantitative evaluation for CD8, CD57, p53, and Ki-67 and a statistical analysis were performed. Results: As compared to groups A and B, the samples from group C patients showed an acanthotic epidermis, a dermal band of lymphoid infiltrate with a significant enhancement of CD8+ CD57+ lymphocytes, and a keratinocytic hyperplasia with an overexpression of Ki67+ and p53+ cells. Conclusions: Immunohistological findings confirmed an immune reaction and proliferative behavior in juvenile LS of foreskin. We believe that radical circumcision should be the first treatment of choice in pediatric patients with clinical suspicious of LS for the potential risk of transformation to SCC in adulthood. Lichen sclerosus (LS), first described by Hallopeau in 1887, is a chronic inflammatory disorder of unclear etiology involving the skin and mucosa ,3. In paIn particular, in circumcised children affected by phimosis, LS has been found in 5 to 50%, with the peak of incidence at 7–8 years age . PhimosiAzurdia et al. studied the correlation between autoimmune disease and LS of foreskin, reporting that only 3% of 58 patients with LS had a personal history of an autoimmune disease, and 10% had a first-degree relative who had an autoimmune disease . Despite+ cells, trigger an immune attack against basal keratinocytes, assisted by other helper T cells via secretion of TH1 cytokines [Histologically, genital LS in males affects almost exclusively the inner surface of the foreskin, and it is characterized by band-like lymphocytic inflammatory infiltrate with a predominant T-cell phenotype associated with dermal edema and sclerosis, epidermal atrophy, and hyperkeratosis . Atrophyytokines . Even ifytokines . In thisytokines . On the ytokines . In partytokines .The etiology, maintenance, and progression of chronic inflammatory diseases, including LS, may be caused by oxidative stress. Low levels of antioxidant enzymes such as superoxide dismutase have been associated with lipid peroxidation in keratinocytes, oxidative DNA damage, and protein oxidation in LS areas .In addition to causing inflammation, vascular sclerosis also contributes to oxidative stress in LS, which results in the downregulation of tumor suppressor genes and overexpression of p53 in the skin, both of which are associated with the emergence of skin cancers. Only a partial understanding exists of the precise order of events and how they interact .Ki67 is a common indicator of cell proliferation. The Ki67 protein is expressed as cells undergoing mitosis, and is phosphorylated and dephosphorylated in vivo during mitosis, making it vulnerable to protease destruction. It has been discovered that the expression of p53 and Ki67 are connected in a number of cancer types, including breast cancer and oral squamous cell cancer. It is still unclear how p53 may impact the expression of the Ki67 gene .To the best of our knowledge, the immunohistochemical changes in foreskin of children affected by LS have not yet been elucidated. The aim of this study was to define the LS immunohistochemical profile of foreskin in children, in particular focusing on tissue immune response and cell proliferation markers.Thirty specimens of foreskins removed during circumcision from pediatric patients were included in the study. In particular, 6 samples were harvested during ritual operation (group A), 12 from patients with phimosis (group B), and 12 from patients with phimosis with histological diagnosis of LS (group C). This latter group was revaluated by two expert pathologists (GT and AI), taking into consideration the principal histological parameters affecting either the epidermis  or the dermis .Patients older than 16, those with a history of penile surgery, those with aberrant genetic pathologies and chromosomal problems, and those with dermatological diseases were excluded from the study.The ages of the patients were 5.3 ± 1.5, 6.1 ± 1.9, and 6.6 ± 1.6 years for each group, respectively. From the corresponding tissue blocks, formalin-fixed paraffin-embedded sections were cut and routinely stained with hematoxylin and eosin (H&E) for histomorphological analysis. Five-micron thick sections were successively obtained for immunohistochemical procedures; after deparaffinization by xylene and washing in descending alcohol scale, sections were treated using 3% hydrogen peroxide for 10 min in order to abolish endogenous peroxidase. They were then washed in deionized water three times and incubated with normal sheep serum to avoid unspecific adherence of serum proteins for 30 min at room temperature. The following pre-diluted primary antibodies were applied for 30 min at 37 °C: rabbit monoclonal anti-CD8 (clone SP57), mouse monoclonal anti-CD57 (clone NK-1), mouse monoclonal antip53 (clone Bp53-11), and rabbit monoclonal anti-Ki-67 (clone 309); all antisera were commercially obtained from Roche Diagnostics GmbH, Mannheim Germany. Next, the sections were washed three times with PBS and incubated with a biotinylated goat anti-mouse IgG secondary antibody  for 20 min at room temperature, subsequently incubated with horseradish peroxidase-labeled secondary antibody for 30 min, and then developed with diaminobenzidine tetrahydrochloride and counterstained with Mayer’s hematoxylin using the ULTRA Staining system . Negative controls were obtained by omitting the specific antisera and substituting them with PBS. The quantitative immunohistochemical analysis of CD8+, CD57+, p53+, and Ki67+ cells was performed by two expert observers (GT and AI). Only elements with nuclear brown-colored staining were considered positive, although the intensity of the staining was not considered. The percentage of positive cells was evaluated in 400 consecutive epithelial cells of selected areas by recording the locations of the positive cells in the levels of the epidermis . This evaluation was achieved using digital image analysis of microscopic images with a DS-Ri2 color video camera (Nikon Instruments) mounted on a conventional light microscope (Nikon Eclipse Ci). The images were acquired using a ×20 objective  and a ×40 objective . Before analysis of the immunohistochemical slides, an image of an empty microscopic field was taken to be used for the ideal correction of unequal illumination.Numerical data were expressed as mean, standard deviation (S.D.), median, and range (minimum and maximum). A non-parametric approach was used since the numerical variables were not normally distributed, as verified by the Kolmogorov–Smirnov test.In order to identify possible significant differences among the three groups of patients , the non-parametric ANOVA  was applied for all parameters . Post hoc two-by-two comparisons between types of surgery were performed using the Dunn test. For this analysis, Bonferroni’s correction was used; the adjusted alpha level was obtained by dividing the alpha significance level by the number of possible two-by-two comparisons between types of surgery (0.050/3 = 0.017). Some plots were realized in order to better visualize the distribution of each variable into one of three groups.Statistical analyses were performed using IBM SPSS for Windows, Version 22 .p-value lower than 0.05 was considered to be statistically significant.A Foreskins from ritual circumcisions showed regular stratified squamous keratinized epithelia, as well as loose connective tissue with sparse, focal lymphocytic infiltrate and discontinuous smooth bundles a. The skIn groups A and B, immunohistochemical evaluation showed few positive CD8+ CD57+ lymphocytes  b,c; a grThe results of the statistical analysis are summarized in Penile LS, firstly described by Stuhmer in 1928 , is consIn this regards, genital LS has been linked to chronic exposure to urine as a cause . Even ifDespite a significant incidence of penile LS in patients of pediatric age, which is strictly correlated with phimosis, circumcision , whetherIt is extremely rare for a man who was circumcised at birth to acquire LS.According to Edmonds et al. , less thLS impacted the prepuce in 70% of males, the glans in 60%, and both the prepuce and glans in 40%. The involvement of the meatal/urethral system was present in 17% . In thisWhether adult and pediatric LS-related conditions are the same disease entity is still unclear. Edmonds et al. demonstrated that the expression genic profiles from adult and pediatric samples were similar, indicating the same disease process . The hisIndependently of the LS subtype, oxidative stress and inflammation may cause the overexpression of wild-type p53 in basal keratinocytes. Additionally, the limitation of oxygen flow causes ischemic stress, which intensifies the p53 overexpression as a result of the formation of sclerotic arteries and poor oxygenation .Studies on oxidative stress in LS by Sander et al. , who havA complicated regulation of the antioxidant defense system can be seen in the reports linking altered antioxidant enzymes to aging, photoaging, and carcinogenesis in human skin ,41,42.Although the role of p53 overexpression in LS is still debated, it has been stated that its upregulation serves as a useful marker of malignant potential in LS, and may be related to the malignant progression of LS to SCC . MoreoveAs in adult penile LS, our immunohistochemical analysis of the LS-affected foreskin of children showed a similar involvement of inflammatory responses and the proliferative status of basal cheratinocytes. It is known that the immune response plays a crucial role in cells’ growth and differentiation, regulating the balance between apoptosis and proliferation . ChronicAlthough clear clinical evidence that juvenile LS of the foreskin can evolve into SCC has not yet been described, an incidence of 2.6% of vulvar SCC following juvenile vulvar LS, with a standardized incidence ratio of 33.6 compared with the control population, has been documented . Our datThis shows how, when there is a clinical suspicion of penile LS, it is not suggested to perform a partial circumcision in order to preserve the foreskin, but it is important to carry out a radical prepuce excision. In fact, it has been reported that up to 50% of pediatric patients undergoing a foreskin-conservative procedure had a recurrence .Although the current European guidelines suggest, with strong evidence, that circumcision should be performed in the case of LS suspicion , a conseTopical testosterone is another option for treating LS, but it is not as effective as ultrapotent topical corticosteroids ,57,58.Photodynamic treatment, phototherapy, and photodynamic therapy, according to multiple case studies, appear to be somewhat successful alternative therapeutic approaches for treating LS that is resistant to standard treatment ,60.Indeed, circumcision is the only option in 96% of instances, and the use of topical steroids after circumcision is crucial for preventing complications associated with LS [However, while medical therapy is effective for symptomatic relief and reductions in atrophy, scarring, and strictures in juvenile penile LS, it remains controversial whether medical treatment will prevent the development of SCC .In conclusion, our immunohistological findings confirm an immune reaction and a proliferative behavior in juvenile LS of the foreskin, similar to adult genital LS. We believe that radical circumcision should be the first choice of treatment in pediatric patients with clinical suspicions of LS due to the potential risk of transformation to SCC in adulthood. In this regard, in the case of medical or foreskin-preserving therapy for LS, short- and long-term follow-ups are warranted in order to identify LS-related sequelae in the early stages.


The liver is a key target organ for colorectal and gastric cancer metastasis. One of the challenges in the treatment of colorectal and gastric cancers is the management of liver metastasis. This study aimed to investigate the efficacy, adverse effects, and coping strategies of oncolytic virus injection in patients with liver metastases of gastrointestinal malignancies.We prospectively analyzed patients treated at Ruijin Hospital affiliated with Shanghai Jiao Tong University School of Medicine from June 2021 to October 2022. 47 patients with gastrointestinal cancer liver metastasis were included in the study. The data, including clinical manifestations, imaging, tumor markers, postoperative adverse reactions, psychological intervention, dietary guidance, and adverse reaction management were evaluated.Oncolytic virus injection was successful in all patients, and no drug injection-related deaths occurred. The adverse effects, such as fever, pain, bone marrow suppression, nausea, and vomiting, were mild and resolved subsequently. Based on the comprehensive intervention of nursing procedures, the postoperative adverse reactions of patients were effectively alleviated and treated. None of the 47 patients had any puncture point infections, and the pain caused by the invasive operation was relieved quickly. After 2 courses of oncolytic virus injection, postoperative liver MRI showed 5 partial remissions, 30 stable diseases, and 12 progressive diseases in target organs.Interventions based on nursing procedures can ensure the smooth treatment of recombinant human adenovirus type 5 in patients with liver metastases of gastrointestinal malignant tumors. This is of great importance for clinical treatment and significantly reduces patient complications and improves the patient’s quality of life. Liver metastasis is the leading cause of death in patients with colorectal and gastric cancer , with thOncolytic viruses are a class of natural or recombinant viruses that selectively infect and kill tumor cells without damaging normal cells , 6. CompThe present study protocol was approved by the Ethical Investigation Committee of Ruijin Hospital, affiliated with the School of Medicine, Shanghai Jiaotong University, China. Written informed consent was obtained from every patient. Questionnaires were filled to collect and analyze the applicable clinical data.We prospectively analyzed the clinical data of patients with liver metastasis of gastrointestinal malignant tumors who received oncolytic virus injections at Ruijin Hospital, School of Medicine, China from June 2021 to October 2022.The inclusion criteria were as follows: (1) patients need sign an informed consent to participate in the study; (2) the injectable lesions in the liver meet the requirements of the RECIST1.1 for measurable target lesion; (3) the longest diameter of the liver lesions is no greater than 100 mm, and diameter of the injection lesion is between 10 mm and 80 mm; and (4) current physical condition and following treatment plan were confirmed consistent to the protocol by investigator. The exclusion criteria were as follows: (1) injectable lesions had received ablation, intervention, offshore knife, and other local treatments before; (2) oncolytic virus or similar drug (such as T-VEC) was performed before; (3) received antiviral treatment, such as acyclovir, ganciclovir, and alsidine, within 4 weeks before the first dose of the trial treatment; (4) pregnant or breastfeeding women or those ready to conceive or feed during the study; and (5) combined with other diseases that could influence the study.The attending performed the oncolytic interventional surgery and managed the adverse reactions before and after surgery along with the nurses according to the nursing procedures. The nursing procedure involves evaluation, diagnosis, planning, implementation, and evaluation Figure 1The patient’s allergy history was asked in detail, and the allergy was confirmed during the operation. Prior to the surgery, parameters such as tumor markers, coagulation function, blood routine, and liver function were checked. Further, the nurse instructed the patient to have a light diet the day before the surgery and also to fast after 10 p.m. Before the surgery, the patient’s vital signs were evaluated again, and the patient was transported to the B-ultrasound room in a flat car . Before 11 vp/0.5ml/branch, milky white suspension, main component name: recombinant human adenovirus 5 particles with E1B-55 kD and E3 region gene fragment (78.3–85.8 mu). Usage: After diluting the recombinant human adenovirus 5 injection with normal saline, three injection points were selected according to the longest tumor diameter under the guidance of B-ultrasound. The injection dose is determined according to the tumor size: if the longest diameter of the injected lesion was between 10 mm and 40 mm, 2 doses were injected; if the longest diameter of the injected lesion was between > 40 mm and 80 mm, 4 doses were applied. The recommended injection time was one cycle every 14 days and a total of two cycles intratumorally.Before the procedure, target liver lesion biopsy under the guidance of B-ultrasound was performed. Recombinant human adenovirus 5 injection , with the following specification, was used: 5.0 × 10Patients were given psychological support before and after the procedure. The patients were guided after each intervention for both physical and mental relaxation . For thiAfter 4h post-infusion, the patient was allowed to consume a small amount of a light diet, followed by a high-calorie, high-vitamin, high-protein, warm, and cool semi-liquid diet the second day. Food that is fried, hard, boney, rough, prickly, or that requires chewing hard was avoided. Patients were encouraged to drink 2000–3000 ml of water or juice every day to reduce kidney complications .Routine blood work, liver function, DIC, tumor markers, and other tests, as well as a liver magnetic resonance examination, were completed 1 month after the operation to evaluate the curative effect. Vital signs such as blood pressure, heart rate, pulse, and respiration were closely monitored after the drug injection to assess the symptoms of pain and liver bleeding. If the patient appears pale, develops a cold sweat, exhibits a drop in pulse and blood pressure, or shows any other symptoms, timely symptomatic treatment is initiated .Local observation and nursing of the puncture point are performed by covering with sterile gauze and then pressurizing with the abdominal belt. If necessary, the puncture point was pressed and the dressing was observed closely . After 2RECIST 1.1 is an internationally recognized guideline for evaluating the efficacy of malignant tumors . It takeCarcinoembryonic antigen (CEA) is an important tumor marker, and the National Comprehensive Cancer Network (NCCN)  indicateLiver function impairment classification , also knEvaluation and follow-up of liver function impairment: An increase in ALT exceeding the upper limit of normal (40 u/L) was defined as liver function impairment. Liver function impairment was graded according to the criteria of chemotherapy drugs and the NCI-CTC (3.0), which classified the liver function impairment into the following degrees: 0 degree indicates normal, and I degree is defined as aspartate aminotransferase/alanine aminotransferase (AST/ALT) 1.0 to 2.5 times the upper limit of normal [ULN] or total bilirubin (TB) 1.0 to 1.5 times ULN; II degree as AST/ALT 2.6 to 5 times ULN or TB 1.6 to 3 times ULN; III degree as AST/ALT 5.1 to 20 times ULN or TB 3.1 to 10 times ULN; IV degree as AST/ALT over 20 times ULN or TB over 10 times ULN .The National Cancer Institute Common Toxicity Classification Criteria version 3.0 was used . DigitalData were analyzed using the SPSS 24.0 software , and thePatients were followed up for 6 months after the interventional therapy Forty-seven patients with recurrent liver metastasis of gastrointestinal malignant tumors admitted to our hospital from June 2021 to October 2022 met the diagnosis criteria for gastric adenocarcinoma or colorectal adenocarcinoma. A total of 47 patients, 34 (72%) males and 13 females (28%), with a mean age of 59.96 ± 13.43 years, comprised the study cohort. Of these 47 subjects, 22 patients had hypertension (47%), 8 patients had diabetes mellitus (17%), and 1 patient (2%) had a stroke. As per the tissue classification, 46 subjects had adenocarcinoma (97.9%). Further, 11 (23.4%) subjects were treated with chemotherapy plus immunotherapy, and 36 (76.6%) subjects received chemotherapy plus targeted therapy Table 1.All 47 patients in this group received two injections.All 47 patients with liver metastasis of gastrointestinal malignant tumors were treated with oncolytic virus injection, followed by a liver MRI to evaluate the disease state. Our results suggest that 5 subjects were in remission, 30 had stable disease, and 12 subjects indicated a progressive disease. After symptomatic treatment and care for the adverse reactions, all patients were discharged smoothly Table 2.CEA is an important broad-spectrum tumor marker that was first identified in colon cancer and embryonic tissues. Although it cannot be used as a specific index for the diagnosis of a certain malignant tumor, it still has a certain value in the disease monitoring and efficacy evaluation of malignant tumors. To evaluate whether the oncolytic virus treatment has clinical benefit, we quantified CEA and found that CEA decreased after oncolytic virus injection compared to before injection and fluctuated within the normal range Figure 4Following the oncolytic virus injection, patients experienced fever and pain Table 3.After six months of postoperative follow-up, one patient died of systemic organ failure at the end of the follow-up period, and the remaining patients had not reached the OS endpoint.After interventional treatment, the necrotic tumor tissue is absorbed by the body, resulting in fever, which can occur 6 hours after surgery. Body temperature can reach up to 39°C, with symptoms lasting 3–4 days but usually subsiding within 1–3 days. In this study group, 37 patients (78.7%) developed a fever with a high body temperature .In the process of interventional treatment, the liver tumor lesions caused by liver ischemia could stimulate the liver capsule, which would make the patient feel high pain. This may aggravate the patient’s concern about the disease and affect the patient’s confidence to fight it. In our study, 27 cases (57.4%) had muscle pain and pain at the puncture site. The pain score was 3–6 and was spontaneously relieved after 2–3 days through psychological care and relaxation therapy without any analgesics .The patients were closely monitored for mucosal bleeding, ecchymosis, petechiae, hematuria, and bloody stools . ParametNausea and vomiting are caused by the toxic effect of chemotherapy drugs on the gastrointestinal mucosa during the interventional process . HoweverOncolytic viruses have been taking the front stage in biological therapy for cancer recently . OncolytIntratumoral injection is the most commonly used method of administration of oncolytic viruses, with safety evidence available from several phase III clinical trials, albeit insufficient. Intratumoral injections are complex to perform and are limited to tumors that are accessible through clinical palpation or direct imaging , 37. On The combination of an oncolytic virus with chemotherapy , radiothIn this study, 47 patients received an intratumoral injection of an oncolytic virus combining chemotherapy, targeted therapy, and immunotherapy . As an eThe original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.The studies involving human participants were reviewed and approved by the Ethical Investigation Committee of Ruijin Hospital affiliated with the School of Medicine, Shanghai Jiaotong University, China. Ethical approval code: (2020). Written informed consent was obtained from each patient in the form of a questionnaire for the collection and analysis of applicable clinicaldata. The patients/participants provided their written informed consent to participate in this study.JiZ, QH and MW, LH contributed in the study design, data collection, data analysis, data interpretation, literature search, and writing of the article. JiZ contributed in the literature search and writing of the article. JiZ, QH, DM contributed in the data collection, analysis, and interpretation. JiZ, MW, and DM contributed in the data analysis and data interpretation. JuZ and MW contributed in the study design and data interpretation. All authors contributed to the article and approved the submitted version.


At the household level, the odds of IDA among CU5 were higher in the poorest households , with ≥5 CU5 , and with no access to improved sanitation facilities . For WRA, the multivariable logistic regression found that the odds of IDA were higher among women with vitamin A deficiency , zinc deficiency , no education , and from severely food insecure households . The odds of IDA were lower among women whose body mass index was overweight  or obese . Conclusions: The child’s age, presence of diarrhea or fever, place of residence, household size, wealth status, and access to sanitation facilities were significantly associated with IDA among CU5 in Pakistan. For WRA, education, body mass index, vitamin A and zinc status, household food security status, wealth status, and access to sanitation facilities were significantly associated with IDA. Large, well-established, government-funded programmes focused on micronutrient supplementation, food fortification, the diversification of food supplies, and the treatment and prevention of infectious and parasitic diseases are needed to prevent IDA and all forms of anemia among children and women in Pakistan.Introduction: Anemia remains a global public health problem, especially in developing countries. It affects primarily children under five (CU5), women of reproductive age (WRA), and pregnant women due to their higher need for iron. The most common form of anemia is iron-deficiency anemia (IDA). IDA is estimated to cause half of all anemia cases and one million deaths per year worldwide. However, there remains a lack of well-documented and biochemically assessed prevalence of IDA based on the representative population-based samples globally and regionally. In this study, we aimed to assess the National Nutrition Survey (NNS) 2018 to identify the prevalence and risk factors of IDA in Pakistani CU5 and WRA. Methods: Secondary analysis was conducted on the NNS 2018, a cross-sectional survey, which collected data on dietary practices, malnutrition, and food insecurity. Anemia was defined as hemoglobin levels < 11.0 g/dL in children and 12.0 g/dL in women. IDA was defined as low hemoglobin and low ferritin (<12 ng/mL) levels, adjusted for inflammation using AGP and CRP biomarkers in CU5 and WRA. Univariate and multivariable logistic regressions were conducted using Stata statistical software (version 16). We also compared the IDA rates of NNS 2018 and 2011. Results: A total of 17,814 CU5 and 22,114 WRA were included in the analysis. Of the CU5, 28.9% had IDA, while 18.4% of WRA reported to experience IDA. Among the CU5, IDA was most prevalent among male children aged 6–23 months living in rural areas and with the presence of diarrhea and fevers in the last 2 weeks. Children whose mothers had no education, were aged 20–34 years, and employed, had a higher prevalence of IDA. Married WRA, who are employed, living in rural areas, and with no education, had a higher prevalence of IDA. In the multivariable logistic regression, children aged 6–23 months (AOR = 1.19, 95% CI [1.08–1.33],  Anemia remains a global public health problem, especially in developing countries ,2,3. It Over the past 20 years, the prevalence of anemia in CU5 (53.7% in 2018) and WRA (42.7% in 2018) has remained a severe public health problem in Pakistan . There hThe National Nutrition Survey 2018, a cross-sectional survey, collected quantitative and qualitative data at the household level across the country . A two-sp < 0.25 were considered for inclusion in the multivariate model. Covariates that were not significant at the multivariate level were dropped from the model after careful assessment of confounding. The final model was selected based on theoretical and statistical significance of predictors. The Type 1 error was set at 0.05. The model estimates are presented with the adjusted odds ratios (AOR) and 95% CI.Secondary data from 17,814 CU5  and 22,114 WRA was used to identify the prevalence and risk factors of IDA by maternal age, education, and employment; child gender, age, and presence of disease; women’s age, education, employment, and presence of disease; household socioeconomic status and place of residence. Univariate logistic regression was conducted to identify factors associated with IDA in CU5 and WRA. All data analyses were conducted in STATA version 16. Since IDA was the main outcome measure, women and children with results available for both hemoglobin and ferritin were included in the analysis. The frequencies, along with weighted percentages, were reported for selected predictors. The analysis started with simple univariate analysis followed by multivariate logistic regression. Unadjusted odds ratios with their 95% CIs were reported for the bivariate analysis. Variables significant at The presence of anemia and IDA was assessed in CU5 and WRA via blood samples and an on-the-spot hemoglobin test using a HemoCue 301 machine. Anemia was defined as hemoglobin levels <11.0 g/dL in children and 12.0 g/dL in women . IDA wasTo determine the plasma content of vitamin A (retinol), a reverse-phase high-pressure liquid chromatographic (HPLC) technique was employed. This analytical method helps separate and quantify different components in a mixture based on their chemical properties and retention times. The retinol levels were quantified using an Agilent 1200 series HPLC analyzer  with UV/Visible detection. To separate the components, a ZORBAX C-18 column measuring 4.6 × 150 mm with a particle size of 5 µm was utilized, and the analyte’s concentration was measured at 325 nm. The mobile phase consisted of 100% methanol, maintained at a constant composition throughout the analysis. In order to correct for variable recovery, retinyl acetate was employed as an internal standard.The measurement of plasma levels of 25-hydroxy vitamin D was performed using an automatic immunoanalyzer called Diasorin Liaison . The technique employed for this analysis was a direct competitive chemiluminescence immunoassay (CLIA), which utilizes the principle of competition between the analyte (25-hydroxy vitamin D) and a labelled counterpart for binding to a specific antibody. Analytical Measuring Range (AMR) for the Liaison XL 25 OH Vitamin D assay is 4 to 130 ng/mL. Values < 20 were considered to be associated with vitamin D deficiency . A countOut of the 17,814 CU5, 51.0% were male, with the majority aged 24–59 months (80.6%) and living in rural areas (62.1%) . The maj2), normal vitamin A (72.9%), and zinc serum levels (77.8%). Additionally, about 79% of WRA were found to be deficient in vitamin D. More than ½ of the WRA had no education (53.7%), while a ¼ had completed secondary (12.9%) or higher education (11.7%). Most of these women were housewives (86.5%), belonging to households with ≤6 family members (58.0%) and had access to improved drinking water (92.4%) and improved sanitation facilities (84.8%). Furthermore, 60.3% of households with the WRA were food secure, with 19.6% reporting severe food insecurity. A total of 5 out of 100 households (5.2%) reported receiving some form of financial assistance from the government in the last 12 months.Out of the 22,114 WRA, 93.1% were married, with the majority aged 30–49 years (55.1%) and living in rural areas (60.3%) . The majp = 0.002) with the presence of diarrhea  or fever  in the last 2 weeks compared with children aged 24–59 months with no diarrhea or fever (p = 0.017) or primary levels of education . Children with employed mothers  had higher odds of IDA compared with children whose mothers were housewives but not significantly. In addition, the odds of IDA among children decreased with an increase in the mother’s age; however, the odds ratios were not statistically significant for mothers aged 20–34 years  and 35–49 years , compared to mothers <20 years of age. The odds of IDA in children were higher in households with ≥7 members , ≥5 CU5 , and no access to improved sanitation facilities  compared with households having ≤6 members, <5 CU5, and access to improved sanitation facilities. The odds of IDA increased with the severity of food insecurity experienced by households but was only statistically significant among households experiencing moderate food insecurity  compared with food secure households. Similarly, the odds of IDA in children increased as the wealth status of households worsened. Across the wealth quintiles, the poorest households  were most at risk of experiencing IDA in children compared with the richest households. The odds of IDA were lower among children whose households did not receive financial assistance in the last 12 months  compared with households who received assistance and located in Punjab , Sindh , erstwhile FATA , Balochistan , Khyber Pakhtunkhwa , and AJK  continued to experience higher odds of IDA compared with households located in GB.In the univariate logistic analysis, the odds of IDA were higher among children under two years of age  with the presence of diarrhea in the last 2 weeks  or fever  remained at risk of IDA compared with children aged 24–59 months with no diarrhea or fever in the last 2 weeks. The relationship between the risk of IDA among CU5 and maternal age, education, and employment status did not remain apparent, which was initially found to be significant in the univariate analysis. At the household level, the risk of IDA among CU5 remained higher in households with ≥5 CU5 , and with no access to improved sanitation facilities  compared with households with <5 CU5 and access to improved sanitation facilities. Similarly, the poorest households  remained most at risk of experiencing IDA, with the risk gradually decreasing across the wealth quintiles relative to the richest households. Households located in Punjab , Sindh , erstwhile FATA , Balochistan , Khyber Pakhtunkhwa , and AJK  continued to experience higher odds of IDA compared with households located in GB.In the multivariable logistic regression, children aged 6–23 months , with the presence of vitamin A deficiency , zinc deficiency , and an underweight body mass index  compared with women from urban areas, with no vitamin A deficiency, zinc deficiency, and an average body mass index (p < 0.001) or obese  body mass index compared with an average body mass index. Compared with women having higher education, the odds of IDA were higher among women with no education  or lower levels of education . Employed women  had higher odds of IDA compared with housewives. The odds of IDA decreased with an increase in the women’s age; however, the odds ratios were not statistically significant for women aged 30–49 years  relative to women 15–29 years of age. Similarly, marital status had no statistically significant association with IDA among women. The odds of IDA were higher in households with no access to improved sanitation facilities  and were experiencing food insecurity  compared with households having access to improved sanitation facilities and being food secure. The odds of IDA increased with the severity of food insecurity and poverty experienced by households. The poorest households  were most at risk of experiencing IDA compared with the richest households. Similar to CU5, the odds of IDA were lower among WRA whose households did not receive financial assistance in the last 12 months  and were located in Khyber Pakhtunkhwa , and ICT  compared with households who received assistance and were located in GB. However, households located in Sindh  were found to have a higher risk of IDA in WRA compared to GB.In the univariate logistic analysis, the odds of IDA were higher among women from rural areas  and zinc deficiency  remained at risk of IDA compared with women with no vitamin A deficiency and zinc deficiency. The relationship between the risk of IDA and women’s education remained apparent; however, the odds ratios decreased with no education  and lower levels of education . The odds of IDA were lower among women whose body mass index was overweight  or obese  compared with average body weight women. At the household level, the risk of IDA remained higher in households experiencing severe food insecurity  and located in Sindh  compared with households experiencing food security and located in GB. Similarly, the risk of IDA remained lower in households located in Khyber Pakhtunkhwa  compared to households in GB.In the multivariable logistic regression, women with the presence of vitamin A deficiency  in this study. This finding is consistent with anemia-related studies conducted in Bangladesh, Bhutan, Nepal, and India ,40,41,42Policies and programmes supporting micronutrient supplementation, food fortification, diversification of food supplies, and treatment and prevention of infectious and parasitic diseases  are essential to address IDA  among CU5 and WRA in Pakistan . A multiThe major strength of this study is the use of consistent serum hemoglobin and serum ferritin, adjusted for inflammation using AGP and CRP biomarkers, to assess IDA among CU5 and WRA at the population level. Another strength is the use of the most recent, largest nationally representative sample, with a 90% response rate. Some limitations include the use of cross-sectional data, which cannot establish a causal relationship between IDA and the associated risk factors in CU5 and WRA. There have been suggestions that other biomarkers, such as hepcidin  and hemoIn conclusion, the study findings reflected that 28.9% of CU5 and 18.4% of WRA had experienced IDA. Regarding the risk factors of the IDA, this study found that the child’s age, presence of diarrhea or fever, place of residence, household size, wealth status, and access to sanitation facilities are significantly associated with IDA among CU5 in Pakistan. For WRA, this study found education, body mass index, vitamin A and zinc status, household food security status, wealth status, and access to sanitation facilities are significantly associated with IDA. Large, well-established, government-funded programmes focused on micronutrient supplementation, food fortification, diversification of food supplies, and treatment and prevention of infectious and parasitic diseases are needed to prevent IDA and all forms of anemia among children and women in Pakistan.