1.Medication rules and mechanisms of treating chronic renal failure by Jinling medical school based on data mining, network pharmacology, and experimental validation.
Jin-Long WANG ; Wei WU ; Yi-Gang WAN ; Qi-Jun FANG ; Yu WANG ; Ya-Jing LI ; Fee-Lan CHONG ; Sen-Lin MU ; Chu-Bo HUANG ; Huang HUANG
China Journal of Chinese Materia Medica 2025;50(6):1637-1649
This study aims to explore the medication rules and mechanisms of treating chronic renal failure(CRF) by Jinling medical school based on data mining, network pharmacology, and experimental validation systematically and deeply. Firstly, the study selected the papers published by the inherited clinicians in Jinling medical school in Chinese journals using the subject headings named "traditional Chinese medicine(TCM) + chronic renal failure", "TCM + chronic renal inefficiency", or "TCM + consumptive disease" in China National Knowledge Infrastructure, Wanfang, and VIP Chinese Science and Technology Periodical Database and screened TCM formulas for treating CRF according to inclusion and exclusion criteria. The study analyzed the frequency of use of single TCM and the four properties, five tastes, channel tropism, and efficacy of TCM used with high frequency and performed association rule and clustering analysis, respectively. As a result, a total of 215 TCM formulas and 235 different single TCM were screened, respectively. The TCM used with high frequency included Astragali Radix, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Poria, and Atractylodis Macrocephalae Rhizoma(top 5). The single TCM characterized by "cold properties, sweet flavor, and restoring spleen channel" and the TCM with the efficacy of tonifying deficiency had the highest frequency of use, respectively. Then, the TCM with the rules of "blood-activating and stasis-removing" and "diuretic and dampness-penetrating" appeared. In addition, the core combination of TCM [(Hexin Formula, HXF)] included "Astragali Radix, Rhei Radix et Rhizoma, Poria, Salviae Miltiorrhizae Radix, and Angelicae Sinensis Radix". The network pharmacology analysis showed that HXF had 91 active compounds and 250 corresponding protein targets including prostaglandin-endoperoxide synthase 2(PTGS2), PTGS1, sodium voltage-gated channel alpha subunit 5(SCN5A), cholinergic receptor muscarinic 1(CHRM1), and heat shock protein 90 alpha family class A member 1(HSP90AA1)(top 5). Gene Ontology(GO) function analysis revealed that the core targets of HXF predominantly affected biological processes, cellular components, and molecular functions such as positive regulation of transcription by ribonucleic acid polymerase Ⅱ and DNA template transcription, formation of cytosol, nucleus, and plasma membrane, and identical protein binding and enzyme binding. Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis revealed that CRF-related genes were involved in a variety of signaling pathways and cellular metabolic pathways, primarily involving "phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt) pathway" and "advanced glycation end products-receptor for advanced glycation end products". Molecular docking results showed that the active components in HXF such as isomucronulatol 7-O-glucoside, betulinic acid, sitosterol, and przewaquinone B might be crucial in the treatment of CRF. Finally, a modified rat model with renal failure induced by adenine was used, and the in vivo experimental confirmation was performed based on the above-mentioned predictions. The results verify that HXF can regulate mitochondrial autophagy in the kidneys and the PI3K-Akt-mammalian target of rapamycin(mTOR) signaling pathway activation at upstream, so as to alleviate renal tubulointerstitial fibrosis and then delay the progression of CRF.
Data Mining
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Drugs, Chinese Herbal/chemistry*
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Network Pharmacology
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Humans
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Kidney Failure, Chronic/metabolism*
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Medicine, Chinese Traditional
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China
2.Role and mechanism of caffeic acid in a mouse model of severe acute pancreatitis
Siyu XU ; Tao LIU ; Lulu LAN ; Yining XUE ; Wei WEI ; Yi HAN ; Sucheng MU ; Haiyan SONG ; Shilin DU
Journal of Clinical Hepatology 2025;41(4):722-730
ObjectiveTo investigate the effect and potential mechanism of caffeic acid (CA) on severe acute pancreatitis (SAP) induced by caerulein combined with lipopolysaccharide (LPS), and to provide a basis for the research on novel drugs for the treatment of SAP. MethodsC57BL/6J mice, aged 6 weeks, were divided into control group, model group, CA group, and octreotide acetate (OA) group, with 6 mice in each group. The mice in the control group were given injection of normal saline, and those in the other groups were given intraperitoneal injection of caerulein combined with LPS to establish a mouse model of SAP. At 1 hour after the first injection of caerulein, the mice in the CA group and the OA group were given intraperitoneal injection of CA or subcutaneous injection of OA at an interval of 8 hours. The general status of the mice was observed after 24 hours of modeling, and serum, pancreas, lung, and colon samples were collected. HE staining was used to observe the histopathological changes of the pancreas and lungs, and the serum levels of α-amylase, lipase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), alanine aminotransferase, aspartate aminotransferase, and creatinine were measured. RT-PCR was used to measure the expression of proinflammatory factors in the pancreas and lungs; myeloperoxidase (MPO) immunohistochemistry was used to observe the degree of neutrophil infiltration; Western blot was used to measure the activation of nuclear factor-kappa B (NF-κB) and the level of citrullinated histone H3 (CitH3), a marker for the formation of neutrophil extracellular traps (NETs), in the pancreas and lungs, as well as the expression level of ZO-1 in colon tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the Dunnett’s t-test was used for further comparison between two groups. ResultsCompared with the control group, the model group had severe injury in the pancreas and lungs and significant increases in the activity of serum α- amylase and lipase and the levels of the proinflammatory cytokines IL-6, interleukin-1β (IL-1β), and TNF-α in serum and lung tissue (all P<0.05), as well as significant increases in NF-κB activation, neutrophil infiltration, and the formation of NETs in the pancreas and lungs (all P<0.05). Compared with the model group, the CA group had alleviated pathological injury of the pancreas and lungs and significant reductions in the activity of serum α-amylase and the levels of the proinflammatory cytokines IL-6, IL-1β, and TNF-α in serum and lung tissue (all P<0.05), as well as significant reductions in NF-κB activation, neutrophil infiltration, and the formation of NETs in the pancreas and lungs (all P<0.05). ConclusionCA can alleviate SAP induced by caerulein combined with LPS in mice, possibly by inhibiting neutrophil recruitment and the formation of NETs.
3.Causal Associations between Particulate Matter 2.5 (PM 2.5), PM 2.5 Absorbance, and Inflammatory Bowel Disease Risk: Evidence from a Two-Sample Mendelian Randomization Study.
Xu ZHANG ; Zhi Meng WU ; Lu ZHANG ; Bing Long XIN ; Xiang Rui WANG ; Xin Lan LU ; Gui Fang LU ; Mu Dan REN ; Shui Xiang HE ; Ya Rui LI
Biomedical and Environmental Sciences 2025;38(2):167-177
OBJECTIVE:
Several epidemiological observational studies have related particulate matter (PM) exposure to Inflammatory bowel disease (IBD), but many confounding factors make it difficult to draw causal links from observational studies. The objective of this study was to explore the causal association between PM 2.5 exposure, its absorbance, and IBD.
METHODS:
We assessed the association of PM 2.5 and PM 2.5 absorbance with the two primary forms of IBD (Crohn's disease [CD] and ulcerative colitis [UC]) using Mendelian randomization (MR) to explore the causal relationship. We conducted two-sample MR analyses with aggregated data from the UK Biobank genome-wide association study. Single-nucleotide polymorphisms linked with PM 2.5 concentrations or their absorbance were used as instrumental variables (IVs). We used inverse variance weighting (IVW) as the primary analytical approach and four other standard methods as supplementary analyses for quality control.
RESULTS:
The results of MR demonstrated that PM 2.5 had an adverse influence on UC risk (odds ratio [ OR] = 1.010; 95% confidence interval [ CI] = 1.001-1.019, P = 0.020). Meanwhile, the results of IVW showed that PM 2.5 absorbance was also causally associated with UC ( OR = 1.012; 95% CI = 1.004-1.019, P = 0.002). We observed no causal relationship between PM 2.5, PM 2.5 absorbance, and CD. The results of sensitivity analysis indicated the absence of heterogeneity or pleiotropy, ensuring the reliability of MR results.
CONCLUSION
Based on two-sample MR analyses, there are potential positive causal relationships between PM 2.5, PM 2.5 absorbance, and UC.
Humans
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Mendelian Randomization Analysis
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Particulate Matter/analysis*
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Polymorphism, Single Nucleotide
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Inflammatory Bowel Diseases/genetics*
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Air Pollutants/analysis*
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Crohn Disease/genetics*
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Colitis, Ulcerative/genetics*
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Genome-Wide Association Study
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Risk Factors
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Environmental Exposure
4.Survey on current status of"Perioperative Infection Control"initiative monitoring indicators in 138 medical institutions in Guizhou Province
Yao YAO ; Yan XU ; Xia MU ; Tingxiu YANG ; Lan TANG ; Liyuan CHEN ; Guiqin DU ; Jing LI ; Zhaofeng JING ; Liming WANG ; Qin WU ; Qingyang ZHAO ; Yufei ZHANG ; Min HE ; Ximin FAN
Chinese Journal of Nosocomiology 2025;35(20):3068-3073
OBJECTIVE To investigate the current status of monitoring indicators related to the"Perioperative In-fection Control"in medical institutions above the secondary level in Guizhou Province,and to delve into the imple-mentation of key measures for infection prevention and control during the perioperative period for patients under-going surgical operations.METHODS Based on the"Implementation Plan for the'Perioperative Infection Control'Initiative in Guizhou Province",a"Case Investigation Form on Key Measures for Infection Prevention and Control During the Perioperative Period for Patients Undergoing Surgical Operation"was developed.A total of 138 medi-cal institutions participated in the case investigation,and a total of 2 128 cases were investigated.RESULTS The overall monitoring indicators for the"Perioperative Infection Control"initiative in the 138 medical institutions a-bove the secondary level in Guizhou Province were at a relatively low level.The skin cleansing compliance rate was 80.32%,the hair removal compliance rate was 16.43%,the prophylactic antibacterial drug administration rate within 0.5-1 hour before surgery was 55.94%and the antibacterial drug discontinuation rate within 24 hours after prophylactic medication for type Ⅰ incision surgeries was 56.48%.The hair removal compliance rate was higher in tertiary medical institutions(19.21%)than in secondary medical institutions(14.34%)(P=0.039).The distri-bution of the four monitoring indicators varied in clinical departments and surgery types,with statistically signifi-cant differences(P<0.05).The preferred method for surgical site skin cleansing in medical institutions across the province was local wiping,primarily with clean water(57.21%).The primary method for hair removal was razors(68.82%),and hair removal on the day of surgery was most common(61.75%).CONCLUSIONS Conduc-ting a survey on the current status of"Perioperative Infection Control"initiative monitoring indicators in medi-cal institutions in Guizhou Province helps to understand the implementation of key measures for perioperative in-fection prevention and control and set intervention targets,thus providing references for establishing a dynam-ic monitoring indicator change mechanism.
5.Effects of liver fibrosis induced by iron overload on M2 polarization of macrophages in mice.
Jiawen YU ; Yi ZHOU ; Chunmei QIAN ; Lan MU ; Renye QUE
Journal of Southern Medical University 2025;45(4):684-691
OBJECTIVES:
To observe the evolution of intrahepatic macrophage polarization in mice with liver fibrosis induced by iron overload.
METHODS:
Thirty-two C57BL/6 mice (6-8 weeks) were randomized into control group (n=8) and liver fibrosis model group (n=24) induced by aidly intraperitoneal injection of iron dextran. At the 3rd, 5th, and 7th weeks of modeling, 8 mice in the model group were sacrificed for observing liver fibrosis using Masson, Sirius Red and immunohistochemical staining and detecting serum levels of ALT, AST and the levels of serum iron, ferritin, liver total Fe and ferrous Fe. iNOS+/F4/80+ cells and CD206+/F4/80+ cells were detected by double immunofluorescence assay to observe the proportion and distribution of M1 and M2 macrophages. The hepatic expressions of Arg-1, iNOS, IL-6, IL-10, and TNF‑α proteins were detected using Western blotting or ELISA, and the expression of CD206 mRNA was detected using RT-PCR.
RESULTS:
The mice in the model group showed gradual increase of fibrous tissue hyperplasia in the portal area over time, structural destruction of the hepatic lobules and formation of pseudolobules. With the passage of time during modeling, the rat models showed significantly increased hepatic expressions of α-SMA and COL-1, elevated serum levels of ALT, AST, Fe, ferritin, and increased liver total Fe and ferrous Fe levels. The expressions of M1 polarization markers IL-6, TNF‑α, and iNOS all increased with time and reached their peak levels at the 3rd week; The expressions of M2 polarization markers (IL-10 and Arg-1 proteins and CD206 mRNA) significantly increased in the 3rd week and but decreased in the 5th and 7th weeks.
CONCLUSIONS
Iron overload promotes M1 polarization of macrophages in mice. Liver fibrosis in the early stage promotes M2 polarization of macrophages but negatively regulate M2 polarization at later stages.
Animals
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Mice
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Mice, Inbred C57BL
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Iron Overload/pathology*
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Macrophages/metabolism*
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Male
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Liver Cirrhosis/etiology*
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Nitric Oxide Synthase Type II/metabolism*
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Interleukin-10/metabolism*
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Liver/pathology*
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Interleukin-6/metabolism*
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Mannose Receptor
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Tumor Necrosis Factor-alpha/metabolism*
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Mannose-Binding Lectins/metabolism*
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Arginase
6.Free inferior gluteal perforator flap for immediate breast reconstruction: a case report and literature review
Lan MU ; Junbo PAN ; Guisheng HE ; Xiuxiu CHEN ; Tao SONG ; Haohao JIAN ; Zuolei YANG ; Sisi WANG ; Huangfu WU ; Yazhen ZHANG ; Kun XIE ; Chuanwei SUN ; Wentian XU ; Guanghua FU ; Junzhang CHEN ; Bo LI ; Hengyu CHEN ; Yilian XU ; Mingmei HE ; Jinhui HUANG ; Peng LI
Chinese Journal of Microsurgery 2025;48(2):161-166
Objective:To explore the possibility of using a inferior gluteal artery perforator flap (IGAPF) for breast reconstruction in the patient who did not have suitable donor site in back and abdomen.Methods:In November 2024, a 25-year-old unmarried and childless woman with right breast cancer received immediate right breast reconstruction by a right free IGAPF after modified right mastectomy in the Department of Breast and Thyroid Surgery, Second Affiliated Hospital of Hainan Medical University. The locations of perforators were confirmed by both Multi-detector computed tomography angiography (MDCTA) and portable Doppler blood flow detector before surgery. The IGAPF was designed to take the inferior gluteal wrinkle as the lower edge, the axis of the flap was parallel to the inferior gluteal wrinkle, and the width of the flap was estimated where the incision could be directly closed. The size of right IGAPF was 6.0 cm×19.0 cm. Sharp dissection was performed between the sarcolemma and muscle fibres of gluteus, then the perforators were dissected along the direction of muscle fibres of gluteus. The vascular pedicle was kept at about 8.0 cm in length. The diameter of artery was about 2.0 mm and that for the veins was about 1.5 mm. End-to-end anastomoses with the right thoracodorsal artery and vein were successfully carried out. The donor site was directly closed, and it was hidden in the inferior gluteal wrinkle. Postoperative outpatient clinical review was made.Results:Pathological examination reported: an invasive carcinoma of right breast, axillary lymph node metastasis (2/10). The patient recovered well and the flap survived without any complication, i.e. ischemic necrosis, infection and haematoma. The patient was off-bed at 3 days and discharged at 13 days after surgery. At the 40 days of postoperative follow-up, the patient achieved a good recovery and the lower limb activity was not affected by the surgery. The patient was satisfied with the reconstructed breast and donor site recovery. The patient followed with scheduled chemotherapy and subsequent radiotherapy. The volume of reconstructed breast was smaller than the other breast, of which the patient was fully informed before the surgery.Conclusion:A free IGAPF provides an alternative donor sites for achieving a breast reconstruction due to the reliable pedicle vessels and invisible donor scars.
7.Synthesis and Applications of Indole-3-formylhydrazine Modified Pyrene Schiff Base Compound as Copper Ion Fluorescence Probe
Mu-Xi WANG ; Zhen-Yu HUANG ; Xiao-Feng LIN ; Xiao-Lan LEI ; Jian SUN ; Li-Jun MA
Chinese Journal of Analytical Chemistry 2025;53(7):1108-1117
In this work,a fluorescent probe PIN was synthesized using indole-3-carbohydrazide and pyrenecarboxaldehyde as raw materials.PIN showed weak fluorescence emission in aqueous solution with acetonitrile volume fraction of 70%.However,when Cu2+was added to this aqueous solution of PIN,a new fluorescence emission peak appeared at 495 nm,and the intensity of this peak gradually increased with the increase of concentration of Cu2+,and also caused a significant change in the fluorescence color of the solution.In contrast,the addition of 15 kinds of other common metal ions did not cause such change.The detection limit of PIN for Cu2+was 78.7 nmol/L,which was much lower than the maximum permitting level of Cu2+in drinking water in hygienic standard for drinking water in China.Therefore,PIN was a highly selective and sensitive fluorescence-enhanced probe for Cu2+.Meanwhile,the addition of Cu2+could also cause a new absorption peak at 440 nm in the ultraviolet-visible absorption spectrum of the aqueous solution of PIN,and meanwhile the colorless PIN solution changed into yellow,exhibiting the performance of PIN as a colorimetric probe for Cu2+.By fitting with the Levenberg-Marquardt algorithm equation,the binding ratio of PIN to Cu2+was 2:1,and the binding constant was 3.42×1012 L2/mol2.In addition,the binding mode of PIN with Cu2+was explored by using proton nuclear magnetic resonance(1H NMR)titration experiments and density functional theory simulations.The results showed that the addition of Cu2+could cause the aggregation of PIN molecules to form excimers,thus showing highly selective recognition.Finally,PIN was made into a simple test strip,which could achieve rapid and convenient fluorescence detection of Cu2+in actual water samples.
8.Research hotspots on invasive fungal infections in China from 2000 to 2024:a visualization analysis
Chan NIE ; Xueyun LI ; Lan TANG ; Liyuan CHEN ; Ling HE ; Yan XU ; Xia MU
Chinese Journal of Infection Control 2025;24(5):584-590
Objective To analyze the research hotspots and trends of invasive fungal infections(IFIs)in China over the past 24 years,and provide references and suggestions for future research.Methods Literatures on IFIs re-search in China from 2000 to 2024 were retrieved from China National Knowledge Infrastructure(CNKI)and Web of Science(WOS).CiteSpace software was employed to conduct collaboration network analysis on authors' institu-tions,and co-occurrence,clustering,and burst analyses were conducted on key words.Results A total of 2 479 li-teratures retrieved from CNKI and 1 149 from WOS were included in the analysis,involving 295 research institu-tions,with no core research team identified having a intermediary centrality>0.1.Institutions with intermediary centrality>0.1 included Chinese Academy of Sciences,Peking University,Fudan University,Sun Yat-sen Univer-sity and Zhejiang University.Key words with high centrality included"diagnosis""risk factor""voriconazole"and"Candida albicans".Clustering analysis grouped the co-occurrence network of key words into 6 clusters,mainly covering fungal diagnosis,treatment,and susceptible factors.Since 2020,focuses on the safety of antifungal treat-ment agents and primary prevention have emerged,with hot topics including pharmacokinetics,children,clinical features,and risk factors.Conclusion Currently,research teams are dispersed with insufficient interdisciplinary collaboration.Research topics are relatively simple.It is necessary to strengthen research on fungal resistance and healthcare-associated infection prevention and control.Risk factors and prevention measures for IFIs may be the fo-cus of future research.
9.Survey of genetic diversity of select tick species in Inner Mongolia
Meng-yu CUI ; Si SU ; Lan MU ; Rui-juan GAO ; Qi-qi GUO ; Hong REN ; Li-li BAO ; Jing-feng YU
Chinese Journal of Zoonoses 2025;41(2):171-177
The aim of this study was to understand the internal genetic diversity and population history dynamics of ticks in Inner Mongolia,to provide data for designing effective vector control programs and revealing ticks'transmission mechanisms.From 2022 to 2023,the manual collection method was used to collect samples in Inner Mongolia.The 16S rDNA and COI gene sequences of ticks were used to identify Hyalomma marginatum,Haemaphysalis concinna,and Argas persicus,and analyze the sequence characteristics and genetic diversity within the populations.Base composition analysis indicated that the average A+T content of the 16S rDNA gene and CO I gene in the three ticks was significantly higher than that of C+G.Moreover,22 haplotypes of the COI gene and 12 haplotypes of the 16S rDNA sequence were identified in Hyalomma marginatum.Eleven haplotypes were identified according to the COI gene,and nine haplotypes were identified according to the16S rDNA sequence of Haemaphysalis concinna.Two haplotypes were identified on the basis of the COI gene,and six haplotypes were identified on the basis of the 16S rDNA sequence of Ar gas persicus.The minimum 16S rDNA haplotype diversity was 0.264 for Ar gas persicus and 0.579 for the other two species.The nucleotide diversity of the three tick species was less than 0.05.Tajima's val-ue and Fu's Fs value of the neutrality test were negative.Base saturation substitution analysis indicated that neither of the two genes in the three tick species reached saturation.The phylogenetic tree revealed that Hyalomma marginatum,Haema physalis concinna,and Ar gas persicus in Inner Mongolia independently aggregated into branches.In conclusion,the base content of Hyalomma marginatum,Haemaphysalis concinna,and Argas persicus genes in Inner Mongolia was consist-ent with the characteristics of insect mitochondrial DNA content.Furthermore,the three tick populations showed rapid evolu-tionary population expansion,and the phylogeny of three tick species showed independent aggregation into clades,with no pop-ulation isolation.
10.Analysis of Clinical Features and Multi-Slice Spiral CT Image Features of Acute Appendicitis in Soldiers Who Have Been Living in Plateau for A Long Time
Li-na YUE ; Juan-qin NIU ; Gang CHEN ; Man-ping CHENG ; Ning-xia MU ; Jia FAN ; Kang LIU ; Yu-lan NIU ; Ya-ping HE ; Zhong-hua LI
Progress in Modern Biomedicine 2025;25(11):1869-1878
Objective:To investigate the clinical features and multi-slice spiral computed tomography(CT)imaging features of acute appendicitis in soldiers who have been living in plateau for a long time.Methods:The clinical features and imaging data of 56 cases of acute appendicitis in soldiers who have been living in plateau for a long time confirmed by surgery from February 2022 to August 2024 were retrospectively analyzed.Results:In 56 cases with acute appendicitis in soldiers who have been living in plateau for a long time,the appendectomy position results showed:anterior ileum 4 cases(7.14%),lower ileum 10 cases(17.86%),posterior cecum 16 cases(28.57%),lower cecum 9 cases(16.07%),lateral cecum 2 cases(3.58%),posterior ileum 6 cases(10.71%),high(subhepatic)9 cases(16.07%),and left lower abdominal 0 cases,retroperitoneal appendicitis 0 cases,which was suggested that the anatomical position variation of appendicitis in soldiers with acute appendicitis who have been living at high altitude for a long time was relatively large.The direct manifestations of multi-slice spiral CT showed:appendectomy enlarged diameter>6 mm in 49 cases(87.50%),appendicular wall thickening>2 mm in 42 cases(75.00%),ppendiceal dilation lumen and effusion in 29 cases(51.79%),appendix indistinctness in 3 cases(5.36%),lppendix fecalith:27 cases(48.21%),gas in the appendix in 16 cases(28.57%).Indirect findings of multi-slice spiral CT showed that,periappendiceal exudation with shadow in 32 cases(57.14%),appendiceal cellulitis with peripheral abscess in 9 cases(16.07%),peritonitis and ascites in 13 cases(23.21%),ileocecal intestinal wall thickening in 22 cases(39.29%),mesenteric lymph node enlargement in 16 cases(28.57%),reflexive intestinal stasis in ileocecal region was observed in 19 cases(33.93%).Conclusion:In the officers and soldiers with acute appendicitis who lived at high altitude for a long time,multi-slice spiral CT showed the direct manifestations of appendiceal thickening,tube wall thickening,lumen dilatation,fluid accumulation,etc.,and the indirect manifestations were periappendiceal exudation with shadow,appendiceal cellulitis with peripheral abscess,ileocecal intestinal wall thickening,reflexes of small intestine and mesenteric lymph node enlargement.Multi-slice spiral CT has the advantages of clear and intuitive,high safety,high resolution and simple operation in the diagnosis of acute appendicitis.

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