Objective Corruption is the most common cadaver phenomenon in forensic practice and an important basis for inferring time of death(PMI),but the definition of corruption degree and the construction of model inference models have always been difficult in the practice of forensic science.Methods In this study,the late postmortem phenomena were observed.Meanwhile,the microbial flora structure of gut and gravesoil and the nature of gravesoil were detected,for analyzing the changes before and after the key moment of abdominal rupture which naturally happened during the cadaver decay.Results The results found that from the macroscopic and microscopic levels,there were significant differences in cadaver decay,including microbial flora structure and gravesoil properties before and after the key moment of the natural abdominal rupture during cadaver decay.The phenomena are highly observable and can be accurately judged by forensic examinations,as well as related means in the field of biology and physiochemistry.In this study,this critical event was called Rupture Point.Conclusion The Rupture Point can be used as an important node for the assessment of cadaver decay degree in the practice of forensic medicine.It can be utilized for a cut-off point as well when constructing PMI inference models based on microbial flora structure changes.The accuracy of PMI inference models can be improved when the models were constructed in segments.

Objective To investigate the clinical significance of the expression of antioxidant 1 copper chaperone protein(ATOX1)in hepatocellular carcinoma(HCC)and its relationship with tumor proliferation,migration and invasion.Methods The expression of ATOX1 mRNA in HCC cancer tissue and normal liver tissue was analyzed using the Human Genome Atlas database.Immunohistochemical experiment was used to detect the expression of ATOX1 in 15 cases of HCC cancer tissue and adjacent tissue.Human HCC cell lines Hep3B and HepG2 were divided into the control group(NC),the ATOX1 knockdown group 1(si-ATOX1#1)and the ATOX1 knockdown group 2(si-ATOX1#2).The effects of ATOX1 knockdown on the malignant biological behavior of HCC cells were observed through CCK-8 cell proliferation experiment,scratch experiment and Transwell invasion experiments.A nude mouse xenograft tumor model was constructed to analyze the effect of ATOX1 knockdown on the quality and volume of transplanted tumors.Western blot assay was used to detect the relationship between ATOX1 and JAK2/STAT3 pathway protein expression.Results Bioinformatics analysis showed that expression of ATOX1 mRNA in HCC cancer tissue was higher than that in adjacent normal tissue(P＜0.05).The immunohistochemical staining results showed that the positive rate of ATOX1 protein was higher in HCC cancer tissue than that in adjacent tissue(93.33%vs.13.33%,P＜0.01).In vitro experimental results showed that siRNA knockdown of ATOX1 protein expression in Hep3B and HepG2 cells significantly reduced the proliferation,migration and invasion abilities of cancer cells(P＜0.05).In vivo experiments in mice showed that the volume and weight of subcutaneous xenograft tumors were significantly smaller in the sh-ATOX1 group than those in the sh-con group(P＜0.05).The expression levels of JAK2/STAT3 pathway-related proteins p-JAK2,p-STAT3,CyclinD1 and MMP2 were significantly lower in the subcutaneous transplanted tumor tissue of the sh-ATOX1 group than that of the sh-con group(P＜0.05).Conclusion ATOX1 can promote the proliferation,migration and invasion of HCC through JAK2/STAT3 pathway,which can potentially become a potential tumor marker and therapeutic target.

Tuberculosis is caused by Mycobacterium tuberculosis,and the problem of its drug resistance has become increasingly prominent in recent years,attracting widespread attention globally.Currently,the situation of drug-resistant tuberculosis is grim,and effective strategies are urgently needed to deal with it.Understanding the drug resistance mechanism and treatment status of drug-resistant tuberculosis can provide an important basis for clinical prevention and treatment of drug-resistant tuberculosis.This paper reviews the progress of drug resistance mechanism and treatment of drug-resistant tuberculosis,in order to provide a reference for clinical intervention.

OBJECTIVE: To explore the clinical characteristics and genetic basis for a child with X-linked lissencephaly with abnormal genitalia (XLAG). METHODS: A child with XLAG who had presented at the Third Affiliated Hospital of Zhengzhou University in May 2021 was selected as the study subject. Peripheral blood samples of the child and his parents were collected and subjected to high-throughput sequencing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the result was analyzed by using bioinformatic software. RESULTS: The child was found to have harbored a hemizygous c.945_948del variant in exon 2 of the ARX gene, which as a frameshifting variant has resulted in a truncated protein. His mother was found to be heterozygous for the variant, whilst his father was of wild type. The variant was unreported previously. CONCLUSION The hemizygous c.945_948del variant of the ARX gene probably underlay the XLAG in this patient. Above finding has provided a basis for the diagnosis and genetic counseling for this family.
Humans ; Child ; Classical Lissencephalies and Subcortical Band Heterotopias ; Exons ; Computational Biology ; Genetic Counseling ; Genitalia ; Transcription Factors ; Homeodomain Proteins

Objective:Currently,patients with pre-exsiting donor-specific antibody(DSA)are prone to antibody-mediated rejection(AMR)after surgery and are at a relatively high risk of postoperative complications and graft failure.The risk of postoperative complications and graft failure is relatively high.This study aims to discuss the clinical outcome of DSA-positive kidney transplantation and analyze the role and safety of preoperative pretreatment in DSA-positive kidney transplantation,providing single-center treatment experience for DSA-positive kidney transplantation. Methods:We retrospectively analyzed the clinical data of 15 DSA-positive kidney transplants in the Department of Renal Transplantation of First Affiliated Hospital of Zhengzhou University from August 2017 to July 2022.Eight cases were organ donation after citizen's death(DCD)kidney transplant recipients,of which 3 cases in the early stage were not treated with preoperative desensitisation therapy(DCD untreated group,n=3),and 5 recipients were treated with preoperative rituximab desensitisation(DCD preprocessing group,n=5).The remaining 7 cases were living related donors recipients(LRD)who received preoperative desensitisation treatment with rituximab and plasma exchange(LRD preprocessing group,n=7).We observed and recorded the incidence of complications with changes in renal function and DSA levels in the recipients and the survival of the recipients and transplanted kidneys at 1,3 and 5 years,and to compare the differences in recovery and postoperative complications between 3 groups. Results:All 15 recipients were positive for preoperative panel reactive antibody(PRA)and DSA and were treated with methylprednisolone+rabbit anti-human thymocyte immunoglobulin induction before kidney transplantation.DCD untreated group all suffered from DSA level rebound,delayed renal graft function(DGF)and rejection reaction after surgery.After the combined treatment,DSA level was reduced and the graft renal function returned to normal.The DCD preprocessing group were all without antibody rebound,1 recipient developed DGF and the renal function returned to normal after plasmapheresis,and the remaining 4 recipients recovered their renal function to normal within 2 weeks after the operation.In the LRD preprocessing group,2 cases had antibody rebound and 1 case had rejection,but all of them recovered to normal after treatment,and DSA was maintained at a low level or even disappeared.The incidence of DGF and rejection in the DCD untreated group were significantly higher than that in the DCD preprocessing group and the LRD preprocessing group;and there were no significant difference in the incidence of postoperative haematuria,proteinuria,bacterial and fungal infections,and BK virus infection between the 3 groups(all P>0.05).A total of 11 of the 15 recipients were followed up for more than 1 year,6 for more than 3 years,and 1 for more than 5 years,and the survival rates of both the recipients and the transplanted kidneys were 100%. Conclusion:Effective preoperative pretreatment with desensitization therapy can effectively prevent antibody rebound in DSA-positive kidney transplantation and reduce perioperative complications.

Objective:To compare the clinical efficacy of percutaneous transhepatic gallbladder drainage (PTGBD) combined with delayed laparoscopic cholecystectomy (LC) with direct LC in the treatment of acute cholecystitis.Methods:A single-center case-control retrospective study was used. Sixty-three patients with acute cholecystitis with onset time ≥ 72 hours during the period from August 1, 2021 to December 10, 2022 in the Department of Hepatobiliary Surgery of the 900TH Hospital of Joint Logistics Support Force were selected. There were 38 males and 25 females, aged (57.3±15.4) years, with an age range of 28-87 years. According to whether PTGBD treatment was performed before LC, they were divided into experimental group ( n=29) and control group ( n=34). Experimental group was treated with PTGBD combined with delayed LC and control group was treated with LC only.The differences in operative time, intra-operative bleeding, intra-operative transit open rate, post-operative hospital days, total hospital days, hospital costs, short-term post-operative complications of LC and post-operative time to exhaustion were compared and analysed between the two groups. Measurement data with normal distribution were expressed as mean±standard deviation ( ± s), and independent sample t-test was used for comparison between groups.Measurement data with skewed distribution were expressed as M( Q1, Q3), and rank sum test was used for comparison between groups; Chi-square test was used to compare the counting data groups. Results:Intraoperative bleeding, total hospital days, hospital costs and postoperative time to exhaustion were 0(0, 50) mL, 13(11, 18) d, 29 015.0 (22 791.6, 39 000.8) yuan and 1(1, 2) d in the experimental group and 50(0, 88) mL, 7(6, 11) d, 16 015.0 (15 832.1, 22 185.1) yuan, 2(1, 3) d, the difference was statistically significant between the two groups( P<0.05). In the experimental group, the operative time, the intraoperative transit open rate, the number of postoperative hospital days, and the incidence of short-term postoperative complications of LC were 80 (55, 115) min, 13.8%, 5 (3, 7) days, 34.5%, respectively, compared with 98(70, 125) min, 20.6%, 5(3, 6) days, 38.2% in the control group, the difference between the two groups was not statistically significant ( P>0.05). Conclusion:The clinical efficacy of PTGBD combined with delayed LC is better than direct line LC, and it is feasible and effective for patients with cholecystitis whose inflammatory indexes have returned to normal and who have high gallbladder tone.

Humans ; Gastrointestinal Microbiome ; Diabetes Mellitus, Type 2/complications* ; Cholelithiasis

Objective:To investigate the association between the rehabilitation of visual function and retinal nerve fiber layer (RNFL) thickness in Leber hereditary optic neuropathy (LHON) patients receiving gene therapy for the disease.Methods:A multi-center, non-randomized, single-arm clinical trial was conducted.A total of 159 LHON patients were enrolled in Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Taihe Hospital and Ezhou Central Hospital from December 2017 to December 2018.All of the patients were administered with a single unilateral intravitreal injection (0.05 μl) of recombinant adeno-associated virus 2 carrying reduced nicotinamide adenine dinucleotide dehydrogenase subunit 4 (rAAV2-ND4) and were followed up before and 1, 3, 6 and 12 months after treatment.The best corrected visual acuity (BCVA) converted to logarithm of the minimum angle of resolution (LogMAR) unit was assessed with a standard logarithmic visual acuity chart.Perimetry indicators including visual field index (VFI) and mean deviation (MD) were measured with Humphrey Field Analyzer.RNFL thickness in the superior, inferior, temporal, nasal optic disc and the average RNFL thickness were detected with Spectralis ? HRA+ OCT.The 12-month postoperative BCVA, visual field, and RNFL thickness were taken as the primary outcomes.According to the improvement of BCVA, VFI and MD at 12 months after therapy, there were 81 vision improved eyes with injection, 62 vision unimproved eyes with injection, 65 vision improved eyes without injection, and 78 vision unimproved eyes without injection, 48 VFI improved eyes with injection, 71 VFI unimproved eyes with injection, 47 VFI improved eyes without injection, and 72 VFI unimproved eyes without injection, 52 MD improved eyes with injection, 67 MD unimproved eyes with injection, 47 MD improved eyes without injection, and 72 MD unimproved eyes without injection.The correlations between BCVA, VFI, MD and RNFL thickness were evaluated by Pearson linear correlation analysis.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committees of Wuhan Tongji Hospital (No.TJ-IRB20180316), Taihe Hospital (No.2017-01), Ezhou Central Hospital (No.2017-K-05) and People's Hospital of Wuhan University (No.WDRY2020-K202).Written informed consent was obtained from each patient or custodian prior to entering the study cohort. Results:Among the patients receiving rAAV-ND4 gene therapy, the 12-month postoperative BCVA (LogMAR) in the injected eyes and uninjected eyes was 1.37±0.55 and 1.29±0.59, which were significantly better than 1.70±0.41 and 1.53±0.51 before treatment (baseline), respectively ( t=4.920, 3.550; both at P<0.001).The 12-month postoperative VFI of the patients were significantly improved and the 12-month postoperative MD of the patients were significantly lowered in comparison with those at baseline in the injected eyes (both at P<0.001).Similar improvements of VFI and MD were observed in the uninjected eyes (both at P<0.01).RNFL of the patients was thinner after the therapy.In the vision improved eyes with injection, the BCVA was negatively correlated with superior, inferior, temporal, nasal and average RNFL thickness ( r=-0.362, -0.292, -0.307, -0.308; all at P<0.05).In the VFI improved eyes with injection, VFI was positively correlated with superior, inferior, nasal and average RNFL thickness ( r=0.439, 0.356, 0.294, 0.401; all at P<0.05).In the MD improved eyes with injection, MD was positively correlated with superior, inferior, nasal and average RNFL thickness ( r=0.495, 0.424, 0.377, 0.474; all at P<0.05). Conclusions:The recovery of visual function is associated with RNFL thickness after the intravitreal injection of rAAV2-ND4 in LHON eyes.Recovery of visual acuity is better in the eyes with thicker RNFL.

Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

Objective:To explore the effects of the extract of Sanchen powder(ESCP)combined with vancomycin on methicillin-resistant Staphylococcus aureus(MRSA)planktonic cells,biofilms,and virulence factors.Methods:The herbs in Sanchen powder(SCP)were extracted separately with 50％ethanol.Then,the content of hydroxysafflower yellow A(HSYA)and cholic acid in the extract of artificial cattle bezoar(artificial Calculus bovis)and safflower(Carthamus tinctorius L.)was measured by ultraviolet visible-vis spectrophotometry and high-performance liquid chromatography.The effects of ESCP combined with vancomycin on MRSA by observing its biofilm viability were assessed using a 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium5-carboxanilide reduction assay and scanning electron microscopy.Additionally,enzyme activity was measured by plasma coagulase test and DNase test.Results:The cholic acid content of the artificial C.bovis extract was 7.34(0.81)mg/g,and the HSYA content of the C.tinctorius extract was 9.18(0.09)mg/g.The minimal inhibitory concentrations of ESCP and vancomycin were 25.6 mg/mL and 2 μg/mL.The minimum bactericidal concentration of ESCP was 51.2 mg/mL.ESCP combined with vancomycin could inhibit the expression of coagulase and bacteria in mature biofilms.Neither ESCP nor vancomycin had a significant effect on DNase.Conclusion:This study is the first to show that ESCP combined with vancomycin inhibits coagulase and MRSA embedded in mature biofilms and that it represents a promising treatment for MRSA infection.