ObjectiveThe proteome of biological evidence contains rich genetic information, namely single amino acid polymorphisms (SAPs) in protein sequences. However, due to the lack of efficient and convenient analysis tools, the application of SAP in public security still faces many challenges. This paper aims to meet the application requirements of SAP analysis for forensic biological evidence’s proteome data. MethodsThe software is divided into three modules. First, based on a built-in database of common non-synonymous single nucleotide polymorphisms (nsSNPs) and SAPs in East Asian populations, the software integrates and annotates newly identified exonic nsSNPs as SAPs, thereby constructing a customized SAP protein sequence database. It then utilizes a pre-installed search engine—either pFind or MaxQuant—to perform analysis and output SAP typing results, identifying both reference and variant types, along with their corresponding imputed nsSNPs. Finally, SAPTyper compares the proteome-based typing results with the individual’s exome-derived nsSNP profile and outputs the comparison report. ResultsSAPTyper accepts proteomic DDA mass spectrometry raw data (DDA acquisition mode) and exome sequencing results of nsSNPs as input and outputs the report of SAPs result. The pFind and Maxquant search engines were used to test the proteome data of 2 hair shafts of2 individuals, and both obtained SAP results. It was found that the results of the Maxquant search engine were slightly less than those of pFind. This result shows that SAPTyper can achieve SAP fingding function. Moreover, the pFind search engine was used to test the proteome data of 3 hair shafts from 1 European person and 1 African person in the literature. Among the sites fully matched by the literature method, sites detected by SAPTyper are also included; for semi-matching sites, that is, nsSNPs are heterozygous, both literature method and SAPTyper method had the risk of missing detection for one type of the allele. Comparing the analysis results of SAPTyper with the SAP test results reported in the literature, it was found that some imputed nsSNP sites identified by the literature method but not detected by SAPTyper had a MAF of less than 0.1% in East Asian populations, and therefore they were not included in the common nsSNP database of East Asian populations constructed by this software. Since the database construction of this software is based on the genetic variation information of East Asian populations, it is currently unable to effectively identify representative unique common variation sites in European or African populations, but it can still identify SAP sites shared by these populations and East Asian populations. ConclusionAn automated SAP analysis algorithm was developed for East Asian populations, and the software named SAPTyper was developed. This software provides a convenient and efficient analysis tool for the research and application of forensic proteomic SAP and has important application prospects in individual identification and phenotypic inference based on SAP.

Helicobacter pylori(HP)infection is a Class Ⅰ carcinogen in gastric cancer,closely related to the occurrence of gastric cancer.Many studies have shown that HP eradication has a preventive effect on gastric cancer.However,2.7%-6.1%of patients with early gastric cancer who have been eradicated after endoscopic submucosal dissection(ESD)can still develop metachronous gastric cancer(MGC),and the mechanism of its occurrence is still unclear.In this review,the atrophy of gastric mucosa and intestinal metaplasia cannot be completely reversed after HP eradication,the excessive proliferation of gastric mucosa epithelial cells,the accumulation of genetic abnormalities,the homeostasis imbalance of the epigenetic group,changes in immune microenvironment,the abnormality of stem cells in gastric mucosa,chromatin accessibility,and changes in chromosome remodeling were discussed in the mechanism of carcinogenesis caused by the above molecular changes after ESD and HP eradication in early gastric cancer.

Objective To investigate the effects of microRNA(miR)-30a-regulated MAPK pathway on the formation of intercalation,inflammatory factors and vasoconstriction in a rat model of aortic coarctation.Methods Fifty SD rats were selected to establish the rat model of aortic coarctation,and were randomly divided into control group,model group,miR-NC group,miR-30a group and miR-30a inhibitor group,10 rats in each group.Histopathological changes in the aortic tissue and changes in the elastic fibers and collagen fibers of the aortic mesothelium were observed;The expression of miR-30a,systolic blood pressure before and after the intervention and the expression of serum inflammatory factors in each group were measured by PCR,tail artery manometry and ELISA;Matrix metalloproteinase(MMP)-6,MMP-2 protein expression and MAPK pathway were measured by Western blotting in each group.The expression of MMP-6,MMP-2 and MAPK pathway related proteins were measured by Western blotting.Results The miR-30a inhibitor group improved the degree of vessel wall tearing and disorganized internal arterial wall arrangement;The miR-30a group improved vascular remodeling;miR-30a expression was higher in the model group compared with the control group,and lower in the miR-30a group and miR-30a inhibitor group compared with the miR-NC group,P<0.05;Before the intervention,the difference in systolic blood pressure between the groups compared was not statistically significant,P>0.05;Compared with the control group,systolic blood pressure was higher in the model group,higher expression in the miR-30a group and lower expression in the miR-30a inhibitor group compared with the miR-NC group,P<0.05;compared with the control group,tumor necrosis factor(TNF)-α,interleukin(IL)-6,IL-1β expression was higher in the model group,higher expression in the miR-30a group compared with the miR-NC group,lower expression in the miR-30a inhibitor group,P<0.05;higher expression of TNF-α,MMP-6,MMP-2,Ras,Raf,P38 MAPK,ERK1/2 proteins in the model group compared with the control group,higher expression in the miR-30a group compared with the miR-NC group,lower expression in the miR-30a inhibitor group,P<0.05.Conclusion MiR-30a is involved in the process of aortic coarctation formation,inflammatory response,and regulation of aortic coarctation vascular remodeling,possibly through regulation of the MAPK signaling pathway.

Objective To evaluate the effects of ketamine combined with sufentanil on postoperative analgesia and depression in patients undergoing hip arthroplasty.Methods A total of 60 patients who underwent elective hip arthroplasty were selected and divided into the S group,the SK1 group and the SK2 group according to the patient-controlled intravenous analgesia regimen,with 20 cases in each group.Patients in the S group were received 2 μg/kg of sufentanil for postoperative analgesia,patients in the SK1 group were received 1 mg/kg of esketamine and 2 μg/kg of sufentanil for postoperative analgesia,and patients in the SK2 group were received 2 mg/kg of esketamine and 2 μg/kg of sufentanil for postoperative analgesia.At 1,4,24,and 48 hours after surgery,the analgesic effect of patients was evaluated using the numeric rating scale(NRS),and the sedation effect of patients was evaluated using the Ramsay sedation score.Depression of patients before and 48 hours after surgery was assessed by self-rating depression scale(SDS).The adverse reactions such as nausea and vomiting,dizziness and headache,respiratory depression,and mental symptoms within 48 hours after surgery of patients were recorded.Results The NRS scores 1,4,and 24 hours after surgery of patients in the SK1 group and the SK2 group were lower than those in the S group(P<0.05);there was no statistically significant difference in the NRS scores 48 hours after surgery of patients among the three groups(P>0.05);there was no statistically significant difference in the NRS scores at different postoperative points of patients between the SK1 and SK2 groups(P>0.05).The SDS scores 48 hours after surgery of patients in each group were lower than those before surgery(P<0.05).There was no statistically significant difference in the Ramsay scores at different postoperative points of patients among the three groups(P>0.05).The incidence of adverse reactions 48 hours after surgery in the SK2 group was higher than those in the S group and the SK1 group(P<0.05).Conclusion Using 1 mg/kg of esketamine combined with 2 μg/kg of sufentanil after hip arthroplasty has a good analgesic effect without obvious increase of adverse reactions or significant effect on improving depression of patients.

Objective To evaluate the diagnostic value of histopathological examination of ultrasound-guided puncture biopsy samples in extrapulmonary tuberculosis(EPTB). Methods This study was conducted at the Shanghai Public Health Clinical Center.A total of 115 patients underwent ultrasound-guided puncture biopsy,followed by MGIT 960 culture(culture),smear,GeneXpert MTB/RIF(Xpert),and histopathological examination.These assays were performed to evaluate their effectiveness in diagnosing EPTB in comparison to two different diagnostic criteria:liquid culture and composite reference standard(CRS). Results When CRS was used as the reference standard,the sensitivity and specificity of culture,smear,Xpert,and histopathological examination were(44.83%,89.29%),(51.72%,89.29%),(70.11%,96.43%),and(85.06%,82.14%),respectively.Based on liquid culture tests,the sensitivity and specificity of smear,Xpert,and pathological examination were(66.67%,72.60%),(83.33%,63.01%),and(92.86%,45.21%),respectively.Histopathological examination showed the highest sensitivity but lowest specificity.Further,we found that the combination of Xpert and histopathological examination showed a sensitivity of 90.80%and a specificity of 89.29%. Conclusion Ultrasound-guided puncture sampling is safe and effective for the diagnosis of EPTB.Compared with culture,smear,and Xpert,histopathological examination showed higher sensitivity but lower specificity.The combination of histopathology with Xpert showed the best performance characteristics.

Aim To observe the effects of Wenfei Jiangzhuo formula(WFJZF)on rats with vascular de-mentia and investigate its possible mechanism of ac-tion.Methods Thirty-six healthy male SD rats were randomly divided into the sham group,model group,donepezil group,and low-dose,medium-dose and high-dose groups of Wenfei Jiangzhuo formula,with six rats per group.Except for the sham group,the other groups were prepared as VaD models,and each group was gavaged with the corresponding drugs after suc-cessful modeling,and tests were performed after three weeks of treatment.Behavioral,hippocampal CA1 area morphology,neural dendrites and mitochondrial chan-ges were observed in all groups of rats,and phospho-glycerate mutase 5(PGAM5),dynamics-related pro-teins1(Drp1),opticatrophyprotein-1(OPA1),and other proteins were detected in each group.Results Compared with the sham group,rats in the model group and each intervention group had prolonged es-cape latency(P＜0.05),a shorter number of travers-als across the platforms(P＜0.05),a sparse morphol-ogy of hippocampal neurons,a reduction in the number of secondary dendritic spines,and a rupture of the out-er membrane of the mitochondria;the expression of the PGAM5 and Drp1 proteins in hippocampal tissues was elevated(P＜0.05),and the expression of the OPA1 and Mfn1/2 protein expression decreased(P＜0.05);compared with the model group,donepezil group and Wenfei Jiangzhuo formula high-dose group of rats had shorter evasion latency(P＜0.05),increased number of times to traverse the platform(P＜0.05),increased number of hippocampal neurons,tightly packed,more secondary dendritic structures,and reduced mitochon-drial damage;the expression of PGAM5 and Drp1 pro-teins was reduced(P＜0.05),and the expression of OPA1 and Mfn1/2 proteins was elevated(P＜0.05).Conclusions Wenfei Jiangzhuo formula can regulate the PGAM5-Drp1 signaling axis to improve the balance of mitochondrial homeostasis,thus improving the cog-nitive condition of the brain and exerting cerebroprotec-tive effects.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

An UHPLC-Q-exactive orbitrap MS method for the simultaneous determination of 19 chemical components in Qilong Zhuang'er oral liquid was established and the quality differences between different batches of samples was compared by chemometric analysis to provide a basis for the quality evaluation of the preparation. The contents of allantoin, L-proline, pyroglutamic acid, hordenine, adenosine, L-phenylalanine, guanosine, L-tryptophan, caffeic acid, calycosin-7-glucoside, verbascoside, isoacteoside, ononin, calycosin, 3-hydroxy-9,10-dimethoxyptercarpan, formononetin, atractylenolide III, atractylenolide II and astragaloside A were analyzed by cluster heat map, principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) using Hiplot platform and Markerlynx^XS software to comprehensively evaluate the quality difference of different batches of Qilong Zhuang'er oral liquid. The 19 chemical compounds showed good linearity in their respective concentration ranges (r ≥ 0.999). The RSD of precision, repeatability and stability (24 h) tests were all less than 1.94%. The average recovery was 97.24%-102.75% (RSD < 2.74%, n = 6). The 10 batches of samples were divided into two categories by cluster heat map and PCA analysis. 3-Hydroxy-9,10-dimethoxyptercarpan, atractylenolide III, calycosin, atractylenolide II, formononetin, allantoin and caffeic acid were identified as differential markers by PLS-DA. The established multi component quantitative method of Qilong Zhuang'er oral liquid combined with chemometric analysis can provide reference for the quality evaluation of the preparation.

This study compared the effects of Curcuma longa before and after processing with vinegar on the rat model of dysmenorrhea with the syndrome of liver depression and Qi stagnation to reveal the mechanism of vinegar processing in improving the role of C. longa in soothing liver and relieving pain. The rat model of dysmenorrhea with the syndrome of liver depression and Qi stagnation was established according to the Preparation of the Animal Model of Dysmenorrhea(Draft) and the chronic unpredictable stress me-thod. The changes in the body weight, organ indexes, writhing latency, writhing score, and serum levels of six liver function indicators, sex hormones, pain factors, and blood rheological indicators were measured to evaluate the efficacy of C. longa processed with vinegar or not in treating dysmenorrhea in the rats with syndrome of liver depression and qi stagnation. Compared with the model group, the C. longa group(processed with vinegar or not) showed slow weight loss, increase in writhing latency, and decrease in writhing response(P<0.05). The inhibition rates on writhing in raw C. longa, vinegar-processed C. longa, and positive groups were 33.780%, 64.611%, and 62.466%, respectively. The significantly higher inhibition rate of the vinegar processing group indicated that vinegar-processed C. longa demonstrated more significant therapeutic effect. The vinegar-processed C. longa group showed lower levels of alanine aminotransferase(ALT), alkaline phosphatase(ALP), aspartate aminotransferase(AST), direct bilirubin(DBIL), and total bilirubin(TBIL) and higher level of albumin(ALB)(P<0.05), which indicated that vinegar processing enhanced the therapeutic effect of C. longa on liver injury. The serum levels of estradiol(E_2) and oxytocin(OT) were lower in the vinegar-processed C. longa group(P<0.05), indicating that the vinegar-processed C. longa could regulate the sex hormone levels, reduce the activity of uterine smooth muscle and contraction of uterus, and alleviate the symptoms of dysmenorrhea in rats. Moreover, the vinegar-processed C. longa group showed lower interleukin-6(IL-6) and arginine vasopressin(AVP) levels and higher beta-endorphin(β-EP) level(P<0.05), which indicated that vinegar-processed C. longa regulated the levels of pain factors to exert the pain-relieving effect. Drug intervention decreased the whole blood viscosity low-cut, medium-cut and high-cut values, plasma viscosity, whole blood reduction viscosity low-cut and high-cut values, erythrocyte cumulative pressure, and equation K value of erythrocyte sedimentation rate(P<0.05), and the vinegar-processed C. longa group outperformed other groups. This result indicated that vinegar processing enhanced the function of C. longa in improving the local blood rheology. C. longa processed with vinegar can enter the liver to relieve the da-mage to the heart, liver, kidney, and uterus, repair the liver function, and recover the sex hormone levels and immune function by regulating the levels of sex hormones and pain factors and improving the blood rheology. It activates the pain-relieving mechanism to relieve the pain, protect the liver, and fight inflammation, which is consistent with the theory that vinegar processing facilitates C. longa entering the liver to sooth liver and relieve pain.