Based on the species-specific peptides of Pheretima and its common counterfeit (Metaphire magna), an identification method was established using ultra-high performance liquid chromatography tandem triple quadrupole mass spectrometry (UHPLC-MS/MS) for quality evaluation of Pheretima and its preparations. Separation was performed on a CORTECS T3 C18 column with 0.1% formic acid and acetonitrile as the mobile phases. Mass spectrometry with multiple reaction monitoring (MRM) using ESI⁺ mode was used to simultaneously monitor three ion pairs. The results indicated that the method was specific and could distinguish Guang Dilong, Hu Dilong, and M. magna, which were consistent with those of DNA barcode identification. The adulteration test showed that the LOD of peptide M was 1 μg·g^-1. Peptide M could be detected when 1% M. magna was added to Guang Dilong, indicating the high sensitivity of the method. Fifty-four batches of commercially available samples contained 35% Guang Dilong, 35% Hu Dilong, and 15% M. magna. No ions were detected in 15% of the samples, and DNA barcode identification revealed that they were mainly from Amynthas, with similar appearance to Hu Dilong. The analysis results of the formulation showed that no peptide ions were detected in 3 batches of Xiaohuoluo pills (3/6) and M. magna were detected in 2 batches of Shenjindan capsules (2/4). The developed method in the study has good specificity, sensitivity, and feasibility, and could be used for quality control of Pheretima and its related preparations. It is of great significance for improving quality standards and regulating the medicinal market of Pheretima.

Objective To evaluate the effect of delayed cleaning on the cleaning and disinfection quality of gastro-scopes after pre-treatment with different solutions.Methods According to the factorial design table,combination of the pre-treatment cleaning solutions(factor A)(including multi-enzyme cleaning solution[A1],clean water[A2])and delayed cleaning durations(factor B)(including 0 minutes after pre-treatment[B1],30 minutes after pre-treat-ment[B2],1 hour after pre-treatment[B3],and 3 hours after pre-treatment[B4])yielded eight groups(A1B1,A1B2,A1B3,A1B4,A2B1,A2B2,A2B3,A2B4).According to the usage order of gastroscopes,96 gastroscopes used in the digestive endoscopy center of a tertiary first-class hospital from May to September,2023 were randomly assigned to each group by random number table method,with 12 gastroscopes in each group.Specimens were taken at four time points:after pre-treatment,before cleaning,after cleaning,and after disinfection.Due to instant clea-ning,no specimen before cleaning were taken from A1B1 and A2B1 groups,thus only 3 specimens were taken from these two groups each.Four specimens were taken from gastroscopes in the rest groups,resulting in 360 specimens in total.The internal condition of the biopsy cavity was observed through a cavity detector during each delayed cleaning period after pre-treatment,and specimens were taken at the subsequent reprocessing processes of the gas-troscopes.The microbial conditions of the gastroscopes after pre-treatment,before cleaning,after cleaning,and af-ter disinfection were compared.Results After pre-treatment with multi-enzyme cleaning solution and clean water,there was no statistically significant difference in microbiological detection result(P＞0.05).The biopsy cavity re-mained moist during the delayed cleaning period.There was no statistically significant difference in the microbial de-tection results of factors A and B before and after delayed cleaning as well as after disinfection(all P＞0.05).There was no interaction effect between factor A and B.The distribution of bacterial colonies and disinfection qualified rate of gastroscopes after pre-treatment with two cleaning solutions were also not statistically different(both P＞0.05).Conclusion Delayed cleaning for 30 minutes,1 hour,and 3 hours after pre-treatment does not affect the cleaning and disinfection quality of gastroscopes.When clinical demand is urgent,immediate cleaning should be carried out.However,a certain buffering time(no longer than 3 hours)before cleaning is acceptable,when cleaning and disin-fection workload is heavy and timely cleaning cannot be carried out.

On May 13, 2020, a 56-year-old man with extensive burns caused by flames and heavy metal-containing hydrothermal fluids was admitted to the General Hospital of Western Theater Command. After being admitted to the hospital, most of the burn wounds healed after treatments such as debridement, expansion, skin grafting, anti-shock, anti-infection, fluid replacement, and wound dressing change, etc. However, in the middle and late stages of treatment, the patient's burn wounds gradually showed repeated skin ulceration and inflammation. After excluding the cause of physical, bacterial infection and others, IgG4-related skin diseases was finally diagnosed by histopathological examination of tissue biopsy and concentration measurement of IgG4 in interstitial fluid, and the condition was improved after hormone treatment. This suggests that extensive burns may lead to the occurrence of autoimmune skin diseases. For the diagnosis of such diseases, it is necessary to combine clinical manifestations, serological examinations, and histopathological biopsy, etc. to avoid diagnostic pitfalls and draw correct conclusions.
Male ; Humans ; Middle Aged ; Wound Healing ; Treatment Outcome ; Burns/surgery* ; Skin Transplantation ; Skin Ulcer ; Metals, Heavy

OBJECTIVE: To investigate a family with congenital dysfibrinogenemia, and analyze the risk of hemorrhage and thrombosis and blood transfusion strategies. METHODS: Prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) of the proband and her family members were detected by automatic coagulometer, fibrinogen (Fg) activity and antigen were detected by Clauss method and PT algorithm respectively. Meanwhile, thromboelastometry was analyzed for proband and her family members. Then, peripheral blood samples of the proband and her family members were collected, and all exons of FGA, FGB and FGG and their flanks were amplified by PCR and sequenced to search for gene mutations. RESULTS: The proband had normal APTT and PT, slightly prolonged TT, reduced level of Fg activity (Clauss method). The Fg of the proband's aunt, son and daughter all decreased to varying degrees. The results of thromboelastogram indicated that Fg function of the proband and her family members (except her son) was basically normal. Gene analysis showed that there were 6233 G/A (p.AαArg35His) heterozygous mutations in exon 2 of FGA gene in the proband, her children and aunt. In addition, 2 polymorphic loci were found in the family, they were FGA gene g.9308A/G (p.AαThr331Ala) and FGB gene g.12628G/A (p.BβArg478Iys) polymorphism, respectively. The proband was injected with 10 units of cryoprecipitate 2 hours before delivery to prevent bleeding, and no obvious bleeding occurred during and after delivery. CONCLUSION Heterozygous mutation of 6233G/A (p.AαArg35His) of FGA gene is the biogenetic basis of the disease in this family with congenital dysfibrinogenemia.
Humans ; Child ; Female ; Fibrinogen/genetics* ; Pedigree ; Afibrinogenemia/genetics* ; Mutation ; Blood Transfusion

BACKGROUND: The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). METHODS: A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated. RESULTS: A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98). CONCLUSIONS Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

ObjectiveTo investigate the biological effect of circ_0036176 on myocardial fibrosis. MethodsLevels of circ_0036176 and its host gene Myo9a were determined by real-time quantitative polymerase chain reaction （RT-qPCR） assay in human myocardial tissue， including 22 healthy organ donors and 26 patients with heart failure （HF）. A cell model of angiotensin Ⅱ （Ang-Ⅱ）-induced fibrosis in human atrial fibroblasts （HAFs） was achieved. To test the typical ring structure of circ_0036176， actinomycin D treatment and RNase R exonuclease digestion were performed. The expression of fibrosis-related gene in HAFs with overexpression of circ_0036176 was detected at mRNA and protein level. To select miRNAs that can effectively bind to circ_0036176， dual luciferase reporter gene assay and RNA antisense purification assay （RAP） were conducted， respectively. The neonatal mouse cardiac fibroblasts （mCFs） were used to study whether mir-218-5p mediates the effect of circ_0036176 on myocardial fibrosis phenotype. ResultsThe expression of circ_0036176 was up-regulated in the myocardium of HF patients （P＜0.001）， and the expression of circ_0036176 and the host gene Myo9a was down-regulated in Ang-Ⅱ-induced HAFs （P＜0.01）. In response to actinomycin D treatment and RNase R exonuclease digestion， circ_0036176 was more stable than Myo9a mRNA. The expression of COL1A1， COL3A1， TGF-β1 and ACTA2 was down-regulated in HAFs with overexpression of circ_0036176 （P＜0.05）. Results of dual luciferase reporter gene assay and RAP assay confirmed the interaction between miR-218-5p and circ_0036176. Overexpression of miR-218-5p could promote the expression of fibrosis-related genes， and attenuate the inhibitory effect of circ_0036176 on cardiac fibrosis. ConclusionsCirc_0036176 is up-regulated in the myocardium of HF patients， and circ_0036176 inhibits the expression of fibrosis-related gene through sponging miR-218-5p in CFs.

Objective: To assess the effect of gene mutations on the efficacy of ruxolitinib for treating myelofibrosis (MF) . Methods: We retrospectively analyzed the clinical data of 56 patients with MF treated with ruxolitinib from July 2017 to December 2020 and applied second-generation sequencing (NGS) technology to detect 127 hematologic tumor-related gene mutations. Additionally, we analyzed the relationship between mutated genes and the efficacy of ruxolitinib. Results: ①Among the 56 patients, there were 36 cases of primary bone marrow fibrosis (PMF) , 9 cases of bone marrow fibrosis (ppv-mf) after polycythemia vera, and 11 cases of bone marrow fibrosis (PET-MF) after primary thrombocytosis (ET) . ②Fifty-six patients with MF taking ruxolitinib underwent NGS, among whom, 50 (89.29%) carried driver mutations, 22 (39.29%) carried ≥3 mutations, and 29 (51.79%) carried high-risk mutations (HMR) . ③ For patients with MF carrying ≥ 3 mutations, ruxolitinib still had a better effect of improving somatic symptoms and shrinking the spleen (P=0.001, P<0.001) , but TTF and PFS were significantly shorter in patients carrying ≥ 3 mutations (P=0.007, P=0.042) . ④For patients carrying ≥ 2 HMR mutations, ruxolitinib was less effective in shrinking the spleen than in those who did not carry HMR (t= 10.471, P=0.034) , and the TTF and PFS were significantly shorter in patients carrying ≥2 HMR mutations (P<0.001, P=0.001) . ⑤Ruxolitinib had poorer effects on spleen reduction, symptom improvement, and stabilization of myelofibrosis in patients carrying additional mutations in ASXL1, EZH2, and SRSF2. Moreover, patients carrying ASXL1 and EZH2 mutations had significantly shorter TTF [ASXL1: 360 (55-1270) d vs 440 (55-1268) d, z=-3.115, P=0.002; EZH2: 327 (55-975) d vs 404 (50-1270) d, z=-3.219, P=0.001], and significantly shorter PFS compared to non-carriers [ASXL1: 457 (50-1331) d vs 574 (55-1437) d, z=-3.219, P=0.001) ; 428 (55-1331) d vs 505 (55-1437) d, z=-2.576, P=0.008]. Conclusion: The type and number of mutations carried by patients with myelofibrosis and HMR impact the efficacy of ruxolitinib.
Humans ; Mutation ; Nitriles ; Primary Myelofibrosis/genetics* ; Pyrazoles ; Pyrimidines ; Retrospective Studies ; Technology ; Transcription Factors/genetics*

Objective: To describe the distribution characteristics of coronary heart disease in adult twins recruited from Chinese Twin Registry (CNTR), and provide clues and evidence for the effect of genetic and environmental influences on coronary heart disease. Methods: By using the data of CNTR during 2010-2018, a total of 34 583 twin pairs aged ≥18 years who completed questionnaire survey and had related information were included in the current study to analyze the population and area distribution characteristics of coronary heart disease. Random effect models were used to compare the differences between groups. The concordane rate of coronary heart disease were calculated respectively in monozygotic (MZ) twin pairs and dizygotic (DZ) twin pairs to estimate the heritability. Results: The twin pairs included in this analysis were aged (34.2±12.4) years. The overall prevalence rate of coronary heart disease in twin pairs was 0.7%. Twin pairs who were women, older, obese and lived in northern China had higher prevalence of coronary heart disease (P<0.05). Intra-pair analysis in the same-sex twin pairs found that the concordane rate of coronary heart disease was higher in MZ twin pairs (25.3%) than in DZ twins (7.4%), and the difference was statistically significant (P<0.001). The overall heritability of coronary heart disease was 19.3% (95%CI: 11.8%-26.8%). Stratified by gender, age and area, the concordane rate was still higher in MZ twin pairs than in DZ pairs. Participants who were women, aged 18-30 years or ≥60 years and lived in northern China had a higher heritability of coronary heart disease. Conclusion: The distribution of coronary heart disease in twin pairs differed in populations and areas. The prevalence of coronary heart disease was affected by genetic factors, but the effect varied with age, gender and area.
Adolescent ; Adult ; China/epidemiology* ; Coronary Disease/genetics* ; Diseases in Twins/genetics* ; Female ; Humans ; Male ; Twins, Dizygotic ; Twins, Monozygotic/genetics*

OBJECTIVE: To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC). METHODS: This phase I, open-label study was conducted at 6 Chinese sites from August 4, 2016 to April 15, 2019. The patients were ≥18 years old with a histologically documented incurable or metastatic solid tumor that was advanced or recurrent and had progressed since the last anti-tumor the-rapy. The PK phase characterized PK and safety of atezolizumab following multiple-dose administration when atezolizumab was administered as a single agent. The extension phase studied safety and efficacy of atezolizumab, as monotherapy (EC, GC, HCC, NPC) and with chemotherapy (NSCLC). RESULTS: This study enrolled 120 patients (PK phase: n=20; extension phase: n=20/cohort). Fourty-two patients (42.0%) were PD-L1 positive in atezolizumab monotherapy group (100 patients), of the 9 patients (9.0%) with microsatellite instability-high (MSI-H) tumors. Atezolizumab clearance was 0.219 L/d, and steady state was reached after 6 to 9 weeks (2-3 cycles) of repeated dosing. Objective response rates (ORRs) in EC, GC, HCC, NPC, and NSCLC were 10.0%, 15.0%, 10.0%, 5.0%, and 40.0%, respectively. In the patients with PD-L1 positive tumors, ORR was 11.9% with atezolizumab and 46.2% with atezolizumab plus gemcitabine and cisplatin. Two GC patients achieved durable response after pseudo-progression. The most common treatment-related adverse events in the atezolizumab monotherapy group were fatigue, anemia, fever, and decreased white blood cell count. The most common treatment-related adverse events in the combination group were anemia, decreased white blood cell count, and decreased appetite. No new safety signals were identified. CONCLUSION Atezolizumab's PK, efficacy, and safety were similar in Chinese patients vs. global patients in previous studies.
Adolescent ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carcinoma, Hepatocellular/drug therapy* ; Cisplatin/therapeutic use* ; Humans ; Liver Neoplasms/drug therapy* ; Lung Neoplasms/pathology* ; Nasopharyngeal Neoplasms/drug therapy*

OBJECTIVE: To explore the influence of nutritional status on 90-day functional outcomes of stroke patients with acute large vessel occlusion in the anterior circulation after endovascular treatment (EVT). METHODS: We retrospectively analyzed the baseline, laboratory, surgical and 90-day follow-up data of patients with stroke resulting from acute large vessel occlusion in the anterior circulation, who underwent emergency endovascular treatment in our hospital from July, 2015 to December, 2020. A favorable outcome was defined as a modified Rankin scale score ≤2 at 90 days. Univariate and multivariate regression analyses were performed to explore the relationship between nutritional status and 90-day functional outcomes of the patients. RESULTS: A total of 459 patients (mean age of 68.29±11.21 years, including 260 males) were enrolled in this study. According to their prognostic nutritional index (PNI), the patients were divided into normal nutrition group (392 cases, 85.4%), moderate malnutrition group (44 cases, 9.6%), and severe malnutrition group (23 cases, 5.0%). Univariate analysis showed that the patients with good clinical outcomes had a lower proportion of malnutrition with a younger age, a lower rate of diabetes, lower baseline blood pressure, lower baseline NIHSS score, higher baseline ASPECT score, and higher rates of good collateral circulation and complete vascular recanalization. Multivariate analysis showed that in addition to age, diabetes, baseline systolic blood pressure, successful recanalization, baseline ASPECT score, baseline NIHSS score and collateral circulation, a greater PNI was a protective factor for a good 90-day outcome of patients after EVT (moderate vs severe: OR=0.245, 95% CI: 0.066-0.908, P=0.035; normal vs severe: OR=0.185, 95% CI: 0.059-0.581, P=0.004). CONCLUSION Nutritional status an important factor affecting the 90-day outcomes after EVT of stroke patients with acute large vessel occlusion in the anterior circulation.
Aged ; Brain Ischemia/etiology* ; Endovascular Procedures/methods* ; Humans ; Male ; Malnutrition/etiology* ; Middle Aged ; Nutritional Status ; Retrospective Studies ; Stroke/surgery* ; Thrombectomy/methods* ; Treatment Outcome