Objective To investigate the expression of YWHAQ protein in gastric adenocarcinoma tissues and its correlation with clinical pathological features and prognosis. Methods A total of 127 patients with gastric cancer who underwent radical surgery were enrolled. Clinical data and postoperative cancer tissue samples were collected from the patients. Immunohistochemistry was used to detect the protein expression of YWHAQ in gastric adenocarcinoma tissues. The relationship between YWHAQ expression and clinical pathological features and prognosis was analyzed. Bioinformatics prediction was performed to identify potential pathways regulated by YWHAQ in gastric adenocarcinoma. A protein-protein interaction network for YWHAQ was constructed using the STRING database. Results YWHAQ gene expression was significantly higher in gastric adenocarcinoma tissues than in normal tissues (P<0.05). The expression level of the YWHAQ protein was significantly correlated with age, tumor invasion depth, lymph node metastasis, and tumor stage (P<0.05). Kaplan-Meier survival analysis showed that patients with high YWHAQ expression had significantly poorer long-term survival than those with low expression (P<0.0001). Cox regression analysis revealed that high YWHAQ expression and distant metastasis were independent risk factors for gastric cancer (HR>1, P<0.05). Enrichment analysis indicated that YWHAQ positively regulated processes such as cell cycle, angiogenesis, and DNA damage repair. Conclusion YWHAQ is highly expressed in gastric adenocarcinoma tissues and may be associated with the occurrence, invasion, and metastasis of gastric adenocarcinoma. High YWHAQ expression and distant metastasis are independent risk factors for the prognosis of gastric adenocarcinoma patients.

[摘 要] 目的：基于公开的卵巢癌（OC）单细胞测序数据并利用生物信息学方法构建OC上皮细胞亚型，探究上皮细胞异质性及其对OC肿瘤微环境（TME）的影响。方法：使用GSE118828卵巢癌单细胞数据集的分析得到的8种细胞类型及基因表达矩阵结果，使用反卷积方法估计整体转录组测序（bulk RNA-seq）数据中的细胞组成，依据上皮细胞丰度将OC分为高上皮细胞亚型（C1型）和低上皮细胞亚型（C2型）。分析C1型与C2型患者的生存时间及免疫微环境差异。基于C1、C2型及OC早期（Ⅰ~Ⅱ期）、晚期（Ⅲ~Ⅳ期）组间的差异表达基因（DEG），筛选与OC进展相关的上皮细胞相关基因并分析其对TME的影响。通过人类蛋白质图谱（HPA）数据库数据验证OC进展中上皮细胞相关基因的蛋白表达水平。结果：C1型患者的OS明显优于C2型患者（P < 0.05）。C1、C2型具有完全不同的免疫微环境浸润特性，C1型中辅助性T（Th）细胞、M1型巨噬细胞和激活的树突状细胞浸润程度显著高于C2型（均P < 0.05）。晚期高上皮细胞OC患者HAS1、DAPL1、ADH1B基因表达增加（均P < 0.05），同时，DAPL1基因在OC中的表达与巨噬细胞、Treg细胞的浸润程度呈正相关（P < 0.05）。HPA数据库数据证实，DAPL1蛋白在OC组织中表达显著增加。结论：卵巢癌高上皮细胞亚型可能由于Th细胞、M1型巨噬细胞和激活的树突状细胞的高度浸润发挥抗肿瘤作用；上皮细胞相关基因DAPL1的高表达可能会诱导巨噬细胞、Treg细胞的浸润程度，从而促进OC的进展。

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Objective To investigate the status of familial aggregation of Helicobacter pylori (Hp) infection in Jinniu District, Chengdu, and analyze its risk factors so as to provide a basis for developing prevention and control strategies of family aggregation of Hp infection. Methods A total of 172 subjects in the Second Affiliated Hospital of Chengdu Medical College · 416 Hospital of Nuclear Industry from January 2022 to January 2023 were selected as the research subjects. All subjects underwent 13C-urea breath test (13C-UBT) to diagnose whether there was Hp infection. Analyze the current situation of family aggregation of Hp infection in the region, collect general data of survey subjects, analyze the relevant factors affecting Hp family aggregation infection, and develop prevention and control strategies based on this. Results A total of 242 people from 97 households were surveyed, and the Hp family aggregation rate was 29.33%. Univariate analysis showed that there were statistically significant differences in family aggregation of Hp infection in terms of different age groups (χ²=9.719, P=0.008), marital status (χ²=8.496, P=0.014), occupations (χ²=19.462, P<0.001), frequencies of dining out (χ²=5.457, P=0.019), previous Hp test results (χ² =4.131, P=0.042) and test results after treatment (χ²=12.000, P=0.001), with statistical significance (P<0.05). Multivariate logistic regression analysis showed that the frequency of dining out 2 days or more per week and a positive Hp test results in the past were risk factors for family aggregation of Hp infection, while the occupation of teachers/medical staff/management/technology personnel and a negative Hp results after treatment were protective factors (P<0.05). Conclusion Family aggregation of Hp infection is related to family members' occupation, frequency of dining out, previous Hp test results and Hp test results after eradication, which deserves attention in clinical practice.

ObjectiveTo investigate the value of serum Fetuin-A and Fetuin-B combined with Homeostasis Model Assessment of Insulin Resistance （HOMA-IR） in predicting nonalcoholic fatty liver disease （NAFLD）. MethodsA total of 120 patients with NAFLD who attended Department of Gastroenterology， The First Affiliated Hospital of Dali University， from June 2020 to June 2021， and 120 healthy individuals who underwent physical examination at Physical Examination Center during the same period of time were enrolled as subjects， and clinical data were collected from all subjects. The serum levels of Fetuin-A and Fetuin-B were measured. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups； the multivariate Logistic regression analysis was used to assess the risk factors for NAFLD. The receiver operating characteristic （ROC） curve was plotted to evaluate the predictive efficacy of Fetuin-A and Fetuin-B combined with HOMA-IR in NAFLD patients. ResultsCompared with the healthy control group， the NAFLD group had significantly higher levels of body mass index， systolic blood pressure， diastolic blood pressure， alanine aminotransferase， aspartate aminotransferase， fasting blood glucose， fasting insulin， triglycerides， HOMA-IR， Fetuin-A， and Fetuin-B （all P<0.05）. The multivariate Logistic regression analysis showed that Fetuin-A （odds ratio ［OR］=1.010， 95% confidence interval ［CI］： 1.001‍‍‍ ‍‍‍—‍‍‍ ‍‍1.020， P<0.05）， Fetuin-B （OR=1.113， 95%CI： 1.021‍ ‍‍—‍‍ ‍1.214， P<0.05）， and HOMA-IR （OR=24.053， 95%CI： 2.624‍ ‍‍—‍‍ ‍220.470， P<0.05） were independent risk factors for NAFLD. The ROC curve analysis showed that Fetuin-A， Fetuin-B or HOMA-IR alone had an area under the ROC curve （AUC） of 0.637 （95%CI： 0.551‍ ‍—‍ ‍0.722）， 0.853 （95%CI： 0.796‍ ‍—‍ ‍0.912）， and 0.837 （95%CI： 0.763‍ ‍—‍ ‍0.912）， respectively， and Fetuin-A combined with Fetuin-B， Fetuin-A combined with HOMA-IR， and Fetuin-B combined with HOMA-IR had an AUC of 0.853 （95%CI： 0.795‍ ‍—‍ ‍0.911）， 0.843 （95%CI： 0.770‍ ‍—‍ ‍0.916）， 0.922 （95%CI： 0.877‍ ‍—‍ ‍0.967）， respectively， while the combination of these three indicators had an AUC of 0.922 （95%CI： 0.877‍ ‍—‍ ‍0.966）. ConclusionFetuin-A and Fetuin-B have a certain value in predicting NAFLD， and Fetuin-B combined with HOMA-IR tends to have a higher predictive value.

Objective:To analyze the risk factors for asparaginase-associated pancreatitis (AAP) in children with acute lymphoblastic leukemia (ALL) after treatment with pegaspargase and evaluate the predictive value of pediatric sequential organ failure assessment (SOFA) score, pediatric acute pancreatitis severity (PAPS) score, Ranson′s score and pediatric Ministry of Health, Labour and Welfare of Japan (JPN) score for severe AAP.Methods:Cross-sectional study.The clinical data of 328 children with ALL who received pegaspargase treatment in the Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University from January 2014 to August 2021, as well as their clinical manifestations, laboratory examinations, and imaging examinations were collected.The SOFA score at the time of AAP diagnosis, PAPS score and Ranson′s score at 48 hours after AAP diagnosis, and JPN score at 72 hours after AAP diagnosis were calculated, and their predictive value for severe AAP was evaluated by the receiver operating characteristic (ROC) curve.Results:A total of 6.7%(22/328) of children had AAP, with the median age of 6.62 years.AAP most commonly occurred in the induced remission phase (16/22, 72.7%). Three AAP children were re-exposed to asparaginase, and 2 of them developed a second AAP.Among the 22 AAP children, 16 presented with mild symptoms, and 6 with severe symptoms.The 6 children with severe AAP were all transferred to the Pediatric Intensive Care Unit (PICU). There were no significant differences in gender, white blood cell count at first diagnosis, immunophenotype, risk stratification, and single dose of pegaspargase between the AAP and non-AAP groups.The age at diagnosis of ALL in the AAP group was significantly higher than that in the non-AAP group ( t=2.385, P=0.018). The number of overweight or obese children in the AAP group was also higher than that in the non-AAP group ( χ2=4.507, P=0.034). The areas under the ROC curve of children′s JPN score, SOFA score, Ranson′s score, and PAPS score in predicting severe AAP were 0.919, 0.844, 0.731, and 0.606, respectively.The JPN score ( t=4.174, P=0.001) and the SOFA score ( t=3.181, P=0.005) showed statistically significant differences between mild and severe AAP. Conclusions:AAP is a serious complication in the treatment of ALL with combined pegaspargase and chemotherapy.Older age and overweight or obesity may be the risk factors for AAP.Pediatric JPN and SOFA scores have predictive value for severe AAP.

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Objective To analyze the spatiotemporal distribution characteristics of respiratory bacterial infections in Sanmenxia City from 2012 to 2022, and explore key areas for respiratory infection prevention and control. Methods Respiratory bacterial infection cases admitted to our hospital from 2012 to 2022 was collected, use OpenGeoDal software for spatial autocorrelation analysis, and SaTScan software for spatiotemporal scanning analysis. Results From 2012 to 2022, 8762 cases of respiratory bacterial infection were reported in Sanmenxia , with an average annual incidence of 173.47/100 000 and a standardized incidence of 132.63/100 000，and the overall incidence showed a downward trend (χ²=48.093，P<0.01). The incidence of respiratory tract bacterial infection has gender characteristics,the incidence of respiratory tract bacterial infection is the highest among people aged 50 years and above (P<0.05). There was no global spatial autocorrelation, and local autocorrelation results showed that the "high-high" clustering area was mainly located in Yima City. The spatiotemporal scanning results showed that the first level aggregation area was located in Yima City, with a time span of 2020-2022 and a radiation radius of 4.57 km (LLR=40.19, RR=3.27, P<0.001). Conclusion The overall trend of respiratory bacterial infections in Sanmenxia City is decreasing, and Yima City is a ^“high- high^” gathering area, which is a key region to prevention and control.

Objective To investigate the mechanisms of microRNA-211-5p (miR-211-5p) in regulation of proliferation, apoptosis, migration, invasion, and collagen synthesis of human hypertrophic scar fibroblasts (HSFBs) via the transforming growth factor (TGF)-β1/Smad homolog 2 (Smad2) signaling pathway. Methods HSFBs were randomly divided into control, miR-NC, miR-211-5p mimic, anti-miR-211-5p, and miR-211-5p mimic + SB431542 (TGF-β1/Smad2 signaling pathway inhibitor) groups. After 72 hours of continuous culture, quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to detect miR-211-5p expression, western blot was employed to assess TGF-β1 and Smad2 protein levels, methyl-thiazoldiphenyl-tetrazolium (MTT) assay was performed to measure cell proliferation, flow cytometry was utilized to analyze apoptosis rates, Transwell chambers were applied to evaluate cell invasion and migration, and western blot was again utilized to quantify type I collagen (Col-Ⅰ) and type Ⅲ collagen (Col-Ⅲ) protein expressions. An animal model of hypertrophic scars was established in rats using a constant temperature and pressure electric scalding apparatus. Following successful modeling, rats in each group received tail vein injections of miR-NC or miR-211-5p mimic. Scar healing was assessed, and histopathological changes in scar tissue were observed via hematoxylin and eosin (HE) staining. Results Compared with the control and miR-NC groups, the miR-211-5p mimic group exhibited increased miR-211-5p, TGF-β1, and Smad2 protein expressions, enhanced cell proliferation, reduced invasion and migration capabilities, decreased apoptosis rates, and elevated Col-Ⅰ and Col-Ⅲ protein expressions (P < 0.05). Conversely, the anti-miR-211-5p group displayed opposite trends, and significant differences were observed between the anti-miR-211-5p and miR-211-5p mimic groups for the aforementioned indicators (P < 0.05). Compared to the miR-NC group, the miR-211-5p mimic group had higher scar healing rates and fibroblast counts (P < 0.05). Compared to the miR-211-5p mimic group, the miR-211-5p mimic + SB431542 group showed reduced TGF-β1, Smad2 protein expressions, and weakened cell invasion and migration capabilities (P < 0.05). Conclusion MiR-211-5p may regulate proliferation, apoptosis, migration, invasion, and collagen synthesis of HSFBs by activating the TGF-β1/Smad2 signaling pathway.

Objective:To investigate the clinical and imaging characteristics of patients with cryptogenic stroke with different right-to-left shunt (RLS) and possible mechanisms.Methods:Acute ischemic stroke patients aged 18-65 years, who admitted to the Department of Neurology, the First Affiliated Hospital of Fujian Medical University from April 2012 to July 2022, were etiologically classified according to the TOAST criteria. Cryptogenic stroke patients further underwent contrast-enhanced transcranial Doppler (cTCD) examination. Patients with RLS (RLS grade Ⅰ-Ⅳ) were divided into large shunt group (RLS grade Ⅲ-Ⅳ, under normal breathing or after Valsalva manoeuvre) and small shunt group (RLS grade Ⅰ-Ⅱ, under normal breathing or after Valsalva manoeuvre). The chi-square test,Fisher's exact probability method and one-way analysis of variance were used to compare clinical and neuroimaging data between the 2 groups. And the RLS related factors as well as mechanisms of RLS-related stroke were further discussed through Spearman correlation and multiple Logistic regression analysis.Results:A total of 167 cryptogenic stroke patients with RLS were included in this study. The male to female ratio was 88∶79. The onest age was (45.27±9.02) years. In the large shunt group, there were 92 patients (55.1%) with onset age of (45.61±9.32) years. In this group, 35 patients (38.0%) were males, 9 (9.8%) had hypertension, and 18 (19.6%) had smoking history; the Risk of Paradoxical Embolism (RoPE) score was 7.08±0.12. In the small shunt group, there were 75 patients (44.9%) with onest age of (44.85±8.68) years. In this group, 53 patients (70.7%) were males, 29 (38.7%) had hypertension, and 31 (41.3%) had smoking history; the RoPE score was 6.20±0.14. Males (χ 2=17.640, P<0.001) as well as hypertension (χ 2=19.611, P<0.001) and smoking history (χ 2=9.443, P<0.01) were significantly less common in the large shunt group than in the small shunt group, while the RoPE score in the large shunt group was higher than that in the small shunt group ( F=21.580, P<0.001). All 6 pulmonary arteriovenous fistula cases (6.5%, 6/92) belonged to the large shunt group. There was no pulmonary arteriovenous fistula patient in the small shunt group ( P<0.05). There were no statistically significant differences in age of onset, hyperlipidemia, diabetes, previous stroke/transient ischemic attack, or family history of stroke between the 2 groups (all P>0.05). Multiple Logistic regression analysis showed that female ( OR=2.848, 95 %CI 1.223-6.632, P<0.05) and no history of hypertension ( OR=3.937, 95 %CI 1.593-9.727, P<0.01) were significantly associated with large shunt. The neuroimaging features were analyzed through comparing offending vessels as well as spatial distribution of lesions between the 2 groups. Results:showed that infarct location of 54 cases (58.7%) was in the unilateral anterior circulation area, 34 cases (37.0%) in the posterior circulation area, no case in the bilateral anterior circulation area, and both of anterior and posterior circulation areas were involved in 4 cases (4.3%) in the large shunt group. Of all the large shunt group patients, 31 (33.7%) had cortical infarcts, 9 (9.8%) had subcortical infarcts, 36 (39.1%) had deep infarcts, and 16 (17.4%) had mixed multiple infarcts. In the small shunt group, infarct location of 36 cases (48.0%) was in the unilateral anterior circulation area, 29 cases (38.7%) in the posterior circulation area, 4 cases (5.3%) in the bilateral anterior circulation area, and both of anterior and posterior circulation areas were involved in 7 cases (9.3%). Of all the small shunt group patients, 7 (9.3%) had cortical infarcts, 8 (10.7%) had subcortical infarcts, 39 (52.0%) had deep infarcts, and 21 (28.0%) had mixed multiple infarcts. Logistic regression analysis showed that cortical infarction was associated with large shunt ( OR=5.981,95 %CI 1.882-19.007, P<0.01), and there was no statistically significant difference in other types of infarction distribution between the 2 groups (all P>0.05). Conclusions:Among cryptogenic stroke patients with RLS, large shunt was more common in females, patients with no history of hypertension, and those with higher RoPE score as well as more cortical infarction, suggesting that there was a strong link between stroke and large RLS, which revealed the underlying mechanism of embolism in patients with stroke and large RLS. In the small shunt group, there were more males and hypertensive patients, suggesting atherosclerosis was more likely involved in pathogenic mechanism of stroke patients with small RLS.