Objective　To study the clinical and epidemiological characteristics of the monkeypox epidemic in Longgang District, Shenzhen, and conduct a comprehensive analysis and discussion to provide a reference for monkeypox epidemic prevention and control. Methods An epidemiological investigation was conducted on 16 monkeypox cases found in the medical institutions of Longgang District on June 2023. The distribution of cases, high-risk exposure characteristics (contact objects, methods, locations, etc.), incidence characteristics, and medical treatment situation were analyzed. Relevant discussions on epidemic prevention and control were further conducted in light of the actual situation and the problems encountered. Results The cases were all unmarried young men and men who have sex with men (MSM) population. The disease was transmitted from person to person through same-sex contact, with non-fixed sexual partners as the source of infection and exposure locations being relatively concealed, and the average incubation period was 8.42 days. Most cases were discovered through active seeking medical attention, accounting for 68.78% (11/16). Fever was the primary initial symptom accounting for 56.25% (9/16), with the main symptoms being a rash and fever, at 100% and 68.75% (11/16), respectively. Time from fever to rash onset was mainly 0-3 days, accounting for 90.91% (10/11). The eruption site involveed multiple different parts of the body, and there was no special order of eruption. The time interval from onset to seeking medical attention and from onset to discovery was similar, with 5.91 days and 5.94 days respectively. The majority of cases were HIV infected, accounting for 68.75% (11/16)。Conclusions The monkeypox epidemic is prevalent in MSM populations and is transmitted through male to male contact through human transmission. However, due to unstable sexual partners and concealed exposure locations, tracing the source is difficult, with an average incubation period of 8.42 days. The symptoms are mainly fever and rash, with a long time from onset to medical treatment. The initial manifestations are mild, leading to missed diagnoses on the first visit, resulting in difficulty in timely discovery and prevention of further cases. At the same time, investigating and handling the epidemic are challenging, making the prevention and control of the outbreak a difficult task.

Objective To explore the immune mechanism of Tibetan medicine Twelve Flavors Yishou San in intervening with acute lung injury.Methods Construct a lipopolysaccharide(LPS)-induced acute lung injury rat model and treated it with Twelve Flavors Yishou San.The intervention effect of Twelve Flavors Yishou San on LPS induced acute lung injury was determined through lung pathological sections and blood gas analysis.Enzyme linked immunosorbent assay(ELISA)was used to detect the expression of pro-inflammatory cytokine tumor necrosis factor-α(TNF-α)and anti-inflammatory cytokine interleukin(IL)-10 in rat's bronchoalveolar lavage fluid.Flow cytometry was used to detect changes in immune cells in rat's bronchoalveolar lavage fluid,lungs,spleen and peripheral blood.Results LPS successfully induced an acute lung injury model in rats,and Twelve Flavors Yishou San could alleviate the exudation of inflammatory cells,elevated oxygen partial pressure in LPS induced acute lung injury to varying degrees.The ELISA results of rat bronchoalveolar lavage fluid showed that compared with normal control group,the TNF-α level in the bronchoalveolar lavage fluid of rats with acute lung injury was increased and the IL-10 level was decreased,while the Twelve Flavors Yishou San could alleviate this effect.The results of flow cytometry showed that Twelve Flavors Yishou San could significantly reduce neutrophil infiltration in rat bronchoalveolar lavage fluid,but had no significant effect on macrophages and adaptive immune response.Conclusion Twelve Flavors Yishou San can alleviate LPS induced acute lung injury by inhibiting neutrophil infiltration,providing an important experimental basis for fully understanding the therapeutic mechanism of Twelve Flavors Yishou San.

infC gene encodes the translation initiation factor IF3 in bovine Pasteuella multocida,but it whether or not regulation to the virulence and cross-protection in P.multocida is still not well understood.In this study,the infC gene mutant(△infC)derived from bovine P.multocida type A strain CQ2 was constructed using by homologous recombination method.Compared with wild strain,the △infC showed significant increasing in biofilm formation,but the capsule produc-tion,virulence and bacterial loading in organs were significant decreased,and the IL-1β secretion of mouse peritoneal macrophage increased.Along with the infC gene deletion,the expression of genes related to capsule synthesis and LPS synthesis and transport were significantly down-regulated,while that of genes related to biofilm synthesis and outer membrane protein were significantly up-regulated.The inactivated vaccines of wild type and mutant were prepared and mice were immu-nized twice then challenged with wild type strains,respectively.The immuno-protection rate of△in fC inactivated vaccine against bovine P.multocida type A,B and F were 100.0％,83.3％and 0.0％,respectively,and the immuno-protection rate that against rabbit type P.multocida was 33.3％.The results indicated that infC gene could affect the virulence of P.multocida by regula-ting the production of capsule and the expressions of virulence related factors,and the deletion of infC gene conferred a certain cross-protection property of strains.This study provided a certain foundation for the development of P.multocida vaccine.

AIM:To investigate the impact of aquaporin 4(AQP4)expression inhibition on autophagy and apoptosis in a mouse model of cerebral ischemia-reperfusion(I/R)injury,and to elucidate its underlying mechanism.METHODS:Cerebral I/R injury was induced in mice via transient middle cerebral artery occlusion(tMCAO).Totally 60 mice were randomly divided into sham group,I/R group,AQP4 inhibition group,and 3-methyladenine(3-MA)group,with 15 mice in each group.Among them,the mice in sham and I/R groups received intraperitoneal injections of normal saline,while those in AQP4 inhibition group and 3-MA group received intraperitoneal injections of AER-271(2 mg·kg-1·d-1)and AER-271+3-MA(2 mg·kg-1·d-1)for 3 d,respectively,once per day.Longa score was adopted to assess the neu-rological function,and to record changes in body weight.Cerebral infarction volume and histopathological alterations were evaluated using hematoxylin-eosin staining.Western blot analysis was performed to determine the levels of AQP4,LC3-Ⅱ,P62 and cleaved caspase-3,while the LC3-Ⅱ,P62,cleaved caspase-3 and NeuN(neuronal marker)colocalization and expression assessment were conducted with immunofluorescence.RESULTS:The mice in I/R and AQP4 inhibition groups exhibited extensive cerebral infarction,cerebral edema,and elevated Longa scores.However,in comparision to I/R group,the mice in AQP4 inhibition group showed significantly reduced cerebral infarct volume,cerebral edema vol-ume,and Longa score(P<0.05).Additionally,in contrast to sham group,the mice in I/R group displayed increased ex-pression of AQP4,LC3-Ⅱ and cleaved caspase-3(P<0.01),accompanied by decreased body weight and P62 expression(P<0.05 or P<0.01).Furthermore,compared with I/R group,the mice in both AQP4 inhibition group and 3-MA group demonstrated a decrease in the expression levels of AQP4,LC3-Ⅱ and cleaved caspase-3(P<0.05 or P<0.01),along with increased body weight and P62 expression(P<0.05 or P<0.01).Nonetheless,no significant differences were ob-served between AQP4 inhibition group and 3-MA group regarding Longa score,cerebral infarct volume,body weight,and the expression of AQP4,LC3-Ⅱ,cleaved caspase-3 and P62.CONCLUSION:Inhibition of AQP4 expression signifi-cantly reduces cerebral infarction area and nerve injury severity in tMCAO mice.Moreover,AQP4 expression inhibition decelerates autophagy and apoptosis after cerebral infarction,with the additional autophagy inhibitor showing no notable impact on the protective effect of AQP4 inhibition.

AIM:To investigate the interaction mechanisms of estrogen receptor β(ERβ),nuclear factor-κB(NF-κB)and activator protein-1(AP-1)in colorectal cancer by analyzing the transcriptome data after tumor necrosis fac-tor α(TNF-α)treatment and combining it with NF-κB/p65 and ERβ cistrome data in colon cancer cell lines HT29 and SW480.METHODS:The TNF-α transcriptome was integrated with p65 and ERβ cistrome data.Protein interaction net-works of TNF-α,NF-κB/p65 and ERβ were constructed in colon cancer cell lines HT29 and SW480 using R.RE-SULTS:TNF-α regulated genes through p65 DNA binding,which were mainly enriched in the NF-κB and mitogen-acti-vated protein kinase(MAPK)pathways.Components of the NF-κB/p65 and MAPK pathways had potential interactions with AP-1 family proteins.ERβ overexpression did not significantly affect TNF-α-mediated gene regulation but may regu-late AP-1 activity through the MAPK and phosphatidylinositol 3-kinase(PI3K)/Akt pathways.Furthermore,ERβ de-creased p65 DNA binding sites in HT29 but increased p65 binding sites in SW480,suggesting cell line-specific regulation of NF-κB by ERβ.CONCLUSION:In colorectal cancer,NF-κB,ERβ and AP-1 have potential interactions:TNF-α can regulate AP-1 through NF-κB,while ERβ overexpression can alter NF-κB-mediated regulation,and the influence of ERβ on NF-κB may be gender-related.

Objective To discuss the clinical application value of super selective renal artery embolization-assisted(SRAE-assisted)laparoscopic partial nephrectomy(LPN).Methods A retrospective analysis of the clinical data of patients with stage T1 renal carcinoma,who received LPN,was conducted.The patients were divided into SRAE group(performing LPN without adopting renal hilum vascular clamping)and VC group(performing LPN with adopting renal hilum vascular clamping).The time spent for operation,amount of intraoperative blood loss,and preoperative and postoperative renal functions were compared between the two groups.According to the warm ischemia time(WIT),the patients of the VC group were subdivided into WIT＜25 min subgroup and WIT≥25 min subgroup,and the preoperative and postoperative renal functions were compared between the two subgroups.Results A total of 59 patients with renal carcinoma were enrolled in this study,including 12 patients in SRAE group and 47 patients in VC group.In VC group,WIT＜25 min subgroup had 33 patients and WIT≥25 min subgroup had 14 patients.In both SRAE group and VC group,no patient was referred to open surgery or total nephrectomy.No patient in SRAE group was referred to traditional LPN.The time spent for operation in SRAE group and VC group was 100.50(73.75,132.50)min and 120.00(90.00,145.00)min respectively,the difference between the two groups was not statistically significant(P＞0.05).The postoperative estimated glomerular filtration rate(eGFR)in SRAE group was 100.56(82.85,106.81),which was remarkably higher than 84.66(70.84,94.85)in VC group(P＜0.05).The postoperative serum creatinine level in VC group was 90.50(77.10,104.90)μmol/L,which was strikingly higher than 72.24(65.97,80.27)μmol/L in SRAE group(P＜0.05).The amount of intraoperative blood loss in SRAE group was 50(50,50)mL,which was lower than 50(50,100)mL in VC group(P＜0.05).In VC group,the postoperative eGFR in WIT≥25 min subgroup was 66.13(47.08,82.50),which was lower than 90.80(77.18,98.78)in WIT＜25 min subgroup(P＜0.05).During the postoperative one-year follow-up,no recurrence was observed in both groups.Conclusion Compared with traditional LPN,SRAE-assisted LPN doesn't need to obstruct the renal hilus during surgery,which can avoid the ischemic impairment of the residual renal function and reduce the amount of intraoperative blood loss,moreover,it doesn't increase the operation time,doesn't increase the incidence of complications such as postoperative bleeding,etc.and doesn't affect the curative efficacy and patient's prognosis.

Viral pneumonia （VP） is an inflammatory disease caused by one or more viruses that infect the upper respiratory tract and spread downward. Causing varying degrees of pulmonary parenchymal damage， VP poses a serious threat to the society and public health. The treatment of VP now faces the dilemma of drug shortage， since Western medicine can only alleviate symptoms and lacks specific treatment methods. In traditional Chinese medicine （TCM）， VP is assigned as an epidemic disease， with the etiology attributed to epidemic toxin and six excesses and the pathological factors of dampness， heat， toxin， deficiency， and stasis. The basic pathogenesis of VP is Yin-Yang imbalance， dysfunction of Zang-Fu organs， and healthy Qi deficiency. Accordingly， the treatment should follow the principle of replenishing healthy Qi and expelling pathogen. The treatment method of VP is mainly developed based on syndrome differentiation of six meridians， defense-Qi-nutrient-blood， and triple energizer. Xuanfei Baidu prescription （XFBD） is an effective prescription developed by Academician ZHANG Boli and Professor LIU Qingquan by literature research and selection of multi-component Chinese medicine. It is the product of modern research combined with TCM. XFBD is modified from Maxing Shigantang， Maxing Yigantang， Tingli Dazao Xiefeitang， Qianjin Weijingtang， and Buhuanjin Zhengqisan. It is mainly used to treat epidemic diseases with the syndrome of dampness toxin stagnating in the lung， with the effects of ventilating lung and resolving dampness， clearing heat and expelling pathogen， purging lung， and removing toxin， demonstrating the potential for the prevention and treatment of VP. This paper reviews the research progress of XFBD in combating VP in terms of the prescription composition， compatibility ideas， indications， and clinical new applications， as well as the pharmacological mechanisms of inhibiting virus， reducing inflammation， regulating immune system， ameliorating pulmonary fibrosis， and modulating intestinal flora. In addition， we put forward our thoughts and suggestions on the problems in the research， with a view to informing the clinical use of drugs and the basic research on the treatment of VP including COVID-19.

To investigate the differences in methylation levels of cuproptosis related genes in cervical cancer and their effects on clinical prognosis.Methods:The methylation data of 310 cervical tissue specimens were acquired from public databases. The UALCAN database was used to analyze the methylation level differences of 12 cuproptosis-related genes and study their level in different stages or grades of cervical cancer. Genes with statistically significant differences were selected for prognosis analysis using the EWAS datahub. Finally, gene-enrichment analysis, pathway analysis, immune infiltration analysis, the mutation rate and tumor mutation burden (TMB) of the genes in cervical cancer were analyzed using the cBioportal database. Two independent samples rank-sum test was used for differences in methylation levels and immune cell infiltration; comparative analyses of overall survival were performed using KM survival curves and Log-rank two-sided tests. TMB analyses were performed using the Wilcoxon Test for statistical analyses; Pearson correlation analysis was used for assessment in GSEA and pathway analyses.Results:The methylationβvalue of Cyclin Dependent Kinase Inhibitor 2A (CDKN2A gene) in the cervical cancer tissues of patients was 0.075 which was significantly higher than the methylationβvalue of 0.049 in normal human tissues ( P=0.008). Dihydrolipoamide S-Acetyltransferase (DLAT gene) methylation with a β value of 0.102 was significantly higher than normal human tissue methylation with a β value of 0.08 ( P=0.002), and the methylation level β value of Lipoyltransferase 1 (LIPT1 gene) in cervical cancer tissues was 0.06,which was significantly lower than normal human tissue methylation value of 0.092 ( P=0.009). Patients with CDKN2A gene methylation levels≥0.199 had an overall survival of 14.75 years, which was lower than that of patients with methylation levels<0.199 (17.56 years) ( P=0.034).The results of gene enrichment analysis indicated that it mainly involves biological processes such as the response to type I interferon and DNA replication. The expression of CDKN2A gene is positively correlated with the number of neutrophils and dendritic cells in the tumor microenvironment( P<0.05), and negatively correlated with the number ofmacrophages( P<0.05). TMB was higher in the group of variants of the CDKN2A gene than in the group of non-variants ( P=0.019). Conclusion:CDKN2A methylation is a potential biomarker for predicting the prognosis of cervical cancer.

Objective:To explore the application value of PAX1/JAM3 methylation detection by cervical self-collected specimen in cervical cancer screening and the management of premenopausal and postmenopausal women.Method:This study is a single center cross-sectional study. From January 2023 to November 2023, cervical self-collected and physician-collected specimens at the colposcopy clinic were detected the PAX1/JAM3 methylation (PAX1 m/JAM3 m) testing. The consistency between self-collected and physician-collected specimens for PAX1 m/JAM3 m detection were compared based on histopathology. In addition, the clinical efficacy of methylation detection with high-risk human papillomavirus (hrHPV), liquid-based cytology (LBC), and their combination for cervical cancer screening were compared in the study. Results:A total of 301 women were recruited to undergo referral colposcopy examination, and statistical analysis was conducted on 272 women with pathological and diagnostic information. Among them, 102 cases (37.5%) were diagnosed as normal cervical tissue or chronic cervicitis, 72 cases (26.4%) were cervical intraepithelial neoplasia grade 1 (CIN1), 43 cases (15.8%) were CIN2, 29 cases (10.7%) were CIN3, and 26 cases (9.6%) were cervical cancer. According to the minimum quantity formula, they were divided into a consistency cohort of 81 participants and a validation cohort of 191 participants. The consistency between cervical self-collected and physician-collected specimens for detecting PAX1 m/JAM3 m. Results from spearman correlation analysis showed a positive correlation between the self-collected and physician-collected results of PAX1 m/JAM3 m detection, and the correlation coefficient R values are 0.858 ( P<0.001) and 0.828 ( P<0.001). The sensitivity and specificity of PAX1 m/JAM3 m detection for diagnosing CIN2 or more severe lesions (CIN2+) were 77.6% [95% confidence interval ( CI) 65.3%-86.4%] and 87.2% (95% CI 80.5%-91.9%), respectively. In clinical performance comparison, the sensitivity of PAX1 m/JAM3 m combined with HPV16/18 detection, 89.7% (95% CI 79.2%-95.2%), was the same as that of hrHPV detection in CIN2+and 96.0% (95% CI 80.4%-99.3%) in CIN3+, which is higher than 92.0% (95% CI 75.0%-97.8%) of hrHPV and 82.6% (95% CI 62.9%-93.0%) of LBC or the combination of sPAX1 m/JAM3 m and LBC low-grade and higher squamous intraepithelial lesion testing [87.0% (95% CI 67.9%-95.5%)]. Conclusions:Self-collected specimens by women for detection of PAX1 and JAM3 methylation as a promising screening tool for cervical cancer has operational and clinical feasibility. The methylation test can optimize the current cervical cancer screening plan, reduce the number of referral women with false positive diagnosis to colposcopy, and is of great significance for reducing fertility protection and preventing missed diagnosis in women of childbearing age.

Melatonin receptor 1B (MT2, encoded by the MTNR1B gene), a high-affinity receptor for melatonin, is associated with glucose homeostasis including glucose uptake and transport. The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus (GDM); however, the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood. This article aims to investigate the relationship between rs10830963 variants and GDM development, as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts. TaqMan-MGB (minor groove binder) probe quantitative real-time polymerase chain reaction (qPCR) assays were used for rs10930963 genotyping. MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence, western blot, and qPCR. The relationship between MT2 and glucose transporters (GLUTs) or peroxisome proliferator-activated receptor γ (PPARγ) was established by western blot, and glucose consumption of trophoblasts was measured by a glucose assay kit. The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women (P<0.05). The fasting, 1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers (P<0.05). Besides, the protein and messenger RNA (mRNA) expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women (P<0.05). Melatonin could stimulate glucose uptake and GLUT4 and PPARγ protein expression in trophoblasts, which could be attenuated by MT2 receptor knockdown. In conclusion, the rs10830963 variant was associated with an increased risk of GDM. The MT2 receptor is essential for melatonin to raise glucose uptake and transport, which may be mediated by PPARγ.
Female ; Humans ; Pregnancy ; Blood Glucose/metabolism* ; Diabetes, Gestational/metabolism* ; Glucose/metabolism* ; Melatonin/metabolism* ; Polymorphism, Genetic ; PPAR gamma ; Receptor, Melatonin, MT2/genetics*