ObjectiveTo analyze the incidence and spatiotemporal distribution of typhus fever in Baoshan City, Yunnan Province from 2005 to 2023, to identify high-risk populations and regions, so as to provide a scientific basis for optimizing the allocation of local prevention and control resources and developing targeted intervention measures. MethodsData of typhus fever cases in Baoshan City from 2005 to 2023 were obtained from the Infectious Disease Information Management System of the Chinese Center for Disease Control and Prevention. Descriptive epidemiological methods were used to analyze the temporal, spatial and demographic distribution of typhus fever cases. Spatial clustering was assessed using spatial dynamic window scan statistics (circular and elliptical windows), flexible spatial scan statistics, and local spatial autocorrelation methods (including local Moran’s I, local Geary’s C, and Getis-Ord G_i*). Retrospective spatiotemporal scan statistics were employed to detect spatiotemporal clusters. ResultsA total of 1 099 typhus fever cases were reported in Baoshan City from 2005 to 2023. The incidence rate peaked at 6.31/ 100 000 in 2007, followed by a decline until reaching its lowest level at 0.21/100 000 in 2015 , and subsequently rebounded during 2016‒2023. The highest proportion of cases was among children under 10 years of age (31.12%), and the top three occupations of cases were farmers, students, and children, accounting for 88.62% of all cases. Cases occurred predominantly between June and September each year. The incidence was relatively high in Jiucheng Town (62.58/100 000), Yaoguan Town (57.15/100 000), and Dianyang Town (46.81/100 000) of Shidian County. Spatial clustering analyses indicated that high-risk areas were mainly located in the southern part of Baoshan City, showing a south-to-north trend. Spatiotemporal scan analyses identified five clusters, with the most likely cluster centered around Yaoguan Town, covering ten towns (subdistricts) during the period 2007‒2010. ConclusionThe incidence of typhus fever in Baoshan City exhibits a clear seasonal and spatial clustering pattern, with peak incidence occurring in summer and autumn. Spatially, cases are primarily distributed in the southern part of Baoshan City, and high-risk clusters exhibit a south-to-north trend. Farmers, students, and children are the high-risk groups.

ObjectiveTo investigate the current status of HIV-related health service uptake among cross-border couples (Chinese husbands and Myanmar wives) in Dehong Dai and Jingpo Autonomous Prefecture (hereinafter referred to as Dehong Prefecture), and to provide evidence for optimizing HIV prevention and control strategies in border areas. MethodsA cross-sectional survey was conducted from September 2022 to September 2023 among 14 662 cross-border couples (Chinese husbands and Myanmar wives) in Dehong Prefecture. Data on sociodemographic characteristics, HIV/AIDS knowledge awareness, and utilization of HIV-related health services within the past year were collected. Multivariable logistic regression was used to analyze factors associated with HIV testing uptake among husbands and wives. ResultsA total of 29 324 individuals (14 662 couples) were included. The overall awareness rate of HIV/AIDS was 82.09%, with the rate among husbands significantly higher than that among wives (85.17% vs. 79.01%, P<0.001). Overall, 94.98% of participants had received at least one HIV-related health service, and the HIV testing rate in the past year was 65.52%. Multivariable logistic regression analysis showed that, compared with participants married for 0‒3 years, those married for 4‒10 years and ≥11 years were more likely to have received HIV testing. The corresponding ORs were 1.344 (95%CI: 1.187‒1.521) and 1.381 (95%CI: 1.211‒1.574) among husbands, and 1.308 (95%CI: 1.155‒1.481) and 1.344 (95%CI: 1.178‒1.533) among wives, respectively. Compared with those holding a marriage certificate, those possessing a border marriage registration certificate were positively associated with HIV testing uptake, with ORs of 1.710 (95%CI: 1.575‒1.857) among husbands and 1.700 (95%CI: 1.565‒1.847) among wives. Compared with illiterate participants, those with primary school education showed lower testing rates, with ORs of 0.738 (95%CI: 0.650‒0.837) among husbands and 0.827 (95%CI: 0.766‒0.891) among wives. Additionally, a history of sexually transmitted diseases (OR=3.656, 95%CI: 1.243‒15.589) and participation in the New Rural Cooperative Medical Scheme (OR=1.51, 95%CI: 1.179‒1.935) were independently associated with higher testing rates among husbands. ConclusionThe overall utilization of HIV-related health services among cross-border couples in Dehong Prefecture is satisfactory, but significant gender disparities exist, with foreign wives showing lower rates of knowledge awareness and lower proportions obtaining such knowledge through certain channels compared with their Chinese husbands. Couples with shorter marriage duration, those with primary school education, and those not included in the border marriage registration system are vulnerable groups with lower HIV testing uptake. Future interventions should prioritize cross-border marriage families at the early stage of entry and in the newly married period. Based on the border marriage registration management system and primary healthcare networks, health education and HIV testing services targeting foreign spouses should be strengthened to improve service accessibility and equity.

Breast cancer is the leading cause of cancer-related mortality among women worldwide and has drawn extensive research attention.Owing to its molecular heterogeneity,drug resistance,and low therapeutic response,single-modality treatments often fail to achieve satisfactory efficacy or broad applicability.Combination therapy,designed based on the pathophysiological characteristics,related signaling pathways,and biomarkers of breast cancer,has emerged as a promising approach for improving therapeutic outcomes.With the advancement of research on combination strategies,the understanding of their molecular mechanisms—particularly key signaling pathways and biomarkers—has become increasingly important.However,comprehensive reviews addressing these molecular mechanisms and synergistic strategies remain scarce.This article summarizes recent advances in combination therapy for breast cancer,providing a comprehensive review of recent combination therapies for breast cancer and their underlying molecular mechanisms,and focusing on key signaling pathways involved in combination therapy and synergistic strategies,thereby providing theoretical insights and reference for researchers,graduate students,and clinicians engaged in the development of novel combination therapeutic strategies for breast cancer and related malignancies.

Emergence agitation(EA)is a common complication after general anesthesia,especially in children and adolescents.Remifentanil,as a short-acting μ-receptor agonist,has become an important drug for the prevention and treatment of EA due to its rapid recovery and low risk of respiratory depression.This article reviews the mechanism of action and clinical research progress of remifentanil in the prevention and treatment of EA.Its mechanism of action involves the inhibition of pain signals mediated by traditional μ-receptor activation and potential new mechanism based on neural-endocrine-immune network,including regulation of microglial inflammatory pathways,and the modulation of cytokines and chemokines,etc.Clinical studies have shown that remifentanil can significantly shorten the recovery time,reduce the incidence of EA,and further optimize the analgesic effect and recovery quality by combining with other drugs(such as local anesthetics,sedatives,and opioid drugs).Future research should further explore the mechanism of action of remifentanil,optimize clinical treatment strategies,and conduct large-scale clinical trials to standardize the drug use plan,while paying attention to its long-term effects and the development of multimodal treatment plans to promote the further development of EA prevention and treatment plans.

Objective:To analyze the evolution of ceftazidime/avibactam (CZA) resistance phenotyes and clinical features of 11 ST11-KL64 carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates carrying bla KPC. Methods:Eleven CRKP isolates, designated K01 to K11, obtained from infected liver transplant patients from June to September 2024 were retrospectively studied. Broth microdilution method, whole genome sequencing (WGS) and plasmid conjugation assays were employed to investigate the antimicrobial susceptibility, resistance mechanisms, and genetic structural characteristics of these CRKP isolates. Clinical data were simultaneously collected and organized to analyze the correlation between bla KPC gene mutations and the clinical efficacy of antimicrobial therapy. Results:All eleven isolates of CRKP exhibited multidrug resistance phenotypes. Among them, K01-K09 and K11 were sensitive to CZA and resistant to carbapenems, while K10 was resistant to CZA and displayed sensitivity or intermediate resistance to carbapenems. WGS analysis showed that all 11 CRKP isolates belonged to the ST11-KL64 clonal type. Among these isolates, the K01-K09 and K11 isolates carry the bla KPC-2 gene, whereas the K10 isolate carries the bla KPC-33 gene. A single nucleotide mutation in bla KPC-2 (G532T) resulted in a substitution of tyrosine (Y) for aspartic acid (D) at Ambler position 179 (D179Y), causing resistance of CRKP to CZA and reduced sensitivity to Imipenem and Meropenem. The conjugative plasmid was successfully constructed, and compared to the parental strain, its minimum inhibitory concentration (MIC) to CZA increased 32 folds. Clinical data revealed that the patient developed the bla KPC-33 mutation after 51 days of CZA treatment. Conclusions:The bla KPC-33 mutation following CZA treatment for CRKP infection exhibits a considerable delay. It is essential to dynamically monitor the evolution of CRKP resistance to ensure timely adjustment of therapeutic strategies in case of the occurrence of mutations such as bla KPC-33.

Objective:To investigate lipid metabolism gene mutations and pathogenicity of hypertriglyceridemia acute pancreatitis (HTG-AP) patients.Methods:Clinical data of 495 HTG-AP patients admitted from June 2018 to June 2020 in the center for severe acute pancreatitis of Eastern Theater General Hospital were retrospectively analyzed. Whole-exome sequencing and mutation verification were performed by next-generation sequencing technology and Sanger sequencing. The pathogenicity of gene mutation was analyzed by population mutation ratio, pathogenicity prediction software, conservation scoring software, protein structure prediction, and in vitro experiments. Results:The mutation ratio of lipid metabolism-related genes, namely LPL, APOA5, LMF1, GPIHBP1, and APOC2, were 14.81%, 55.78%, 43.61%, 1.62%, and 0.61%, respectively. Among them, 44 heterozygous mutations in LPL gene were detected including 36 missense mutations, 5 nonsense mutations and 3 frameshift mutations, which were all rarely carried in single patient. Six HTG-AP patients carried the LPL gene heterozygous mutation c.835C>G (p.Leu279Val). The mean level of serum triglyceride at the onset of HTG-AP was 27.4 mmol/L. All of them had a history of recurrent HTG-AP, and most of them had severe acute pancreatitis. The serum LPL concentration and activity were lower than the normal level. The pathogenicity analysis results suggested that the LPL p.Leu279Val was a rare, highly possible pathogenic and highly conserved gene mutation. The in vitro results showed that the LPL p.Leu279Val could significantly reduce the synthesis and secretion ability of LPL as well as its enzymatic activity. Conclusions:The mutation ratio of lipid metabolism-related genes, including LPL, APOA5, LMF1, GPIHBP1, and APOC2, are relatively high in the HTG-AP patients. The LPL p.Leu279Val is a rare and highly possible pathogenic gene mutation, which may lead to recurrent episodes of HTG-AP.

Objective To investigate the effects of Huayu Xiaopi Decoction on the proliferation and migration of AGS cells;To explore its mechanism in treating precancerous lesions of gastric cancer.Methods AGS cells were divided into blank group,inhibitor group and Huayu Xiaopi Decoction high-,medium-and low-dosage groups.The blank group was cultured with 15%control serum,the inhibitor group was cultured with 10 μmol/L HIF-1α inhibitor,and the Huayu Xiaopi Decoction high-,medium-and low-dosage groups were cultured with 12%,6%and 3%drug containing serum,respectively.CCK-8 method was used to detect cell survival rate,cell migration ability was detected by scratch test,immunofluorescence was used to detect the expressions of proliferating cell nuclear antigen(PCNA),matrix metalloproteinase(MMP)-2 and MMP-9 in AGS cells,the expressions of HIF-1α,COX-2,VEGF,VEGFR2,MMP-2,MMP-9 mRNA and HIF-1α,COX-2,VEGF,VEGFR2 proteins in AGS cells were detected by RT-PCR and Western blot.Results Compared with the blank group,the cell survival rate and migration rate were significantly decreased in the inhibitor group and each dosage of Huayu Xiaopi Decoction groups(P<0.05),the expressions of PCNA,MMP-2 and MMP-9 significantly decreased in the inhibitor group and Huayu Xiaopi Decoction high-and medium-dosage groups(P<0.05),the mRNA expressions of HIF-1α,COX-2,VEGF,VEGFR2,MMP-2,MMP-9 and the protein expression of HIF-1α,COX-2,VEGF,VEGFR2 were significantly decreased(P<0.05).Conclusion Huayu Xiaopi Decoction can inhibit the proliferation and migration of AGS cells,and its mechanism is related to the regulation of the expression of key molecules in HIF-1α/VEGF signaling pathway.

Cytoglobin(Cygb)is a recently discov-ered astrocyte specific globin that is widely distrib-uted in mammalian visceral organs such as the lung,heart,spleen,liver,pancreas,stomach,small intestine,kidney,neuron,and bone tissue.It plays an important role in clearing reactive oxygen spe-cies,nitric oxide and nitrite signal transduction,al-leviating oxidative stress,anti-fibrosis,regulation of cell apoptosis and treatment of cancer,etc.It is worth noting that the anti-fibrosis role of Cygb has attracted increasing attention in recent years.The existing research has involved various fibrotic dis-eases such as the liver,pancreas,kidney,spleen,etc.,especially in the study of liver fibrosis,which has made great progress.This article system re-views the role of Cygb in various fibrotic diseases,with a focus on its mechanism of alleviating oxida-tive stress.Although the application of Cygb in fi-brotic diseases is still in its infancy and the underly-ing mechanisms still require extensive research and exploration,there is no doubt that Cygb can serve as a promising therapeutic target,with the poten-tial to be widely used in the prevention and treat-ment of fibrotic diseases.

ObjectiveTo investigate the potential mechanism of Shenqi Yiliu Formula （参芪抑瘤方） in treating precancerous lesions of gastric cancer （PLGC） by the Wnt/β-catenin signaling pathway. MethodsThe CCK-8 assay was used to determine the optimal intervention time for Shenqi Yiliu Formula drug-containing serum and the concentration of the Wnt/β-catenin pathway inhibitor XAV939 depends on the survival rate of AGS gastric cancer cell line. AGS cells were divided into the gastric cancer cell group （15% blank serum）， inhibitor group （selected concentration of XAV939）， high-dose Shenqi Yiliu Formula group （12% Shenqi Yiliu Formula drug-containing serum + 3% blank serum）， medium-dose Shenqi Yiliu Formula group （6% Shenqi Yiliu Formula drug-containing serum + 9% blank serum）， and low-dose Shenqi Yiliu Formula group （3% Shenqi Yiliu Formula drug-containing serum + 12% blank serum）. Each group was tested in triplicate. After culturing for 24 and 48 hours， cell migration and invasion were assessed by scratch assays； after a selected intervention period （48 hours）， cell cycle distribution was analyzed using flow cytometry， Ki67 protein levels were detected by immunofluorescence， the protein levels of Wnt， β-catenin， GSK-3β， and intranuclear T-cell specific factor（TCF） were measured by the protein immunoblotting assay， and the mRNA expressions of these above factors were determined by quantitative real-time PCR. ResultsThe optimal intervention time for Shenqi Yiliu Formula drug-containing serum was determined to be 48 hours， and the effective concentration of XAV939 was 20 μmol/L. Compared with the gastric cancer cell group， Shenqi Yiliu Formula at all doses reduced the cell migration rate at 24 and 48 hours （P＜0.05）， except for the low-dose group at 24 hours. Compared to the low-dose group at corresponding time points， high- and medium-dose Shenqi Yiliu Formula groups showed significantly reduced migration rates， particularly the high-dose group at 48 hours （P＜0.05）. Compared with the gastric cancer cell group， the high-dose Shenqi Yiliu Formula and inhibitor groups exhibited reduced protein and mRNA levels of Wnt， β-catenin， and TCF， along with reduced Ki67 protein levels and a decreased proportion of cells in the S and G2 phases of the cell cycle， but GSK-3β protein levels， GSK-3β mRNA expression， and the proportion of cells in the G1 phase increased （P＜0.05）. Compared to the inhibitor group， the high-dose Shenqi Yiliu Formula group showed a decreased proportion of G1-phase cells and an increased proportion of G2-phase cells （P＜0.05）， although differences in Wnt and β-catenin protein levels and mRNA expressions were not statistically significant （P＞0.05）. ConclusionShenqi Yiliu Formula drug-containing serum inhibits the migration and invasion of gastric cancer AGS cells and block the cell cycle at G1 phase， and its underlying mechanism may be related to the regulation of the Wnt/β-catenin signaling pathway.