Objective To establish a highly efficient and sensitive technical system for the identification and analysis of platycodin-type saponins, systematically compare the differences in platycodin-type saponins among Platycodon grandiflorum from different producing areas, and provide scientific references for the screening of high-quality Platycodon grandiflorum resources, authenticity evaluation, and construction of standardized quality control systems. Methods A total of 45 batches of P. grandiflorum medicinal materials from 3 producing areas （Anhui, Henan, and Jilin, with 15 batches per area） were selected as research objects. Qualitative identification and semi-quantitative analysis of saponin components were performed based on ultra-high performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry （UHPLC-Q-TOF/MS） technology. Meanwhile, two multivariate statistical methods, principal component analysis （PCA） and partial least squares-discriminant analysis （PLS-DA）, were combined to analyze the differences in platycodin-type saponins of Platycodon grandiflorus from different producing areas. Results A total of 28 saponin components were identified from Platycodon grandiflorus of the three producing areas. PCA results showed that there were minor differences in platycodin-type saponins between Henan Platycodon grandiflorus and Jilin Platycodon grandiflorus, while Anhui P. grandiflorum exhibited significant differences from both. PLS-DA further screened 15 major differential compounds. Among them, the contents of 6 components including 3''-O-acetylpolygalacin D2 and platycodin H in Anhui Platycodon grandiflorus were higher than those in Henan and Jilin Platycodon grandiflorus; platycodigenic acid A had the highest content in Jilin Platycodon grandiflorus; the contents of platycodin D3, polygalacin J, and polygalacin D were relatively higher in Henan Platycodon grandiflorus. Conclusion This study clarified the characteristic differences in core components of Platycodon grandiflorus from the three major producing areas, which provided an important theoretical basis for the screening of high-quality Platycodon grandiflorus resources, elucidation of the mechanism underlying its authenticity, and construction of a standardized quality control system.

OBJECTIVE To explore the mechanism of Chaiqi yigan granules （CQYG） against liver cancer through the ferroptosis pathway. METHODS Network pharmacology combined with ferroptosis-related database was used to screen key targets and main effective components of CQYG against liver cancer via regulating ferroptosis； molecular docking technology was employed to analyze the binding ability of main active components to key targets. Human liver Huh-7 cells were divided into blank serum control （CON） group， CQYG drug-containing serum （CQYGKL） group， ferroptosis inducer （RSL3） group， mammalian target of rapamycin complex 1 （mTORC1） inhibitor （RMC-5552） group， mTORC1 agonist （CCT007093） group， and CCT007093+CQYGKL group. The levels of Fe 2+ ， malondialdehyde （MDA）， and glutathione （GSH） in the cells were detected in the former three groups； mRNA expressions of mammalian target of rapamycin （mTOR）， sterol regulatory element-binding protein 1 （SREBP1）， and stearoyl-CoA desaturase 1 （SCD1）， protein expressions of SREBP1 and SCD1 as well as phosphorylation levels of mTOR and ribosomal S6 kinase （S6K） proteins were detected in all groups. RESULTS Key targets of CQYG for anti-liver cancer through the ferroptosis pathway were mTOR， SREBP1， SCD1，etc. The main active components included quercetin， tanshinone Ⅱ A ， baicalein， etc. The binding energies of main active components to key targets were all less than －5 kJ/mol. Compared with CON group， the levels of Fe 2+ and MDA in the cells in CQYGKL group and RSL3 group were significantly increased， while the levels of GSH were significantly decreased （ P ＜0.05）. mRNA expressions of mTOR， SREBP1 and SCD1， protein expressions of SREBP1 and SCD1， as well as the phosphorylation levels of mTOR and S6K proteins were significantly decreased in the CQYGKL group， RSL3 group， and RMC-5552 group， whereas all the above indicators were significantly increased in the CCT007093 group （ P ＜0.05）. Compared with CCT007093 group， the changes in all the above indicators were significantly suppressed in the CCT007093+CQYGKL group （ P ＜0.05）. CONCLUSIONS CQYG may induce ferroptosis by inhibiting mTORC1/SREBP1/SCD1 axis， thereby exerting anti-liver cancer effects.

Since the founding of the People’s Republic of China, remarkable achievements have been gained in infectious disease prevention and control, and rich practical experiences have been accumulated. If these experiences are shared with developing countries, it will greatly contribute to global infectious disease control and global health security. Under the framework of Forum on China-Africa Cooperation, a series of China-Africa public health capacity training programs have been recently held in China, in order to help improve the capability of infectious disease control in African countries. This article summarized and refined good design concepts and practices from these programs, so as to provide insights into sustainable optimization of China-Africa public health capacity training and improvements of the training effectiveness.

Objective To analyze the differences in the epidemiological characteristics,susceptible popula-tions,and laboratory index of patients with common acute upper respiratory tract infections(novel coronavir-us infection,influenza A and influenza B)between plateau and plain areas.Methods Clinical data of 408 008 patients with symptoms of fever or upper respiratory tract infection in the fever clinic of the Second Affiliated Hospital of Zhejiang University and General Hospital of Xizang Military Command from January 2023 to Au-gust 2024 were collected.The epidemic characteristics,susceptible populations,and peripheral blood test data were compared and analyzed.Results The total positive rate of novel coronavirus infection,influenza A virus and influenza B virus infection in plain group(17.86％)was higher than that in plateau group(14.49％),and the difference was statistically significant(P＜0.05).The positive rates(17.98％and 17.76％)of male and female upper respiratory tract infection pathogens(novel coronavirus,influenza A virus and influenza B virus)in plain group were higher than those in plateau group(13.94％and 16.00％),and the differences were statis-tically significant(P＜0.05).The total positive rates of three kinds of upper respiratory tract infection patho-gens were 16.21％,18.27％and 14.63％in the plain group,and 14.62％,14.06％and 21.26％in the plateau group,respectively.According to the results of pathogen analysis of susceptible populations,whether it was plateau or plain,the positive rate of influenza A virus was higher in the minor group,the positive rate of influ-enza B virus was highest in the adult group,and the positive rate of novel coronavirus was highest in the elder-ly group.In terms of epidemic season,plateau and plain areas were different,and the epidemic occurred earlier in the plain area.In terms of peripheral blood test indicators,there were statistically significant differences in lymphocyte count,monocyte count,neutrophil to lymphocyte ratio and other indicators between plateau group and plain group(P＜0.05),while there were no statistically significant differences in white blood cell count between plateau group and plain group(P＞0.05).Conclusion The epidemiological characteristics of acute upper respiratory tract infection in plateau area are obviously different from those in plain area,which may be related to the natural environment and human geography environment.

Bone and joint infections(BJI)are serious postoperative complications,and traditional bacterial culture techniques serve as the gold standard for diagnosis,but there are problems with untimely or undiag-nosed diagnosis.Metagenomics next-generation sequencing(mNGS),as an emerging technology,can detect various pathogens such as bacteria,viruses,parasites,and fungi in samples without bias,providing a new ap-proach for the diagnosis of BJI.This article reviews the application progress of mNGS in BJI,including techni-cal principles,advantages,limitations,and clinical application status.mNGS exhibits high sensitivity and speci-ficity in the diagnosis of prosthetic joint infections(PJI),and its advantages are obvious especially in cultiva-ting negative cases.In addition,mNGS can optimize traditional culture methods,improve the sensitivity of in-traoperative culture,and be used to guide antibiotic selection.However,mNGS has limitations such as slow database updates,sample contamination,and high costs.Further research is needed in the future to elucidate its complete clinical benefits and promote its widespread application in the field of orthopedics.

Purpose To explore the clinical and pathological characteristics of gastric amphicrine carcinoma(AC).Methods Clinical data of 12 patients with gastric AC were collected,and their clinical pathological character-istics and histological morphology were observed.Immunohistochemical staining,special staining,and electron micros-copy techniques were used to analyze their immune phenotype and ultrastructure.Molecular pathology was used to de-tect microsatellite status.Relevant literature was reviewed.Results Ten cases of gastric AC were located at the junc-tion of the esophagus and stomach/cardia,1 case at the gastric angle,and 1 case in the gastric antrum.The average maximum diameter of tumors was 4.25 cm.There were different proportions of tumor cells with signet-ring like charac-teristics in all cases.Four cases had neuroendocrine carcinoma components,and another 4 had adenocarcinoma.Elev-en cases had nerve invasion and vascular cancer thrombus.Eleven cases invaded the serosal layer/submucosal layer,and 1 case invaded the submucosal layer.Ten cases had lymph node metastasis.All 12 cases showed diffuse expression of CKpan and Syn,with 3 cases showed diffuse expression of CgA and 7 cases showed diffuse expression of CD56.The average proliferation index of Ki67 was 78.9％.Special staining showed clear intracellular mucus.Electron microscopy examination revealed electron dense particles and mucus particles within the tumor cells.A total of 10 patients were fol-lowed up,of which 7 survived,and 3 patients died from multiple systemic metastases at 0,24,and 30 months postop-eratively.Conclusion Gastric AC was more common in the junction of the esophagus and stomach/cardia,and histol-ogy shows a higher invasiveness.Their clear diagnosis depends on histological morphology,immunohistochemistry,and special staining.

Objective:To investigate the effects of two anastomosis methods on perioperative and pathological outcomes during totally laparoscopic right hemicolectomy (TLRH).Methods:In a national multicenter snapshot study, 1,854 patients who underwent laparoscopic right hemicolectomy were enrolled from 52 tertiary hospitals across China. The post-hoc analysis based on this study compared the data of 303 patients who underwent TLRH. Patients were divided into the antiperistaltic group (33 cases) and the isoperistaltic group (270 cases) according to type of anastomosis. Due to the significant difference in sample size between the two groups, propensity score matching (PSM) was performed to eliminate the influence of baseline characteristic discrepancies. The matching was based on the following known confounding factors: age, gender, body mass index (BMI), history of abdominal surgery, and history of diabetes, with a caliper value of 0.2. Perioperative and pathological outcomes were compared between the two groups.Results:After PSM, 33 patients were included in the antiperistaltic group and 65 patients in the isoperistaltic group. There were no statistically significant differences in baseline data between the two groups (all P>0.05). No significant differences were observed between the two groups in terms of operation time, blood loss, time to first defecation, time to first oral intake, or the incidence and grading of complications either (all P>0.05). However, length of postoperative hospital stay in the isoperistaltic group was significantly shorter than that in the antiperistaltic group, however (7.0 [6.0, 9.0] days vs. 8.0 [7.0, 10.5] days, P=0.049). In terms of pathological outcomes, there were also no statistically significant differences between the two groups in the number of harvested lymph nodes or the number of positive lymph nodes (all P>0.05). Conclusions:The two digestive tract reconstruction modalities, antiperistaltic and isoperistaltic anastomosis, have comparable perioperative safety and efficacy in TLRH. The isoperistaltic group had better outcomes in terms of postoperative hospital stay.

The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

OBJECTIVES: To investigate the inhibitory effect of multimerin-2 (MMRN2) overexpression on growth and metastasis of cutaneous melanoma cells. METHODS: Clinical data of patients with cutaneous melanoma were obtained from the GEO database to compare MMRN2 expressions between normal and tumor tissues. A protein-protein interaction network was constructed using the STRING database, and the intersecting genes from GEPIA2.0 were subjected to GO and KEGG enrichment analysis. The prognostic relevance of MMRN2 expression level was assessed using Cox regression and "timeROC". The correlations of MMRN2 expression level with immune infiltration and angiogenesis-related genes were analyzed using GSCA database and the ssGSEA algorithm. Colony-forming assay, Transwell assay, and wound healing assay were used to examine the changes in proliferation and migration of cultured cutaneous melanoma cells following MMRN2 knockdown. In a mouse model bearing cutaneous melanoma xenograft, the effect of MMRN2 knockdown on vital organ pathologies, survival of the mice and GM-CSF, CXCL9, and TGF‑β1 protein expressions were analyzed. RESULTS: MMRN2 was significantly upregulated in metastatic cutaneous melanoma (P<0.001). Protein interaction network analysis identified 15 intersecting genes, which were enriched in endothelium development and cell-cell junctions. In patients with cutaneous melanoma, a high MMRN2 expression was correlated with a poor prognosis, an advanced T stage, a greater Breslow depth, and ulceration (P<0.05). MMRN2 expression level was strongly correlated with 24 immune cell types (P<0.001), fibroblasts, endothelial cells, and expressions of the pro-angiogenic genes (KCNJ8, SLCO2A1, NRP1, and COL3A1; P<0.001). In cultured B16F10 cells, MMRN2 knockdown significantly suppressed cell proliferation, migration and invasion and caused remo-deling of the immunosuppressive microenvironment. CONCLUSIONS MMRN2 overexpression drives progression of cutaneous melanoma by enhancing tumor metastasis, angiogenesis and immune evasion, highlighting its potential as a therapeutic target for melanomas.
Humans ; Melanoma/metabolism* ; Animals ; Cell Movement ; Prognosis ; Skin Neoplasms/metabolism* ; Mice ; Cell Proliferation ; Neoplasm Invasiveness ; Cell Line, Tumor ; Protein Interaction Maps