Objective To explore the dynamic changes of gut microbiota metabolites in septic patients following admission, as well as the correlations between these metabolites, the gut microbiota, and the prognosis of septic patients. Methods A total of 119 fecal samples were collected from 23 septic patients, 16 non-septic patients admitted to the Emergency Intensive Care Unit (ICU), and 20 healthy controls at Zhongshan Hospital, Fudan University, from January to August 2019. The 16S rRNA gene sequencing technology was applied to analyze the microbiome, while ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was used for metabolomics research. The R software was used to analyze the gut microbiota and metabolite data. Based on 180-day survival status after admission, the sepsis group was divided into the survival group (n＝15) and the death group (n＝8) to analyze differential metabolites between the two groups. Spearman correlation coefficients were used to assess correlations between gut microbiota and metabolites. Results In the first week of ICU stay, gut microbiota metabolites such as nicotinic acid, methylsuccinic acid, and glutaric acid were significantly lower in septic patients than in healthy controls (P＜0.05), whereas tryptophan, histidine, valine, and pyroglutamic acid were higher in septic patients (P＜0.05). The methylsuccinic acid and phenylacetic acid levels in the first week were lower in the death group than those in the survival group (P＜0.05), and the levels of methylsuccinic acid, phenylacetic acid, and glutaric acid were lower in the third week (P＜0.05). Further analysis indicated that methylsuccinic acid was closely associated with sepsis prognosis. These differential metabolites involved in metabolic pathways such as phenylalanine metabolism and β-alanine metabolism. Most differential amino acids were positively correlated with opportunistic pathogens but negatively correlated with normal gut microbiota. Conversely, metabolites such as nicotinic acid, phenylacetic acid, methylsuccinic acid, and glutaric acid were negatively correlated with opportunistic pathogens and positively correlated with normal gut microbiota. Conclusions Significant dynamic changes occur in gut microbiota metabolites in septic patients, with methylsuccinic acid, phenylacetic acid, and glutaric acid potentially playing important roles in determining patient prognosis.

[摘 要] 目的：探讨X连锁锌指蛋白（ZFX）通过Nectin-4表达影响食管鳞状细胞癌（ESCC）进展的分子机制及其对PI3K/AKT信号通路的激活作用。方法：收集2022年8月至2023年7月在南充市中心医院手术切除的30对ESCC组织及癌旁组织标本。采用人食管上皮细胞HET-1A及ESCC细胞KYSE-30、KYSE-150、KYSE-410、KYSE-510和TE-1。基于2018年至2019年收集的6例ESCC配对标本转录组测序数据筛选Nectin-4，通过TIMER2.0数据库、RT-qPCR和WB法、免疫组织化学（IHC）检测ESCC组织及细胞中Nectin-4的表达水平。采用shRNA技术在KYSE-410和KYSE-510细胞中敲低Nectin-4，通过CCK-8、克隆形成、划痕愈合及Transwell实验检测敲低Nectin-4对细胞增殖、迁移和侵袭能力的影响，采用WB法检测敲低Nectin-4对细胞PI3K/AKT通路及EMT相关蛋白表达水平的影响。通过生物信息学预测并结合双萤光素酶报告基因实验，鉴定并验证ZFX作为Nectin-4的上游转录调控因子。结果：综合分析显示，ESCC组织及细胞系中Nectin-4表达显著高于癌旁组织及HET-1A细胞（均P < 0.01）。功能研究表明，敲低Nectin-4显著抑制KYSE-410和KYSE-510细胞的增殖活性、克隆形成能力，以及迁移和侵袭能力（均P < 0.01）。机制方面，敲低Nectin-4时细胞中E-cadherin表达上调、N-cadherin下调（均P < 0.01），并抑制PI3K/AKT通路相关蛋白的磷酸化水平（P < 0.01）。结论： ZFX通过上调Nectin-4表达激活PI3K/AKT信号通路促进ESCC进展，为ESCC的治疗提供了潜在的新靶点。

Hepatic sinusoidal capillarization is the first event in the process of fibrogenesis， and inhibiting hepatic sinusoidal capillarization can effectively improve the pathological process of liver fibrosis. Various studies have shown that traditional Chinese medicine can significantly inhibit hepatic sinusoidal capillarization. This article systematically reviews the effective constituents， monomers， and compound prescriptions of traditional Chinese medicine， summarizes their mechanism of action in inhibiting hepatic sinusoidal capillarization， and analyzes the theoretical core of traditional Chinese medicine in inhibiting hepatic sinusoidal capillarization from the perspective of traditional Chinese medicine， in order to provide ideas and literature support for the treatment of liver fibrosis.

ObjectiveTo analyze the clinical treatment plan and traditional Chinese medicine （TCM） medication rule of children with primary nephrotic syndrome （PNS） in the First Affiliated Hospital of Henan University of Chinese Medicine. MethodsThe gender and age of children firstly diagnosed with nephrotic syndrome in the pediatric nephrology department of the First Affiliated Hospital of Henan University of Chinese Medicine from November 2019 to December 2022 were collected， and the use of immunosuppressive agents and related frequencies were counted. According to the inclusion and exclusion criteria， an independent TCM prescription database for children with nephrotic syndrome was established. Excel was used to analyze the relevant information of the literature. The frequency counting， association rule analysis， and cluster analysis were carried out on TCM in the prescription， and the high-frequent drugs were analyzed. Results（1） General information： A total of 711 children were included， consisting of 522 males （73.42%） and 189 females （26.58%）. The ratio of male to female was about 2.76∶1. The disease mainly occurred in infants and preschool age， and the average age of onset was （4.74 ± 3.48） years old. （2） Clinical treatment plan and use of immunosuppressive agents： Of the 711 children with PNS， 237 were treated with hormone alone （32.33%）， and 474 （66.67%） received immunosuppressive agents combined with hormones. In the initial treatment， hormone combined with Tacrolimus （TAC） was the preferred treatment （32.91%）. For children with refractory PNS who exhibited poor clinical efficacy， Rituximab （RTX） was mostly used for treatment， with a ratio of up to 23.63%. （3） TCM syndrome and medication rule： In PNS syndrome differentiation， Qi and Yin deficiency was identified as the main syndrome. This involved a total of 477 cases， accounting for 67.09%. Yang deficiency of spleen and kidney was observed in 118 cases， accounting for 16.60%. A total of 711 children were included， of which 706 children were treated with TCM. This involved a total of 706 prescriptions， 226 TCM， and 9 793 frequencies. There were 30 herbs used more than 95 times. The top five TCM were Radix et Rhizoma Glycyrrhizae （81.16%）， Radix Astragali （71.81%）， Poria （68.84%）， Rhizoma Atractylodis Macrocephalae （63.60%）， and Fructus Corni （57.37%）. The drug association rules and network diagram showed that the combination of ''Radix Astragali-Rhizoma Atractylodis Macrocephalae-Poria'' was the closest， and five types of combinations were obtained by cluster analysis. ConclusionIn the diagnosis and treatment of PNS in children， TAC combined with hormones shows good clinical efficacy and high safety. For children with refractory PNS， RTX combined with hormones can be used. TCM medication for PNS should follow the basic principles of strengthening the body and vital Qi and make good use of drugs such as Radix Astragali， Poria， Rhizoma Atractylodis Macrocephalae， and cornus to regulate the Yin and Yang balance and achieve better clinical efficacy.

ObjectiveTo analyze the clinical treatment plan and traditional Chinese medicine （TCM） medication rule of children with primary nephrotic syndrome （PNS） in the First Affiliated Hospital of Henan University of Chinese Medicine. MethodsThe gender and age of children firstly diagnosed with nephrotic syndrome in the pediatric nephrology department of the First Affiliated Hospital of Henan University of Chinese Medicine from November 2019 to December 2022 were collected， and the use of immunosuppressive agents and related frequencies were counted. According to the inclusion and exclusion criteria， an independent TCM prescription database for children with nephrotic syndrome was established. Excel was used to analyze the relevant information of the literature. The frequency counting， association rule analysis， and cluster analysis were carried out on TCM in the prescription， and the high-frequent drugs were analyzed. Results（1） General information： A total of 711 children were included， consisting of 522 males （73.42%） and 189 females （26.58%）. The ratio of male to female was about 2.76∶1. The disease mainly occurred in infants and preschool age， and the average age of onset was （4.74 ± 3.48） years old. （2） Clinical treatment plan and use of immunosuppressive agents： Of the 711 children with PNS， 237 were treated with hormone alone （32.33%）， and 474 （66.67%） received immunosuppressive agents combined with hormones. In the initial treatment， hormone combined with Tacrolimus （TAC） was the preferred treatment （32.91%）. For children with refractory PNS who exhibited poor clinical efficacy， Rituximab （RTX） was mostly used for treatment， with a ratio of up to 23.63%. （3） TCM syndrome and medication rule： In PNS syndrome differentiation， Qi and Yin deficiency was identified as the main syndrome. This involved a total of 477 cases， accounting for 67.09%. Yang deficiency of spleen and kidney was observed in 118 cases， accounting for 16.60%. A total of 711 children were included， of which 706 children were treated with TCM. This involved a total of 706 prescriptions， 226 TCM， and 9 793 frequencies. There were 30 herbs used more than 95 times. The top five TCM were Radix et Rhizoma Glycyrrhizae （81.16%）， Radix Astragali （71.81%）， Poria （68.84%）， Rhizoma Atractylodis Macrocephalae （63.60%）， and Fructus Corni （57.37%）. The drug association rules and network diagram showed that the combination of ''Radix Astragali-Rhizoma Atractylodis Macrocephalae-Poria'' was the closest， and five types of combinations were obtained by cluster analysis. ConclusionIn the diagnosis and treatment of PNS in children， TAC combined with hormones shows good clinical efficacy and high safety. For children with refractory PNS， RTX combined with hormones can be used. TCM medication for PNS should follow the basic principles of strengthening the body and vital Qi and make good use of drugs such as Radix Astragali， Poria， Rhizoma Atractylodis Macrocephalae， and cornus to regulate the Yin and Yang balance and achieve better clinical efficacy.

As the application of immune checkpoint inhibitors(ICIs)in the perioperative treatment of melanoma is increasingly introduced at earlier stages,it presents a critical opportunity for the development and clinical translation of neoadjuvant therapy.The results of phaseⅠ/Ⅱ clinical trials on neoadjuvant ICI therapy for melanoma demonstrate that neoadjuvant ICIs effectively improve the pathologic re-sponse rate in melanoma patients.Recent studies have shown that combining ICIs with other treatment modalities,including radiotherapy,chemotherapy,and targeted therapies,can enhance antitumor efficacy of neoadjuvant treatment for patients with melanoma.Optimizing treatment regimens,managing adverse events,identifying and addressing pseudoprogression,and handling cases of oligoprogression have become key areas of research in incorporating ICI regimens into neoadjuvant treatment for patients with melanoma.The search for bio-markers to monitor immunotherapy efficacy is expected to become a major focus of future research.This article provides a review of the re-search progress,controversies,and challenges in the application of ICIs in the neoadjuvant treatment of melanoma,and discusses future re-search directions,aiming to offer insights into the clinical application and development of ICIs in melanoma neoadjuvant therapy.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To investigate the feasibility and clinical outcomes of using the deep inferior epigastric perforator flap to repair stage Ⅳ pressure ulcers in elderly patients with the femoral trochanter.Methods:Retrospective analysis of clinical data of elderly patients with stage Ⅳ pressure ulcers of the femoral trochanter treated at the Medical Center of Burn Plastic and Wound Repair, the First Affiliated Hospital of Nanchang University from May 2018 to May 2023 using the deep inferior epigastric perforator flap.The deep inferior epigastric perforator flap was designed on the same side of the abdomen based on the preoperative detection of the paraumbilical perforating branch.The axis of the inferior epigastric artery was determined by the line connecting the femoral artery pulsation point at the inguinal ligament and the obvious paraumbilical perforating branch point. The axis of the skin flap was determined by the line connecting the obvious paraumbilical perforating branch point and the subscapular angle. Combined with the situation of the sinus after pressure ulcer debridement and the range of skin and soft tissue defects, the inferior epigastric artery perforating branch skin flap was cut and repaired. The pedicle of the inferior epigastric artery was freed to the required length according to the location of the pressure ulcer, and the wound was transferred and repaired through a subcutaneous tunnel. The donor area was directly pulled and sutured. The survival of the skin flap and the healing of the donor site wound after surgery were observed, and the recurrence of pressure ulcers, the appearance and texture of the skin flap, and the recovery of the donor site were followed up regularly.Results:A total of 11 patients were included, including 7 males and 4 females; age ranged from 66 to 83 years old, with an average of 72.1 years old. There were total of 11 pressure ulcers in the femoral trochanter, with an area of 5.0 cm × 3.0 cm-13.0 cm ×6.0 cm before debridement and an area of 8.0 cm × 5.0 cm-16.0 cm × 8.0 cm after debridement. The deep inferior epigastric perforator flap was used to repair the wound. The flap was cut with an area of 10.0 cm × 6.0 cm-18.0 cm × 9.0 cm, and the length of the blood vessels in the flap pedicle was 12-16 cm, with an average of 14 cm. After surgery, 9 of the 11 flaps survived completely. One skin flap developed purplish discoloration at the distal end 24 hours after surgery, which was relieved by removing the suture at the site with high tension at the wound edge. One skin flap also showed slight necrosis at the distal end. The flap was removed under local anesthesia at the bedside of the ward, and the surgical wound was directly sutured. After dressing change, it healed. The wounds in the donor area all healed well. Follow up for 3-15 months postoperatively, with an average of 11 months, showed no recurrence of pressure ulcers in all patients. The skin flap had a soft texture, and its color and appearance were similar to those of the surrounding skin. No abdominal wall hernia was observed in the inferior epigastric donor area.Conclusion:The deep inferior epigastric perforator flap has a long vascular pedicle, reliable blood supply, sufficient tissue volume for cutting, no recurrence of pressure ulcers after surgery, good appearance and texture of the affected area, and no secondary abdominal wall hernia in the donor site. It is an effective method for repairing stage Ⅳ pressure ulcers of the femoral trochanter in elderly patients.

Objective To comprehensively evaluate the multidimensional impact of the"Tianjin Experience"of Chest Pain Center(CPC)development on in-hospital mortality,optimization of treatment workflows,and regional coordination of care for patients with acute myocardial infarction(AMI),with the aim of providing scientific evidence to further improve the model and enhance AMI treatment outcomes.Methods This study analyzed data from the"Cardiovascular and Cerebrovascular Acute Events Surveillance System"maintained by the Tianjin Center for Disease Control and Prevention from 2013 to 2024.A segmented regression model was applied to assess the long-term trends in in-hospital mortality from acute myocardial infarction(AMI),with a particular focus on evaluating the impact of the chest pain center program on treatment outcomes.Additionally,supplementary analyses were conducted using surveillance data from the Tianjin Chest Pain Center Quality Control Team between 2017 and 2024.To verify the effectiveness of treatment process optimization,temporal trends in key time-based process indicators were assessed,including Door-in-Door-out(DIDO)time at non-PCI hospitals,Door-to-Wire(D-to-W)time,and First Medical Contact to Wire(FMC-to-W)to wire time.Results According to the data from the Tianjin Center for Disease Control and Prevention,the average 28-day AMI mortality rate in the overall patient population was 9.85％.Between 01/2013 and 12/2014,the mortality rate showed a significant upward trend(P＜0.01),followed by a downward trend from 01/2015 to 12/2024,although the latter did not reach statistical significance(P＞0.05).From 2013 to 2024,a total of 27 633 AMI cases with complete clinical records were collected from Tianjin Chest Hospital,with an average 28-day mortality rate of 4.55％.The mortality rate exhibited a decreasing trend from 01/2013 to 12/2016,with an annual percent change(APC)of-7.56(P＜0.05).From 01/2017 to 12/2024,the trend stabilized,with an APC of 0.39(P＞0.05).Conclusions The development of the CPC system in Tianjin significantly reduced key treatment times and improved the overall efficiency of AMI management.While population-level AMI mortality rates began to decline after 2015,the rate of improvement has slowed,indicating a continued need for optimizing the regional coordinated care system to further enhance patient outcomes.

Objective:To investigate the effect of Yiqi Shengqing Formula on neuronal damage in ischemic stroke(IS)rats by regulating brain-derived neurotrophic factor(BDNF)-extracellular regulated protein kinase(ERK)-cyclic adenosine monophosphate-responsive element binding protein(CREB)signal pathway.Methods:IS rat model was prepared by modified thread suppository method,and randomly divided into model group,low dose Yiqi Shengqing Formula(3 g/kg)group,high dose Yiqi Shengqing Formula(6 g/kg)group,high dose Yiqi Shengqing Formula(6 g/kg)+empty load group,high dose Yiqi Shengqing Formula(6 g/kg)+BDNF knockdown group,with 10 rats in each group,another 10 healthy rats were set as sham operation group.After intervention with Yiqi Shengqing Formula and plasmid,neural function of rats in each group was scored with Longa scoring method;Morris water maze test was used to detect cognitive impairment of rats in each group;Nissl staining was used to detect the number of neurons in ischemic peripheral brain tissue and hippocampus of rats in each group;synaptic morphology of ischemic peripheral brain tissue was detected by silver staining;levels of TNF-α and IL-8 in brain tissue and serum of rats in each group were measured by ELISA;expressions of BDNF-ERK-CREB signal pathway related proteins in rat brain were detected by Western blot.Results:Compared with sham operation group,synaptic morphology of ischemic peripheral brain tissue in model group was severely damaged,retention time in target quad-rant,times of crossing platform,the number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were decreased significantly(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were increased significantly(P<0.05).Compared with model group,synaptic morphological damage of ischemic peripheral brain tissue in rats in low dose Yiqi Shengqing Formula group and high dose Yiqi Shengqing Formula group was alleviated,retention time in target quadrant,times of crossing platform,the number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were increased(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were decreased(P<0.05).Compared with low dose Yiqi Shengqing Formula group,damage of synaptic morphology in ischemic peripheral brain tissue of rats in high dose Yiqi Shengqing Formula group was further alleviated,retention time in target quadrant,times of crossing platform,the number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were further increased(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were further reduced(P<0.05).Compared with high dose Yiqi Shengqing Formula group,synaptic morphological damage of ischemic peripheral brain tissue in high dose Yiqi Shengqing Formula+BDNF knockdown group was aggravated,retention time in target quadrant,times of crossing the platform,number of neurons in ischemic peripheral brain tissue and hippocampus,expressions of BDNF protein and p-ERK/ERK,p-CREB/CREB in brain tissue were decreased(P<0.05),while neurological function score and levels of inflammatory factors TNF-α and IL-8 in brain tissue and serum were increased(P<0.05);there was no significant changes in each index of rats in high dose Yiqi Shengqing Formula+empty load group(P>0.05).Conclusion:Yiqi Shengqing Formula can inhibit the neuroinflammation of IS rats by activating BDNF-ERK-CREB signal,thereby reducing the damage of its neurons and improving its neural function.