ObjectiveTo investigate the efficacy and underlying mechanisms of Gynostemma pentaphyllum alcohol extract in improving glucose and lipid metabolism disorders in db/db mice through transcriptomics and gut microbiota analysis. MethodsEighteen db/db mice were randomly assigned to the model（DM） group， metformin（MET） group， and G. pentaphyllum alcohol extract（GP） group， with six mice in each group， based on stratification of fasting blood glucose and body weight. An additional six db/m mice were selected as the normal control（NC） group. Mice in the NC and DM groups were administered deionized water （10 mL·kg^-1） daily. The MET group received metformin （0.195 g·kg^-1） by gavage. The GP group was treated with G. pentaphyllum alcohol extract （3.9 g·kg^-1） by gavage for six weeks. Fasting blood glucose was measured every two weeks. After six weeks of intervention， serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， and blood urea nitrogen （BUN） were assessed. Enzyme-linked immunosorbent assay （ELISA） was used to measure insulin （FINS）， adiponectin （ADP）， and tumor necrosis factor-α （TNF-α）. Hematoxylin-eosin （HE） staining was used to observe liver histomorphology， periodic acid-Schiff （PAS） staining was employed to assess hepatic glycogen synthesis， and Oil Red O staining was used to detect hepatic lipid deposition. Liver transcriptomic data were used to identify differentially expressed genes in the liver and conduct enrichment analysis. Real-time PCR was employed to verify the expression levels of adiponectin gene （Adipoq）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， AMP-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor α （PPARα）， glucokinase （GCK）， forkhead box （Fox）O1， FoxO3， phosphoenolpyruvate carboxykinase （PEPCK）， and glucose-6-phosphatase （G6PC）. Metagenomic sequencing was conducted to analyze changes in gut microbiota composition. ResultsCompared with the NC group， the DM group exhibited significantly elevated fasting blood glucose （P<0.01）， serum AST， ALT， TC， TG， LDL-C， and HDL-C （P<0.01）. FINS， homeostatic model assessment for insulin resistance （HOMA-IR）， and the inflammatory cytokine TNF-α were significantly increased （P<0.01）， while ADP was significantly decreased （P<0.05）. Histological analysis confirmed severe hepatic steatosis and excessive lipid accumulation in the DM group， along with markedly reduced glycogen synthesis. Compared with the DM group， the GP group showed significantly decreased fasting blood glucose （P<0.01）， reduced serum TC， LDL-C， and HDL-C levels （P<0.05）， significantly decreased serum TG and AST levels （P<0.01）， significantly reduced FINS， HOMA-IR， and TNF-α levels （P<0.01）， and significantly increased ADP （P<0.01）. Hepatic steatosis and lipid deposition were significantly alleviated， while glycogen synthesis was markedly enhanced. Transcriptomic differential and enrichment analyses suggested that the mechanisms by which G. pentaphyllum alcohol extract improved hepatic glucose and lipid metabolism in db/db mice may involve regulation of the AMPK and FoxO signaling pathways. Real-time PCR results confirmed that expression of PGC-1α， PEPCK， G6PC， FoxO1， and FoxO3 was significantly downregulated following treatment with G. pentaphyllum alcohol extract （P<0.05， P<0.01）， whereas mRNA expression of Adipoq， PPARα， GCK， and AMPK was significantly upregulated （P<0.05， P<0.01）. Metagenomic analysis showed that the relative abundance of Lactobacillus， Alistipes， and Akkermansia species was higher in the GP group than in the DM group. ConclusionG. pentaphyllum alcohol extract may improve glucose and lipid metabolism disorders in db/db mice by regulating the hepatic AMPK/PPARα pathway to suppress lipid deposition and alleviate hepatic steatosis， by inhibiting gluconeogenesis through the AMPK/PGC-1α and FoxO pathways to lower fasting blood glucose， and by increasing the abundance of beneficial gut bacteria such as Lactobacillus， Alistipes， and Akkermansia to restore gut microbiota balance.

ObjectiveTo investigate the efficacy and underlying mechanisms of Gynostemma pentaphyllum alcohol extract in improving glucose and lipid metabolism disorders in db/db mice through transcriptomics and gut microbiota analysis. MethodsEighteen db/db mice were randomly assigned to the model（DM） group， metformin（MET） group， and G. pentaphyllum alcohol extract（GP） group， with six mice in each group， based on stratification of fasting blood glucose and body weight. An additional six db/m mice were selected as the normal control（NC） group. Mice in the NC and DM groups were administered deionized water （10 mL·kg^-1） daily. The MET group received metformin （0.195 g·kg^-1） by gavage. The GP group was treated with G. pentaphyllum alcohol extract （3.9 g·kg^-1） by gavage for six weeks. Fasting blood glucose was measured every two weeks. After six weeks of intervention， serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， and blood urea nitrogen （BUN） were assessed. Enzyme-linked immunosorbent assay （ELISA） was used to measure insulin （FINS）， adiponectin （ADP）， and tumor necrosis factor-α （TNF-α）. Hematoxylin-eosin （HE） staining was used to observe liver histomorphology， periodic acid-Schiff （PAS） staining was employed to assess hepatic glycogen synthesis， and Oil Red O staining was used to detect hepatic lipid deposition. Liver transcriptomic data were used to identify differentially expressed genes in the liver and conduct enrichment analysis. Real-time PCR was employed to verify the expression levels of adiponectin gene （Adipoq）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， AMP-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor α （PPARα）， glucokinase （GCK）， forkhead box （Fox）O1， FoxO3， phosphoenolpyruvate carboxykinase （PEPCK）， and glucose-6-phosphatase （G6PC）. Metagenomic sequencing was conducted to analyze changes in gut microbiota composition. ResultsCompared with the NC group， the DM group exhibited significantly elevated fasting blood glucose （P<0.01）， serum AST， ALT， TC， TG， LDL-C， and HDL-C （P<0.01）. FINS， homeostatic model assessment for insulin resistance （HOMA-IR）， and the inflammatory cytokine TNF-α were significantly increased （P<0.01）， while ADP was significantly decreased （P<0.05）. Histological analysis confirmed severe hepatic steatosis and excessive lipid accumulation in the DM group， along with markedly reduced glycogen synthesis. Compared with the DM group， the GP group showed significantly decreased fasting blood glucose （P<0.01）， reduced serum TC， LDL-C， and HDL-C levels （P<0.05）， significantly decreased serum TG and AST levels （P<0.01）， significantly reduced FINS， HOMA-IR， and TNF-α levels （P<0.01）， and significantly increased ADP （P<0.01）. Hepatic steatosis and lipid deposition were significantly alleviated， while glycogen synthesis was markedly enhanced. Transcriptomic differential and enrichment analyses suggested that the mechanisms by which G. pentaphyllum alcohol extract improved hepatic glucose and lipid metabolism in db/db mice may involve regulation of the AMPK and FoxO signaling pathways. Real-time PCR results confirmed that expression of PGC-1α， PEPCK， G6PC， FoxO1， and FoxO3 was significantly downregulated following treatment with G. pentaphyllum alcohol extract （P<0.05， P<0.01）， whereas mRNA expression of Adipoq， PPARα， GCK， and AMPK was significantly upregulated （P<0.05， P<0.01）. Metagenomic analysis showed that the relative abundance of Lactobacillus， Alistipes， and Akkermansia species was higher in the GP group than in the DM group. ConclusionG. pentaphyllum alcohol extract may improve glucose and lipid metabolism disorders in db/db mice by regulating the hepatic AMPK/PPARα pathway to suppress lipid deposition and alleviate hepatic steatosis， by inhibiting gluconeogenesis through the AMPK/PGC-1α and FoxO pathways to lower fasting blood glucose， and by increasing the abundance of beneficial gut bacteria such as Lactobacillus， Alistipes， and Akkermansia to restore gut microbiota balance.

Objective:To explore the clinical characteristics and risk factors of acute kidney injury (AKI) in patients with diquat mixed with paraquat poisoning.Methods:We retrospectively analyzed the clinical data of 210 patients admitted to the department of emergency at our hospital with paraquat, diquat or mixed poisoning from January 20, 2016, to June 10, 2024. Based on the detection results of plasma toxicants, patients were categorized into three groups: the paraquat group (PQ group), and the diquat group (DQ group), the diquat-paraquat mixed group (mixed group). We compared clinical indices, occurrence, and severity of AKI among these groups. In the mixed group, patients were further divided into AKI and non-AKI subgroups based on the presence of AKI during hospitalization, and differences in clinical indices between these subgroups were analyzed. Univariate logistic regression and least absolute shrinkage and selection operator (Lasso) regressions were used to screen risk factors, and multivariate logistic regression was applied to establish the model. ROC curves were generated, and factors influencing AKI occurrence in the mixed group were identified.Results:A total of 88 patients were included in the PQ group, 28 in the DQ group, and 57 in the mixed group. Significant differences were observed among the three groups in terms of age, mortality rate, ingestion amount, body mass index(BMI), occurrence of AKI, the incidence of organ support therapy, SIRS score, PSS score, and APACHE Ⅱ score on admission ( P < 0.05). All three groups exhibited various degrees of AKI, with the mixed group showing a higher proportion and more severe conditions. In the mixed group, compared with the non-AKI group, the AKI group showed significantly higher values for age, number of deaths, ingestion amount, SIRS score, PSS score, APACHE Ⅱ score, plasma PQ concentration on admission, plasma DQ concentration on admission, white blood cell count (WBC), neutrophil count (NEUT), monocyte count (MONO), serum creatinine (SCr), procalcitonin (PCT), c-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood lactic acid (Lac), and cystatin C (CysC) ( P < 0.05). Conversely, the estimated glomerular filtration rate (eGFR) and partial pressure of carbon dioxide (PCO2) were significantly lower in the AKI group ( P < 0.05). Additionally, in the mixed group, SCr levels at various times post-poisoning were significantly higher compared with the non-AKI group ( P < 0.05), showing an increasing trend and peaking at 212.19 ± 101.67 μmol/L on the fifth day after poisoning. Age, ingestion amount, SIRS score on admission, WBC, MONO, and PCO 2 were extracted by Lasso-Logistic regression. Multivariate logistic regression identified ingestion amount and SIRS score on admission as the independent risk factors for the occurrence of AKI in the mixed group. The area under the ROC curve for ingestion amount and SIRS score on admission was 0.991 (95% CI: 0.976-1.000), the sensitivity was 0.940 and the specificity was 1.000. Conclusions:The diquat mixed with paraquat poisoning is associated with a higher incidence and greater severity of AKI compared with poisoning with either PQ or DQ alone. Additionally, ingestion amount and SIRS score on admission have been identified as independent risk factors for the occurrence of AKI in patients with the mixed poisoning. The combined assessment of these two factors improves AKI prediction in patients with the mixed poisoning.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Objective To prepare a postbiotic using soybean fermentation product of Lactobacillus paracasei TK1501 and evaluate its inhibitory effect against Helicobacter pylori(Hp)infection in mice.Methods L.paracasei TK1501 was cultured for 32 h at 37℃in an anaerobic condition for solid substrate fermentation with a solid to water ratio of 1:1.5 in the substrate and an inoculation density of 5×107 CFU/mL.The postbiotic was isolated and purified using macroporous resin XAD-16N adsorption,cation exchange chromatography and HPLC,and its stability and antibacterial activity were assessed.The inhibitory effect of this postbiotic against Hp infection was evaluated in a mouse model with gastric mucosal Hp infection,which were treated with the postbiotic via gavage for 4 weeks at the dose of 0.02 or 0.1 mL.Serum levels of TNF-α and IL-1β of the mice were analyzed after the treatments,and gastric tissues of the mice were collected for HE staining.Results L.paracasei TK1501 postbiotic could be easily degraded by protease and had good thermal stability and tolerance to exposures to acid,base,and organic solvents.In the in vitro experiment,the postbiotic showed strong inhibitory effects in bacterial cultures of Staphylococcus aureus,Hp and other common pathogenic bacteria without obviously affecting the resident bacteria in the digestive tract.In the mouse models,treatment with the postbiotic at the dose of 0.1 mL significantly alleviated Hp infection and lowered the serum levels of TNF-α and IL-1β of the mice.Conclusion L.paracasei TK1501 postbiotic has strong inhibitory effects on Hp and Staphylococcus aureus but not on normal intestinal flora in mice.

Objective To prepare a postbiotic using soybean fermentation product of Lactobacillus paracasei TK1501 and evaluate its inhibitory effect against Helicobacter pylori(Hp)infection in mice.Methods L.paracasei TK1501 was cultured for 32 h at 37℃in an anaerobic condition for solid substrate fermentation with a solid to water ratio of 1:1.5 in the substrate and an inoculation density of 5×107 CFU/mL.The postbiotic was isolated and purified using macroporous resin XAD-16N adsorption,cation exchange chromatography and HPLC,and its stability and antibacterial activity were assessed.The inhibitory effect of this postbiotic against Hp infection was evaluated in a mouse model with gastric mucosal Hp infection,which were treated with the postbiotic via gavage for 4 weeks at the dose of 0.02 or 0.1 mL.Serum levels of TNF-α and IL-1β of the mice were analyzed after the treatments,and gastric tissues of the mice were collected for HE staining.Results L.paracasei TK1501 postbiotic could be easily degraded by protease and had good thermal stability and tolerance to exposures to acid,base,and organic solvents.In the in vitro experiment,the postbiotic showed strong inhibitory effects in bacterial cultures of Staphylococcus aureus,Hp and other common pathogenic bacteria without obviously affecting the resident bacteria in the digestive tract.In the mouse models,treatment with the postbiotic at the dose of 0.1 mL significantly alleviated Hp infection and lowered the serum levels of TNF-α and IL-1β of the mice.Conclusion L.paracasei TK1501 postbiotic has strong inhibitory effects on Hp and Staphylococcus aureus but not on normal intestinal flora in mice.

Food poisoning caused by Nassariidaes has occurred frequently in coastal areas of China, especially in summer and autumn. Nassariidaes poisoning can be manifested as lip and tongue paralysis, dizziness, headache, nausea and vomiting, arrhythmia and even respiratory failure. We admitted a case of respiratory failure caused by eating Nassariidaes. After timely respiratory support, hemoperfusion and other active treatment, the patient was recovered and was discharged. This paper summarized clinical characteristics and treatment of Nassariidaes poisoning, in order to provide reference for clinical diagnosis and treatment of similar cases.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Objective:To systematically review qualitative research on the experiences of palliative care patients and caregivers in home medication management, so as to improve their drug management capabilities and optimize grassroots palliative care services as a reference.Methods:This review was conducted using databases including the Cochrane Library, PubMed, Embase, Web of Science, CINAHL, China National Knowledge Infrastructure, Wanfang Data, VIP Database, and China Biology Medicine disc, searching for qualitative research on the medication management experiences of palliative care patients and caregivers up to April 30, 2024. The quality of the literature was assessed using the Australian Joanna Briggs Institute Evidence-Based Health Care Center standards for qualitative research quality assessment. A convergent integrated approach was employed to synthesize and integrate the findings.Results:Eleven articles were included, all of which were from abroad, synthesizing 51 findings into 7 new categories, which were then integrated into 3 composite outcomes: complex feelings of patients and caregivers in home medication management, including responsibility and self-efficacy, anxiety and fatigue; challenges in home medication management, including polypharmacy and experiences using pain medication, disagreements over medication management at home, and perceived inadequacies in primary healthcare resources;the need for multifaceted support, including desires for more medication guidance and communication with palliative care professionals in the community.Conclusions:Due to the complexity of medication needs and insufficient regulatory support, home medication management in palliative care presents challenges. It is recommended to enhance the self-efficacy and medication management skills of patients and caregivers, improve risk response capabilities, optimize medication administration processes, and strengthen training for healthcare professionals. Government agencies should also support policies to ensure a safe and comfortable home medication environment for palliative care patients in China.

Food poisoning caused by Nassariidaes has occurred frequently in coastal areas of China, especially in summer and autumn. Nassariidaes poisoning can be manifested as lip and tongue paralysis, dizziness, headache, nausea and vomiting, arrhythmia and even respiratory failure. We admitted a case of respiratory failure caused by eating Nassariidaes. After timely respiratory support, hemoperfusion and other active treatment, the patient was recovered and was discharged. This paper summarized clinical characteristics and treatment of Nassariidaes poisoning, in order to provide reference for clinical diagnosis and treatment of similar cases.