This study explores the therapeutic differences and mechanisms of salt-processed Phellodendri Chinensis Cortex in improving insulin resistance(IR) based on network pharmacology, molecular docking, and cellular experiments. The components and intersection targets of Phellodendri Chinensis Cortex in improving IR were collected from databases, and a "drug-component-target-disease" network and protein-protein interaction(PPI) network were constructed to screen core components and targets. A total of 29 active components and 240 intersection targets were identified, of which 13 were core targets. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were used to identify key signaling pathways, and molecular docking was performed to validate the binding activity between core components and targets. An IR model in HepG2 cells was induced using insulin combined with high glucose, and the effects of Phellodendri Chinensis Cortex before and after salt-processing on cell glucose consumption were evaluated. The expression of proteins related to the mitogen-activated protein kinase(MAPK) and phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT) signaling pathways was detected by Western blot. The cellular experimental results showed that, compared with the model group, glucose consumption in the drug-treated groups was significantly increased(P<0.01), the phosphorylation level of extracellular regulated protein kinase(ERK) was decreased(P<0.05), the phosphorylation levels of PI3K and AKT were increased, and the expression of glucose transporter 4(GLUT4) was also upregulated(P<0.05). Furthermore, the effect of salt-processed Phellodendri Chinensis Cortex was better than that of raw Phellodendri Chinensis Cortex. The study demonstrates that Phellodendri Chinensis Cortex, both before and after salt-processing, improves IR by regulating the expression of related proteins in the MAPK and PI3K-AKT signaling pathways, with enhanced effects after salt-processing.
Humans ; Network Pharmacology ; Phellodendron/chemistry* ; Insulin Resistance ; Drugs, Chinese Herbal/chemistry* ; Hep G2 Cells ; Signal Transduction/drug effects* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Proto-Oncogene Proteins c-akt/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Glucose/metabolism*

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

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: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.

Objective To investigate the mechanisms by which paeoniflorin improves tissue and cell damage caused by diabetic retinopathy(DR)through the hypoxia-induced factor-1α(HIF-1α)pathway.Methods Thirty rats were ran-domly divided into a control group(10 normal rats),a DR group(10 diabetic model rats)and a paeoniflorin group(10 dia-betic model rats given 80 mg·kg-1 paeoniflorin by gavage).Rat retinal microvascular endothelial cells(rRMECs)were di-vided into a control group(cultured with 5 mmol·L-1 glucose),a high glucose group(cultured with 30 mmol·L-1 glu-cose)and a paeoniflorin group(cultured with 30 mmol·L-1 glucose and 20 mol·L-1 paeoniflorin).The three groups of cells were all cultured for 24 h.Fasting blood glucose was measured by a glucose meter.Hematoxylin and eosin(HE)stai-ning was used to detect the retinal histopathological structure.The levels of HIF-1α and vascular endothelial growth factor(VEGF)proteins and mRNAs in retinal tissues and rRMECs were detected by Western blotting and real time quantitative polymerase chain reaction(RT-qPCR).The proliferative ability of rRMECs was detected by the EdU kit.The serum levels of total cholesterol(TC),triglyceride(TG),low density cholesterol(LDL-C),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in retinal tissues and rRMECs were detected by kits.The activity and invasive ability of rRMECs were measured by CCK-8 and Transwell assay,respectively.The levels of HIF-1α and VEGF proteins in rRMECs were detected by immunofluorescence staining.Results Compared with those in the DR group,the fasting blood glucose,TC,TG and LDL-C levels in the paeoniflorin group were significantly decreased(all P＜0.05).The retinal tissue was loose with an un-clear boundary in the DR group,compared with that in the control group.The retinal tissue in the paeoniflorin group was less loose with a clearer boundary than that in the DR group.The levels of HIF-1α and VEGF proteins and mRNAs,TNF-αand IL-6 in retinal tissues of the DR group were significantly higher than those of the control group(all P＜0.05).The lev-els of HIF-1α and VEGF proteins and mRNAs,TNF-α and IL-6 in retinal tissues of the paeoniflorin group were significantly lower than those in the DR group(all P＜0.05).The activity,proliferation and invasive abilities of rRMECs in the high glu-cose group were higher than those in the control group(all P＜0.05).Compared with those in the high glucose group,rRMECs in the paeoniflorin group showed decreased cell activity,proliferation and invasive abilities(all P＜0.05).The lev-els of HIF-1α and VEGF proteins and mRNAs,TNF-α and IL-6 in the rRMECs of the high glucose group were higher than those of the control group(all P＜0.05).The levels of HIF-1α and VEGF proteins and mRNAs,TNF-α and IL-6 in the rRMECs of the paeoniflorin group were lower than those of the high glucose group(all P＜0.05).Conclusion Paeoni-florin can down-regulate the HIF-1α/VEGF pathway to improve the inflammatory injury of the retinal tissue and inhibit rRMEC activity,proliferation and invasive abilities in DR rats,thereby preventing angiogenesis and reducing the incidence of DR.

Objective:To observe the efficacy and safety of polatuzumab vedotin(pola)combined with chemotherapy in the treatment of relapsed and refractory diffuse large B-cell lymphoma(R/R DLBCL).Methods:A total of 23 patients with R/R DLBCL treated at the First Affiliated Hospital of Zhejiang University and its Liangzhu Branch from April 2023 to March 2024 were retrospectively collected.All patients were treated with pola combined with chemotherapy regimens such as BR,R-GDP,R-CHOP,or other regimens.Results:All 23 patients were evaluable for efficacy,with 10 achieving complete response(CR),7 partial response(PR),3 stable disease(SD),and 3 progressive disease(PD).The most common adverse events included myelosuppression,fever,and pulmonary infection.No severe adverse events resulted in drug withdrawal.Conclusion:Pola combined with chemotherapy demonstrates promising efficacy and a favorable safety profile in the treatment of R/R DLBCL.

Objective To explore the effect of curcumin(CUR)on oxidative damage of keratinocytes induced by ultraviolet B(UVB)irradiation through Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/nucleotide-binding oligomerization domain-containing protein 3(NLRP3)signaling pathway.Methods Human keratinocytes of HaCaT were cultured normally in vitro,and the keratinocyte oxidative damage model was established by the irradiation of 57 mJ/cm2 UVB.The cells with normal culture were as the control group,the cells treated after modeling were as the UVB group,the cells treated with 5 μmol/L CUR after modeling were as the CUR group,the cells treated with 100 μg/L TLR4 inhibitor of TAK-242 after modeling were as the TAK-242 group,and the cells treated with 5 μmol/L CUR and 100 nmol/L TLR4 activator of lipopolysaccharide(LPS)were as the CUR+LPS group.qRT-PCR was applied to detect the relative expression levels of TLR4,NF-κB,and NLRP3 mRNAs of cells in each group.CCK-8 was applied to detect the cell proliferation in each group.The relative content of reactive oxygen species(ROS),the viabilities of superoxide dismutase(SOD)and catalase(CAT),and the concentrations of glutathione(MDA)and glutathione(GSH)of cells in each group were detected by fluorescence assay according to the kit instruction.ELISA kit was used to detect the expression of inflammatory factors of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)of cells in each group.Flow cytometry was applied to detect the cell apoptosis in each group.Western blot was applied to detect the expression of proliferation related protein of proliferating cell nuclear antigen(PCNA),apoptosis related proteins[B-cell lymphoma-2(Bcl-2)and Bcl-2-associated X protein(Bax)],and TLR4/NF-κB/NLRP3 signaling pathway related proteins(TLR4,NF-κB and NLRP3)of cells in each group.Results Compared with the Control group,the cell survival rate,the expression levels of PCNA and Bcl-2 proteins,the viabilities of SOD and CAT,and the GSH concentration in the UVB group decreased,while the apoptosis rate,the level of Bax protein,the relative content of ROS,the concentration of MDA,the levels of TNF-α and IL-1β,and the mRNA and protein levels of TLR4,NF-κB and NLRP3 increased(P<0.05).Compared with the UVB group,the cell survival rate,the expression levels of PCNA and Bcl-2 proteins,the viabilities of SOD and CAT,and the GSH concentration in the TAK-242 group and CUR group increased,while the apoptosis rate,the level of Bax protein,the relative content of ROS,the concentration of MDA,the levels of TNF-α and IL-1β,and the mRNA and protein levels of TLR4,NF-κB and NLRP3 decreased(P<0.05).Compared with the CUR group,the cell survival rate,the expression levels of PCNA and Bcl-2 proteins,the viabilities of SOD and CAT,and the GSH concentration in the CUR+LPS group decreased,while the apoptosis rate,the level of Bax protein,the relative content of ROS,the concentration of MDA,the levels of TNF-α and IL-1β,and the mRNA and protein levels of TLR4,NF-κB and NLRP3 increased(P<0.05).Conclusion CUR can increase the antioxidant stress level of keratinocytes,alleviate inflammatory response,promote cell proliferation,and improve cell damage caused by UVB irradiation,which may be related to the inhibition of TLR4/NF-κB/NLRP3 signaling pathway.

Objective To investigate the mechanisms by which paeoniflorin improves tissue and cell damage caused by diabetic retinopathy(DR)through the hypoxia-induced factor-1α(HIF-1α)pathway.Methods Thirty rats were ran-domly divided into a control group(10 normal rats),a DR group(10 diabetic model rats)and a paeoniflorin group(10 dia-betic model rats given 80 mg·kg-1 paeoniflorin by gavage).Rat retinal microvascular endothelial cells(rRMECs)were di-vided into a control group(cultured with 5 mmol·L-1 glucose),a high glucose group(cultured with 30 mmol·L-1 glu-cose)and a paeoniflorin group(cultured with 30 mmol·L-1 glucose and 20 mol·L-1 paeoniflorin).The three groups of cells were all cultured for 24 h.Fasting blood glucose was measured by a glucose meter.Hematoxylin and eosin(HE)stai-ning was used to detect the retinal histopathological structure.The levels of HIF-1α and vascular endothelial growth factor(VEGF)proteins and mRNAs in retinal tissues and rRMECs were detected by Western blotting and real time quantitative polymerase chain reaction(RT-qPCR).The proliferative ability of rRMECs was detected by the EdU kit.The serum levels of total cholesterol(TC),triglyceride(TG),low density cholesterol(LDL-C),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in retinal tissues and rRMECs were detected by kits.The activity and invasive ability of rRMECs were measured by CCK-8 and Transwell assay,respectively.The levels of HIF-1α and VEGF proteins in rRMECs were detected by immunofluorescence staining.Results Compared with those in the DR group,the fasting blood glucose,TC,TG and LDL-C levels in the paeoniflorin group were significantly decreased(all P＜0.05).The retinal tissue was loose with an un-clear boundary in the DR group,compared with that in the control group.The retinal tissue in the paeoniflorin group was less loose with a clearer boundary than that in the DR group.The levels of HIF-1α and VEGF proteins and mRNAs,TNF-αand IL-6 in retinal tissues of the DR group were significantly higher than those of the control group(all P＜0.05).The lev-els of HIF-1α and VEGF proteins and mRNAs,TNF-α and IL-6 in retinal tissues of the paeoniflorin group were significantly lower than those in the DR group(all P＜0.05).The activity,proliferation and invasive abilities of rRMECs in the high glu-cose group were higher than those in the control group(all P＜0.05).Compared with those in the high glucose group,rRMECs in the paeoniflorin group showed decreased cell activity,proliferation and invasive abilities(all P＜0.05).The lev-els of HIF-1α and VEGF proteins and mRNAs,TNF-α and IL-6 in the rRMECs of the high glucose group were higher than those of the control group(all P＜0.05).The levels of HIF-1α and VEGF proteins and mRNAs,TNF-α and IL-6 in the rRMECs of the paeoniflorin group were lower than those of the high glucose group(all P＜0.05).Conclusion Paeoni-florin can down-regulate the HIF-1α/VEGF pathway to improve the inflammatory injury of the retinal tissue and inhibit rRMEC activity,proliferation and invasive abilities in DR rats,thereby preventing angiogenesis and reducing the incidence of DR.

Objective:To observe the efficacy and safety of polatuzumab vedotin(pola)combined with chemotherapy in the treatment of relapsed and refractory diffuse large B-cell lymphoma(R/R DLBCL).Methods:A total of 23 patients with R/R DLBCL treated at the First Affiliated Hospital of Zhejiang University and its Liangzhu Branch from April 2023 to March 2024 were retrospectively collected.All patients were treated with pola combined with chemotherapy regimens such as BR,R-GDP,R-CHOP,or other regimens.Results:All 23 patients were evaluable for efficacy,with 10 achieving complete response(CR),7 partial response(PR),3 stable disease(SD),and 3 progressive disease(PD).The most common adverse events included myelosuppression,fever,and pulmonary infection.No severe adverse events resulted in drug withdrawal.Conclusion:Pola combined with chemotherapy demonstrates promising efficacy and a favorable safety profile in the treatment of R/R DLBCL.