ObjectiveTo investigate the role and underlying mechanisms of Tongxinluo submicron powder in regulating renal PANoptosis， alleviating pathological injury in diabetic kidney disease （DKD）， reducing urinary albumin excretion， and improving renal function in DKD mice. MethodsSix 6-week-old male C57BL/Ks mice were assigned into the normal group. Eighteen 6-week-old male BKS-db；Nos3KO mice were randomly divided into three groups： model group， Tongxinluo group （0.75 g·kg^-1·d^-1）， and dapagliflozin group （0.001 g·kg^-1·d^-1）， and were administered by gavage for 12 consecutive weeks. General conditions of the mice were observed. At weeks 0， 4， 8， and 12 after administration， body weight， fasting blood glucose （FBG）， urine albumin-to-creatinine ratio （UACR）， and urinary albumin excretion rate （AER） were measured. After treatment， mice were anesthetized for sample collection. Blood was obtained by orbital enucleation and centrifuged to collect supernatant. Serum creatinine （SCr）， urea （UREA）， β₂-microglobulin （β₂-MG）， retinol-binding protein （RBP）， and serum cystatin C （CysC） were measured. Renal histopathological changes were evaluated using hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson's trichrome staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of inflammatory cytokines， including interleukin-1β （IL-1β）， interleukin-18 （IL-18）， and tumor necrosis factor-α （TNF-α）. Serum levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， and glutathione peroxidase （GSH-Px） were also measured. Western blot analysis was performed to quantify the expression of key PANoptosis-related proteins in renal tissue， including Z-DNA-binding protein 1 （ZBP1）， Caspase-1， cleaved Caspase-1， gasdermin D （GSDMD） and its N-terminal fragment （GSDMD-N）， Caspase-8， cleaved Caspase-8， Caspase-3， cleaved Caspase-3， mixed lineage kinase domain-like protein （MLKL）， and phosphorylated MLKL （p-MLKL）. ResultsCompared with the normal group， the model group showed significant obesity and continuously increased blood glucose levels （P<0.05）. Renal function indicators （UREA， β₂-MG， CysC） were significantly increased （P<0.05）， and urinary albumin excretion indicators （UACR， AER） were markedly elevated （P<0.05）. Renal histopathology showed enlarged glomeruli， diffuse thickening of the basement membrane， and significant expansion of the mesangial matrix. Masson staining revealed extensive blue collagen fiber deposition， suggesting glomerulosclerosis and interstitial fibrosis. Meanwhile， serum levels of inflammatory cytokines （IL-1β， IL-18， and TNF-α） were significantly increased （P<0.05）. SOD and GSH-Px levels were decreased， while MDA levels were increased （P<0.05）. The expression of key PANoptosis-related proteins （ZBP1， cleaved Caspase-1， GSDMD， GSDMD-N， cleaved Caspase-8， Caspase-3， cleaved Caspase-3， and p-MLKL） in renal tissue was significantly upregulated （P<0.05）. After intervention， compared with the model group， renal function indicators （UREA， β₂-MG， CysC） and urinary albumin excretion indicators （UACR， AER） in the Tongxinluo group were significantly decreased （P<0.05）， and all were superior to those in the dapagliflozin group （P<0.05）. Renal pathological injury was markedly alleviated， with reduced mesangial proliferation and collagen fiber deposition. In addition， serum levels of IL-1β， IL-18， and TNF-α were significantly decreased （P<0.05）. SOD and GSH-Px levels were increased， while MDA levels were decreased （P<0.05）. Western blot results showed that the expression of key PANoptosis-related proteins （ZBP1， cleaved Caspase-1， GSDMD， GSDMD-N， cleaved Caspase-8， Caspase-3， cleaved Caspase-3， and p-MLKL） in renal tissue was significantly downregulated （P<0.05）. ConclusionTongxinluo submicron powder can inhibit renal PANoptosis in DKD mice， alleviate renal inflammatory response and pathological injury， reduce urinary albumin excretion， and improve renal function.

In recent years, gastrointestinal stromal tumors (GIST) have increased incidence and mortality, and most GIST is caused by the activation mutation of the c-KIT gene. Therefore, c-KIT has become a promising therapeutic target of GIST. At present, the drugs approved for the treatment of GIST including imatinib, sunitinib, regorafenib and ripretinib, are mostly prone to developing resistance and accompanied by various degrees of adverse reactions. Therefore, there is an urgent need to develop new c-KIT inhibitors to solve the problem of resistance. In this study, we investigated the anti-tumor effect of a novel c-KIT inhibitor PN17-1 on gastrointestinal stromal tumor GIST-882 cells in vitro. We found that PN17-1 significantly inhibited the proliferation, colony formation and migration ability of GIST-882 cells, and significantly downregulated the protein expression levels of p-c-KIT and its downstream signals p-AKT, p-STAT5 and p-ERK in GIST-882 cells. In addition, PN17-1 induced apoptosis in GIST-882 cells, and the apoptosis may be mainly related to the mitochondrial-dependent endogenous pathway. In conclusion, the novel c-KIT inhibitor PN17-1 is a promising anti-GIST drug, and this study provides new ideas for further development of c-KIT inhibitors in the future.

The ethnic medicine for external use is an important dosage form in the external treatment methods of ethnic medicine.China has made significant progress in related research and applications.However,the regulations and guidelines for clinical research on external medicine are limited,and the related technologies and quality standards are not yet well-established in China.This article summarized the specific issues during the implementation of clinical research on ethnic medicine of external use:the research design failing to reflect the value and unique characteristics of these medicine;the big difficulty in the recruitment of participants,leading to delays in progress;inconsistent implementation of interventions;and the quality of research data needing to be improved,etc.Combining the authors'experience in project implementation management,this article proposed solutions to improve research quality and progress,including incorporating experts from various fields including ethnic medicine and research centers;refining participant recruitment strategies;analyzing factors affecting progress and optimizing the implementation process;and strengthening overall management and establishing a competitive enrollment mechanism.The article also shared a case study of the Tibetan medicine Qingpeng Ointment for the treatment of acute gouty arthritis,aiming to provide a reference for the clinical research on ethnic medicine of external use.

Chinese patent medicines for external use represent a distinct category of clinical drugs with unique therapeutic characteristics.At present,the research foundation of some topical Chinese patent medicines for external use is weak,and the accuracy and standardization of clinical application need to be improved.The research on clinical positioning of Chinese patent medicines for external use is of great significance for standardizing clinical medication,exploring the differentiated value of drugs and similar products,enhancing the safety of drug use,improving the efficiency of medical resource use,and promoting the secondary development and cultivation of drugs after listing.On the basis of summarizing the research status of clinical positioning of Chinese patent medicines for external use,this article put forward the significance,necessity and challenges of carrying out this research.Combined with the authors'practical experience,the authors put forward five experiences to carry out the post marketing clinical positioning research of Chinese patent medicines for external use,including distinguishing the theory of external treatment of Chinese materia medica,paying attention to the unmet needs in the modern medical system,not separating from the actual efficacy and dosage form characteristics of Chinese patent medicines for external use,clarifying the mechanism of"same treatment for different diseases",and verifying the clinical positioning hypothesis,which can provide references for relevant research.

Objective:To investigate the feasibility of the bortezomib, lenalidomide, and dexamethasone (VRD) regimen combined with autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with multiple myeloma (MM) and renal impairment, analyze treatment efficacy and renal responses stratified based on renal dysfunction severity, and explore the prognostic significance of early renal response and its affecting factors.Methods:This retrospective study, conducted at the First Affiliated Hospital of Soochow University, categorized 316 patients with newly diagnosed MM (NDMM) from August 2018 to October 2022 based on renal function for analysis of clinical characteristics, treatment response, and prognosis. Continuous variables were compared using t-tests or Mann-Whitney U tests, categorical variables utilizing Chi-square tests, survival outcomes employing Kaplan-Meier and Log-rank tests, and renal response predictors with logistic regression.Results:Patients were stratified based on baseline estimated glomerular filtration rate (eGFR) : normal [≥90 ml·min -1· (1.73 m 2) -1, n=160], mild [≥60 ml·min -1· (1.73 m 2) -1 to <90 ml·min -1· (1.73 m 2) -1, n=55], moderate [≥30 ml·min -1· (1.73 m 2) -1 to <60 ml·min -1· (1.73 m 2) -1, n=39], and severe impairment [<30 ml·min -1· (1.73 m 2) -1, n=62]. Moderate and severe renal impairment correlated with advanced International Staging System/Revised International Staging System classification, lower hemoglobin levels, frailty, and higher light-chain/IgD subtype prevalence ( P<0.05). Despite younger age ( P=0.001) and higher transplant rates ( P=0.041) in severe cases, overall response rates ( ORR: 93.7% ; ≥VGPR: 82.9% ) were comparable across groups ( P>0.05). Among 24 dialysis-dependent patients at diagnosis, 11 (45.8% ) achieved dialysis independence after induction [median: 3.0 (0.5–4.0) months], including 10 undergoing auto-HSCT. In 89 evaluable patients [baseline eGFR <50 ml·min -1· (1.73 m 2) -1], renal ORR (RORR) was 70.8% [rapid complete response: 31.5% ; rapid partial response: 11.2% ; rapid minimal response (RMR) : 28.1% ]. Renal response predicted better survival (overall survival: HR=0.36, 95% CI: 0.13–0.99, P=0.049). Moderate-to-severe renal impairment was associated with increased transplant-related adverse events and delayed engraftment ( P<0.05) ; however, auto-HSCT significantly improved outcomes after 33.5-month median follow-up (range: 2–65 months). Multivariate analysis identified 1q21+ ( OR=3.58, 95% CI: 1.17–11.02, P=0.026) and light-chain subtype ( OR=2.86, 95% CI: 1.08–7.69, P=0.036) as independent predictors of poor renal response. Conclusion:VRD regimen plus auto-HSCT demonstrates robust efficacy in NDMM, including patients with renal impairment, with a 70.8% RORR and manageable toxicity. Achieving ≥RMR correlates with superior prognosis, whereas 1q21+ and light-chain subtype independently predict inferior renal response.

Objective:To observe any effect of oscillating positive expiratory pressure training on the airway clearing ability of postoperative esophageal cancer patients after neoadjuvant chemotherapy.Methods:Forty postoperative esophageal cancer patients undergoing neoadjuvant chemotherapy were enrolled and randomized into a control group and an experimental group, each of 20. Both groups received conventional postoperative rehabilitation starting on the first postoperative day, while the experimental group additionally underwent oscillating positive expiratory pressure training (3 sets/day, 30 breaths/set) for five consecutive days. Peak cough flow was measured using a peak flow meter before and 1, 3 and 5 days after the operation. Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF) were also measured on the 5th day after the operation using spirometry. Any postoperative pulmonary complications were recorded.Results:On the 1st day after the operation, peak cough flow had decreased significantly in both groups compared to preoperative levels. However, it had increased significantly on days 3 and 5 in both groups, with the average increase in the experimental group significantly greater than in the control group. On day 5 the average FEV1, forced vital capacity and PEF in both groups were significantly lower than the preoperative values, while the experimental group demonstrated significantly higher average FEV1s (2.22±0.51L) and PEFs (5.09±1.26L/s) compared to the control group.Conclusions:Early postoperative oscillating positive expiratory pressure training can improve the peak cough flow and airway clearing ability of esophageal cancer patients after neoadjuvant chemotherapy, promoting the recovery of their lung function.

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 analyze the genetic characteristics and evolutionary origin of hepatitis B virus (HBV) subgenotype D3 in China in 2020.Methods:Serum samples and demographic details from patients infected with HBV D3 subgenotype were collected. HBV genomic sequences were obtained by nested PCR amplification and subsequent sequencing. Phylogenetic analysis, nucleotide homology, amino acid mutation and evolution rate of the S protein were conducted by comparing with reference sequence using bioinformatics tools.Results:The complete HBV gene sequences of 14 samples of D3 subtype HBV were obtained. Compared with 97 reference sequences, it was found that the sequences with the highest homology were from India, Mongolia, Iran and China, with the homology ranging from 96.0% to 97.9%. Mutations of 24 amino acids were found in 14 strains of D3 subtype. Among them, T131A, Y134F and T140I were associated with immune escape-related mutations. The genetic diversity of HBV D3 subtype increased slowly before 1975, remained relatively constant from 1975 to 2000, and began to decline after 2000. Evolutionary rate analysis showed that samples QGLD D3-02 and 03 originated from a common ancestor with the Iranian reference strain in 1872, and the other 12 samples QGLD D3-04-17 originated from a common ancestor with the Mongolian reference strain in 1843.Conclusions:The gene sequence of HBV D3 subtype in China had the highest homology with reference sequences from India, Iran, Mongolia and China. Evolutionary rate analysis revealed that 14 cases of HBV D3 subtype originated from a common ancestor with reference strains from Mongolia and Iran, which enriched the sequence and evolution information of HBV D3 subtype and provided a reference basis for the molecular epidemiological study of HBV.

Hypertensive nephropathy is one of the common chronic kidney diseases in China,the morbidity and mortality are increasing year by year,which seriously endangers the physical and mental health of patients.Traditional Chinese medicine believes that human is an organic whole,the five viscera and six organs are closely related in physiology and pathology,based on the theory of"holistic concept",the application of Chinese medicine in the treatment of hypertensive nephropathy can effectively improve kidney function and reduce the occurrence of adverse reactions.Therefore,based on the theory of"five viscera in one",this paper summarizes the etiology and pathogenesis of hypertensive nephropathy and the treatment of hypertensive nephropathy from the five aspects of liver,heart,spleen,lung and kidney,aiming to provide new ideas for the prevention and treatment of kidney disease by traditional Chinese medicine.

The MXene/MF microspheres were prepared by coating MXene nanosheets on melamine formaldehyde(MF)resin microspheres.Co(NO3)2 was adsorbed on the surface of the microspheres by impregnation,and then calcined at high temperature in an argon atmosphere.MF pyrolysis generated reducing gases such as CO and NH3,reducing Co2+to elemental Co,which was then used as a catalyst for in situ growth of carbon nanotube(CNT)through chemical vapor deposition(CVD),forming MXene-Co-CNT microspheres(MXene-Co-CNT MS).During this process,the pyrolysis of MF microspheres had dual effects.On one hand,the template was sacrificed to produce an internal hollow structure,and on the other hand,the generated gas worked as carbon source to generate CNT,forming an external sea urchin-like structure.Both of them promoted the formation of a novel structure,which combined the advantages of large specific surface area and good conductivity,thus possessing excellent electrocatalytic activity.The MXene-Co-CNT MS was modified on glassy carbon electrode(GCE)and further used in highly sensitive detection of nitroaromatic compounds(NACs).The detection limits of MXene-Co-CNT MS/GCE for 2,4,6-trinitrotoluene(TNT),1,3,5-nitrobenzamide(TNB),2,4-dinitrotoluene(DNT),1,3-dinitrobenzene(DNB),1-Cl-2,4-dinitrotoluene(Cl-DNB),and 4-nitrophenol(4-NP)were 26.84,31.60,35.03,54.14,43.86 and 28.67 nmol/L,respectively.It also had excellent anti-interference ability,and was used to detect NACs in environmental water samples accurately.