Diabetic nephropathy （DKD）， as a common microvascular complication of diabetes mellitus （DM）， is a major cause of end-stage renal disease （ESRD）. Its clinical manifestations include increased urinary protein excretion， thickening of the glomerular basement membrane， and renal tubulointerstitial fibrosis. The pathogenesis of DKD is complex and involves multiple factors， including disordered glucose metabolism， hemodynamic alterations， and oxidative stress. Although modern medical approaches can alleviate certain symptoms， they still have limitations such as insufficient therapeutic targeting and prominent adverse effects. The transforming growth factor-β/Smad （TGF-β/Smad） signaling pathway is not only a tissue fibrosis pathway that has attracted considerable attention in recent years， but also regulates multiple protein molecules， including the glomerular podocyte slit diaphragm protein Podocin， interleukin-1β （IL-1β）， and superoxide dismutase （SOD）， thereby participating in various pathological processes and ultimately mediating renal injury. Flavonoid compounds， owing to their sustained pharmacological effects， broad spectrum of action， and high safety profile， have become ideal candidates for targeted therapy research in DKD. Existing studies have shown that these compounds can exert inhibitory effects on renal fibrosis， alleviate inflammatory responses， protect podocytes， and reduce oxidative stress by regulating the interactions between the TGF-β/Smad signaling pathway and the aforementioned protein molecules， thereby maintaining renal structure and function， reducing proteinuria， and significantly improving DKD lesions. This review briefly outlines the composition and functions of the TGF-β/Smad signaling pathway， elucidates the mechanisms by which this pathway regulates DKD， and focuses on summarizing major studies from the past decade on flavonoid-based interventions in DKD through targeted inhibition of the TGF-β/Smad signaling pathway. Furthermore， it discusses the considerable therapeutic potential of flavonoids in the treatment of this disease， aiming to provide a scientific basis for future clinical prevention and treatment of DKD and to promote the development of targeted drugs.

Objective To study the photodynamic performance and the killing effect of photodynamic therapy on lung cancer of novel chlorin compounds 2-（4-（5,15,20-triphenyl-7H,8H-porphyrin-10-yl） phenoxy） acetic acid（D1）and 4-（4-（5,15,20-triphenyl-7H,8H-porphyrin-10-yl） phenoxy） butanoic acid （D2）. Methods The ultraviolet visible absorption spectrum and fluorescence spectrum of D1 and D2 were determined. The singlet oxygen generation capacity of D1 and D2 was measured by using DPBF as singlet oxygen capture agent. Fluorescence assay was used to detect the cellular phagocytosis rate of the compounds in A549 cells, and MTT assay was used to detect their dark toxicity and phototoxicity. A nude mouse model of lung cancer was established to investigate the antitumor activity of the compounds mediated photodynamic action in vivo, and the blood concentration of D2 in nude mice, its distribution in tumor tissue and skin tissue were further detected. Results D1 and D2 had strong absorption at 652 nm with the best excitation wavelength at 429 nm and 427 nm, and the optimal emission wavelength was at about 659 nm. They also had a higher singlet oxygen generation rate than the control drug m-THPC. D1 and D2 had no dark toxicity at concentrations below 10 μmol/L, and could be ingested by A549 cells, basically reaching saturation in 18~24 hours. After laser irradiation at 650 nm wavelength, D1 and D2 showed significant antitumor activity in vivo and in vitro （P<0.01）. However, D2 could selectively accumulate in tumor tissues after administration, and the optimal treatment time was less than 30 min after administration. Conclusion D2 had excellent photodynamic antitumor activity and could selectively aggregate in tumor tissues, which had the potential to be a candidate drug for photosensitizer and treatment of lung cancer with independent intellectual property rights, and was worth further research.

ObjectiveTo investigate the effects of 7-dehydrocholesterol reductase （DHCR7） in promoting proliferation， migration， and invasion of lung adenocarcinoma cells and the underlying signaling mechanisms. MethodsThe expression level of DHCR7 in lung adenocarcinoma and its prognosis were analyzed by using public databases. DHCR7 protein expression levels in the lung adenocarcinoma cell lines H1299 and A549 were assessed by Western blot， using the normal lung epithelial cell line BEAS-2B as a control. Small interfering RNA （siRNA） was used to knock down DHCR7 expression in H1299 and A549 cells. Assays including colony formation， CCK-8， wound healing， and Transwell experiments were conducted to assess the proliferation， migration， and invasion of the knockdown cells. Next， Western blot was employed to assess the phosphorylation levels of key signaling molecules in the phosphoinositide 3-kinase/protein kinase B （PI3K/AKT）， janus kinase/signal transducer and activator of transcription 3 （JAK/STAT3），mitogen-activated protein kinase/extracellular signal-regulated kinase pathway （MAPK/ERK） （p-AKT， p-STAT3， p-ERK）. ResultsBioinformatics results indicated that both DHCR7 mRNA and protein were highly expressed in lung adenocarcinoma compared with normal tissues adjacent to cancer. Furthermore， higher DHCR7 mRNA level was associated with poor prognosis （P<0.001）. The expression levels of DHCR7 were significantly higher in both H1299 and A549 cells than that in BEAS-2B cells （P<0.05， P<0.01）. Compared with si-control， the proliferation， migration， and invasion abilities of si-DHCR7 H1299 and A549 cells significantly decreased. Among the phosphorylated signaling molecules detected， p-ERK was significantly downregulated （P<0.000 1， P<0.01） whereas p-AKT and p-STAT3 levels were not significantly changed. ConclusionDHCR7 has prominent effects in promoting the proliferation， migration， and invasion of lung adenocarcinoma cells， and the underlying mechanisms are related to the MAPK/ERK signaling pathway.

ObjectiveTo construct an interleukin-9 （Il9） gene knockout mouse model on a C57BL/6N background， establish a reliable genotyping method， and provide a standardized animal model for investigating Il9-related immune mechanisms and diseases. MethodsIl9 knockout mouse strain （C57BL/6N-Il9^em1Cya） was generated using conventional gene knockout technology. The method for DNA extraction from mouse tails was optimized to ensure template quality. Two sets of specific primers （F1/R1 and F1/R2） were designed to amplify target fragments by PCR， and mouse genotypes were determined by agarose gel electrophoresis. Specifically， primer pair F1/R1 targeted the knockout sequence with an expected product of 465 bp， while F1/R2 targeted the wild-type sequence with an expected product of 703 bp. Subsequently， Western blot was performed to verify the knockout efficiency of Il9 in primary immune cells and key organs of the offspring mice， and flow cytometry was used to assess the effects of Il9 deficiency on the function of the immune system in major immune cell populations. ResultsIl9 knockout mice were successfully bred and genotyped. PCR identification showed that homozygous mice （-/-） exhibited only a 465 bp band， wild-type mice （+/+） displayed only a 703 bp band， and heterozygous mice （+/-） showed both bands simultaneously. Meanwhile， Western blot analysis revealed significantly decreased IL-9 expression in various organs of the offspring mice （P<0.001）. Flow cytometric results demonstrated that Il9 deficiency exerted no obvious effects on the proportions of peripheral blood lymphocytes， splenic lymphocytes， and peritoneal macrophages. ConclusionAn Il9 gene knockout mouse model on a C57BL/6N background is successfully constructed. The established PCR genotyping system is highly efficient and accurate， which can effectively distinguish mice of different genotypes. This model provides a stable and reliable experimental basis for subsequent functional studies of Il9 and exploration of the mechanisms underlying Il9-related diseases.

ObjectiveTo construct a chimeric antigen receptor macrophage （CAR-M） targeting interleukin-13 receptor α （IL-13Rα） and intracellular domain integration， which can double activate the signal adaptor protein OX40L of macrophages and T cells. MethodsThe CAR molecule targeting IL-13Rα （IL-13Rα-OX40L-CAR） with OX40L as the intracellular signal domain was designed and synthesized， and it was cloned into the adenovirus expression vector. After THP-1 cells were induced to differentiate into macrophages （THP-1-M） by phorbol ester， the cells were infected with recombinant adenovirus to construct THP-1 macrophages stably expressing green fluorescent protein （GFP） labeled anti-IL-13RαCAR. The expression efficiency of CAR molecules was monitored by flow cytometry. The empty vector group was used as the negative control， the CD3ζ group was used as the positive control， and the CD3ζ-OX40L group was used as the experimental group. The phagocytic function of macrophages in each group on IL-13Rα high expression glioma cells （U251） and low expression glioma cells （T98G） was detected by in vitro co-culture experiments. ResultsCAR adenovirus was efficiently transfected into THP-1-M to obtain anti-IL-13RαCAR-M. After co-cultured with glioma cells with different expression levels of IL-13Rα， the results of flow cytometry showed that there was no significant difference among the three groups for T98G cells with low expression of IL-13Rα. After co-culture with U251 cells with high expression of IL-13Rα， the CD3ζ group showed enhanced phagocytosis compared with the empty vector group （P<0.05）. Compared with the CD3ζ group， the phagocytosis ability of the CD3ζ-OX40L group was further enhanced （P<0.05）. ConclusionAnti-IL13Rα- OX40L-CAR-M is successfully constructed by constructing IL-13Rα-OX40L-CAR adenovirus and transfecting PMA-induced differentiated THP-1-M. It can engulf glioma cells with high expression of IL-13Rα by specific targeting， and shows activation of intracellular domain superior to traditional CD3ζ.

OBJECTIVE To explore the working model and practical effectiveness of surgical pharmacists participating in the rational medication management of urology department under the background of diagnosis related groups （DRGs） payment system.METHODS In the context of DRGs， surgical pharmacists have constructed a rational drug use control model for key DRGs disease groups with a high number of urological cases in three stages： the pre stage， which includes developing perioperative drug use guidelines and implementing a rational drug use management system intervention； the mid-term stage， which includes conducting specialized evaluations in conjunction with DRGs disease groups， conducting pharmaceutical ward rounds and medical order reviews， conducting rational drug use training and science popularization； the post event stage， which includes establishing a performance evaluation system for clinical departments and surgical pharmacists， and collecting reasons why surgical physicians did not adopt surgical pharmacist recommendations. Patients who entered DRGs groups and were discharged from the urology department of Foshan Second People’s Hospital were selected as the research subjects. The changes in departmental DRGs indicators [including number of DRGs groups， total weight， case mix index （CMI）， average length of stay， time consumption index， average cost per case， cost consumption index， average drug cost per case， drug consumption index， and mortality in low- and medium-risk] were compared before pharmacist intervention （June to December 2022）， after 1 year of intervention （June to December 2023）， and after 2 years of intervention （June to December 2024）. The improvement in medication rational rates （for antibiotics， hemocoagulase， and proton pump inhibitors） and pharmacy performance assessment indicators [average drug cost per case， defined daily doses （DDDs， excluding traditional Chinese medicine）， and antibiotic use density （AUD）] in the top 5 DRGs groups by case volume were statistically analyzed. The reasons for non-adoption of medication intervention recommendations by urologists were further analyzed.RESULTS With the participation of surgical pharmacists in the rational medication management of urology department， the number of DRGs groups， total weight， and CMI in the urology department increased year by year， while the average length of stay， average cost per case， and average drug cost per case decreased year by year， there were no low- to medium-risk deaths before and after the medication management. The average drug cost per case， DDDs， and AUD in the top 5 key DRGs groups （LE15， LE13， MC15， MC13， and LK19） were significantly decreased compared with those before intervention （ P ＜0.05）. The medication rational rates （for antibiotics， hemocoagulase， and proton pump inhibitors） in the above 5 key DRGs groups were significantly increased compared with those before intervention （ P ＜0.05）. After 2 years of pharmacist intervention， the non-adoption rates of urologists for medication interventions related to antibiotics， hemocoagulase， and proton pump inhibitors were significantly lower than those after 1 year of intervention （ P ＜0.05）； the main reason for not adopting interventions related to hemocoagulase was that surgeons believed “increasing the daily dose could shorten the hemostasis course”， the main reason for not adopting interventions related to antibiotics was “postoperative elevation of inflammatory indicators necessitates prolonged treatment”.CONCLUSIONS The hospital has successfully established a model of surgical pharmacists participating in the rational medication management of urology department. This model has improved departmental DRGs indicators and pharmacy performance assessment indicators， and enhanced the medication rational rate.

Adipose tissue is a critical energy reservoir in animals and humans, with multifaceted roles in endocrine regulation, immune response, and providing mechanical protection. Based on anatomical location and functional characteristics, adipose tissue can be categorized into distinct types, including white adipose tissue (WAT), brown adipose tissue (BAT), beige adipose tissue, and pink adipose tissue. Traditionally, adipose tissue research has centered on its morphological and functional properties as a whole. However, with the advent of single-cell transcriptomics, a new level of complexity in adipose tissue has been unveiled, showing that even under identical conditions, cells of the same type may exhibit significant variation in morphology, structure, function, and gene expression——phenomena collectively referred to as cellular heterogeneity. Single-cell transcriptomics, including techniques like single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq), enables in-depth analysis of the diversity and heterogeneity of adipocytes at the single-cell level. This high-resolution approach has not only deepened our understanding of adipocyte functionality but also facilitated the discovery of previously unidentified cell types and gene expression patterns that may play key roles in adipose tissue function. This review delves into the latest advances in the application of single-cell transcriptomics in elucidating the heterogeneity and diversity within adipose tissue, highlighting how these findings have redefined the understanding of cell subpopulations within different adipose depots. Moreover, the review explores how single-cell transcriptomic technologies have enabled the study of cellular communication pathways and differentiation trajectories among adipose cell subgroups. By mapping these interactions and differentiation processes, researchers gain insights into how distinct cellular subpopulations coordinate within adipose tissues, which is crucial for maintaining tissue homeostasis and function. Understanding these mechanisms is essential, as dysregulation in adipose cell interactions and differentiation underlies a range of metabolic disorders, including obesity and diabetes mellitus type 2. Furthermore, single-cell transcriptomics holds promising implications for identifying therapeutic targets; by pinpointing specific cell types and gene pathways involved in adipose tissue dysfunction, these technologies pave the way for developing targeted interventions aimed at modulating specific adipose subpopulations. In summary, this review provides a comprehensive analysis of the role of single-cell transcriptomic technologies in uncovering the heterogeneity and functional diversity of adipose tissues.

The connotation of the "four-dimensional pivot-earth" qi transformation mode is a dialectical system of the ascending and descending of yin-yang qi movement， which presented as "the middle Jiao showing earth qi mediating， the left wheel showing water and wood ascending， and the right wheel showing fire and metal converting and descending". Based on this dialectical thinking， it is believed that the core pathogenesis of myasthenia gravis is deficiency of center qi and transportation failure to pivot-earth； the middle-stage characteristics of the disease progression are the loss of mediation of the central qi， resulting in water coldness and wood constraint， and clear yang failing to ascend； the final outcome of this disease is the loss of astringeing of lung metal and qi sinking. The treatment should be based on the rule of qi movement， so for the start-stage， Buzhong Yiqi Decoction （补中益气汤） should be used as the basis to nourish the earth and consolidate the root， and restrengthen the middle qi； for the middle-stage， herbs like Yingyanghuo （Epimedium brevicornu Maxim.）， Bajitian （Morinda officinalis How） could be combined to warm the water and soothe the wood， raise yang and boost qi； for the final stage， plus Sini Decoction （四逆汤） to astringe metal to stop collapse， and powerfully supplement original qi. All these medicinals can promote pivot-earth re-transportation， four-dimensional transformation， and regular circulation of qi movement， so as to provide thoughts for improving the clinical effectiveness of myasthenia gravis.

Objective To understand the epidemiological characteristics and trends of postoperative pneumonia(POP)in tertiary general hospitals in Jiangsu Province,and provide theoretical basis for carrying out targeted pre-vention and control measures.Methods Surgery patients from 22 tertiary general hospitals in 12 cities in north,central,and south of Jiangsu Province from January 1,2022 to December 31,2023 were chosen as studied subjects,occurrence of POP was analyzed and compared.Results A total of 848 274 surgical procedures were performed in 22 hospitals,and 3 606 cases of POP occurred,with an incidence of 0.43％.The incidence in 2023 was 0.37％,which was lower than that in 2022(0.49％),with statistically significant difference(P＜0.001).The top three de-partments with high incidence of POP were neurosurgery(6.71％),cardiothoracic surgery(2.91％),and general surgery(0.77％).Among hospitals of different grades,the incidence of POP in tertiary first-class hospitals was 0.44％,which was higher than that in other tertiary hospitals(0.37％).There was no statistically significant difference in the incidence of POP between municipal and district/county hospitals(P＞0.05).The incidence of POP in hospitals with a bed:infection control full-time staff ratio＜200∶1 was lower than that in hospitals with the ratio ≥200∶1(0.39％vs 0.47％,P＜0.001),while the incidence of POP in hospitals with a proportion ≥30％of full-time staff being doctors was higher than that in hospitals with a proportion＜30％(0.45％vs 0.36％,P＜0.001).The incidence of POP in male patients was higher than that in female patients(0.62％vs 0.26％,P＜0.001).The incidence of POP in elderly patients aged≥65 was higher than that in patients aged＜65(0.73％vs 0.26％,P＜0.001).A total of 2 667 strains of infectious pathogens were detected,with the top three being Acine-tobacter baumannii,Klebsiella pneumoniae,and Pseudomonas aeruginosa,accounting for 28.95％,22.72％,and 15.45％,respectively.The detection rates of carbapenem-resistant Acinetobacter baumannii(CRAB),carba-penem-resistant Klebsiella pneumoniae(CRKP),and carbapenem-resistant Pseudomonas aeruginosa(CRPA)were 60.75％,21.45％,and 32.28％,respectively.The detection rate of CRKP decreased in 2023 compared with 2022,with statistically significant difference(P＜0.05).Conclusion The overall incidence of POP in tertiary general hos-pitals in Jiangsu Province is relatively low,but there are significant differences among different hospitals.There-fore,perioperative prevention and control measures should be carried out based on the epidemiological characteristics of patients.