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.

SMARCA4-deficient non small cell lung cancer (SMARCA4-dNSCLC) has recently garnered increasing attention due to its high malignancy and poor prognosis. The literature suggests that in non small cell lung cancer (NSCLC), the loss of SMARCA4 frequently co-occurs with mutations in KRAS, KEAP1, and STK11 rather than in EGFR, ALK, and ROS1. Herein, we present the first documented case of SMARCA4-dNSCLC accompanied with rare mutations of EGFR exon 20 S768I and exon 18 G719X. The patient achieved partial response with afatinib for 17 months. Our case highlights the importance of EGFR mutations in the precision targeted treatment of SMARCA4-dNSCLC.
Humans ; Afatinib/therapeutic use* ; Antineoplastic Agents/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/pathology* ; DNA Helicases/genetics* ; ErbB Receptors/genetics* ; Lung Neoplasms/pathology* ; Mutation ; Nuclear Proteins/genetics* ; Transcription Factors/genetics*

Objective To study the role of photobiomodulation(PBM)in promoting the repair of spinal cord injury(SCI)by regulating microglial cells.Methods Forty-five C57BL/6J mice were randomly divided into the sham operation(Sham)group,surgery(SCI)group and the treatment(SCI+PBM)group,with 15 mice in each.After laminectomy of the T10 vertebral body in the three groups of mice,the SCI group and the SCI+PBM group were used to construct the model of spinal cord hemisection.The SCI+PBM group received immediate PBM treatment after spinal cord injury,while the other two groups did not.On the 1st,3rd,7th,14th,21st and 28th days(D1,D3,D7,D14,D21,D28)after the operation,the Basso Mouse Scale(BMS)was used to assess the recovery of the hind limb motor function of the mice.On the 28th day post operatively,immunofluorescence was used to detect the changes of neurons in the areas of injury in the three groups of mice.Quantitative real-time PCR and Western blotting experiments were used to detect the phenotypic changes of BV2 cells under the interventions of PBM with inflammatory stimulation.Western blotting experiments were conducted to detect the effects of PBM on the nuclear factor kappa-B(NF-κB)pathway.Results On the 28th day after the operation,the results of the mouse motor assessment showed that the BMS scores and related behaviors of the mice in the SCI+PBM group were better than those of the mice in the SCI group(P＜0.05),and the neurons in the SCI+PBM group far outnumbered those in the SCI group(P＜0.05).The results of quantitative real-time PCR and Western blotting experiments showed that on the 14th day after the operation,PBM promoted the activation of M2-type microglial cells in vivo but inhibited the activation of M1-type microglial cells.In vitro experiments confirmed that PBM could promote the polarization of BV2 cells towards M2-type microglial cells.In addition,PBM inhibited the activation of the NF-κB pathway in injured spinal cords and in activated BV2 cells.Conclusion PBM can promote the repair of spinal cord injury in SCI mice by promoting microglial cells through inhibiting the NF-κB pathway.

Objective:To evaluate the residual risk (RR) of transfusion transmitted HIV (TT-HIV) after the implementation of nucleic acid amplification test (NAT) in blood screening test among blood centers in China.Methods:The data of blood donors and HIV infection markers from 2017 to 2020 were collected from 28 blood centers via the Platform of Comparison of blood establishments Practice in Chinese Mainland. The new infection rate/window period mathematical model was used for two types of blood screening strategies, namely, two rounds ELISA plus individual NAT take turn with pooling NAT (2ELISA+ ID-NAT/MP-NAT) and two ELISA plus one round pooling NAT (2ELISA+ MP-NAT), and the RR of HIV infection was estimated also based on first donors (FDs) and repeated donors (RDs) in different blood donation years. T-test analyses were conducted for comparing TT HIV RR among FDs and RDs in different blood donation years with two blood screening strategies, and the variation trend of RR in HIV test was observed.Results:From 2017 to 2020, the RR of FDs in 2ELISA+ ID-NAT/MP-NAT blood screening strategy was 2.869/10 6 person-year, 3.795/10 6 persons-year, 3.879/10 6 person-year, and 2.890/10 6 person-year respectively. The RR of RDs was 1.797/10 6 person-year, 1.502/10 6 person-year, 1.857/10 6 person-year, and 1.483/10 6 person-year respectively. Significant difference exists between RR of FDs and RDs, with F=9.898 and p<0.05. In 2ELISA+ MP-NAT strategy, the RR of FDs was 3.508/10 6 person-year, 1.868/10 6 person-year, 2.204/10 6 person-year, and 1.765/10 6 person-year respectively. The RR of RDs was 0.948/10 6 person-year, 0.926/10 6 person-year, 0.748/10 6 person-year, and 0.682/10 6 person-year respectively. Statistical difference existed between RR of FDs and RDs, with F=17.126 and P<0.05. There was no significant difference between the RR of FDs in these two strategies with F=3.493 and P>0.05, while there was a difference between the RR of RDs in these two strategies with F=24.516 and P<0.05, and a difference between the RR of total donors (TDs) in these two strategies F=20.216 and P<0.05. Conclusions:The RR of TT HIV significantly decreased after the introduction of NAT into blood test among blood centers in China. There were some differences in the RR of HIV testing among different blood screening strategies. There could be significant differences in the RR of HIV testing among different groups of blood donors. Compared with FDs, RDs is the low risk group for HIV.

Objective: To summarize the experience of endoscopic endonasal approach in the treatment of anterior skull base with intra-extracranial extension meningioma, and to analyze the perioperative quality of life of patients, and to discuss the safety and efficacy of the treatment. Methods: A total of 83 cases of anterior skull base with intra-extracranial extension meningioma admitted to Xuanwu Hospital, Capital Medical University from October 2007 to October 2019, who underwent endoscopic endonasal approach tumor resection, were retrospectively analyzed. The quality of life of the patients were evaluated by Anterior Skull Base Questionnaire (ASBQ) before and after surgery. The surgical techniques, extent of tumor resection, postoperative complications and the changes of patients' quality of life were summarized and analyzed. SPSS 23.0 software was used for statistical analysis. Results: A total of 57 anterior skull base with intra-extracranial extension meningioma patients were enrolled according to the inclusion and exclusion criteria, including 23 males and 34 females, aging (48.6±16.6) years. Fifty cases (87.7%) reached or exceeded Simpson gradeⅠ resection, and 7 cases underwent subtotal resection. Symptoms relief was as follows: headache relief in 45/50 (90%), vision improvement in 18/19 (94.7%), olfaction improvement in 6/45 (13.3%), mental symptoms improvement in 3/9 (33.3%), and seizure relief in 5/7 (71.4%). Postoperative complication included mental symptoms in 5 cases, cerebrospinal fluid leakage in 2 cases, epilepsy in 2 cases, frontal lobe hemorrhage in 1 case, and intracranial infection in 1 case. The follow-up period was 38 to 144 months. There were two cases recurring and no death. ASBQ assessment showed significant improvement in general condition, physical function, role function, mood disorder, pain, vision impairment, and sleep disturbance at 1 month postoperatively, with continued improvement thereafter, and reached stable at 6 months postoperatively. Conclusion: Endoscopic endonasal approach surgery is able to achieve safe and effective tumor resection for anterior skull base intra-extracranial extension meningioma, and the quality of life of patients can be improved steadily.
Female ; Humans ; Male ; Meningeal Neoplasms/surgery* ; Meningioma/surgery* ; Neoplasm Recurrence, Local/pathology* ; Postoperative Complications ; Quality of Life ; Retrospective Studies ; Skull Base/surgery* ; Skull Base Neoplasms/surgery*

Objective: To investigate the expression of miR-155 in peripheral blood of type 2 diabetes patients(T2 DM) associated with diabetic foot ulcer(DFU) and its relationship with the onset of DFU. Methods: Sixty newly diagnosed T2 DM patients without DFU(T2 DM group), 112 T2 DM patients with DFU(DFU group), and 60 healthy controls with normal glucose tolerance(NC group) were included. MiR-155 levels were determined by quantitative real-time PCR, while clinical features and risk factors of DFU were explored. Results: A significant decrease in the expression level of miR-155 in peripheral blood was observed in T2 DM group compared with NC group(P<0.05), and a markedly increased miR-155 expression level was noted in DFU group compared with T2 DM group(P<0.01). Moreover, there was a positive correlation between the expression level of miR-155 in peripheral blood and the course of foot ulcer and Wagner grade of foot ulcer(P=0.02,P=0.01) while a negative correlation in the expression level of miR-155 with healing rate of DFU after eight weeks(P=0.04). The multiple stepwise logistic regression analysis confirmed that a high expression of miR-155 was an independent risk factor for DFU(OR=3.98,P=0.002). Conclusion An increased expression of miR-155 in peripheral blood of T2 DM patients is an independent risk factor for DFU and is closely related to the prognosis of DFU.