ObjectiveTo investigate the protective effects and mechanisms of Zhenzhu Tiaozhi capsules on the kidneys in the mouse model of diabetic kidney disease. MethodsThirty male C57BL/6J mice were selected as experimental objects. The model of diabetic kidney disease was induced by intraperitoneal injection of streptozotocin （STZ） at 40 mg·kg^-1 for 5 days combined with a high-fat diet （HFD）. Fasting blood glucose （FBG） ≥ 11.1 mmol·L^-1， increased urine volume， and continuous appearance of proteinuria indicated successful modeling. Mice were grouped as follows： Blank， model， low- and high-dose （0.98 and 1.96 g·kg^-1， respectively） Zhenzhu Tiaozhi capsules， and losartan potassium （30 mg·kg^-1）， with six mice in each group. After 12 weeks of continuous gavage， urine and kidney specimens were collected， and the 24-h urinary protein and the urinary albumin-to-creatinine ratio （UACR） in mice were measured. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson staining were performed for observation of histopathological changes in kidneys. Immunofluorescence assay was employed to detect the positive expression of the podocyte marker protein nephrin. Oil red O staining was used to detect renal lipid deposition. Enzyme linked immunosorbent assay was employed to measure the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the renal tissue. Western blot was employed to determine the expression levels of sterol regulatory element-binding protein cleavage-activating protein （SCAP）， sterol regulatory element-binding protein-1c （SREBP-1c）， and NOD-like receptor protein 3 （NLRP3） in the renal tissue. ResultsCompared with the blank group， the model group showed increases in 24-h urinary protein and UACR （P<0.05）， glomeruli exhibiting capsule adhesion， collagen fiber deposition， mesangial proliferation， and inflammatory cell infiltration， elevated levels of IL-1β， IL-6， and TNF-α （P<0.05）， reduced positive expression of nephrin （P<0.05）， increased lipid deposition （P<0.05）， and up-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. Compared with the model group， the treatment with losartan potassium or high-dose Zhenzhu Tiaozhi capsules for 12 weeks decreased 24-h urinary protein and UACR （P<0.05）， and the treatment with low-dose Zhenzhu Tiaozhi capsules for 12 weeks reduced the 24-h urinary protein （P<0.05）. Pathological staining results revealed that kidney damage in mice from all treatment groups was alleviated， with reduced inflammatory infiltration， collagen fiber deposition， and mesangial proliferation， and increased positive expression of nephrin in the renal tissue （P<0.05）. In addition， all the treatment groups showed reduced lipid droplets （P<0.05）， lowered levels of IL-1β， IL-6， and TNF-α （P<0.05）， and down-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. ConclusionZhenzhu Tiaozhi capsules can ameliorate kidney damage in the mouse model of diabetic kidney disease by inhibiting the activation of the SCAP-SREBP-1c/NLRP3 signaling pathway， which reduces renal lipid deposition and inflammation.

ObjectiveTo investigate the protective effects and mechanisms of Zhenzhu Tiaozhi capsules on the kidneys in the mouse model of diabetic kidney disease. MethodsThirty male C57BL/6J mice were selected as experimental objects. The model of diabetic kidney disease was induced by intraperitoneal injection of streptozotocin （STZ） at 40 mg·kg^-1 for 5 days combined with a high-fat diet （HFD）. Fasting blood glucose （FBG） ≥ 11.1 mmol·L^-1， increased urine volume， and continuous appearance of proteinuria indicated successful modeling. Mice were grouped as follows： Blank， model， low- and high-dose （0.98 and 1.96 g·kg^-1， respectively） Zhenzhu Tiaozhi capsules， and losartan potassium （30 mg·kg^-1）， with six mice in each group. After 12 weeks of continuous gavage， urine and kidney specimens were collected， and the 24-h urinary protein and the urinary albumin-to-creatinine ratio （UACR） in mice were measured. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson staining were performed for observation of histopathological changes in kidneys. Immunofluorescence assay was employed to detect the positive expression of the podocyte marker protein nephrin. Oil red O staining was used to detect renal lipid deposition. Enzyme linked immunosorbent assay was employed to measure the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the renal tissue. Western blot was employed to determine the expression levels of sterol regulatory element-binding protein cleavage-activating protein （SCAP）， sterol regulatory element-binding protein-1c （SREBP-1c）， and NOD-like receptor protein 3 （NLRP3） in the renal tissue. ResultsCompared with the blank group， the model group showed increases in 24-h urinary protein and UACR （P<0.05）， glomeruli exhibiting capsule adhesion， collagen fiber deposition， mesangial proliferation， and inflammatory cell infiltration， elevated levels of IL-1β， IL-6， and TNF-α （P<0.05）， reduced positive expression of nephrin （P<0.05）， increased lipid deposition （P<0.05）， and up-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. Compared with the model group， the treatment with losartan potassium or high-dose Zhenzhu Tiaozhi capsules for 12 weeks decreased 24-h urinary protein and UACR （P<0.05）， and the treatment with low-dose Zhenzhu Tiaozhi capsules for 12 weeks reduced the 24-h urinary protein （P<0.05）. Pathological staining results revealed that kidney damage in mice from all treatment groups was alleviated， with reduced inflammatory infiltration， collagen fiber deposition， and mesangial proliferation， and increased positive expression of nephrin in the renal tissue （P<0.05）. In addition， all the treatment groups showed reduced lipid droplets （P<0.05）， lowered levels of IL-1β， IL-6， and TNF-α （P<0.05）， and down-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. ConclusionZhenzhu Tiaozhi capsules can ameliorate kidney damage in the mouse model of diabetic kidney disease by inhibiting the activation of the SCAP-SREBP-1c/NLRP3 signaling pathway， which reduces renal lipid deposition and inflammation.

Myelodysplastic syndrome (MDS), a myeloid tumor derived from the malignant clones of hematopoietic stem cells, has an annually increasing incidence. The contemporary research direction has shifted to analyzing the synergistic effect of immune surveillance collapse and abnormal bone marrow microenvironment in the pathological process of MDS. Against this backdrop, the immune checkpoint molecule TIM3 has emerged as a key target because of its persistently high expression on the surface of important immune cells such as T and NK cells. The abnormal activation of the TIM3 pathway is the mechanism by which solid tumors and hematological malignancies achieve immune escape and is a key hub in the formation of immune exhaustion phenotypes. This work integrates the original discoveries of our team with the latest international progress, systematically demonstrating the bidirectional regulatory network of TIM3 between the malignant clone proliferation of MDS and the immunosuppressive microenvironment. Integrating the evidence from emerging clinical trials allows us to consider the clinical significance of TIM3-targeted blocking for MDS, providing a transformative path to overcome the resistance of traditional treatments and marking a new chapter in the active immune reconstitution of MDS treatment.

In recent years,with the continuous innovation of modern war mode,weapons and protective equipment,the mechanism and mode of war trauma have also produced great changes.The widespread use of bulletproof vest and improvised explosive devices has led to increasing incidence of genitourinary trauma.The pattern of genitourinary trauma has also transformed from internal structures(kidney,ureters,bladder)to external structures(scrotum,testes,penis,urethra),suggesting that the research focus of genitourinary system war trauma should be gradually transformed to trauma research of lower urinary tract and external genitalia.This article reviews the incidence,treatment and prognosis of genitourinary trauma in several modern wars,and mainly describes the relevant conditions of lower urinary tract and external genitalia trauma and the relevant progress in the treatment in recent years.

Objective The aim of this study was to assess the impact of bisphenol A (BPA) and its substitute, bisphenol F (BPF), on the colonic fecal community structure and function of mice.Methods We exposed 6-8-week-old male C57BL/6 mice to 5 mg/(kg·day) and 50 μg/(kg·day) of BPA or BPF for 14 days. Fecal samples from the colon were analyzed using 16S rRNA sequencing. Results Gut microbiome community richness and diversity, species composition, and function were significantly altered in mice exposed to BPA or BPF. This change was characterized by elevated levels of Ruminococcaceae UCG-010 and Oscillibacter and decreased levels of Prevotella 9 and Streptococcus. Additionally, pathways related to carbohydrate and amino acid metabolism showed substantial enrichment. Conclusion Mice exposed to different BP analogs exhibited distinct gut bacterial community richness, composition, and related metabolic pathways. Considering the essential role of gut bacteria in maintaining intestinal homeostasis, our study highlights the intestinal toxicity of BPs in vertebrates.

Given the constraints imposed by the “14-day ethics” rule, numerous critical events occurring between the second and fourth weeks of embryonic development remain poorly understood. This underscores the necessity of a detailed understanding of embryonic development and regulation during this period, which is indispensable for preventing pregnancy failure, treating birth defects, and promoting human reproductive health.Rodents, characterized by their small size, rapid growth, strong reproductive capacity, and fully sequenced genomes, are widely used as crucial models for studying embryonic development. However, the substantial physiological differences between rodents and primates due to evolutionary divergence make it challenging to directly apply findings from rodent studies to primates. Besides, primates, our closest relatives in terms of evolutionary phylogenetics and physiological characteristics, share more than 95% genetic homology with humans, underscoring the urgent need for primate research. Furthermore, early-stage embryonic cells are both scarce and diverse, making their regulatory mechanisms and developmental pathways typically elucidated through single-cell sequencing. For instance, three significant articles published in Science in 2018 mapped the complete atlas of organ and tissue development from fertilization and captured dynamic gene expression profiles in zebrafish and frogs through single-cell transcriptomics. Unfortunately, relying solely on single-cell omics analysis falls short in effectively and comprehensively deciphering the intricate cellular network information. Single-cell multi-omics empower researchers to systematically decode cell heterogeneity and developmental trajectories at the individual cell level by combining transcriptomics, epigenomics, proteomics, and metabolomics analyses. These emerging technologies play a significant role in life sciences, enabling the elucidation of critical early primate embryonic development events from a multi-dimensional perspective, including zygotic genome activation (ZGA), X-chromosome dosage compensation, origins of primordial germ cells (PGCs), mechanisms of cell fate determination, and pivotal events in gastrulation and early organogenesis.This article chronicles the advancement of pivotal technologies, from single-cell histology to multi-omics, beginning with the single-cell transcriptome and culminating in a comprehensive analysis according to the central dogma of molecular biology. It highlights the transition from a singular to a holistic perspective in cellular analysis and reviews the application of multi-omics techniques in unveiling early primate embryonic development. Finally, it delves into the application of multi-omics technologies in enhancing our understanding of early primate embryonic development and explores future possibilities, directions, and challenges in this rapidly evolving field. In doing so, it emphasizes the critical role of interdisciplinary approaches, combining insights from genetics, molecular biology, and bioinformatics to foster innovations in reproductive medicine and developmental biology. The integration of such technologies offers the promise of breakthroughs in understanding complex biological processes, potentially leading to novel therapeutic strategies and advancements in reproductive health and medicine.

Background::A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA) has previously shown its preliminary efficacy in ST elevation myocardial infarction (STEMI) patients. This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase (rt-PA) in Chinese patients with STEMI.Methods::In this multicenter, randomized, open-label, non-inferiority trial, patients with acute STEMI were randomly assigned (1:1) to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min. The primary endpoint was recanalization defined by thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3. The secondary endpoint was clinically justified recanalization. Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events (MACCEs) and safety endpoints.Results::From July 2016 to September 2019, 767 eligible patients were randomly assigned to receive rhTNK-tPA ( n = 384) or rt-PA ( n = 383). Among them, 369 patients had coronary angiography data on TIMI flow, and 711 patients had data on clinically justified recanalization. Both used a –15% difference as the non-inferiority efficacy margin. In comparison to rt-PA, both the proportion of patients with TIMI grade 2 or 3 flow (78.3% [148/189] vs. 81.7% [147/180]; differences: –3.4%; 95% confidence interval [CI]: –11.5%, 4.8%) and clinically justified recanalization (85.4% [305/357] vs. 85.9% [304/354]; difference: –0.5%; 95% CI: –5.6%, 4.7%) in the rhTNK-tPA group were non-inferior. The occurrence of 30-day MACCEs (10.2% [39/384] vs. 11.0% [42/383]; hazard ratio: 0.96; 95% CI: 0.61, 1.50) did not differ significantly between groups. No safety outcomes significantly differed between groups. Conclusion::rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery, a validated surrogate of clinical outcomes, among Chinese patients with acute STEMI.Trial registration::www.ClinicalTrials.gov (No. NCT02835534).

Objective To summarize and analyze the surgical evolution and clinical efficacy of benign prostatic hyperplasia(BPH)surgery.Methods A retrospective cohort study was used to analyze the clinical data of 2050 patients who underwent surgery for BPH in the Department of Urology,the First Medical Center of PLA General Hospital from January 2012 to August 2022.These patients were divided into 3 groups in chronological order:the early group(n=683),the middle group(n=683)and the late group(n=684).The cumulative time of patients in each group was from January 2012 to February 2017,March 2017 to September 2020 and October 2020 to August 2022.The indicators,such as age,hypertension,diabetes,serum cholesterol,serum triacylglycerol,serum high-density lipoprotein cholesterol,body mass index(BMI),preoperative prostate volume,prostate specific antigen(PSA),free prostate specific antigen(fPSA),operation time,preoperative hospital stay,postoperative hospital stay,postoperative bladder flushing time,postoperative indwelling time,cystostomy situation,intraoperative and postoperative blood transfusion,postoperative readmission rate,and postoperative pathology were collected and compared between 3 groups,and the annual trend of changes in the number of BPH surgeries and surgical methods was analyzed.Results Transurethral resection of prostate(TURP)and TURP+laser resection decreased year by year,while transurethral laser resection of prostate increased and became the mainstream prostate resection method in recent two years,accounting for more than 90%.The patients in the early,middle and late groups were(69.7±7.9)years old,(68.7±7.4)years old and(69.8±8.5)years old(P=0.027);the operation time was 108.0(80.0,130.0)min,80.0(60.0,110.0)min and 75.0(60.0,100.0)min(P<0.001);the postoperative indwelling time was 4.1(2.7,5.9)d,3.9(2.9,4.9)d and 2.7(0.9,3.9)d(P<0.001);the rates of cystostomy were 68.8%,66.6%and 5.0%(P<0.001);the intraoperative and postoperative blood transfusion rates were 4.5%,3.1%and 0.9%(P<0.001);the preoperative hospitalization time was 5.6(3.8,7.1)d,4.7(3.5,5.9)d,and 4.7(3.1,6.7)d(P<0.001);the postoperative hospital stays were 5.7(4.8,7.0)d,4.7(3.0,5.9)d and 2.8(1.0,4.0)d(P<0.001),with statistically significant differences.Thirty-seven cases(1.8%)of BPH patients who underwent surgery in our center for 10 years were re-admitted after surgery,and 64 cases had postoperative pathological abnormalities or were diagnosed with prostate cancer,with a total detection rate of 3.1%.Conclusions Laser enucleation of prostate has become the mainstream surgical treatment of BPH in our center,and perioperative indexes such as operation time,hospital stay,postoperative catheter indwelling time,cystostomy rate,and surgical blood transfusion rate have shown a significant improvement trend.

NLRP3 can recruit proteins such as ASC and pro-caspase1 to form NLRP3 inflammasomes after being stimulated by pathogen and danger signals in vivo,and then induce pyropto-sis and promote the inflammatory reactions to maintain the home-ostasis.However,the overactivation of NLRP3 inflammasomes is closely related to many inflammatory and autoimmune diseases in humans.Targeted inhibition of NLRP3 inflammasomes can sig-nificantly inhibit inflammation and alleviate the relative symp-toms.Therefore,it is an important research direction for treating diseases of NLRP3 inflammasome that searching for effective in-hibitors targeting NLRP3 inflammasome activation and achieving clinical transformation.This review summarizes the latest re-search progress based on the sources of NLRP3 inflammasome inhibitors.

Objective To investigate the effect of elastic pants on coagulation function and deep vein thrombosis by examining blood coagulation function and deep vein thrombosis in patients with liposuction in the thigh before and after operation.Methods 80 patients with liposuction were randomly divided into Ankle-length elastic pants(Ankle group,A group,n=40)and Knee-length elastic pants(Knee group,K group,n=40)from October 2021 to October 2022.After liposuction surgery,the two groups of patients used elastic bandage to initially compress and bind the thigh.According to the length of the patients'thigh,the patients in A group wore appropriate ankle-length elastic pants and the patients in K group wore appropriate knee-length elastic pants.The index were recorded including the popliteal vein flow rate,the common femoral vein flow rate,the instep temperature,the incidence of deep vein thrombosis(DVT),the incidence of intramuscular vein thrombosis of leg and the coagulation indexes(APTT,PT,Fib,D-dimer).Results Compared with pre-operation,the blood flow rate of popliteal vein and common femoral vein in A group was significantly faster,while the blood flow rate of popliteal vein in K group was significantly slower(P＜0.05).There was no significant change in APTT and PT in the two groups after operation(P＞0.05),but the Fib and D-Dimer increased significantly on the first day after operation,and then decreased gradually(P＜0.05).Compared with K group,the blood flow of popliteal vein and common femoral vein in A group was significantly faster at each time point after operation(P＜0.05).The Fib and D-Dimer of patients in A group were significantly lower than those in K group on the 1st,3rd and 7th day after operation(P＜0.05),and the blood coagulation index between the two groups returned to normal around the 14th day.There was no statistically significant difference in the instep temperature between groups and within groups(P＞0.05).No deep venous thrombosis was found in A group after surgery,while there were 3 cases of deep venous thrombosis without clinical symptoms in K group on the 3rd and 7th day,with no statistical difference(P＞0.05).After surgery,patients in A group and K group had intramuscular venous thrombosis of the leg on the 1st,3rd and 7th day after surgery,and there was statistically significant difference on the 3rd and 7th day between the two groups(P＜0.05).Conclusion Thigh liposuction can lead to deep vein thrombosis without obvious clinical symptoms and intramuscular vein thrombosis of leg.Ankle-length elastic pants are more conducive to blood circulation of patients'legs,improve blood hypercoagulability,and reduce the risk of deep vein thrombosis after operation.