ObjectiveZheng’s San Qi San (ZSQS) power, a classic traditional Chinese medicine (TCM) formula, is used for treating soft tissue injuries involving muscles, tendons, and ligaments. However, its underlying therapeutic mechanisms remain unclear. This study aimed to screen and identify pharmaceutically active ingredients and their candidate biomolecule targets, and further elucidate the molecular mechanism of ZSQS in the treatment of skeletal muscle injury. MethodsNetwork pharmacology was employed to construct “ZSQS-component-target”, “protein-protein interaction (PPI)” and “active ingredient-core protein-pathway” networks to predict the key active ingredients and potential core targets of ZSQS for skeletal muscle injury. The predicted results were then validated via microarray data from the GEO database. Molecular docking was then performed to assess the binding ability between the screened active ingredients of ZSQS and the candidate core targets. Moreover, liquid chromatography-mass spectrometry (LC-MS) was used for qualitative and quantitative analysis to verify the active components of the drug and ZSQS serum. Finally, an animal model of eccentric exercise-induced skeletal muscle injury and a myotube cell model of oxidative stress-induced injury were established to validate the effects of ZSQS and its interventional effects on the biological functions of critical targets, thereby demonstrating the potential therapeutic mechanism of ZSQS. ResultsAmong the 111 active components identified in ZSQS and their corresponding 204 targets related to the skeletal muscle injury repair process, 14 core targets (including AKT1) and 4 core active components (quercetin, luteolin, kaempferol, and β‑sitosterol) were screened out, while the corresponding metabolites of quercetin, luteolin and kaempferol were detected in the ZSQS serum. Among these targets, 5 candidate genes (IL-6, CASP3, HIF1A, STAT3, and JUN) overlapped with the differential expression screening results with GEO data, and IL-6 was confirmed to be enriched in the PI3K/AKT pathway. Combined with the prediction results of the AKT expression levels, these findings suggest that the phosphorylation level of AKT1 plays a core role in the therapeutic mechanism of ZSQS. Molecular docking analysis further revealed that the PH domain of AKT1 had high binding energy with all 4 core active components, as verified by LC-MS. Finally, animal model studies have shown the promoting effect of ZSQS administration on skeletal muscle injury repair and its possible antioxidant damage mechanism. Cell model studies further demonstrated that ZSQS-containing serum, core active ingredient combination therapy, and quercetin monomer could increase the phosphorylation level of AKT, promote the nuclear translocation of Nrf2, upregulate the expression of downstream antioxidant enzymes (SOD, GPx, and GR), and inhibit the expression of inflammatory factors (IL-6 and TNF-α), thereby alleviating oxidative stress and the inflammatory response. ConclusionZSQS alleviates skeletal muscle injury mainly by activating the AKT/Nrf2 signaling pathway, enhancing cellular antioxidant and anti-inflammatory capabilities. The results of this study provide a scientific basis for the clinical application and modernized development of ZSQS.

BACKGROUND:The micro/nanostructured gradient biomimetic surface of implant materials can simulate the structure of the extracellular environment in human bone tissue,thereby achieving perfect bone integration function.However,further research is needed on the mechanisms by which the surface microstructure of bone implant materials regulates cell function and promotes osteogenesis. OBJECTIVE:To analyze the effect of titanium sheet microstructure surface on osteogenic differentiation of MC3T3-E1 osteoblasts. METHODS:(1)At a constant voltage of 5 V or 20 V,nanotube arrays of different diameters were prepared on the surface of titanium sheets by acid etching and anodic oxidation techniques,and were recorded as group R5 and group R20,respectively.The surface morphology,roughness,and hydrophilicity of pure titanium sheet(without acid etching or anodizing treatment)were measured in group R5 and group R20.(2)MC3T3-E1 osteoblasts of logarithmic growth stage were inoculated on the surface of pure titanium sheets,R5 group and R20 group respectively.After 24 hours of osteogenic induction culture,the expression of mechanical sensitive channel protein 1 was analyzed by RT-PCR and immunofluorescence staining.Osteoblast inducible base with or without the mechanosensitive channel protein 1 activator Yada1 was added,and alkaline phosphatase staining was performed after 7 days of culture.Alizarin red staining was performed after 14 days of culture. RESULTS AND CONCLUSION:(1)The surface of pure titanium sheets was smooth under scanning electron microscope.Relatively uniform and orderly nanotube arrays with average diameters of about 30 nm and 100 nm were observed on the surface of titanium sheets of groups R5 and R20,respectively.The results of scanning electron microscope were further verified by atomic force microscopy.The surface roughness of titanium sheet of group R5 was higher than that of pure titanium(P<0.05),and the water contact angle was lower than that of pure titanium(P<0.05).The surface roughness of titanium sheet in group R20 was higher than that in group R5(P<0.05),and the water contact angle was lower than that in group R5(P<0.05).(2)RT-PCR and immunofluorescence staining showed that the expression of mechanosensitive channel protein 1 in group R5 was higher than that in pure titanium group(P<0.05),and the expression of mechanosensitive channel protein 1 in group R20 was higher than that in group R5(P<0.05).Under the osteogenic induction,compared with the condition without Yada1,there were no significant changes in the activity of alkaline phosphatase and the deposition of calcified nodules in pure titanium group after Yada1 addition,while the activity of alkaline phosphatase and the deposition of calcified nodules in groups R5 and R20 after Yada1 addition were significantly increased(P<0.05).With or without Yada1,the alkaline phosphatase activity and calcified nodule deposition in group R5 were higher than those in pure titanium group(P<0.05),and the alkaline phosphatase activity and calcified nodule deposition in group R20 were higher than those in group R5(P<0.05).(3)The results show that the surface microstructure of titanium sheet can promote the osteogenic differentiation of osteoblast MC3T3-E1 by activating mechanosensitive channel protein 1.

Objective To explore the long-term efficacy of percutaneous pulmonary valve implantation(PPVI)and the durability of the domestic self-expanding Venus P valve.Methods A total of 8 patients with post-surgical right ventricular outflow tract(RVOT)dysfunction,who were admitted to hospital from October 2014 to July 2016 and deemed anatomically suitable for PPVI with self-expanding valve,were included prospectively.Clinical,imaging,procedural and follow-up data were analyzed.The survival rates,perioperative and long-term complication rates,long-term efficacy of PPVI,and long-term function of Venus P in 8 patients were evaluated.The immediate procedural results were evaluated by clinical implant success rate,which is defined as successful valve implantation with echocardiography-assessed pulmonary regurgitation＜moderate and peak trans-pulmonary pressure gradient＜40 mmHg.Results A total of 8 patients were included,with 7 females,aged 14 to 36 years.The initial diagnosis included post-surgical Tetralogy of Fallot(5 cases),post-surgical Trilogy of Fallot(1 case),post-surgical Quadricuspid pulmonary valve stenosis(1 case)and post-surgical Double-Outlet Right Ventricle(1 case).The indications of PPVI included RVOT-pulmonary obstruction and regurgitation(1 case)and isolated regurgitation(7 cases).Clinical implant success was achieved in all of the 8 patients with firmly fixed valve,and there were no such complications as valve detachment,displacement or stent fracture.All patients experienced significant symptom relief after the procedure.The right ventricular end-diastolic volume index(RVEDVi)measured by CMR 6 months after PPVI showed a significant decrease compared to preprocedural values[(89.99±13.85)ml/m2 vs.(144.93±11.28)ml/m2,P=0.001].Postoperative pulmonary regurgitation were significantly improved or disappeared in all patients,and there was no statistically significant difference in the average peak pressure gradient measured by echocardiogram between preoperative and the latest follow-up[(23.25±8.39)mmHg vs.(18.75±6.28)mmHg,P=0.210].Over an average follow-up period of(9.25±0.71)years,1 case of infective endocarditis occurred 5 years after PPVI.During the follow-up,no death,deterioration of heart failure,malignant arrhythmia or other serious complications were observed.All patients completed 8-year follow-up,and 3 completed 10-year follow-up.All patients were graded as NYHA functional class one at the latest follow-up.Conclusions PPVI using the domestically produced self-expanding Venus P is safe and feasible for the treatment of patients with post-surgical RVOT dysfunction and suitable anatomy.Our study confirms the long-term efficacy and durability of Venus P from multiple perspectives,and no severe stent fracture occurred without pre-stent implantation in the native RVOT.

Objective:To analyze the factors influencing the achievement of "textbook outcome" (TO) after pancreaticoduodenectomy (PD) and explore the relationship of postoperative prognoses with TO.Methods:The clinical and pathological data of 169 patients treated by PD between January 2021 and December 2023 at the First Affiliated Hospital of Harbin Medical University were retrospectively analyzed. The patients were divided into the TO group ( n=91) and the non-TO group ( n=78) based on whether they met the TO criteria after sugery. According to the benignity or malignancy of the tumor, patients in the two groups above were futher divided into a non-malignant tumor subgroup (benign and junctional) and a malignant tumor subgroup, of which there were 10 cases of non-malignant tumor subgroup and 81 cases of malignant tumor subgroup in the TO group, and 9 cases of non-malignant tumor subgroup and 69 cases of malignant tumor subgroup in the non-TO group. Data collected included general patient information, laboratory indices on postoperative day 3, pathological findings, intraoperative blood loss, operative duration, and the like. Patients with malignant tumors were followed up until December 2024. Receiver operating characteristic (ROC) curves were used to determine the optimal cut-off values for clinical data. Univariate and multivariate logistic regression analyses were employed to identify independent risk factors affecting TO achievement. Survival curves for patients with malignant tumors in the TO and non-TO groups were plotted using the Kaplan-Meier method and compared with the Log-rank test. Results:Among the 169 patients, 91 patients (53.8%) achieved TO. There were 150 patients (88.76%) with malignant tumors, all of whom achieved R0 resection. Univariate analysis showed that a history of cardiovascular/cerebrovascular disease, main pancreatic duct diameter, white blood cell count on postoperative day 3, aspartate aminotransferase level, total bilirubin level, serum urea nitrogen level, pancreatic texture, and operative duration were factors influencing TO achievement (all P value <0.05). Multivariate analysis identified that a postoperative white blood cell count greater than 16.35×10 9/L ( OR=3.558, 95% CI 1.319-9.596), a postoperative serum urea nitrogen levels exceeding 5.42 mmol/L ( OR=2.154, 95% CI 1.070-4.334), soft pancreatic texture ( OR=2.321, 95% CI 1.035-5.203), and an operative duration exceeding 312.50 min ( OR=2.043, 95% CI 1.005-4.154) were independent risk factors that prevented the achievement of TO (all P value <0.05). Kaplan-Meier survival analysis revealed that the 1-, 2-, and 3-year survival rates for patients with malignant tumors in the TO group were 67.90%, 47.73%, and 36.84%, respectively, which were significantly higher than those in the non-TO group (57.90%, 32.00%, and 31.58%, respectively; all P value <0.05). The median survival time was 28 months in the TO group and 16 months in the non-TO group, with a statistically significant difference ( P<0.05). Conclusions:Postoperative white blood cell count, serum urea nitrogen level, pancreatic texture, and operative duration are independent risk factors affecting the achievement of TO. For patients with malignant tumors, achieving TO is beneficial for prolonging survival time and improving survival rates.

Objective To explore the clinical and pathological characteristics and oncological outcomes of clear cell borderline ovarian tumor(CCBOT),and provide guidance for the diagnosis and treatment of this disease in the future.Methods A total of 23 CCBOT patients who underwent surgical treatment in our hospital from May 2011 to Aug 2022 were enrolled,and the clinical information of 19 CCBOT patients in the Ricotta's cohort was integrated.The clinical pathological characteristics and oncological outcomes of these 42 patients were retrospectively analyzed.Results This study enrolled 42 CCBOT patients,including 23 from our cohort and 19 from the Ricotta G's cohort.Compared with the Ricotta's cohort,the proportion of CCBOT patients with endometriosis in our cohort(34.8%)was significantly higher than that in the Ricotta's cohort(5.3%)(P<0.05).In our cohort,22 patients had information on intraoperative frozen section evaluation,and the accuracy of intraoperative frozen section evaluation was 50%(11/22).The other 50%(11/22)of patients were underestimated by intraoperative frozen section evaluation.The merged cohort indicated that the median age of the patients was 60 years old,occuring more common in postmenopausal women(66.7%).Most cases presented with pelvic masses(59.5%)and abdominal pain or distension(19.0%).This disease mostly involved unilateral ovaries(90.5%).Information on preoperative tumor markers was largely missed,making it difficult to draw an accurate evaluation for them.Ten cases(23.8%)underwent fertility sparing surgery,and 32 cases(76.2%)underwent radical surgery.The pathologic report indicated that all patients were stage I patients and 21.4%patients had endometriosis.Among these patients,32 patients underwent total hysterectomy,of which 10(31.3%)had concurrent endometrial lesions.The median follow-up time was 68 months,with a minimum follow-up of one month and a maximum follow-up of 231 months,and no recurrence or death was observed.Conclusion CCBOT patients usually had an good prognosis with a low recurrence rate.Fertility sparing surgery was safe and feasible,but attention should be paid to exclude concurrent endometrial lesions.Given the rarity of CCBOT,future multicenter prospective studies are needed to better elucidate the clinical pathological features and prognosis of patients with CCBOT.

Glucose-6-phosphate dehydrogenase (G6PD), the first rate-limiting enzyme of the pentose phosphate pathway (PPP), is aberrantly activated in multiple types of human cancers, governing the progression of tumor cells as well as the efficacy of anticancer therapy. Here, we discovered that cyclin-dependent kinase 5 (CDK5) rewired glucose metabolism from glycolysis to PPP in breast cancer (BC) cells by activating G6PD to keep intracellular redox homeostasis under oxidative stress. Mechanistically, CDK5-phosphorylated G6PD at Thr-91 facilitated the assembly of inactive monomers of G6PD into active dimers. More importantly, CDK5-induced pho-G6PD was explicitly observed specifically in tumor tissues in human BC specimens. Pharmacological inhibition of CDK5 remarkably abrogated G6PD phosphorylation, attenuated tumor growth and metastasis, and synergistically sensitized BC cells to poly-ADP-ribose polymerase (PARP) inhibitor Olaparib, in xenograft mouse models. Collectively, our results establish the crucial role of CDK5-mediated phosphorylation of G6PD in BC growth and metastasis and provide a therapeutic regimen for BC treatment.

This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

Y chromosome microdeletions are an important cause of male infertility. At present, research on the Y chromosome is mainly focused on analyzing the loss of large segments of the azoospermia factor a/b/c (AZFa/b/c) gene, and few studies have reported the impact of unit point deletion in the AZF band on fertility. This study analyzed the effect of sperm quality after sY1192 loss in 116 patients. The sY1192-independent deletion accounted for 41.4% (48/116). Eight patterns were found in the deletions associated with sY1192. The rate of sperm detection was similar in the semen of patients with the independent sY1192 deletion and the combined sY1192 deletions (52.1% vs 50.0%). The patients with only sY1192 gene loss had a higher probability of sperm detection than the patients whose sY1192 gene locus existed, but other gene loci were lost (52.1% vs 32.0%). The hormone levels were similar in patients with sY1192 deletion alone and in those with sY1192 deletion and other types of microdeletions in the presence of the sY1192 locus. After multiple intracytoplasmic sperm injection (ICSI) attempts, the pregnancy rate of spouses of men with sY1192-independent deletions was similar to that of other types of microdeletions, but the fertilization and cleavage rates were higher. We observed that eight deletion patterns were observed for sY1192 microdeletions of AZFb/c, dominated by the independent deletion of sY1192. After ICSI, the fertilization rate and cleavage rate of the sY1192-independent microdeletion were higher than those of other Y chromosome microdeletion types, but there was no significant difference in pregnancy outcomes.
Humans ; Female ; Pregnancy ; Male ; Chromosomes, Human, Y/genetics* ; Adult ; Chromosome Deletion ; Pregnancy Outcome/genetics* ; Infertility, Male/genetics* ; Spermatozoa/physiology* ; Semen Analysis ; Sex Chromosome Disorders of Sex Development/genetics* ; Sperm Injections, Intracytoplasmic ; Azoospermia/genetics* ; Sex Chromosome Aberrations

Objective:To analyze the problems in implementing medical-research-industry collaborative innovation related policies, and propose corresponding countermeasures, for references for promoting the construction and development of collaborative innovation platforms in China.Methods:This study searched official websites such as the State Council, the National Health Commission and the Shanghai Municipal Health Commission for policy documents related to collaborative innovation and the transformation of medical scientific and technological achievements. Based on the Smith-model, 4 plaiforms of Shanghai were took, including the Clinical Science and Technology Innovation Park of Tongji University of Tenth People′s Hospital and other collaborative innovation platforms, as examples to analyze the problems in the implementation process of medical-research-industry collaborative innovation policies.Results:On the basis of national policies, Shanghai had issued a series of relevant guidance policies based on local conditions, creating a favorable policy environment for the construction and development of the medical-research-industry collaborative innovation platforms. However, the policy implications and practical needs related to collaborative innovation still needed to be continuously adjusted; The target demands of policy implementation entities were not unified, and there was a lack of normalized communication mechanisms; The target group lacked endogenous motivation and the policy implementation environment needed to be improved.Conclusions:The implementation of medical-research-industry collaborative innovation policies needed further improvement. It is suggested to optimize the policy supply coordination, performance evaluation and incentive mechanism, supervision and management, collaborative innovation culture atmosphere, and multi-channel funding support to promote the sustainable development of the collaborative innovation platform, and accelerate the efficient transformation of scientific and technological achievements.

Objective:To discuss the risk factors for postoperative venous thromboembolism (VTE) in patients undergoing pancreatic surgery.Methods:The clinical data of 488 patients who underwent pancreatectomy at the First Affiliated Hospital of Harbin Medical University from Jan 2016 to Sep 2024 was retrospectively analyzed.Results:One hundred and sixteen patients (23.8%) developed VTE after pancreatic surgery. Logistic analysis showed that advanced age, abdominal surgery history, high preoperative white blood cell count, high platelet lymphocyte ratio (PLR), distal pancreatectomy with splenectomy, open surgery, conversion to open surgery, and long surgery duration were risk factors.Nomogram prediction model based on the above risk factors was constructed and the area under the ROC curve was subsequently measured to be 0.781 (95% CI: 0.731-0.830). Conclusion:The prevention and control of VTE should be strengthened for patients undergoing pancreatic surgery with advanced age, abdominal surgery history, high preoperative white blood cell count, high PLR, distal pancreatectomy with splenectomy, open surgery, conversion to open surgery, and long surgery duration.