Screening carbonyl reductases with the ability to catalyze the reduction of complex carbonyl compounds is of great significance for the biosynthesis of R-tolvaptan(R-TVP). In this study, the target carbonyl reductase in the crude enzyme extract of rabbit liver was separated, purified, and identified by ammonium sulfate precipitation, gel-filtration chromatography, ion exchange chromatography, affinity chromatography, and protein mass spectrometry. With the rabbit liver genome as the template, the gene encoding the carbonyl reductase rlsr5 was amplified by PCR and the recombinant strain was successfully constructed. After RLSR5 was purified by affinity chromatography, its enzymatic properties were characterized. The results indicated that the gene sequence of rlsr5 was 972 bp, encoding a protein with a molecular weight of 40 kDa. RLSR5 was a dimeric protein, and each monomer was composed of a (α/β)₈-barrel structure. RLSR5 could asymmetrically reduce 7-chloro-1-[2-methyl-4-[(2- methylbenzoyl)amino]benzoyl]-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (prochiral ketone, PK) to synthesize R-TVP. The specific activity of the enzyme was 36.64 U/mg, and the optical purity of the product was 99%. This enzyme showcased the optimal performance at pH 6.0 and 30 °C. It was independent of metal ions, with the activity enhanced by Mn²⁺. This study lays a foundation for the biosynthesis of tolvaptan of optical grade.
Animals ; Rabbits ; Alcohol Oxidoreductases/biosynthesis* ; Recombinant Proteins/metabolism* ; Escherichia coli/metabolism* ; Liver/enzymology*

Glucose metabolic reprogramming is important in promoting the occurrence and development of malignant tumors and meeting the high demands of the malignant proliferation of tumor cells. An in-depth investigation of the mechanism of glucose metabolic reprogramming in lung cancer is important for the development of effective therapeutic strategies for lung cancer. Traditional Chinese medicine (TCM) is characterized by multiple components, targets, and pathways and can exert antitumor effects through multiple mechanisms. This article illustrates systematically the mechanism of action of Chinese herbal monomers and compound formulas regulating glucose metabolic reprogramming in lung cancer and explores deeply their regulatory effects on key enzymes of glycolysis and metabolism-related signaling pathways, and their potential in overcoming the drug resistance of lung cancer. It aims to provide a reference basis for the study of therapeutic targets and mechanisms of action of TCM in prevention and treatment of lung cancer and theoretical sources for the research and development of new medicines.

Objective:To explore the relationship between general demographic characteristics,inflammatory indicators,nutritional indicators,pathological data and lymph node metastasis in endometrial cancer(EC)pa-tients,and to construct and validate a model for preoperative prediction of lymph node status in endometrial canc-er patients.Methods:The preoperative clinical data of 473 patients with EC who underwent surgical treatment in the Zhu Jiang Hospital of Southern Medical University from January 2010 to April 2024 were retrospectively ana-lyzed.The independent risk factors of lymph node metastasis of endometrial cancer were screened by univariate and multivariate Logistic regression analyses,and the nomogram prediction model was constructed by R soft-ware.The performance of the model was evaluated by the receiver operating characteristic(ROC)curve,calibra-tion curve and clinical decision curve.Results:Menopausal status,high grade biopsy pathology,CA125 ≥24.47U/ml,systemic immune inflammatory index(SII)≥710.91,and prognostic nutritional index(PNI)＜52.90 were in-dependent risk factors for lymph node metastasis in endometrial cancer(OR＞1,P＜0.05).The nomogram model constructed based on these five factors had an AUC of 0.853 in the training set and 0.871 in the test set.The cali-bration curve fitted well,and the clinical decision curve shows a positive benefit.Conclusions:The endometrial cancer lymph node metastasis prediction model constructed based on menopausal status,biopsy pathology,CA125,SII,and PNI has good accuracy and fit,with certain clinical application value.

Objective To investigate the influencing factors of pulmonary and extrapulmonary acute re-spiratory distress syndrome(ARDS)caused by sepsis.Methods A total of 126 patients with ARDS admitted to the Department of Critical Care Medicine,General Hospital of Ningxia Medical University,from January 2022 to June 2024 were selected.Patients were divided into pulmonary ARDS and extrapulmonary ARDS groups based on the etiology of ARDS.General data,inflammatory indicators,and prognostic outcomes were compared between the two groups.COX regression analysis was used to identify prognostic factors.Results A-mong the 126 patients,72 were diagnosed with pulmonary ARDS and 54 with extrapulmonary ARDS.The pulmonary ARDS group had significantly lower SOFA scores,fewer organ dysfunctions,a lower incidence of arrhythmia,shorter mechanical ventilation duration,higher Murray scores,and higher Charlson Comorbidity Index(CCI)compared to the extrapulmonary ARDS group(P<0.05).Inflammatory markers,including pro-calcitonin(PCT),C-reactive protein(CRP),interleukin(IL)-4,IL-6,IL-10,and tumor necrosis factor-α(TNF-α),were significantly lower in the pulmonary ARDS group,while interferon-γ(INF-γ)levels were higher(P<0.05).For pulmonary ARDS,CCI and TNF-α were identified as independent risk factors for prog-nosis(P<0.05),with the combination of CCI and TNF-α yielding the highest predictive accuracy(AUC=0.81,95%CI:0.71-0.91).For extrapulmonary ARDS,CCI and CRP were independent risk factors(P<0.05),and their combination achieved the highest predictive performance(AUC=0.91,95%CI:0.84-0.98).Conclusion Inflammatory profiles between pulmonary and extrapulmonary ARDS caused by sepsis are different.CCI and TNF-α are independent risk factors for mortality in pulmonary ARDS,while CCI and CRP are independent risk factors in extrapulmonary ARDS.

Objectives:To analyze the clinical characteristics of upper cervical vertebrae with dumbbell schwannoma,and to explore its clinical symptoms,imaging features,and treatment plans.Methods:A retro-spective analysis was performed on 14 patients with upper cervical intra-and extraspinal dumbbell-shaped schwannoma admitted to the Spinal Surgery Department of Southern Theater General Hospital from January 2022 to June 2024,including 9 males and 5 females,aged 43.64±11.96 years(25-61 years).According to the location,size,scope of the tumor,and relationship with the surrounding important tissue structure in upper cervical spine,the relevant clinical treatment data were analyzed and the surgical treatment plan was dis-cussed.Cervical X-ray,CT and MRI examinations were regularly performed after surgery to evaluate the con-ditions of complete resection of tumor and recurrence,the stability of the upper cervical spine and whether the internal fixation was loose or broken.The recovery of spinal nerve function and pain improvement were evaluated by the Japanese Orthopaedic Association(JOA)and visual analogue scale(VAS)scores.Results:All the patients underwent complete tumor resection in one stage,and the postoperative JOA score(10.14±1.55 vs 13.86±1.06,P=0.005)and VAS score(2.42±1.29 vs 0.64±0.71,P=0.000)were statistically different from those before surgery.Postoperative tumor histopathology was confirmed as schwannoma in all the 14 patients.The follow-up time was 6 months to 2 years.No recurrence of tumor was found,neurological symptoms were significantly improved,and no upper cervical instability appeared.Conclusions:For patients with intra-and extra-spinal dumbbell-shaped schwannoma in the upper cervical spine,complete resection of the tumor in one stage of posterior approach can be given priority.If the important stable tissue structure of the upper cervical spine is destroyed,upper cervical spine fixation and fusion should be performed to ensure the stabil-ity of upper cervical spine after tumor resection.

Objective:To explore the relationship between general demographic characteristics,inflammatory indicators,nutritional indicators,pathological data and lymph node metastasis in endometrial cancer(EC)pa-tients,and to construct and validate a model for preoperative prediction of lymph node status in endometrial canc-er patients.Methods:The preoperative clinical data of 473 patients with EC who underwent surgical treatment in the Zhu Jiang Hospital of Southern Medical University from January 2010 to April 2024 were retrospectively ana-lyzed.The independent risk factors of lymph node metastasis of endometrial cancer were screened by univariate and multivariate Logistic regression analyses,and the nomogram prediction model was constructed by R soft-ware.The performance of the model was evaluated by the receiver operating characteristic(ROC)curve,calibra-tion curve and clinical decision curve.Results:Menopausal status,high grade biopsy pathology,CA125 ≥24.47U/ml,systemic immune inflammatory index(SII)≥710.91,and prognostic nutritional index(PNI)＜52.90 were in-dependent risk factors for lymph node metastasis in endometrial cancer(OR＞1,P＜0.05).The nomogram model constructed based on these five factors had an AUC of 0.853 in the training set and 0.871 in the test set.The cali-bration curve fitted well,and the clinical decision curve shows a positive benefit.Conclusions:The endometrial cancer lymph node metastasis prediction model constructed based on menopausal status,biopsy pathology,CA125,SII,and PNI has good accuracy and fit,with certain clinical application value.

Objectives:To analyze the clinical characteristics of upper cervical vertebrae with dumbbell schwannoma,and to explore its clinical symptoms,imaging features,and treatment plans.Methods:A retro-spective analysis was performed on 14 patients with upper cervical intra-and extraspinal dumbbell-shaped schwannoma admitted to the Spinal Surgery Department of Southern Theater General Hospital from January 2022 to June 2024,including 9 males and 5 females,aged 43.64±11.96 years(25-61 years).According to the location,size,scope of the tumor,and relationship with the surrounding important tissue structure in upper cervical spine,the relevant clinical treatment data were analyzed and the surgical treatment plan was dis-cussed.Cervical X-ray,CT and MRI examinations were regularly performed after surgery to evaluate the con-ditions of complete resection of tumor and recurrence,the stability of the upper cervical spine and whether the internal fixation was loose or broken.The recovery of spinal nerve function and pain improvement were evaluated by the Japanese Orthopaedic Association(JOA)and visual analogue scale(VAS)scores.Results:All the patients underwent complete tumor resection in one stage,and the postoperative JOA score(10.14±1.55 vs 13.86±1.06,P=0.005)and VAS score(2.42±1.29 vs 0.64±0.71,P=0.000)were statistically different from those before surgery.Postoperative tumor histopathology was confirmed as schwannoma in all the 14 patients.The follow-up time was 6 months to 2 years.No recurrence of tumor was found,neurological symptoms were significantly improved,and no upper cervical instability appeared.Conclusions:For patients with intra-and extra-spinal dumbbell-shaped schwannoma in the upper cervical spine,complete resection of the tumor in one stage of posterior approach can be given priority.If the important stable tissue structure of the upper cervical spine is destroyed,upper cervical spine fixation and fusion should be performed to ensure the stabil-ity of upper cervical spine after tumor resection.

BACKGROUND: Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is characterized by synovitis and progressive damage to the bone and cartilage of the joints, leading to disability and reduced quality of life. This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control. METHODS: The study was designed as a multicenter, open-label, randomized controlled trial. Eligible patients who were taking tofacitinib (5 mg twice daily) and had achieved sustained RA remission or low disease activity (disease activity score in 28 joints [DAS28] ≤3.2) for at least 3 months were enrolled at six centers in Shanghai, China. Patients were randomly assigned (1:1:1) to one of three treatment groups: continuation of tofacitinib (5 mg twice daily); reduction in tofacitinib dose (5 mg daily); and withdrawal of tofacitinib. Efficacy and safety were assessed up to 6 months. RESULTS: Overall, 122 eligible patients were enrolled, with 41 in the continuation group, 42 in the dose-reduction group, and 39 in the withdrawal group. After 6 months, the percentage of patients with a DAS28-erythrocyte sedimentation rate (ESR) of <3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups (20.5%, 64.3%, and 95.1%, respectively; P  < 0.0001 for both comparisons). The average flare-free time was 5.8 months for the continuation group, 4.7 months for the dose reduction group, and 2.4 months for the withdrawal group. CONCLUSION: Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy, while standard or reduced doses of tofacitinib maintained a favorable state. TRIAL REGISTRATION Chictr.org, ChiCTR2000039799.
Humans ; Quality of Life ; China ; Arthritis, Rheumatoid/drug therapy* ; Piperidines/therapeutic use* ; Treatment Outcome ; Antirheumatic Agents/therapeutic use* ; Pyrroles/therapeutic use*

Objective:To analyze the current situation of Investigator-Initiated Trials in medical and health institutions in Shandong Province, the problems in the process of conducting clinical research, and put forward proposals for the establishment of a clinical research management system with effective supervision, sound systems and supporting services, taking into account the progress of the projects since the pilot work was carried out.Methods:A questionnaire was created, an online survey was conducted, a database was set up, a status analysis was conducted and a post-launch analysis of the progress of the pilot was carried out using the National Medical Research Registry Information System, culminating in recommendations using the literature summary method and empirical analysis.Results:Statistical analysis of the questionnaire found that 29.39% of the institutions have a dedicated clinical research management department, and 75.97% of the institutions have a management approach. 25.52%, 40.30%, and 43.07% of institutions established biobanks, clinical research centers, and follow-up centers. There was a statistically significant difference in the establishment of clinical research centers, biobanks, and follow-up centers in secondary and tertiary medical institutions ( P<0.05). The number of general clinical research projects filed, the number of submissions and the number of ethics committees filed in the filing system have all increased significantly after the pilot work, with growth percentages of 126%, 141% and 62% respectively. Conclusions:Shandong Province clinical research pilot work has begun to bear fruit, the current clinical research project still exists in the lack of special funding support, perfect service platform and system support and training system to be improved and other issues.

The potential medicinal value of Ma bamboo (Dendrocalamus latiflorus), one of the most popular and economically important bamboo species in China, has been underestimated. In the present study, we found that D. latiflorus leaf extract (DLE) reduced fasting blood glucose levels, body weight, and low-density lipoprotein cholesterol with low liver toxicity in db/db mice. In addition, gene expression profiling was performed and pathway enrichment analysis showed that DLE affected metabolic pathways. Importantly, DLE activated the AKT signaling pathway and reduced glucose production by downregulating glucose-6-phosphatase (G6PC) and phosphoenolpyruvate carboxykinase 1 (PCK1) expression. Moreover, network pharmacology analysis identified rutin as an active component in DLE through targeting insulin growth factor 1 receptor (IGF1R), an upstream signaling transducer of AKT. Due to its hypoglycemic effects and low toxicity, DLE may be considered an adjuvant treatment option for type 2 diabetes patients.