1.NAD+ Ameliorates Endothelial Dysfunction in Hypertension via Activation of SIRT3/IDH2 Signal Pathway
Yumin QIU ; Xi CHEN ; Jianning ZHANG ; Zhangchi LIU ; Qiuxia ZHU ; Meixin ZHANG ; Jun TAO ; Xing WU
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(1):70-80
ObjectiveTo investigate the effect of nicotinamide adenine dinucleotide on vascular endothelial injury in hypertension and its molecular mechanism. MethodsC57BL/6J mice were randomly divided into saline group (Saline) and hypertension group (Ang Ⅱ, which were infused with Ang Ⅱ via subcutaneously implanted osmotic pumps), and supplemented daily with nicotinamide mononucleotide (300 mg/kg), a precursor of NAD+. Blood pressure, endothelial relaxation function and pulse wave velocity were measured after 4 weeks. Wound healing assay and adhesion assay were used to evaluate the function of endothelial cells in vitro. mtROS levels were detected by immunofluorescence staining. RT-PCR was used to detect the mRNA expression of mtDNA, SIRT3 and isocitrate dehydrogenase 2 (IDH2). 8-hydroxy-2'-deoxyguanosine levels were detected by enzyme-linked immunosorbent assay. The protein expression levels of p-eNOS, eNOS, SIRT3 and IDH2 were detected by Western blot. ResultsNMN supplementation reduced blood pressure (P<0.001) and improved endothelial function and arterial stiffness (P<0.001) in hypertensive mice. In vitro, NMN improved endothelial function in AngII-stimulated endothelial cells (P<0.05) and attenuated mitochondrial oxidative stress levels (P<0.001). Mechanistically, NMN elevated SIRT3 activity (P<0.001), which subsequently enhanced IDH activity (P<0.001) and reduced oxidative stress levels in endothelial cells. Conversely, knockdown of IDH2 would reverse the effect of SIRT3 in improving endothelial function (P<0.001). ConclusionNAD+ lowers blood pressure and enhances vascular function in hypertension by reducing the level of oxidative stress in endothelial cells through activation of the SIRT3/IDH2 signal pathway.
2.Application of the combined tumor burden score and platelet-albumin-bilirubin score model for predicting postoperative tumor recurrence in liver transplant recipients with hepatocellular carcinoma
Weidong ZHU ; Junyang XIAO ; Xiaoji QIU ; Lizhi LÜ ; Jianwei CHEN ; Fang YANG
Organ Transplantation 2025;16(4):556-564
Objective To investigate the predictive value of the combined tumor burden score (TBS) and platelet-albumin-bilirubin (PALBI) score model for postoperative tumor recurrence in liver transplant recipients with hepatocellular carcinoma (HCC). Methods The general information of 158 recipients diagnosed with HCC and underwent liver transplantation at the 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army from 2008 to 2021 was collected. Lasso regression analysis combined with multivariate Cox regression analysis were used to identify independent risk factors for postoperative tumor recurrence after liver transplantation with HCC. A nomogram prediction model was constructed based on variables selected by Lasso regression analysis, and the predictive performance of the model was verified by calibration curve and clinical decision curve. The optimal cut-off values for postoperative tumor recurrence in liver transplant recipients with HCC were determined by receiver operating characteristic (ROC) curve, and Kaplan-Meier analysis was used to compare survival differences among different groups. Results Among the 158 liver transplant recipients with HCC, 82 experienced tumor recurrence, with a recurrence rate of 51.9% and a median tumor-free survival time of 10 (4, 25) months. Results of Lasso regression analysis and multivariate Cox regression analysis showed that alpha-fetoprotein (AFP) ≥400 ng/mL, TBS and PALBI score were all independent risk factors for postoperative tumor recurrence in liver transplant recipients with HCC (all P<0.05). The combined high TBS-high PALBI score showed the highest predictive value (hazard ratio 6.909, 95% confidence interval 3.067-15.563, P<0.001). A nomogram prediction model was constructed based on six variables selected by Lasso regression analysis. Calibration curve showed good consistency between the model's predicted results and the ideal curve. Decision curve analysis indicated that the nomogram prediction model provided the highest clinical benefit for predicting 1-year tumor-free survival after liver transplantation with HCC. Time-dependent ROC curves at 1, 3 and 5 years after surgery showed that TBS-PALBI model had good predictive performance, with no significant difference in area under the curve (AUC) compared with TBS-PALBI-AFP model. The optimal cut-off values for predicting postoperative tumor recurrence were determined by ROC curve, with a PALBI score cut-off of −2.334 and a TBS cut-off of 5.305. Recipients were divided into a low TBS-low PALBI score group (n=47) and a low/high TBS-low/high PALBI score group (at least one score was high) (n=111). Kaplan-Meier survival analysis showed that the low TBS-low PALBI score group had a higher tumor-free survival rate than the low/high TBS-low/high PALBI score group, with a significant difference (P<0.05). Conclusions TBS-PALBI model provides a novel, simple and effective tool for assessing the prognosis of liver transplant recipients with HCC. The nomogram model constructed based on this has significant advantages in predictive performance and may serve as a reference for guiding individualized treatment plans and improving clinical outcomes.
3.Research Progress on Immunomodulatory Activity and Mechanism of Polygonatum sibiricum
Jinyu LI ; Ningning QIU ; Chang YI ; Mengqin ZHU ; Yanfeng YUAN ; Guang CHEN ; Xili ZHANG ; Wenlong LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):298-306
Polygonatum sibiricum, as a traditional Chinese medicine with both medicinal and edible properties, has attracted considerable attention due to its functions of nourishing Yin and moistening the lungs, tonifying the spleen and benefiting Qi, and nourishing the kidneys and filling essence. Recent studies have demonstrated that Polygonatum sibiricum plays a significant role in regulating the immune system, effectively enhancing and improving the morphology and function of immune organs, stimulating the proliferation and activation of immune cells, and regulating the secretion and release of immune factors, thereby enhancing the immune function of the body and improving various immune-related diseases. Although a large number of studies have explored the pharmacological effects and mechanisms of P. sibiricum, there has been no systematic review and summary of its immune regulatory activity and mechanisms. Therefore, this article comprehensively reviews the research achievements of P. sibiricum polysaccharides and saponins in the field of immune regulation in recent years, and further sorts out the immune regulatory mechanisms of P. sibiricum in multiple aspects: including increasing the organ index of the spleen and thymus, increasing the number and activity of tumor-suppressive bone marrow hematopoietic stem cells, improving intestinal flora imbalance, regulating the quantity and proportion of T lymphocyte subsets, increasing the level of immunoglobulin, promoting the proliferation of macrophages, enhancing the activity of natural killer cells, increasing the number of white blood cells, and promoting the maturation of dendritic cells, providing a solid theoretical basis and scientific evidence for the research and application of P. sibiricum, and promoting its development and application in traditional Chinese medicine immune enhancers and various functional products.
4.Data Mining of Professor Zhang Farong's Core Prescription for Type 2 Diabetes Mellitus and Its Clinical Efficacy
Wei FANG ; Jie XU ; Huanping WANG ; Xiaoran ZHANG ; Hongxia ZHU ; Qiu CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):174-182
ObjectiveTo explore the medication patterns of Professor Zhang Farong in treating type 2 diabetes mellitus (T2DM) and the clinical efficacy of his core prescription. MethodsClinical case records of T2DM treated by Professor Zhang Farong were collected to establish a prescription database. Frequency statistics, visual analysis, and factor analysis were employed to investigate the characteristics and principle of the prescriptions, and a core prescription was derived. A randomized controlled trial was conducted, enrolling 60 T2DM patients with the dampness-heat syndrome. The patients were allocated into an observation group (core prescription + metformin) and a control group (metformin alone), with both groups undergoing a 12-week treatment course. Changes in TCM symptom scores, glucose metabolism indicators [fasting plasma glucose (FPG), 2-hour postprandial blood glucose (2 hPG), and glycated hemoglobin (HbA1c)], pancreatic function indicators [fasting C-peptide (FCP), 2-hour postprandial C-peptide (2 hCP), and area under the C-peptide curve (AUCcp)], and lipid profiles were measured before and after treatment. The adverse reactions were observed and recorded. ResultsA core prescription named modified Gegen Qinlian Decoction was formulated, comprising Puerariae Lobatae Radix, Coptidis Rhizoma, Scutellariae Radix, Astragali Radix, Lycii Cortex, Mori Cortex, Jineijin Endothelium Corneum Gigeriae Galli, Rehmanniae Radix Praeparata, Atractylodis Rhizoma, Polygonati Rhizoma, and Pogostemonis Herba. The clinical trial results showed that both groups had significantly decreased FPG, 2 hPG, and HbA1c (P0.05), and the observation group outperformed the control group in recovering the level of HbA1c (P0.05). After treatment, both groups had declined TCM symptoms scores (P0.05), and the declines in the observation group were larger than those in the control group (P0.05). After treatment, the TC and LDL-C levels declined in the observation group (P 0.05), while the lipid levels showed a decreasing trend with no statistically significant difference in the control group. After treatment, both groups showed increases in FCP and AUCcp (P0.05), and the 2 hCP in both groups presented a recovering trend with no statistically significant difference. There was no statistically significant difference in the incidence of adverse reactions between the two groups. ConclusionModified Gegen Qinlian Decoction embodies Professor Zhang Farong's academic philosophy of treating consumptive thirst by tonifying the spleen and kidney, replenishing Qi and Yin, clearing deficiency and heat, unblocking stasis in collaterals, and addressing both deficiency and stasis. The combination of the core prescription with metformin alleviates clinical symptoms in T2DM patients with the dampness-heat syndrome, demonstrating potential effects in restoring pancreatic islet function, regulating blood glucose, and improving lipid profiles. It serves as a therapeutic option for T2DM in the patients with the dampness-heat syndrome under syndrome differentiation, meriting broader clinical application.
5.Role of problem chain and course ideological and political cases teaching method in enhancing clinical medication ability research
Zhi-Hua QIN ; Long-Xi PENG ; Gao-Shuang LAN ; Xiao-Bin ZHANG ; Jiao-Jiao YANG ; Liang ZHU ; Xi-Long QIU ; Yun-Long CHEN
The Chinese Journal of Clinical Pharmacology 2024;40(11):1650-1653
Nowadays,with the continuous deepening and development of vocational education teaching reform,medical higher vocational education always takes moral education as the fundamental task.As an independent type of education,vocational education should always deepen the integration of industry and education and the integration of science and education.Through the teaching research of"problem chain+course ideological and political case",this study innovates the coordinated education team of drug nursing curriculum,the collaborative education method and the collaborative education evaluation,and improves the teaching effect.
6.Aphasia in Right Hemiparesis and Pain in Left Waist:A Deceiving Case in Vascular Ehlers-Danlos Syndrome
Yining FU ; Jingmin ZHOU ; Feng LI ; Shangzhi HUANG ; Yining WANG ; Xia HONG ; Ke LYU ; Yaping LIU ; Ling LENG ; Wenjie ZHENG ; Zhengqing QIU ; Yicheng ZHU ; Yuehong ZHENG ; Yuexin CHEN
JOURNAL OF RARE DISEASES 2024;3(2):224-231
The Ehlers-Danlos syndrome(EDS)is a rare inherent connective tissue disorder.The prev-alence of EDS in the population is estimated at one out of ten thousand to one out of a hundred thousand.The vascular EDS(vEDS)are rare among the subtypes but are the worst in prognosis.The article reports a case of vEDS admitted to the hospital.The patient was a young man complaining of a sudden onset of aphasia in right hemiparalysis and severe left abdominal pain for unknown reasons.The diagnosis was made after the genetic testing.The patient suffered from vEDS.Then,the multi-disciplinary team(MDT)made a treatment plan tailored to this young patient.The complexity in classification and delusive presentations of the EDS make the correct diagnosis very challenging.This article hopes to report this case and to share the experiences to the bet-ter understanding of this disease.
7.Research progress on ferroptosis in the treatment of bladder cancer
Jingping QIU ; Lugang ZHU ; Yuanwei CHEN ; Minghong ZHOU ; Yuwan ZHAO ; Jianjun LIU
Journal of Modern Urology 2024;29(9):830-835
Ferroptosis is a new programmed cell death dependent on iron ions.Ferroptosis can be induced by endogenous or exogenous pathways,and cells exhibit specific cell morphological signs and are regulated by a variety of molecular mechanisms.In recent years,more and more studies have shown that ferroptosis plays an important role in the treatment of cancer.This article summarizes the mechanism of ferroptosis in bladder cancer and the regulation of cancer cells,as well as the role of ferroptosis-related factors,non-coding RNA regulation,N6-methyladenosine(m6A),amino acid metabolism and autophagy dependent ferroptosis in the growth and proliferation of bladder cancer,with a view to provide new strategies for the treatment of bladder cancer.
8.Clinical application of inferior pancreaticoduodenal artery management in laparoscopic pancreaticoduodenectomy
Zhantao SHEN ; Zhimin YU ; Xiaosheng ZHONG ; Youxing HUANG ; Chengjiang QIU ; Yanchen CHEN ; Guihao CHEN ; Sheng ZHANG ; Chunbao ZHU ; Zhangyuanzhu LIU ; Yifeng LIU ; Zhijian TAN
Chinese Journal of Surgery 2024;62(10):947-952
Objective:To investigate the clinical effect of proper management of inferior pancreaticoduodenal artery (IPDA) in laparoscopic pancreaticoduodenectomy (LPD).Methods:This is a retrospective case series study. The clinical and pathological data of 70 patients who received LPD due to pancreatic head tumors, periampullary tumors, or distal common bile duct tumors in the Pancreatic Center of the Second Clinical College of Guangzhou University of Chinese Medicine from January to December 2022 were retrospectively collected. There were 47 males(67.1%) and 23 females(32.9%),aged (59.9±12.8)years(range:13 to 87 years).The procedure of IPDA exposure was as follows:a middle approach was utilized to expose the right half of superior mesenteric artery(SMA) and its right branches between the SMA and superior mesenteric vein(SMV) in superior colonic region. In the subcolonic region,SMA trunk exposure via dissection along the jejunal artery from feet to head and identification the association between IPDA and jejunal artery were prior to IPDA root ligation and dissection. The safety and efficacy of intraoperative IPDA handling were assessed based on surgical videos. Follow-up was carried out in outpatient clinic or by telephone, and outpatient follow-up was conducted once every 1 to 3 months after surgery.Results:The percentage of total LPD was 98.6%(69/70),with all patients achieving R0 resection. Nine cases(12.9%) were involved in combined vascular resection and reconstruction,with 1 case (1.4%) requiring additional upper abdominal incision for vascular and gastrointestinal reconstruction,while the remaining eight cases (11.4%) were completed laparoscopically. The operative time was (432.7±115.4)minutes(range:282 to 727 minutes), and the blood loss was (140.0±125.7)ml(range:20 to 800 ml). Only two patients(2.9%) received fresh frozen plasma transfusion,with an average volume of 650 ml. Reliable ligation and safe handling of the IPDA were achieved in 91.4%(64/70) of cases, with 8.6%(6/70) suffering from IPDA injury-related bleeding. No one was converted to opened surgery. Pathologically,the mean tumor size was (3.3±1.6)cm (range:1 to 7 cm),and the mean number of harvested lymph nodes was 17.0±7.3(range:0 to 46). Lymph node metastasis was observed in 13 cases (18.6%). Five cases (13.2%) developed grade B pancreatic fistula,while no grade C pancreatic fistula occurred. Other complications included bile leakage in one case(1.4%),delayed gastric emptying in two cases(2.9%), lymphatic leakage in 2 cases(2.9%),intra-abdominal infection in 9 cases(12.9%),and fat liquefaction of surgical incision in 1 case(1.4%). Two cases(2.9%) experienced postoperative intra-abdominal bleeding,one due to mesangial bleeding of lesser curvature of the stomach and the other due to oozing from the hepatic arterial sheath. These bleeding events were not concerned with IPDA. The average length of postoperative hospital stay was (15.2±4.6)days(range:9 to 28 days).Conclusion:Proper intraoperative management of IPDA in LPD might reduce IPDA-related bleeding during and after surgery and improve the safety of LPD.
9.A real-world study of first-line albumin-bound paclitaxel in the treatment of advanced pancreatic cancer in China
Juan DU ; Xin QIU ; Jiayao NI ; Qiaoli WANG ; Fan TONG ; Huizi SHA ; Yahui ZHU ; Liang QI ; Wei CAI ; Chao GAO ; Xiaowei WEI ; Minbin CHEN ; Zhuyin QIAN ; Maohuai CAI ; Min TAO ; Cailian WANG ; Guocan ZHENG ; Hua JIANG ; Anwei DAI ; Jun WU ; Minghong ZHAO ; Xiaoqin LI ; Bin LU ; Chunbin WANG ; Baorui LIU
Chinese Journal of Oncology 2024;46(11):1038-1048
Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P<0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.
10.Drug resistance and genetic diversity of clinical strains of Helicobacter pylori in the Qiannan Prefecture and Guiyang City,and their relationships with diseases
Yuan-Yuan ZHANG ; Ke PAN ; Meng-Heng MI ; Yu-Zhu GUAN ; Qiu-Dan LU ; Juan ZHENG ; Jin ZHANG ; Tian-Shu WANG ; Qi LIU ; Zheng-Hong CHEN
Chinese Journal of Zoonoses 2024;40(1):46-55
To understand Helicobacter pylori's drug resistance,genetic diversity,and relationship with clinical diseases in the Guiyang and Qiannan minority areas of Guizhou Province,we collected samples through endoscopy,and isolated and cul-tured H.pylori.The drug resistance and genotype characteristics were determined.The differences in different regions and dis-ease types were compared,and the structural characteristics of H.pylori and mixed infections with different strains of H.py-lori in Qiannan Prefecture were analyzed.A difference in the composition ratio of EPYIA typing in the cagA variable region was observed between the two areas(P=0.012),and the composition ratio of the vacA genotype differed(P=0.000).A total of 94.6%(53/56)new sequences of H.pylori strains from two regions were obtained by MLST.The rate of infection by H.pylori mixed with different strains was 44.4%in Qiannan Pre-fecture,and no significant difference was observed in the com-position of H.pylori mixed infections among patients with dif-ferent clinical diseases(P=0.349).Differences in EPI YA typ-ing and the vacA genotype composition ratio in the cagA varia-ble region of H.pylori were observed between the Qiannan Prefecture and Guiyang City.

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