1.Cyclocarya paliurus Polysaccharide Inhibits Benign Prostatic Hyperplasia by Reducing 5α-Reductase 2
Qinhui DAI ; Mengxia YAN ; Chen WANG ; Chenjun SHEN ; Chenying JIANG ; Bo YANG ; Huajun ZHAO ; Zhihui ZHU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):107-114
ObjectiveTo investigate the effect and mechanism of polysaccharide in water extract of Cyclocarya paliurus (CPWP) in inhibiting benign prostatic hyperplasia (BPH). MethodsCPWP was obtained by heating reflux, aqueous extraction, alcohol precipitation, and freeze drying. The chemical composition and structural properties of CPWP were analyzed by high performance liquid chromatography with 1-pheny-3-methyl-5-pyrazolone pre-column derivatization and infrared spectroscopy. Male SD rats were randomly assigned into control, model, finasteride (ig 5 mg·kg-1), and low-, medium-, and high-dose (ig 50, 75, 100 mg·kg-1) CPWP groups, with 8 rats in each group. The BPH model was established by subcutaneously injecting propionate testosterone in castrated rats. The rats in the drug intervention groups were administrated with corresponding drugs, and those in the control group were administrated with an equal volume of normal saline each day. After 30 consecutive days, the rats were sacrificed, and the prostate tissue was separated and weighed. The effects of drug interventions on the body weight, prostate wet weight, and prostate index of rats were examined. The prostate tissue was stained with hematoxylin-eosin (HE) for observation of pathological changes. Enzyme-linked immunosorbent assay was employed to measure the level of dihydrotestosterone (DHT), and immunohistochemical staining was used to detect the expression of steroid 5 alpha-reductase 2 (SRD5A2) and Ki67 in the prostate tissue. ResultsCPWP was identified as a saccharide, with characteristic absorption peaks of saccharides. CPWP showed the total sugar content of 44.15% and molecular weight within the range of 5.5-78.8 kDa, being composed of mannose, rhamnose, galacturonic acid, glucose, galactose, xylose, and arabinose. Compared with the control group, the model group had significantly increased prostate wet weight and prostate index (P<0.01), thick and tall prostate epithelial cells, increased internal wrinkles, papillary expansion into the cavity, an elevation in DHT level in the serum, and up-regulated expression of SRD5A2 and Ki67 in the prostate tissue (P<0.05, P<0.01). Compared with the model group, both the finasteride and CPWP groups showed decreases in prostate wet weight and prostate index (P<0.05, P<0.01), thinned prostate epithelial cells, with only a small portion of internal wrinkles and papillary expansion into the cavity, shortened papillary protrusions, lowered DHT level in the serum, and down-regulated expression of SRD5A2 and Ki67 in the prostate tissue (P<0.01). Moreover, CPWP exerted effects in a dose-dependent manner. ConclusionCPWP inhibits BPH by regulating the expression of SRD5A2.
2.Determination method of plasma concentrations of 7 anti-tumor drugs and its application
Jinxiu LYU ; Nan YAN ; Wenjun XU ; Jing ZHAO ; Hua ZHU ; Pengzhou HANG
China Pharmacy 2025;36(4):475-481
OBJECTIVE To establish a method for simultaneous determination of 7 anti-tumor drugs (irinotecan, capecitabine, paclitaxel, docetaxel, tamoxifen, letrozole and methotrexate) in human plasma and apply it to the clinic. METHODS After precipitating with a methanol-acetonitrile mixture (1∶ 1, V/V) containing 0.1% formic acid, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine the plasma concentration, using deuterium isotopes of each analyte as internal standards. The chromatography was performed on the Agilent Eclipse Plus C18 column with a gradient elution of water (containing 0.1% formic acid+0.04% 5 mmol/L ammonium formate) as mobile phase A and acetonitrile (containing 0.1% formic acid) as mobile phase B. The flow rate was 0.6 mL/min, and the column temperature was set at 40 ℃ . The sample size was 10 μL, and the analysis lasted for 5.5 min. Electrospray ionization was used in positive and negative ion mode, and multiple reaction monitoring mode was used. The ion pairs used for quantitative analysis were m/z 587.1→167.1 (irinotecan), m/z 360.1→244.1 (capecitabine), m/z 876.4→308.0 (paclitaxel), m/z 830.3→304.2 (docetaxel), m/z 372.1→129.1 (tamoxifen), m/z 284.1→242.1 (letrozole), and m/z 455.0→ 308.0 (methotrexate). A total of 97 patients with malignant tumors in our hospital were selected to measure the plasma concentrations of 7 anti-tumor drugs using the above method. RESULTS The linear ranges of irinotecan, capecitabine, paclitaxel, docetaxel, tamoxifen, letrozole and methotrexate were 2-1 000 ng/mL (r=0.994 3), 20-10 000 ng/mL (r=0.997 5), 2-1 000 ng/mL (r=0.997 9), 1-500 ng/mL (r=0.995 8), 1-500 ng/mL (r=0.995 2), 1-500 ng/mL (r=0.996 4), 10-5 000 (r=0.997 7), respectively. The quantitative lower limits were 2, 20, 2, 1, 1, 1 and 10 ng/mL; RSDs of intra-assay precision were 0.08%-14.86% (n=6). RSDs of inter-batch precision were 1.51%-11.55% (n=3), and the accuracies were 89.17%-114.93% (n=6). The matrix effects ranged from 89.89%-119.74% (n=6). RSDs of the stability tests were 1.98%-14.88% (n=6). The results of E-mail:hangpengzhou@163.com clinical application showed, the average plasma concentrations of irinotecan, capecitabine, paclitaxel and docetaxel were 704.09, 909.40, 36.45, 150.43 ng/mL, respectively. The values of the coefficient of variation were 25.24%, 62.65%, 122.69%, and 92.27%. CONCLUSIONS The established LC-MS/MS method is simple and rapid, and can be used for the simultaneous determination of 7 commonly used anti-tumor drugs in the plasma of patients with malignancy.
3.A new glycoside from Alstonia mairei Lévl.
Li-ke WANG ; Bing-yan LI ; Zhen-zhu ZHAO ; Yan-zhi WANG ; Xiao-kun LI ; Wei-sheng FENG ; Ying-ying SI
Acta Pharmaceutica Sinica 2025;60(1):191-195
Nine compounds were isolated and purified from 90% ethanol extract of
4.Influencing factors for meropenem-related liver injury and their predictive value
Yan HE ; Hongqin KE ; Hongliang LI ; Jianyong ZHU ; Lijun ZHAO ; Huibin YU
Journal of Clinical Hepatology 2025;41(3):506-512
ObjectiveTo analyze the factors influencing meropenem-related liver injury (MRLI) and to explore their clinical predictive value. MethodsA retrospective case-control study was conducted, and the Chinese Hospital Pharmacovigilance System (CHPS) was used to establish a retrieval scheme. A total of 1 625 hospitalized cases using meropenem from January 2018 to December 2022 were collected. Patients were divided into case group (n=62) and control group (n=1 563) based on the presence or absence of liver injury. Clinical data and laboratory indicators from both groups were collected and analyzed. The t-test was used for comparison of normally distributed continuous data between the two groups, while the Mann-Whitney U test was used for comparison of continuous data not conforming to a normal distribution. The chi-square test was used for comparison of categorical data between the two groups. A multivariate Logistic regression analysis was performed to identify the influencing factors for MRLI. A Logistic regression equation was established, and the predictive value of these factors was assessed using the receiver operating characteristic (ROC) curve. ResultsThe results of univariate analysis indicated that the rates of male patients, hypoproteinemia, shock, intensive care unit (ICU) admissions, sepsis, and liver, gallbladder, and cardiovascular diseases, the levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), creatinine (CREA), and procalcitonin (PCT), and the number of hospitalization days were significantly higher in the case group than in the control group (P<0.05), and that the platelet levels in the case group were significantly lower than those in the control group (P<0.05). The multivariate Logistic regression analysis showed that male sex (odds ratio [OR]=2.080, 95% confidence interval [CI]: 1.050 — 4.123, P=0.036), admission to the ICU (OR=8.207, 95%CI: 4.094 — 16.453, P<0.001), comorbidity with gallbladder disease (OR=8.240, 95%CI: 3.605 — 18.832, P<0.001), ALP (OR=1.012, 95%CI: 1.004 — 1.019, P=0.004), GGT (OR=1.010, 95%CI: 1.005 — 1.015, P<0.001), and PLT (OR=0.997, 95%CI: 0.994 — 0.999, P=0.020) were the influential factors for MRLI. The areas under the ROC curve of ALP, GGT, and PLT were 0.589, 0.637, and 0.595, respectively, and the AUC of them combined was 0.837. ConclusionMale sex, ICU admission, comorbidity with gallbladder disease, increased ALP, increased GGT, and decreased PLT were influencing factors for MRLI, and a combination of factors has a better predictive value for the occurrence of MRLI.
5.Production of GTKO pigs and kidney xenotransplantation from pigs to rhesus macaques
Yan WANG ; Yue CHANG ; Chang YANG ; Taiyun WEI ; Xiaoying HUO ; Bowei CHEN ; Jiaoxiang WANG ; Heng ZHAO ; Jianxiong GUO ; Hongfang ZHAO ; Xiong ZHANG ; Feiyan ZHU ; Wenmin CHENG ; Hongye ZHAO ; Kaixiang XU ; Ameen Jamal MUHAMMAD ; Zhendi WANG ; Hongjiang WEI
Organ Transplantation 2025;16(4):526-537
Objective To explore the construction of α-1,3-galactosyltransferase (GGTA1) gene-knockout (GTKO) Diannan miniature pigs and the kidney xenotransplantation from pigs to rhesus macaques, and to assess the effectiveness of GTKO pigs. Methods The GTKO Diannan miniature pigs were constructed using the CRISPR/Cas9 gene-editing system and somatic cell cloning technology. The phenotype of GTKO pigs was verified through polymerase chain reaction, Sanger sequencing and immunofluorescence staining. Flow cytometry was used to detect antigen-antibody (IgM) binding and complement-dependent cytotoxicity. Kidney xenotransplantation was performed from GTKO pigs to rhesus macaques. The humoral immunity, cellular immunity, coagulation and physiological indicators of the recipient monkeys were monitored. The function and pathological changes of the transplanted kidneys were analyzed using ultrasonography, hematoxylin-eosin staining, immunohistochemical staining and immunofluorescence staining. Results Single-guide RNA (sgRNA) targeting exon 4 of the GGTA1 gene in Diannan miniature pigs was designed. The pGL3-GGTA1-sgRNA1-GFP vector was transfected into fetal fibroblasts of Diannan miniature pigs. After puromycin selection, two cell clones, C59# and C89#, were identified as GGTA1 gene-knockout clones. These clones were expanded to form cell lines, which were used as donor cells for somatic cell nuclear transfer. The reconstructed embryos were transferred into the oviducts of trihybrid surrogate sows, resulting in 13 fetal pigs. Among them, fetuses F04 and F11 exhibited biallelic mutations in the GGTA1 gene, and F04 had a normal karyotype. Using this GTKO fetal pig for recloning and transferring the reconstructed embryos into the oviducts of trihybrid surrogate sows, seven surviving piglets were obtained, all of which did not express α-Gal epitope. The binding of IgM from the serum of rhesus monkey 20# to GTKO pig PBMC was reduced, and the survival rate of GTKO pig PBMC in the complement-dependent cytotoxicity assay was higher than that of wild-type pig. GTKO pig kidneys were harvested and perfused until completely white. After the left kidney of the recipient monkey was removed, the pig kidney was heterotopically transplanted. Following vascular anastomosis and blood flow restoration, the pig kidney rapidly turned pink without hyperacute rejection (HAR). Urine appeared in the ureter 6 minutes later, indicating successful kidney transplantation. The right kidney of the recipient was then removed. Seven days after transplantation, the transplanted kidney had good blood flow, the recipient monkey's serum creatinine level was stable, and serum potassium and cystatin C levels were effectively controlled, although they increased 10 days after transplantation. Seven days after transplantation, the levels of white blood cells, lymphocytes, monocytes and eosinophils in the recipient monkey increased, while platelet count and fibrinogen levels decreased. The activated partial thromboplastin time, thrombin time and prothrombin time remained relatively stable but later showed an upward trend. The recipient monkey survived for 10 days. At autopsy, the transplanted kidney was found to be congested, swollen and necrotic, with a small amount of IgG deposition in the renal tissue, and a large amount of IgM, complement C3c and C4d deposition, as well as CD68+ macrophage infiltration. Conclusions The kidneys of GTKO Diannan miniature pigs may maintain normal renal function for a certain period in rhesus macaques and effectively overcome HAR, confirming the effectiveness of GTKO pigs for xenotransplantation.
6.A Case Report of Multidisciplinary Management of a Patient with Schimke Immuno-Osseous Dysplasia
Juan DING ; Wei WANG ; Juan XIAO ; Yan ZHANG ; Huijuan ZHU ; Wen ZHANG ; Peng GAO ; Limeng CHEN ; Wei LYU ; Xuan ZOU ; Xiaoyi ZHAO ; Hongmei SONG ; Mingsheng MA
JOURNAL OF RARE DISEASES 2024;3(4):465-470
Schimke immuno-osseous dysplasia (SIOD)caused by
7.Integration model of management, teaching and research for general practice talent training in community teaching bases
Yan LI ; Wei SONG ; Yiming LI ; Xinxin ZHAO ; Qi XU ; Fang CHENG ; Lan TANG ; Shanzhu ZHU
Chinese Journal of General Practitioners 2024;23(1):65-69
The community teaching bases play an important role in training of general practice talents. To raise the training quality, the development of their own capacity is crucial, but community medical institutions also need close cooperation with the departments of general practice in medical schools and the higher-level general hospitals. This article discusses the integration model of management, teaching and research in general practice talent training based on the cooperation of community teaching bases with relevant governmental departments, professional societies/associations, general hospitals and medical schools.
8.Perioperative Animal Care for Xenotransplantation from Genetically Edited Pigs to Monkeys
Chan ZHU ; Dongliang ZHANG ; Deli ZHAO ; Xueqin SHI ; Lei QIAN ; Xuan ZHANG ; Yan JIN ; Wei DUAN ; Ruocheng QI ; Chaohua LIU ; Xuekang YANG ; Juntao HAN ; Dengke PAN
Laboratory Animal and Comparative Medicine 2024;44(5):495-501
Objective To discuss the perioperative care and wound protection of xenotransplantation from genetically edited pigs to monkeys, with the goal of improving the success rate of such experimental procedures. Methods From October 2022 to October 2023, perioperative care and wound protection were performed on 7 recipient rhesus monkeys undergoing xenotransplantation of genetically edited pig tissues and organs. Customized wound protective garments were designed based on monkeys' size and surgical area to protect the wounds, alongside meticulous perioperative care. This included preoperative preparation and medication, intraoperative monitoring of physiological indicators and anesthesia management, and postoperative care comprising wound protection, observation and monitoring, and nutritional support. Results All seven monkeys successfully underwent xenotransplantation. With the aid of protective garments and detailed care, all surgical wounds healed by first intention, and postoperative recovery was satisfactory. Conclusion Proper care and wound protection during xenotransplantation from genetically edited pigs to monkeys not only promote wound healing, but also alleviate pain and harm to animals. This has significant implications for advancing experimental research in pig-monkey xenotransplantation and enhancing animal welfare.
9.Effectiveness of intercostal nerve block and analgesia with bupivacaine liposomes in single-port thoracoscopic lung surgery: A prospective study
Jianguo LU ; Xiangmei ZHAO ; Shaoyin GAN ; Xiaofang CHEN ; Deqi ZHU ; Ershuai YAN ; Xiaojie LI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(10):1442-1447
Objective To compare the analgesic effect, duration and incidence of adverse reactions of liposome bupivacaine (LB) and bupivacaine hydrochloride after intercostal nerve block in single-port thoracoscopic lung surgery. Methods In Department of Thoracic Surgery of the First Affiliated Hospital of Xinxiang Medical University between September 2023 and March 2024, 228 patients who needed to undergo thoracoscopic lung surgery were selected and divided into two groups by random number table method: a group B with bupivacaine hydrochloride (n=118), and a group LB with LB (n=110). Intraoperative intercostal nerve block was performed under endoscopy, and the time of first use of analgesic drugs after surgery, cumulative use of opioids 72 h after surgery, incidence of postoperative nausea and vomiting, length of stay and other indicators were evaluated and recorded. Results Visual analogue scale (VAS) scores at 4 h, 8 h, 12 h, 24 h, 48 h and 72 h in the LB group were significantly lower than those in the group B (P<0.05). The total number of activities within 48 h after surgery in the group B was significantly lower than that in the LB group (P<0.05), and the postoperative hospitalization stay in the LB group was shorter than that in the group B, but the difference was not statistically significant. There was no statistical difference between the two groups in postoperative adverse reactions. Conclusion Intercostal nerve block with LB during single-port thoracoscopic lung surgery can significantly reduce postoperative pain, improve quality of life, and promote recovery of the patients. It is worthy of clinical application.
10.Targeting platelet-immune cell interaction as a new strategy for post-myocardial infarction current evidence and future prospective
Lin-hong HAN ; Yu-han ZHAO ; Xiao-ying WANG ; Yan ZHU
Acta Pharmaceutica Sinica 2024;59(6):1519-1526
Myocardial infarction (MI) is a fatal disease with high morbidity and mortality. Platelets are major players of thrombosis and inflammation after acute myocardial infarction. There is growing evidence that platelets mediate inflammation, participate in dead tissue removal and heart remodeling through direct or indirect interactions with immune cells post-MI. This paper reviews the type of interactions between platelets and immune cells after myocardial infarction, and summarizes the mechanism of platelet interaction with different immune cells, such as neutrophils, monocytes, and macrophages, to mediate cardiac injury and repair through up-regulation of surface receptors and release of immune regulatory mediators post-MI. Therapeutic strategies targeting the interaction between platelets and immune cells for myocardial infarction is also presented, to provide reference for the exploration of new immune therapy targets for myocardial infarction.

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