OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

Objective To investigate the expression level of serine/threonine phosphoprotein phosphatase 4C(PPP4C)in gastric cancer,and analyze its relationship with prognosis and the underlying regulatory mechanism.Methods The clinical data of 104 gastric cancer patients admitted to the First Affiliated Hospital of Bengbu Medical College between January 2012 and August 2016 were collected.Immunohistochemical staining was employed to determine the expression levels of PPP4C and Ki-67 in the gastric cancer tissue.The gastric cancer cell lines BGC823 and HGC27 were cultured and transfected with the vector for PPP4C knockdown,the vector for PPP4C overexpression,and the lentiviral vector(control),respectively.The effects of PPP4C on the cell cycle and proliferation were analyzed and the possible regulatory mechanisms were explored.Results PPP4C was highly expressed in gastric cancer(P<0.001),and its expression promoted malignant progression of the tumor(all P<0.01).Univariate and Cox multivariate analysis clarified that high expression of PPP4C was an independent risk factor affecting the 5-year survival rate of gastric cancer patients(P=0.003).Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis suggested that PPP4C may be involved in the cell cycle.The correlation analysis showed that the expression of PPP4C was positively correlated with that of Ki-67 in gastric cancer(P<0.001).The up-regulation of PPP4C expression increased the proportion of tumor cells in the S phase,alleviated the G2/M phase arrest,and promoted the proliferation of gastric cancer cells and the expression of cyclin D1 and cyclin-dependent kinase 6(CDK6)(all P<0.05).The down-regulation of PPP4C decreased the proportion of gastric cancer cells in the S phase,promoted G2/M phase arrest,and inhibited cell proliferation and the expression of cyclin D1,CDK6,and p53(all P<0.05).p53 inhibitors promoted the proliferation of BGC823 and HGC27 cells in the PPP4C knockdown group(P<0.001,P<0.001),while p53 activators inhibited the proliferation of BGC823 and HGC27 cells in the PPP4C overexpression group(P<0.001,P=0.002).Conclusions PPP4C is highly expressed in gastric cancer and affects the prognosis of the patients.It may increase the proportion of gastric cancer cells in the S phase and alleviate the G2/M phase arrest by inhibiting p53 signaling,thereby promoting cell proliferation.
Humans ; Stomach Neoplasms/genetics* ; Cyclin D1/metabolism* ; Tumor Suppressor Protein p53 ; Phosphoproteins/metabolism* ; Ki-67 Antigen ; Cell Line, Tumor ; Prognosis ; Cell Proliferation ; Phosphoprotein Phosphatases/metabolism* ; Threonine ; Serine

Since the 18th National Congress of the Communist Party of China(CPC), the CPC and the government have highligh-ted the development of traditional Chinese Medicine(TCM) and issued a series of policies, such as the Plan for Protection and Deve-lopment of Chinese Medicinal Materials(2015-2020) forwarded by the General Office of the State Council in 2015, the Plan for Healthy Development of Traditional Chinese Medicine(2015-2020) released by the General Office of the State Council in the same year, the Healthy China 2030 Plan published by the CPC Central Committee and the State Council in 2016, the Law of the People's Republic of China on Traditional Chinese Medicine which took effect on July 2017, On the Preservation and Innovative Development of Traditional Chinese Medicine promulgated by CPC Central Committee and the State Council in 2019, and Plan for the Development of Traditional Chinese Medicine during the 14th Five-Year Plan Period of China released by the General Office of the State Council in March 2022, to promote the development of the TCM industry, which have brought historical opportunities to the TCM industry. However, TCM industry faces various challenges in the development. In terms of drug development in TCM, the current studies mainly focused on the chemical research and technical requests, which neglected TCM characteristics and cased in conformity between new drug transformation of TCM and clinical practice. Therefore, a more considerable and profound authoritative guideline is needed, and innovative thought and research are necessary for academics and the industry. Through the investigation of the development TCM industry in recent years, this study summarized the policies on and trends of Chinese medicinal materials, new drug development in TCM, catalogue of national basic drugs, and national basic health insurance, and proposed suggestions for further development of TCM industry.
China ; Drugs, Chinese Herbal ; Humans ; Industry ; Medicine, Chinese Traditional ; Policy

Aging increases the risk of various diseases. The main goal of aging research is to find therapies that attenuate aging and alleviate aging-related diseases. In this study, we screened a natural product library for geroprotective compounds using Werner syndrome (WS) human mesenchymal stem cells (hMSCs), a premature aging model that we recently established. Ten candidate compounds were identified and quercetin was investigated in detail due to its leading effects. Mechanistic studies revealed that quercetin alleviated senescence via the enhancement of cell proliferation and restoration of heterochromatin architecture in WS hMSCs. RNA-sequencing analysis revealed the transcriptional commonalities and differences in the geroprotective effects by quercetin and Vitamin C. Besides WS hMSCs, quercetin also attenuated cellular senescence in Hutchinson-Gilford progeria syndrome (HGPS) and physiological-aging hMSCs. Taken together, our study identifies quercetin as a geroprotective agent against accelerated and natural aging in hMSCs, providing a potential therapeutic intervention for treating age-associated disorders.

OBJECTIVE: To investigate the significance of neutrophil/lymphocyte ratio(NLR) and platelet/lymphocyte ratio(PLR) in patients with multiple myeloma (MM). METHODS: Eighty patients with multiple myeloma admitted in our hospital from August 2007 to August 2010 were selected. The clinical data of the patients, including hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), white blood cell(WBC) count, absolute neutrophil count (ANC), platelet count (PC), glomerular filtration rate (GFR), calcium, albumin, β2 microglobulin and so on were collected and analyzed. RESULTS: The optimal threshold of NLR was 2.78 (sensitivity: 83.3%, specificity: 43.1%). The optimal threshold of PLR was 155.58 (sensitivity: 67.7%, specificity: 36.9%). All patients were grouped according to NLR and PLR values, patients with high NLR and PLR had lower albumin levels and higher clinical stages. High NLR patients were mainly men, hemoglobin, GFR values, albumin levels were lower, and the white blood cells count and β2 microglobulin level were higher. High PLR patients showed low albumin level and higher clinical stage. Multivariate analysis showed that β2 microglobulin and NLR were prognostic factors in patients with multiple myeloma (P<0.05). Kaplan-Meier survival analysis showed that the median survival time was 37 months (95% CI: 21.80-52.19) for patients with high NLR and 66 months (95% CI: 53.19-78.80) for patients with low NLR. The median survival time was 45 months (95% CI: 0.00 to 91.18) in patients with high PLR and 62 months (95% CI: 45.67-78.33) in patients with low PLR. CONCLUSION High NLR (>2.78) associates with poor prognosis in patients with MM, and it may be considered as an independent prognostic factor for MM patients.
Blood Platelets ; Humans ; Lymphocytes ; Male ; Multiple Myeloma ; Neutrophils ; Prognosis ; Retrospective Studies

OBJECTIVETo explore the expression of phosphatase and tensin homolog deleted on chromosome ten (PTEN) and B-cell lymphoma/leukemia-2 (BCL-2) in acute myeloid leukemia (AML) and its significance.

METHODSThe expression levels of PTEN and BCL-2 mRNA and protein in bone marrow samples from 80 AML patients including 56 de novo patients, 16 patients in remission, 8 relapsed patients and 30 cases of non-hematologic diseases (as control) were detected by real-time PCR and Western blot, respectively, and the relationship between PTEN and BCL-2 expression and clinical pathological parameter was analyzed.

RESULTSThe expression levels of both mRNA and protein of PTEN in newly diagnosed AML group and relapse group were significantly lower than those in the control and remission group (P<0.01). The expression levels of both mRNA and protein of BCL-2 in newly diagnosed group and relapse group were significantly higher than those in the control and remission group (P<0.01). The mRNA expression of PTEN and BCL-2 was did not related with the age, sex and white blood count in AML patients. The expression levels of PTEN negatively correlated with expression BCL-2 with AML(r=-0.432, r=-0.569).

CONCLUSIONPTEN and BCL-2 participate in the occurrence and development of AML, and may be used as indicators for the evaluation of chemotheraeutic efficacy.

ObjectiveTo observe the intervention effect of Qiaoshao Prescription (QSP) on premature ejaculation (PE) induced by 8-OH-DPAT in male rats and explore its possible action mechanism.

METHODSSeventy-two male Wistar rats were equally randomized into six groups, blank control, PE model control, low-, medium- and high-dose QSP, and dapoxetine. The PE model was established by injection of 8-OH-DPAT into the subarachnoid space of the lumbosacral spinal cord. Four weeks after modeling, the rats in the blank control and PE model control groups with gavaged with normal saline at 10 ml/kg/d, those in the low-, medium- and high-dose QSP groups with QSP at 5, 10 and 20 g/kg/d respectively once a day, and those in the dapoxetine group with dapoxetine hydrochloride at 300 mg/kg at 3 hours before mating. Forty-five female Wistar rats were injected subcutaneously with 20 μg estradiol benzoate after removal of bilateral ovaries to induce estrous estrus. Two and 4 weeks later, the male rats were mated with the female ones for 30 minutes per time and meanwhile observed for the mating behavior of the males, including mounting latency (ML), intromission latency (IL), ejaculation latency (EL), mounting frequency (MF), intromission frequency (IF), and ejaculation frequency (EF). After the 4th week of mating, the hypothalamus of the animals was isolated and weighed, and the content of 5-hydroxytryptamine (5-HT) was measured.

RESULTSCompared with the blank control group, the PE model controls showed significantly decreased content of 5-HT in the hypothalamus(1 257.1 vs 923.4 ng/g, P<0.05), ML (［11.22 ± 3.60］ vs ［8.69 ± 2.48］ s, P<0.05), IL (［22.33 ± 2.45］ vs ［12.08±1.39］ s, P<0.05), MF (［13.28 ± 3.24］ vs ［7.53 ± 1.84］ times, P<0.05), and EL (［712.35 ± 36.77］ vs ［502.35 ± 46.72］ s, P<0.05). In comparison with the PE model controls, the rats of the QSP and dapoxetine groups exhibited remarkably increased content of 5-HT (P<0.05) and prolonged EL (P<0.05).

CONCLUSIONSQiaoshao Prescription can prolong EL in PE rats, which might be associated with the increased content of 5-HT in the hypothalamus. Further studies, however, are needed on its underlying mechanisms.

Objective To investigate the effects of ZNF331 overexpression on proliferation and apoptosis of human colon cancer cell HCT116, and the relevant apoptotic mechanism.Methods The lentivirus vector of overexpressed ZNF331,Flag-pLV-Neo-ZNF331,was constructed and packaged.HCT116/p53 +/+(wild type p53)and HCT116/p53 -/-(deficient p53)cells were infected.Clones with ZNF331 overexpression were identified by Western blotting.Cell proliferation assay,colony formation assay and flow cytometry analysis were used to examine the effects of ZNF 331 on cell proliferation and apoptosis.Immunoprecipitation,luciferase reporter gene assay and real-time PCR were performed to detect interactions between ZNF331 and p53, p53 transcriptional activity and the expression of p 53 apoptotic target genes, respectively.Results The lentivirus vector of overexpressed ZNF 331 was successfully generated.Stable clones of ZNF331 overexpression were established.ZNF331 showed no significant effect on cell proliferation of HCT 116/p53 +/+, but inhibited cell proliferation of HCT116/p53 -/-(P<0.01).ZNF331 could interact with p53,dose-dependently inhibit the transcriptional activity of p53 and downregulate the mRNA levels of pro-apoptotic p53 target genes, Puma and p53AIP1 (P<0.05).ZNF331 could suppress p53-induced apoptosis(P <0.01).Conclusion The influence of ZNF331 overexpression on colon cancer cell proliferation is dependent on p 53 status.ZNF331 overexpression can suppress colon cancer cell apoptosis by interacting with p 53 and inhibiting the transcriptional activity of p 53.

BACKGROUND: Investigation on epidemiologic features of knee osteoarthritis in many areas of China has been much reported. However, multicenter studies with large samples have been rarely reported. The published papers cannot give a good description about the epidemiologic features of knee osteoarthritis. OBJECTIVE: To evaluate the epidemiologic features of knee osteoarthritis in the patients aged over 40 years in China. METHODS: Meta-analysis was used to evaluate the data extracted from papers published 2001-2016 on the epidemiology of knee osteoarthritis in the middle-aged and elderly in China. The prevalence rate of knee osteoarthritis in the patients over 40 years of age was summarized, with every 10 years as group, and then analyzed on Stata 12.0 software. RESULTS AND CONCLUSION: Twenty-six articles were included, involving 42 199 people aged more than 40 years old. The total prevalence rate of knee osteoarthritis at the age above 40 years old in China was 17.0% (95% CI:16.7%-17.4%),the prevalence rate was 12.3% in male and 22.2% in female(P<0.05).Noticeably,the prevalence rate increased with age.The total prevalence rate in northern China was 16.1%(95% CI:15.6%-16.6%),12.2% in male and 21.4% in female;the total prevalence in southern China was 18.0%(95%CI:17.5%-18.5%), 12.3% in male and 23.1% in female. There was no significant difference in the prevalence rate between northern and southern China(P>0.05).The total prevalence rate in rural China was 23.6%(95%CI:16.7%-30.4%),with 15.4% in male and 28.1% in female;and the total prevalence in urban China was 20.0%(95% CI:16.2%-23.9%),with 13.7% in male and 24.3% in female. There was no significant difference in the prevalence rate between rural and urban China (P > 0.05). These results suggest that knee osteoarthritis in China is a common disease, characterized by increased prevalence with age, relatively significant difference between male and female, but no difference between northern and southern China as well as between rural and urban China. It is of great significance to timely propagate and perform interventional strategies for prevention and treatment of knee osteoarthritis in China.

Objective: To explore the feasibility and practicability of establishing a rat model of premature ejaculation (PE) by injection of 8-OH-DPAT into the subarachnoid space of the lumbosacral spinal cord segments. METHODS: Twenty-four male Wistar rats were equally randomized into a PE model and a blank control group. The PE model was established by injection of 8-OH-DPAT in 10 ml normal saline at 0.8 mg per kg of the body weight per day into the subarachnoid space of the lumbosacral spinal cord segments and the control rats were injected with the same volume of normal saline only, both for 4 weeks. Another 24 female Wistar rats were injected subcutaneously with benzoic acid estradiol at 20 μg to induce estrus at 36 hours before mated with the male animals. At 2 and 4 weeks, the male rats were mated with the female ones for 30 minutes each time and meanwhile observed for their mating behavior indicators, such as mount latency, intromission latency, ejaculation latency, mount frequency, intromission frequency, and ejaculation frequency. RESULTS: Compared with the controls, the PE model rats showed a significantly lower ejaculation latency (［712.35 ± 36.77］ vs ［502.35 ± 46.72］ s, P<0.05), mount latency (［11.22 ± 3.60］ vs ［8.69 ± 2.48］ s, P<0.05), mount frequency (13.28 ± 0.24 vs 7.53 ± 1.84, P<0.05), and intromission latency (［22.33 ± 2.45］ vs ［12.08 ± 1.39］ s, P<0.05), but a remarkably higher ejaculation frequency (2.01 ± 0.48 vs 4.26 ± 0.89, P<0.05). No statistically significant difference was observed between the control and model animals in the intromission frequency (7.49 ± 2.21 vs 6.45 ± 1.89, P>0.05). CONCLUSIONS A rat model of premature ejaculation was successfully established by injection of 8-OH-DPAT into the subarachnoid space of the lumbosacral spinal cord segments, which is of great significance for further study of the mechanism of premature ejaculation.
8-Hydroxy-2-(di-n-propylamino)tetralin ; administration & dosage ; Animals ; Benzoic Acid ; administration & dosage ; Disease Models, Animal ; Ejaculation ; Estradiol ; administration & dosage ; Estrus ; Feasibility Studies ; Female ; Injections, Spinal ; Male ; Premature Ejaculation ; chemically induced ; physiopathology ; Rats ; Rats, Wistar ; Sexual Behavior, Animal ; Spinal Cord ; Subarachnoid Space