In this study, we investigated the anti-osteoporotic activity and mechanism of action of extract of Panax quiquefolium L. based on zebrafish model combined with metabolomics technology. A zebrafish model of prednisolone-induced osteoporosis was used to compare the anti-osteoporotic activity of Panax quiquefolium L., and the expression of osteoblast-associated genes and osteoclast-associated genes in zebrafish was detected by quantitative real-time PCR (qRT-PCR), using bone fluorescence area and fluorescence density as evaluation indexes. Metabolomics based on ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) was used to explore the change patterns of biomarkers and the metabolic pathways affected. The results showed that the 50% ethanol extracts of Panax quiquefolium L. from Jilin, Canada, Wenden and the United States can significantly improve the bone fluorescence area of zebrafish compared with model group. Furthermore, four sources 50% ethanol extracts of Panax quiquefolium L. except United States also can significantly improve the bone fluorescence density of zebrafish. In addition, PCR showed that extract of Panax quiquefolium L. can significantly up-regulated the expression of vitamin D receptor b (vdrb), collagen type I α2 (col1a2) and cysteine-rich acidic secreted protein (sparc) genes, and down-regulated the expression of matrix metalloproteinase 9 (mmp9), anti-tartrase acid phosphatase (trap) and cathepsin K (ctsk) genes. Metabolomic analysis identified 24 key differential metabolites. Furthermore, pathway analysis showed that Panax quiquefolium L. could regulate the levels of 10 key biomarkers by participating in purine metabolism, tricarboxylic acid cycle and pentose phosphate metabolism and improve the osteoporosis status of zebrafish. This study preliminically revealed the anti-osteoporosis mechanism of 50% ethanol extract from Panax quiquefolium L. through multi-component, multi-target and multi-pathway and also provides theoretical basis for clinical development and utilization of anti-osteoporosis products of Panax quiquefolium L. This experiment was approved by the Experimental Animal Welfare Ethics Committee of the Institute of Biology, Shandong Academy of Sciences (approval number: SWS20181002).

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

OBJECTIVE: To explore the mechanisms underlying the proliferative inhibition of Chinese herbal medicine Kang-Ai injection (KAI) in gastric cancer cells. METHODS: Gastric cancer cell lines MGC803 and BGC823 were treated by 0, 0.3%, 1%, 3% and 10% KAI for 24, 48 and 72 h, respectively. The cell proliferation was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The apoptosis and cell cycle were evaluated by flow cytometry. Interleukin (IL)-6 mRNA and protein expression levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immune sorbent assay (ELISA), respectively. The protein expression levels of cyclin A, cyclin E, cyclin B1, cyclin D1, p21, retinoblastoma (RB), protein kinase B (AKT), extracellular regulated protein kinases (ERK), signal transducer and activator of transcription (STAT) 1 and STAT3 were detected by Western blot. RESULTS: KAI inhibited the proliferation of MGC803 and BGC823 gastric cancer cells in dose- and time-dependent manner. After treated with KAI for 48 h, the proportion of G1 phase was increased, expression level of cyclin D1 and phosphorylation-RB were down-regulated, whereas the expression of p21 was up-regulated (all P<0.01). Furthermore, 48-h treatment with KAI decreased the phosphorylation level of STAT3, inhibited the mRNA and protein expressions of IL-6 (all P<0.01). IL-6 at dose of 10 ng/mL significantly attenuated the proliferative effect of both 3% and 10% KAI, and recovered KAI-inhibited STAT3 phosphorylation and cyclin D1 expression level (all P<0.01). CONCLUSION KAI exerted an anti-proliferative function by inhibiting IL-6/STAT3 signaling pathway followed by the induction of G₁ phase arrest in gastric cancer cells.
Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Cyclin D1/pharmacology* ; Humans ; Interleukin-6/metabolism* ; RNA, Messenger/metabolism* ; STAT3 Transcription Factor/metabolism* ; Stomach Neoplasms/genetics*

Objective: To investigate the relationship between body mass index (BMI) and sexual development in Chinese children. Methods: A nationwide multicenter and population-based large cross-sectional study was conducted in 13 provinces, autonomous regions and municipalities of China from January 2017 to December 2018. Data on sex, age, height, weight were collected, BMI was calculated and sexual characteristics were analyzed. The subjects were divided into four groups based on age, including ages 3-<6 years, 6-<10 years, 10-<15 years and 15-<18 years. Multiple Logistic regression models were used for evaluating the associations of BMI with sexual development in children. Dichotomous Logistic regression was used to compare the differences in the distribution of early and non-early puberty among normal weight, overweight and obese groups. Curves were drawn to analyze the relationship between the percentage of early puberty and BMI distribution in girls and boys at different Tanner stages. Results: A total of 208 179 healthy children (96 471 girls and 111 708 boys) were enrolled in this study. The OR values of B2, B3 and B4+ in overweight girls were 1.72 (95%CI: 1.56-1.89), 3.19 (95%CI: 2.86-3.57), 7.14 (95%CI: 6.33-8.05) and in obese girls were 2.05 (95%CI: 1.88-2.24), 4.98 (95%CI: 4.49-5.53), 11.21 (95%CI: 9.98-12.59), respectively; while the OR values of G2, G3, G4+ in overweight boys were 1.27 (95%CI: 1.17-1.38), 1.52 (95%CI: 1.36-1.70), 1.88 (95%CI: 1.66-2.14) and in obese boys were 1.27 (95%CI: 1.17-1.37), 1.59 (95%CI: 1.43-1.78), and 1.93 (95%CI: 1.70-2.18) (compared with normal weight Tanner 1 group,all P<0.01). Analysis in different age groups found that OR values of obese girls at B2 stage and boys at G2 stage were 2.02 (95%CI: 1.06-3.86) and 2.32 (95%CI:1.05-5.12) in preschool children aged 3-<6 years, respectively (both P<0.05). And in the age group of 6-10 years, overweight girls had a 5.45-fold risk and obese girls had a 12.54-fold risk of B3 stage compared to girls with normal BMI. Compared with normal weight children, the risk of early puberty was 2.67 times higher in overweight girls, 3.63 times higher in obese girls, and 1.22 times higher in overweight boys, 1.35 times higher in obese boys (all P<0.01). Among the children at each Tanner stages, the percentage of early puberty increased with the increase of BMI, from 5.7% (80/1 397), 16.1% (48/299), 13.8% (27/195) to 25.7% (198/769), 65.1% (209/321), 65.4% (157/240) in girls aged 8-<9, 10-<11 and 11-<12 years, and 6.6% (34/513), 18.7% (51/273), 21.6% (57/264) to 13.3% (96/722), 46.4% (140/302), 47.5% (105/221) in boys aged 9-<10, 12-<13 and 13-<14 years, respectively. Conclusions: BMI is positively correlated with sexual development in both Chinese boys and girls, and the correlation is stronger in girls. Obesity is a risk factor for precocious puberty in preschool children aged 3-<6 years, and 6-<10 years of age is a high risk period for early development in obese girls.
Adolescent ; Body Mass Index ; Child ; Child, Preschool ; China/epidemiology* ; Cross-Sectional Studies ; Female ; Humans ; Male ; Obesity/epidemiology* ; Overweight/epidemiology* ; Puberty ; Puberty, Precocious ; Sexual Development

Objective: To evaluate the effects of antiretrovirals on cardiovascular function and some biochemical indexes in gestational female rats. Methods: Nineteen 9-week-old female and six 10-week-old male SD rats were divided into normal control group (CON) and highly active antiretroviral therapy group (HARRT), 9/10 female rats and 3 male rats were combined into one cage, totally 2 cages. Female rats in CON group were intragastrically given with normal saline (NS, 10 ml/kg) every morning and evening, while female rats in HARRT group were treated with equal volume antiretrovirals (AZT 31.25 mg/kg + 3TC 15.63 mg/kg + LPV/r (41.67/10.42) mg/kg) for 3 months. The body weight and survival rate of female rats were recorded. Echocardiography and multichannel physiological recorder were used to detect arterial blood pressure and cardiac hemodynamic parameters. The levels of blood glucose, blood lipids, myocardial enzymes and liver enzymes were detected by corresponding kits. Myocardial collagen fibers were observed by Masson staining and the ultrastructure of myocardial cells were observed by transmission electron microscopy. Results: All female rats in CON group survived (9/9), while only 6 rats in HARRT group survived (6/10). Compared with CON group, the body weight of female rats in HAART group was decreased significantly(P＜0.01); the levels of left ventricular end diastolic diameter (LVDd), interventricular septal thickness (IVST), thickness of left ventricular posterior wall (LVPWT) , left atrial diameter (LAD) and arterial diastolic pressure were increased significantly (P＜0.05); the level of LVP+dP/dtmax was decreased (P＜0.01). The levels of triglyceride, creatine kinase, and glutamic oxaloacetic transaminase were decreased (P＜0.05 or P＜0.01), while the level of glucose was increased (P＜0.05). The collagen fibers were increased in myocardial tissue, and ultrastructure of myocardial cells was abnormal. Conclusion: Antiretrovirals during gestation can cause cardiovascular diseases in female rats.
Animals ; Anti-Retroviral Agents/adverse effects* ; Body Weight ; Cardiotoxicity ; Collagen ; Female ; Myocytes, Cardiac/ultrastructure* ; Pregnancy ; Rats ; Rats, Sprague-Dawley

Objective To study the effect of velvet antler polypeptides (VAP) on antioxidant in Alzheimer' s disease model mice. Methods Eight months old male amyloid precursor protein (APP)/presenilin-l (PS1) double transgenic mice were selected as Alzheimer' s disease (AD) model and divided into the model group and the VAP intervention group, 12 in each group. Besides, normal mice of the same brood (with no transgene) were recruited as a control group (n= 12).After 6 months of intragastric administration, behavior, morphology and oxidative stress related indicators were detected.SH-SY5 cells were used to establish AD model of damaged by Ap2535. The expression levels of APP and p-secreatase-l(BACE1) protein in mouse hippocampus were detected by Western blotting. VAP intervention group SH-SY5Y cells was cultured with VAP (500 g/L) and amyloid P(Ap) 2535(25 ixmol/L) for 24 hours. Control group cells were normally cultured by DMEM medium. Cell apoptosis, membrane potential, reactive oxygen species (ROS) levels and oxidative stress related indexes were detected. Results In animal models, compared with the model group, the escape latency of mice in the VAP intervention group was shortened (P<0. 05). The neuronal cells in the CA1 region of the hippocampus of the model group were reduced and arranged disorderly. The arrangement of the VAP intervention group was relatively regular, and the morphology was significantly improved. Compared with the model group, senile plaques were decreased in the VAP intervention group. Compared with the model group, the malondialdehyde (MDA) content ol the VAP intervention group increased, and the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) content increased, the difference was statistically significant. Compared with the control group, the APP and BACE1 content in the model group increased. Compared with the model group, the contents of APP and BACE1 in the VAP intervention group decreased, and the difference was statistically significant (P<0. 05). In the cell model, the apoptosis rates of the VAP intervention group decreased. Compared with the model group, the mitochondrial membrane potential of the VAP intervention group increased, the content ol ROS decreased, the content of MDA decreased, and the content of SOD and GSH-Px increased. The difference were statistically significant (P<0. 05). Conclusion VAP has a protective effect on oxidative stress damage caused by Alzheimer' s disease model animals and cells, which may be achieved by reducing ROS production and increasing the activity of antioxidant enzymes to reduce Ap deposition.

OBJECTIVE: To evaluate the safety and efficacy of the seven-step two-lobe holmium laser enucleation of the prostate (HoLEP) technique with low power laser device, and to introduce the detailed operating procedures, key points, short-term outcomes of this modified HoLEP technique. METHODS: From March 2016 to November 2017, 90 patients underwent HoLEP in Peking University Third Hospital. The patients were divided into two groups: high-power group (32 patients) were performed with traditional Gilling's three-lobe enucleation using high power (90 W) laser; Low-power group (58 patients) were performed with seven-step two-lobe enucleation using low power (40 W) laser. The main steps of the low power seven-step two-lobe HoLEP phase included: (1) The identification of the correct plane between adenoma and capsule at 5 and 7 o'clock laterally to the veru montanum; (2) The connection of the bilateral plane by making a adenoma incision at the proximal point of veru montanum; (3) The extension of the dorsal plane under the whole three lobes between adenoma and capsule towards the bladder neck; (4) The separation of the middle lobe from two lateral lobes by making two retrograde incisions separately from apex 5 and 7 o'clock towards the bladder neck; (5) The enucleation of the middle lobe adenoma by extending the dorsal plane through into the bladder; (6) The prevention of the apex mucosa by making a circle incision at the apex of the prostate; (7) The en-bloc enucleation of the two lateral lobe adenomas by extending the lateral and ventral plane between adenoma and capsule from 5 and 7 o'clock to 12 o'clock conjunction and through into the bladder. RESULTS: The mean patient age was (66.25±5.37) years vs. (68.00±5.18) years; The mean body mass indexes were (24.13±4.06) kg/m² vs. (24.57±3.50) kg/m²; The mean prostate specific antigen values were (3.23±2.47) μg/L vs. (6.00±6.09) μg/L; The average prostatic volumes evaluated by ultrasound was (49.03±20.63) mL vs. (67.55±36.97) mL. There was no significant difference between the two groups. Furthermore, there were no significant differences in terms of perioperative and follow up data, including operative time; enucleation efficiencies; hemoglobin decrease; blood sodium and potassiumthe change postoperatively; catheterization duration and hospital stay; the international prostate symptom scores and quality of life scores pre- and post-operatively. There was 1 transurethral resection of the prostate (TURP) conversion in high-power group and 1 transfusion in low-power group during the operations. The follow-up one month after operation showed no severe stress incontinence in both the groups, whereas 3 cases ejaculatory dysfunctions in high-power group versus 1 case in low-power group were observed; Other surgeryrelated complications included: 2 cases postoperative hemorrhage (Clavien II and Clavien IIIb) in high-power group, 2 cases postoperative temperature more than 38 °C (Clavien I) and 1 case dysuria following catheter removal (Clavien I) in low-power group. CONCLUSION Low power laser device can be applied safe and effectively for HoLEP procedure using the seven-step two-lobe HoLEP technique. The outcomes comparable with high power laser HoLEP can be achieved.
Holmium ; Humans ; Laser Therapy ; Lasers, Solid-State ; Male ; Prostatic Hyperplasia/surgery* ; Quality of Life ; Transurethral Resection of Prostate ; Treatment Outcome

【Objective】To evaluate the safety and effects of transcatheter arterial chemoembolization using Drug-eluted beads（DEB-TACE）plus apatinib in patients with hepatocellular carcinoma（HCC）.【Methods】A retrospective analysis was performed，which included 11 HCC patients treated with DEB- TACE and followed by a target therapy of apatinib（500 mg QD）in our clinical research center. Radiograph evaluation and tumor biomarker，alpha- fetoprotein（AFP）， were recorded before the procedure and during the follow-up of the first cycle after 4~8 weeks. Adverse events induced by apatinib were recorded. 【Results】 According to the response evaluation criteria in solid tumors （RECIST），modified response evaluation criteria in solid tumors （mRECIST） and European Association for the study of the liver （EASL） criteria，the objective response rate （ORR） was 36.4% ，63.6% ，72.7% respectively，and the disease control rate（DCR）was 90.7% ，72.7% ，81.8% respectively. AFP levels were 44 251.7 μg/L which significantly decreased after the procedure ，compared to 366 336 μ g/L ，the levels before the treatment. Four reversible grade III adverse events were recorded and no grade IV adverse events found in these cases. 【Conclusion】According to the short-term treatment response and safety，DEB- TACE combined with apatinib could be considered as a promising treatment for intermediate and advanced stage hepatoma.

Xanthii Fructus (XF) is one of important drugs for the treatment of sinusitis and headache.It is commonly used in the treatment of diseases relating to immune abnormalities,such as rheumatoid arthritis,acute and chronic rhinitis,allergic rhinitis,and skin diseases,with a high medicinal value.Modern pharmacological studies have showed a wide range of pharmacological effect and a high medicinal value in XF.However,due to long-term or excessive intake,and improper processing of medicinal materials,toxic reactions have often occurred.Toxicological studies have shown that XF poisoning can cause substantial damage to organs,such as the liver,heart and kidney,especially to liver.This paper reviews the pharmacological action,toxic substances and hepatotoxicity mechanism of XF by systematically reviewing and summarizing relevant literatures on XF both at home and abroad.It is concluded that XF has anti-hypertension,anti-allergic,anti-bacterial,anti-inflammatory,analgesic,anti-tumor and lipid-decreasing effects.The toxic components are mainly atractyloside,carboxy atractyloside and 4'-desulphate-atractyloside.The mechanism of hepatotoxicity induced by XF is closely related to lipid peroxidation,bile cholestasis and hepatocyte energy metabolism.Meanwhile,the discovery of novel biomarkers of hepatotoxicity,such as miRNA-122,also provides new ideals for medical research.Toxic traditional Chinese medicine (TCM) is an important part of TCM.Compatibility or processing can reduce or eliminate toxicity and preserve or increase efficacy.At present,there are few reports on the principle of attenuating the production of XF.The author suggests further strengthening the study on the principle of attenuation of XF,giving full play to the unique curative effect of XF and developing its greater medicinal value.

Background: Patients with ST-segment elevation myocardial infarction (STEMI) who present without typical chest pain are associated with a poor outcome. However, whether angiographic characteristics are related to a higher risk of mortality in this population is unclear. This study aimed to investigate whether the higher mortality risk in patients with STEMI without chest pain could be explained by their "high-risk" angiographic characteristics. Methods: We used data of 12,145 patients with STEMI who was registered in China Acute Myocardial Infarction registry from January 2013 to September 2014. We compared the infarct-related artery (IRA), thrombolysis in myocardial infarction (TIMI) flow grade in the IRA, and other angiographic characteristics between patients without and those with chest pain. Multivariable logistic regression model was used to identify independent risk factor of in-hospital mortality. Results: The 2922 (24.1%) patients with STEMI presented without typical chest pain. These patients had a higher TIMI flow grade (mean TIMI flow grade: 1.00 vs. 0.94, P = 0.02) and a lower rate of IRA disease of the left anterior descending artery (44.6% vs. 51.2%, χ² = 35.63, P < 0.01) than did those with typical chest pain. Patients without chest pain were older, more likely to have diabetes, longer time to hospital and higher Killip classification, and less likely to receive optimal medication treatment and primary percutaneous coronary intervention and higher In-hospital mortality (3.3% vs. 2.2%, χ² = 10.57, P < 0.01). After adjusting for multi-variables, presentation without chest pain was still an independent predictor of in-hospital death among patients with STEMI (adjusted odds ratio: 1.36, 95% confidence interval: 1.02–1.83). Conclusions: Presentation without chest pain is common and associated with a higher in-hospital mortality risk in patients with acute myocardial infarction. Our results indicate that their poor prognosis is associated with baseline patient characteristics and delayed treatment, but not angiographic lesion characteristics. Clinical trial registration NCT01874691, https://clinicaltrials.gov.