ObjectiveTo investigate the preventive effect and mechanism of Dendrobium officinale （DO） on non-alcoholic fatty liver disease （NAFLD） by network pharmacology and animal experiments. MethodsDO components in blood after administration were identified and analyzed using ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-QE-HF-MS/MS）. Network pharmacology and molecular docking methods were employed to obtain active ingredients and potential targets of DO for NAFLD control. High-fat feeds were used to replicate the NAFLD rat model. Biochemical kits were used for detecting the expression levels of blood lipids， hepatic lipids， and liver functions of rats. Hematoxylin-eosin （HE） staining and oil red O staining were employed to observe pathological changes in rat liver， and real-time fluorescence quantitative PCR （Real-time PCR） assay was performed to validate potential targets obtained from the network pharmacology analysis. ResultsA total of 13 DO components were identified in blood， including berberine， dihydrosanguinarine， and oxypeucedanin. A total of 14 potential targets were screened through network pharmacology， including Forkhead box protein O1 （FoxO1）， epidermal growth factor receptor （EGFR）， and insulin-like growth factor 1 （IGF-1R）， involving pathways such as the advanced glycation end product （AGE）/receptor for AGE （RAGE） signaling pathway， blood lipids and atherosclerosis， insulin resistance， and FoxO signaling. The results of animal experiments showed that the NAFLD rat model was successfully replicated. After the preventive treatment with DO for NAFLD rats， the indexes of blood lipids， hepatic lipids， and liver function were normalized； lipid deposition and lesions in the liver were significantly improved； the expression level of FoxO1 mRNA in the liver was significantly reduced （P<0.05）， and the mRNA expression levels of phosphatidylinositide 3-kinases （PI3K）， protein kinase B （Akt）， EGFR， and IGF-1R were significantly increased （P<0.05）. ConclusionDO has a preventive effect on NAFLD rats， and the mechanism of action may be related to the modulation of IGF1R and EGFR targets and activation of the PI3K/Akt/FoxO1 signaling pathway.

OBJECTIVE To investigate the intervention effect of kushenol F （KSC-F） on ulcerative colitis （UC） mice. METHODS Totally 30 male C57BL/6J mice were randomly divided into the normal group， model group， positive drug group （sulfasalazine， 703 mg/kg）， KSC-F 50 mg/kg group （KSC-F50 group）， and KSC-F 100 mg/kg group （KSC-F100 group）， with 6 mice in each group. Except for the normal group， the mice in the remaining groups were given 3% dextran sulfate sodium solution continuously for 7 days to induce UC model. Concurrently， administration groups received corresponding drug solution intragastrically， once a day， for 10 consecutive days. During the experiment， the changes in body weight and bowel movements of the mice were observed. Disease activity index scoring was performed after the last administration. The histopathological morphology of colonic tissue was examined. The levels of inflammatory factors in the serum and colon tissue were measured. Additionally， the mRNA expression of inflammatory factors， and the protein expressions of inflammation-related proteins [interleukin-1β （IL-1β）， forkhead box O1（FOXO1）， phosphoinositide 3-kinase（PI3K）， phosphorylated PI3K（p-PI3K）， p38 mitogen-activated protein kinase（p38 MAPK）， phosphorylated p38 MAPK（p-p38 MPAK） and phosphorylated protein kinase B（p- Akt）] were determined in colonic tissue. RESULTS KSC-F could alleviate weight loss and colonic tissue damage in UC mice. KSC- F reduced the levels of IL-1β， IL-6， IL-8 and tumor necrosis factor-α （TNF-α） in serum， as well as IL-1β， IL-6， IL-17 and TNF- α in colonic tissue to varying degrees and increased the levels of IL-10 in both serum and colonic tissue （P＜0.05 or P＜0.01）. Moreover， KSC-F decreased the expression levels of IL-1β， IL-17 and TNF-α mRNA， as well as p-PI3K， p-p38 MAPK， and p- Akt proteins in colonic tissue to varying degrees， and increased the expression levels of IL-10 mRNA and FOXO1 protein in colonic tissue （P＜0.05 or P＜0.01）. CONCLUSIONS KSC-F effectively alleviates UC symptoms in mice by inhibiting PI3K， Akt and p38 MAPK activation， mitigating the release of pro-inflammatory factors such as IL-1β， IL-6， TNF- α，promoting the anti-inflammatory factor IL-10 secretion， and reducing inflammation-induced colonic tissue damage.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Objective:To develop and validate a predictive model of 28-day mortality in sepsis based on lactate dehydrogenase-to-albumin ratio (LAR).Methods:Sepsis patients diagnosed in the department of intensive care medicine of the First Affiliated Hospital of Soochow University from August 1, 2017 to September 1, 2022 were retrospective selected. Clinical data, laboratory indicators, disease severity scores [acute physiology and chronic health evaluation Ⅱ(APACHEⅡ), sequential organ failure assessment (SOFA)] were collected. Patients were divided into death group and survival group according to whether they died at 28 days, and the difference between the two groups was compared. The dataset was randomly divided into training set and validation set according to 7∶3. Lasso regression method was used to screen the risk factors affecting the 28-day death of sepsis patients, and incorporating multivariate Logistic regression analysis (stepwise regression) were included, a prediction model was constructed based on the independent risk factors obtained, and a nomogram was drawn. The nomogram prediction model was established. Receiver operator characteristic curve (ROC curve) was drawn to analyze and evaluate the predictive efficacy of the model. Hosmer-Lemeshow test, calibration curve and decision curve analysis (DCA) were used to evaluate the accuracy and clinical practicability of the model, respectively.Results:A total of 394 patients with sepsis were included, with 248 survivors and 146 non-survivors at 28 days. Compared with the survival group, the age, proportion of chronic obstructive pneumonia, respiratory rate, lactic acid, red blood cell distribution width, prothrombin time, activated partial thromboplastin time, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatinine, blood potassium, blood phosphorus, LAR, SOFA score, and APACHEⅡ score in the death group were significantly increased, while oxygenation index, monocyte count, platelet count, fibrinogen, total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, and blood calcium were significantly reduced. In the training set, LAR, age, oxygenation index, blood urea nitrogen, lactic acid, total cholesterol, fibrinogen, blood potassium and blood phosphorus were screened by Lasso regression. Multivariate Logistic regression analysis finally included LAR [odds ratio ( OR) = 1.029, 95% confidence interval (95% CI) was 1.014-1.047, P < 0.001], age ( OR = 1.023, 95% CI was 1.005-1.043, P = 0.012), lactic acid ( OR = 1.089, 95% CI was 1.003-1.186, P = 0.043), oxygenation index ( OR = 0.996, 95% CI was 0.993-0.998, P = 0.002), total cholesterol ( OR = 0.662, 95% CI was 0.496-0.865, P = 0.003) and blood potassium ( OR = 1.852, 95% CI was 1.169-2.996, P = 0.010). A total of 6 predictor variables were used to establish a prediction model. ROC curve showed that the area under the curve (AUC) of the model in the training set and validation set were 0.773 (95% CI was 0.715-0.831) and 0.793 (95% CI was 0.703-0.884), which was better than APACHEⅡ score (AUC were 0.699 and 0.745) and SOFA score (AUC were 0.644 and 0.650), and the cut-off values were 0.421 and 0.309, the sensitivity were 62.4% and 82.2%, and the specificity were 82.2% and 68.9%, respectively. The results of Hosmer-Lemeshow test and calibration curve showed that the predicted results of the model were in good agreement with the actual clinical observation results, and the DCA showed that the model had good clinical application value. Conclusion:The prediction model based on LAR has a good predictive value for 28-day mortality in patients with sepsis and can guide clinical decision-making.

AIM: To assess the protective effect of adipose tissue-derived mesenchymal stem cells(ADSCs)exosomes on injured retinal ganglion cells(RGCs)by establishing an in vitro rat RGC pressure injury model.METHODS: ADSCs were cultured, and exosomes were extracted from the supernatant and identified. Rat RGCs were divided into a control group, pressure model groups(40, 80, 120 mmHg), and exosome-treated groups under different pressures. Cell proliferation activity was assessed using the CCK-8 assay. The mRNA expression levels of brain-derived neurotrophic factor(BDNF)and Caspase-3 in RGCs were detected by qPCR, and protein levels were measured by Western Blot.RESULTS: The CCK-8 assay showed that cell proliferation activity in the control group increased significantly at 48 h compared to 24 h(P<0.05). At 48 h, cell viability in the exosome-treated groups increased significantly compared to the 40, 80, and 120 mmHg pressure model groups(all P<0.05). qPCR results indicated that BDNF mRNA expression decreased in the 40 mmHg pressure model group without statistical significance(P>0.05), and significantly decreased in the 80 and 120 mmHg pressure model groups(all P<0.05). BDNF mRNA expression significantly increased in the 40 and 80 mmHg pressure model groups after exosome treatment(both P<0.05), and increased in the 120 mmHg pressure model group without statistical significance(P>0.05). Caspase-3 mRNA expression increased in the 40 mmHg pressure model group without statistical significance(P>0.05), and significantly increased in the 80 and 120 mmHg pressure model groups(all P<0.05). Caspase-3 mRNA expression significantly decreased in the 40 and 80 mmHg pressure model groups after exosome treatment(P<0.05), and decreased in the 120 mmHg pressure model group without statistical significance(P>0.05). Western Blot analysis showed that BDNF protein expression decreased in the 40 mmHg pressure model group without statistical significance(P>0.05), and significantly decreased in the 80 and 120 mmHg pressure model groups(all P<0.001). After exosome treatment, BDNF protein expression significantly increased compared to the pressure model groups(all P<0.05). Caspase-3 protein expression increased significantly in all pressure model groups compared to the control group(all P<0.05), and significantly decreased in all exosome-treated groups compared to the model groups(all P<0.05).CONCLUSION: ADSCs-derived exosomes enhance cell proliferation and viability in cultured rat RGCs in vitro under different pressure-induced injuries, enhance BDNF mRNA and protein expression levels, and reduce Caspase-3 mRNA and protein expression levels, suggesting that ADSCs-derived exosomes have a protective effect on pressure-injured in cultured rat RGCs in vitro.

ObjectiveTo explore the effects of body weight and waist circumference on static and dynamic balance function in overweight and obese adults. MethodsParticipants （n=103） were selected by cluster random sampling from the Hypoglycemic Weight Loss Clinic of the Endocrinology Department of the Third Affiliated Hospital of Sun Yat-sen University. All participants were assessed for basic data collection， biochemical test， body weight， waist circumference and height measurement， static balance function assessed by balance error scoring system （BESS） and dynamic balance function assessed by functional reach test （FRT）. The BESS score and FRT distance of all participants were compared among groups according to different BMI grades and WC grades. Multivariate linear regression was used to analyze the influencing factors of participants' dynamic and static balance functions. Results① With the increase of BMI grading， the BESS score showed an upward trend， and the difference between groups was statistically significant （P = 0.004）. The BESS score of normal WC patients was lower than that of central obesity patients （P < 0.001）， which indicated that compared with normal BMI， overweight and obese people had poor dynamic and static balance ability； ② With the BMI grading， the FRT distance increased， showing a downward trend （P < 0.001）. The FRT distance in normal WC patients was significantly higher than that in central obesity patients （P < 0.001）， which indicated that the static and dynamic balance ability of central obesity patients was worse than that of normal WC patients； ③ In BMI overweight group， the FRT distance decreased significantly with the increase of WC （P = 0.02）. The results showed that under the condition of no difference in BMI， Compared with normal WC， the dynamic and static balance ability of central obese patients was worse； ④ The influence of BESS score on BMI（B=4.12，P =0.027， 95% CI=0.48-7.75）and WC（B = 3.47，P = 0.046， 95% CI = 0.07 - 6.88）was significant. The influence of FRT distance on BMI（B = -5.68，P = 0.001， 95% CI = -8.95 - 2.41）and WC（B = -4.71，P = 0.003， 95% CI = -7.83 to -1.61）was significant， which indicated that the static and dynamic balance ability of obese people was worse with the increase of BMI， and the ability of dynamic and static balance of central obesity was worse than that of normal WC. ConclusionWaist circumference is an independent factor affecting the dynamic and static balance function of overweight and obese people. Under similar BMI， the dynamic balance function of central obese people is worse than that of people with normal waist circumference， leading to higher risk of falling.

Objective Dexmedetomidine is a highly selective alpha-2 adrenergic receptor agonist with sedative and analgesic properties but without respiratory depression effect and has been widely used in perioperative anesthesia. Here we performed a systematic review and meta-analysis to evaluate the effect of dexmedetomidine on maintaining perioperative hemodynamic stability in elderly patients.Methods PubMed, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang Data were searched for randomized-controlled trials (RCTs) on the application of dexmedetomidine in maintaining perioperative hemodynamic stability in elderly patients from their inception to September, 2021. The standardized mean differences (SMD) with 95% confidence interval (CI) were employed to analyze the data. The random-effect model was used for the potential clinical inconsistency.Results A total of 12 RCTs with 833 elderly patients (dexmedetomidine group, 546 patients; control group, 287 patients) were included. There was no significant increase in perioperative heart rate (HR), mean arterial pressure (MAP), and diastolic blood pressure (DBP) in the dexmedetomidine group before and during the operation. In addition, the variations of hemodynamic indexes including HR, MAP, SBP (systolic blood pressure), and DBP were significantly lower in the dexmedetomidine group compared with the control group (HR: SMD = -0.87, 95% CI: -1.13 to -0.62; MAP: SMD = -1.12, 95% CI: -1.60 to -0.63; SBP: SMD = -1.27, 95% CI: -2.26 to -0.27; DBP: SMD = -0.96, 95% CI: -1.33 to -0.59). Subgroup analysis found that with the prolongation of 1.0 μg/kg dexmedetomidine infusion, the patient's heart rate declined in a time-dependent way.Conclusion Dexmedetomidine provides more stable hemodynamics during perioperative period in elderly patients. However, further well-conducted trials are required to assess the effective and safer doses of dexmedetomidine in elderly patients.
Humans ; Aged ; Dexmedetomidine/adverse effects* ; Hemodynamics ; Hypnotics and Sedatives/pharmacology* ; Blood Pressure ; Heart Rate

Colorectal cancer is one of the most common malignant tumors of digestive tract. In 2020， 1.93 million new cases of colorectal cancer were diagnosed globally， ranking third in the global incidence spectrum， and 930 000 new deaths were reported， ranking second in the global cause of death spectrum. Meanwhile， the medical cost of metastatic colorectal cancer is the highest among all stages. A large number of studies have demonstrated that traditional Chinese medicine（TCM） treatment can bring clinical benefits to patients with metastatic colorectal cancer with unique efficacy. In order to further standardize the TCM diagnosis and treatment for metastatic colorectal cancer and improve the level of TCM diagnosis and treatment， Xiyuan Hospital， China Academy of Chinese Medical Sciences， together with other relevant units in China， according to the guideline development process of the World Health Organization Handbook for Guideline Development and the relevant requirements of the Clinical Evidence Grading Criteria on TCM Based on Evidence Body， the Regulations for Group Standards of China Association of Chinese Medicine and others， combined with the characteristics of TCM diagnosis and treatment and the actual situation in China， the Guidelines for TCM Diagnosis and Treatment of Metastatic Colorectal Cancer was developed in accordance with the Catalogue of TCM Diagnosis and Treatment Plans for 105 Diseases in 24 Specialties issued by Department of Medical Administration of National Administration of TCM.

Evolution and natural selection have endowed animal venoms, including scorpion venoms, with a wide range of pharmacological properties. Consequently, scorpions, their venoms, and/or their body parts have been used since time immemorial in traditional medicines, especially in Africa and Asia. With respect to their pharmacological potential, bioactive peptides from scorpion venoms have become an important source of scientific research. With the rapid increase in the characterization of various components from scorpion venoms, a large number of peptides are identified with an aim of combating a myriad of emerging global health problems. Moreover, some scorpion venom-derived peptides have been established as potential scaffolds helpful for drug development. In this review, we summarize the promising scorpion venoms-derived peptides as drug candidates. Accordingly, we highlight the data and knowledge needed for continuous characterization and development of additional natural peptides from scorpion venoms, as potential drugs that can treat related diseases.
Animals ; Scorpion Venoms/pharmacology* ; Peptides/pharmacology* ; Scorpions ; Drug Development ; Medicine, Traditional

Objective: To analyze the incidence and related factors of drug resistance in HIV-infected pregnant and postpartum women in some areas of three western provinces of China from 2017 to 2019. Methods: From April 2017 to April 2019, face-to-face questionnaires and blood sample testing were conducted in all health care institutions providing maternal and perinatal care and midwifery-assisted services in 7 prevention of mother-to-child transmissi project areas in Xinjiang, Yunnan and Guangxi provinces/autonomous regions. Information was collected during the perinatal period and viral load, CD4⁺T lymphocytes and drug resistance genes were detected at the same time. The multivariate logistic regression model was used to analyze the relationship between different factors and drug resistance in HIV-infected pregnant and postpartum women. Results: A total of 655 HIV-infected pregnant and postpartum women were included in this study. The incidence of drug resistance was 3.4% (22/655), all of whom were cross-drug resistant. The rate of low, moderate and high drug resistance was 2.1% (14/655), 1.2% (8/655) and 0.8% (5/655), respectively. The drug resistance rate in the people who had previously used antiviral drugs was 1.9% (8/418), and the drug resistance rate in the people who had not used drugs was 5.9% (14/237). The NNRTI drug resistance accounted for 2.8% (18/655) and the NRTI drug resistance rate was 2.5% (16/655). The multivariate logistic regression model showed that the risk of HIV resistance was lower in pregnant women who had previously used antiviral drugs (OR=0.32, 95%CI: 0.11-0.76). Conclusion: Strengthening the management of antiviral drug use and focusing on pregnant and postpartum women who have not previously used antiviral drugs can help reduce the occurrence of drug-resistant mutations. Personalized antiviral therapy should be considered to achieve viral inhibition effects in clinical practice.
Female ; Humans ; Pregnancy ; HIV Infections/drug therapy* ; Incidence ; China/epidemiology* ; Infectious Disease Transmission, Vertical/prevention & control* ; Postpartum Period ; Drug Resistance, Viral/genetics* ; Antiviral Agents/therapeutic use*