To analyze the in vitro antibacterial effects of colistin (COL) or tigecycline (TGC) in combination with imipenem (IPM), amikacin (AMK), and cefoperazone-sulbactam (CSL) against carbapenem-resistant Acinetobacter baumannii(CRAB), so as to provide evidence for screening effective combination regimens for clinical microbial infections.

Objective:To investigate the effect of microwave on human adenovirus type 2 (HAdV-2) capsid protein in simulated infectious wastes.Methods:Droplets of HAdV-2 virus suspension were added to medical disposable gloves to simulate infectious waste, irradiated under different microwave conditions, the temperature change was recorded, and the irradiated viral supernatant was treated with Dnase I and detected by PCR and qPCR to determine the effect of microwave on the integrity of the viral capsid. ELISA was used to detect the effect of microwave irradiation on the structure of viral hexon protein. The virus was treated alone at the highest temperature during microwave irradiation to investigate whether there were non-thermal effects during microwave disinfection.Results:The maximum temperature during microwave irradiation was 76 ℃, and the PCR and qPCR result showed that Dnase I could significantly damage the viral nucleic acid after microwave irradiation, while the virus control group and heat treatment group were not significantly affected, indicating that microwave irradiation could destroy the integrity of the viral capsid. The result of ELISA showed that microwave irradiation could significantly weaken the binding ability of Hexon protein and antibody, and the result of heat treatment group were similar.Conclusions:Microwave irradiation can destroy the integrity of the HAdV-2 capsid and the structure of Hexon protein, in which the damage to the integrity of the capsid is mainly due to non-thermal effects, and the structural changes of hexon protein are mainly due to thermal effects.

Objective To investigate the correlation of platelet-to-lymphocyte ratio (PLR) with depression in patients with maintenance hemodialysis (MHD) based on propensity score matching (PSM). Methods General information such as age, gender and underlying diseases, biochemical indicators, and Beck Depression Inventory (BDI) scores of patients in hemodialysis centers of 20 Grade Ⅲ and Level A hospitals in Guizhou Province from June to August 2023 were collected. Patients were divided into depression group and non-depression group based on the occurrence of depression, and differences in clinical characteristics were compared between the groups. A 1 to 1 propensity score matching was used to obtain patients with similar baseline data (gender, age, education level) in the depression and non-depression groups, and differences in clinical characteristics between the two groups were compared. Participants were divided into Q1, Q2, Q3 and Q4 groups according to the quartiles of PLR, and differences in clinical characteristics among the groups were compared. Logistic regression analysis was used to evaluate the relationship between PLR and depression in MHD patients. Receiver operating characteristic (ROC) curve was used to assess the value of PLR in predicting depression in MHD patients. Results A total of 2, 081 MHD patients were included in this study, including 1, 286 males (61.8%), with a mean age of (54.3±14.7) years. A total of 368 patients (17.7%) had depression, and 359 pairs were successfully matched after propensity score matching. The depression group had higher rates of diabetes and PLR, but lower serum creatinine and hemoglobin levels (P < 0.05). The risk of depression in the PLR Q4 group was 22.654 times than that of the Q1 group (95%CI, 12.713 to 40.369, P < 0.001). After initially adjusting for age, diabetes, and hypertension, the risk of depression in the PLR Q4 group was 28.272 times than that of the Q1 group (95%CI, 15.390 to 51.937, P < 0.001). After further adjusting for serum creatinine, hemoglobin, albumin, white blood cell count, total cholesterol, monocyte-to-lymphocyte ratio, systemic immune-inflammation index, and neutrophil-to-lymphocyte ratio, the risk of depression in the PLR Q4 group was 10.557 times than that of the Q1 group (95%CI, 3.461 to 32.201, P < 0.001). The ROC curve analysis results indicated that the sensitivity of PLR in predicting depression in MHD patients was 78.0%, the specificity was 73.5%, the optimal threshold was 114.14, and the area under the curve was 0.798 (95%CI, 0.765 to 0.832, P < 0.001). Conclusion PLR is an independent risk factor for depression and has a high predictive value for depression in MHD patients.

Objective: To quantitatively assess the pulmonary vasculature using non-contrast computed tomography (CT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) pre- and post-treatment and correlate CT-based parameters with right heart catheterization (RHC) hemodynamic and clinical parameters. Materials and Methods: A total of 30 patients with CTEPH (mean age, 57.9 years; 53% female) who received multimodal treatment, including riociguat for ≥ 16 weeks with or without balloon pulmonary angioplasty and underwent both noncontrast CT for pulmonary vasculature analysis and RHC pre- and post-treatment were included. The radiographic analysis included subpleural perfusion parameters, including blood volume in small vessels with a cross-sectional area ≤ 5 mm 2 (BV5) and total blood vessel volume (TBV) in the lungs. The RHC parameters included mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and cardiac index (CI). Clinical parameters included the World Health Organization (WHO) functional class and 6-minute walking distance (6MWD). Results: The number, area, and density of the subpleural small vessels increased after treatment by 35.7% (P < 0.001), 13.3% (P = 0.028), and 39.3% (P < 0.001), respectively. The blood volume shifted from larger to smaller vessels, as indicated by an 11.3% increase in the BV5/TBV ratio (P = 0.042). The BV5/TBV ratio was negatively correlated with PVR (r = -0.26; P = 0.035) and positively correlated with CI (r = 0.33; P = 0.009). The percent change across treatment in the BV5/TBV ratio correlated with the percent change in mPAP (r = -0.56; P = 0.001), PVR (r = -0.64; P < 0.001), and CI (r = 0.28; P = 0.049).Furthermore, the BV5/TBV ratio was inversely associated with the WHO functional classes I–IV (P = 0.004) and positively associated with 6MWD (P = 0.013). Conclusion Non-contrast CT measures could quantitatively assess changes in the pulmonary vasculature in response to treatment and were correlated with hemodynamic and clinical parameters.

In this study, untargeted metabolomics was conducted using the liquid chromatography-tandem mass spectrometry(LC-MS/MS) technique to analyze the potential biomarkers in the plasma of mice with heart failure with preserved ejection fraction(HFpEF) induced by a high-fat diet(HFD) and nitric oxide synthase inhibitor(Nω-nitro-L-arginine methyl ester hydrochloride, L-NAME) and explore the pharmacological effects and mechanism of Jiming Powder in improving HFpEF. Male C57BL/6N mice aged eight weeks were randomly assigned to a control group, a model group, an empagliflozin(10 mg·kg~(-1)·d~(-1)) group, and high-and low-dose Jiming Powder(14.3 and 7.15 g·kg~(-1)·d~(-1)) groups. Mice in the control group were fed on a low-fat diet, and mice in the model group and groups with drug intervention were fed on a high-fat diet. All mice had free access to water, with water in the model group and Jiming Powder groups being supplemented with L-NAME(0.5 g·L~(-1)). Drugs were administered on the first day of modeling, and 15 weeks later, blood pressure and cardiac function of the mice in each group were measured. Heart tissues were collected for hematoxylin-eosin(HE) staining to observe pathological changes and Masson's staining to observe myocardial collagen deposition. Untargeted metabolomics analysis was performed on the plasma collected from mice in each group, and metabolic pathway analysis was conducted using MetaboAnalyst 5.0. The results showed that the blood pressure was significantly lower and the myocardial concentric hypertrophy and left ventricular diastolic dysfunction were significantly improved in both the high-dose and low-dose Jiming Powder groups as compared with those in the model group. HE and Masson staining showed that both high-dose and low-dose Jiming Powder significantly alleviated myocardial fibrosis. In the metabolomics experiment, 23 potential biomarkers were identified and eight strongly correlated metabolic pathways were enriched, including linoleic acid metabolism, histidine metabolism, alpha-linolenic acid metabolism, glycerophospholipid metabolism, purine metabolism, porphyrin and chlorophyll metabolism, arachidonic acid metabolism, and pyrimidine metabolism. The study confirmed the pharmacological effects of Jiming Powder in lowering blood pressure and ameliorating HFpEF and revealed the mechanism of Jiming Powder using the metabolomics technique, providing experimental evidence for the clinical application of Jiming Powder in treating HFpEF and a new perspective for advancing and developing TCM therapy for HFpEF.
Male ; Mice ; Animals ; Heart Failure/metabolism* ; Powders ; Stroke Volume/physiology* ; Chromatography, Liquid ; NG-Nitroarginine Methyl Ester/therapeutic use* ; Mice, Inbred C57BL ; Tandem Mass Spectrometry ; Metabolomics ; Biomarkers ; Water

Variations in the dynein axonemal heavy chain gene, dynein axonemal heavy chain 6 (DNAH6), lead to multiple morphological abnormalities of the flagella. Recent studies have reported that these deficiencies may result in sperm head deformation. However, whether DNAH6 is also involved in human acrosome biogenesis remains unknown. The purpose of this study was to investigate DNAH6 gene variants and their potential functions in the formation of defective sperm heads and flagella. Whole-exome sequencing was performed on a cohort of 375 patients with asthenoteratozoospermia from the First Affiliated Hospital of Anhui Medical University (Hefei, China). Hematoxylin and eosin staining, scanning electron microscopy, and transmission electron microscopy were performed to analyze the sperm morphology and ultrastructure. Immunofluorescence staining and Western blot analysis were conducted to examine the effects of genetic variants. We identified three novel deleterious variants in DNAH6 among three unrelated families. The absence of inner dynein arms and radial spokes was observed in the sperm of patients with DNAH6 variants. Additionally, deficiencies in the acrosome, abnormal chromatin compaction, and vacuole-containing sperm heads were observed in these patients with DNAH6 variants. The decreased levels of the component proteins in these defective structures were further confirmed in sperm from patients with DNAH6 variants using Western blot. After intracytoplasmic sperm injection (ICSI) treatment, the partner of one patient with a DNAH6 variant achieved successful pregnancy. Overall, novel variants in DNAH6 genes that contribute to defects in the sperm head and flagella were identified, and the findings indicated ICSI as an effective clinical treatment for such patients.

Objective:To study the inactivation effects of microwave on human adenovirus 2 (HAdV-2) in simulated infectied wastes, and to explore its molecular mechanism.Methods:25 μl of HAdV-2 virus suspension was dripped with medical disposable gloves, masks and cotton swabs to simulate infectied wastes, and irradiated under different microwave conditions: gloves and masks were irradiated for 30 s, 60 s, and 90 s at 300 W, 500 W, and 700 W, respectively. Cotton swabs irradiate 60 s, 90 s, 120 s at 500 W and 700 W respectively. Temperature changes were recorded, and the inactivation logarithmic values were calculated by the 50% endpoint method to evaluate the microwave inactivation effects, and the proliferation ability of the virus was detected by qPCR. The damage of Penton, Fiber, Hexon and E2 B genes was detected by PCR. The virus was treated with the highest temperature of 76 ℃ during microwave irradiation to study whether there was non-thermal effect during microwave disinfection. Results:After microwave irradiation of infectied waste, the temperature of masks and gloves carriers rises rapidly, with the highest temperature of 76 ℃. The temperature of the cotton swab carriers rose slowly, and the highest temperature is 65 ℃. The inactivation effect of microwave on HAdV-2 was positively correlated with microwave power and irradiation time. In the mask and glove group, microwave power of 700 W irradiated for 60 seconds, and the inactivation logarithm value could reach 3.0, In the cotton swab group, microwave power of 700 W irradiated for 120 seconds, and the inactivation logarithm value was still less than 3.0. This indicated that there were differences in the conditions for microwave inactivation of the virus in different carriers. The qPCR result showed that microwave irradiation could weak the proliferation ability of the virus. Microwave irradiation had no effect on the virus's Penton and Fiber genes, but caused some damage to the Hexon and E2 B genes. The inactivation effect of individual heat treatment on HAdV-2 was weaker than that of microwave irradiation, and there was no damage to the Hexon, Penton, Fiber, and E2 B genes. This indicated the presence of non thermal effects during the microwave inactivation process. Conclusions:Microwave irradiation can inactivate HAdV-2 in simulated infectied wastes through thermal and non-thermal effects, and its damage to viral DNA is one of the mechanisms of virus inactivation.

Objective:To investigate the workflow, efficacy and safety of MR-Linac in liver malignancies.Methods:Clinical data of 15 patients with hepatocellular carcinomas (HCC) or liver metastases treated with MR-Linac between November 2019 and July 2021 were retrospectively analyzed. The workflow of MR-Linac was investigated and image identification rate was analyzed. Patients were followed up for response and toxicity assessment.Results:Fifteen patients (6 HCC, 8 liver metastases from colorectal cancer, 1 liver metastasis from breast cancer) were enrolled. A total of 21 lesions were treated, consisting of 10 patients with single lesion, 4 patients with double lesions and 1 patient with triple lesions. The median tumor size was 2.4 cm (0.8-9.8 cm). The identification rate for gross tumor volume (GTV) in MR-Linac was 13/15. Although GTV of two patients were unclearly displayed in MR-Linac images, the presence of adjacent blood vessel and bile duct assisted the precise registration. All the patients were treated with stereotactic body radiation therapy (SBRT). For HCC, the median fraction dose for GTV or planning gross tumor volume (PGTV) was 6 Gy (5-10 Gy) and the median number of fractions was 9(5-10). The median total dose was 52 Gy (50-54 Gy) and the median equivalent dose in 2 Gy fraction (EQD 2Gy) at α/ β= 10 was 72 Gy (62.5-83.3 Gy). For liver metastases, the median fraction dose for GTV or PGTV was 5 Gy (5-10 Gy) and the median number of fractions was 10(5-10). The median total dose was 50 Gy (40-50 Gy) and the median EQD 2Gy at α/ β=5 was 71.4 Gy (71.4-107.1 Gy). At 1 month after SBRT, the in-field objective response rate (ORR) was 8/13 and the disease control rate was 13/13. At 3-6 months after SBRT, the in-filed ORR was increased to 6/6. During the median follow-up of 4.0 months (0.3-11.6), 4-month local progression-free survival, progression-free survival and overall survival were 15/15, 11/15 and 15/15, respectively. Toxicities were mild and no grade 3 or higher toxicities were observed. Conclusions:MR-Linac provides a platform with high identification rates of liver lesions. Besides, the presence of adjacent blood vessel and bile duct also assists the precise registration. It is especially suitable for liver malignancies with promising local control and well tolerance.

Objective: Moderate and severe behavioral and psychological symptoms of dementia (BPSD) often need medical treatment to improve symptoms. Agomelatine is a selective melatonergic (MT1/MT2) agonist that has normalizing effects on disturbed circadian rhythms and disrupted sleep−wake cycles. Its activity of 5HT-2C receptor antagonism is associated with lessening depression and anxiety and increasing slow-wave sleep. Based on past clinical records and current findings it suggests that agomelatine can improve BPSD for patients. This retrospective cohort study was designed to compare the BPSD before and after using agomelatine. Methods: Records of dementia cases who had ever received agomelatine treatment for BPSD in a general hospital setting during the past 2.5 years were identified and reviewed. Scores from before and after 3 months of treatment with agomelatine were collected for Neuropsychiatric Inventory (NPI), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression (CGI) to compare and analyze the difference of psychological and behavioral symptoms pre- and post-agomelatine used. Results: Records of 144 cases of dementia with BPSD who had ever used agomelatine from January 2015 to June 2017 were collected. All of the 112 cases had BPRS and CGI scores, of which 75 cases had additional NPI scores. Among these 112 cases, the BPRS and CGI scores were significantly improved in all types of dementia. NPI scores indicated that the use of agomelatine alleviated obvious symptoms and decreased overall distress, especially in the depression/poor mood, anxiety, and sleepight behavior. Conclusion It is consistent with an effective result of agomelatine in improving BPSD.

Bolbostemma paniculatum is a commonly used Chinese medicinal material effective in clearing heat, removing toxin, eliminating phlegm, and alleviating swelling. The anti-tumor activity it possesses makes it a research hotspot. At present, 76 compounds have been isolated from B. paniculatum, including triterpenoids, sterols, alkaloids, anthraquinones, organic acids, etc., with anti-tumor, antiviral, and immunosuppressive pharmacological activities. This study reviewed the research on the chemical constituents and pharmacological effects of B. paniculatum over the past 20 years, aiming to provide a scientific basis for the research on the pharmacodynamic material basis and promote the development and utilization of B. paniculatum.
Cucurbitaceae ; Drugs, Chinese Herbal/pharmacology* ; Edema ; Triterpenes