Effectiveness and safety of azvudine in older adults with mild and moderate COVID-19: a retrospective observational study.

BACKGROUND: Azvudine has clinical benefits and acceptable safety against COVID-19, including in patients with comorbidities, but there is a lack of available data for its use in older adult patients. This study explored the effectiveness and safety of azvudine in older adults with mild or moderate COVID-19. METHODS: This retrospective cohort study included patients aged ≥80 diagnosed with COVID-19 at the Central Hospital of Shaoyang between October and November 2022. According to the therapies they received, the eligible patients were divided into the azvudine, nirmatrelvir/ritonavir, and standard-of-care (SOC) groups. The outcomes were the proportion of patients progressing to severe COVID-19, time to nucleic acid negative conversion (NANC), and the 5-, 7-, 10-, and 14-day NANC rates from admission. RESULTS: The study included 55 patients treated with azvudine (n = 14), nirmatrelvir/ritonavir (n = 18), and SOC (n = 23). The median time from symptom onset to NANC of the azvudine, nirmatrelvir/ritonavir, and SOC groups was 14 (range, 6-25), 15 (range, 11-24), and 19 (range, 18-23) days, respectively. The median time from treatment initiation to NANC of the azvudine and nirmatrelvir/ritonavir groups was 8 (range, 4-20) and 9 (range, 5-16) days, respectively. The median length of hospital stay in the three groups was 10.5 (range, 5-23), 13.5 (range, 10-21), and 17 (range, 10-23) days, respectively. No treatment-related adverse events or serious adverse events were reported. CONCLUSION: Azvudine showed satisfactory effectiveness and acceptable safety in older adults with mild or moderate COVID-19. Therefore, azvudine could be a treatment option for this special patient population.

The association between endometrial polyps and insulin resistance from the expression of PI3K and AKT proteins perspective.

BACKGROUND: Insulin resistance (IR) induces hyperinsulinemia, which activates downstream signaling pathways such as the phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) pathway, ultimately leading to abnormal proliferation and apoptosis of endometrial cells. This is thought to be a key pathogenic mechanism underlying the development of endometrial polyps (EP). This study aims to investigate the relationship between IR and the development of EP, the expression levels of downstream signaling molecules, including PI3K and AKT, and related laboratory parameters were examined. METHODS: A total of 100 patients who visited the gynecology outpatient clinic of Zhongda Hospital affiliated with Southeast University from May 2021 to March 2023 and were diagnosed with abnormal endometrial echoes by vaginal ultrasound and underwent hysteroscopic diagnostic curettage were enrolled in this study. General data and relevant hematological indicators were compared, and intraoperative specimens were obtained for pathological examination. Possible factors influencing the development of endometrial polyps were analyzed using Pearson correlation analysis and logistic regression analysis. RESULTS: In terms of body mass index, waist circumference, fasting insulin, insulin resistance index, serum total testosterone, and free testosterone index, women of childbearing age in the endometrial polyp group had higher values than those in the non-polyp group, while sex hormone-binding globulin in the endometrial polyp group was lower than that in the non-polyp group, and the differences were statistically significant (P < 0.05). The expression scores and mRNA expression levels of PI3K and AKT proteins were higher in the EP group than in the non-EP group (p < 0.05). Pearson correlation analysis showed a positive correlation between HOMA-IR and the expression scores of PI3K and AKT proteins (p < 0.01). CONCLUSIONS: Insulin resistance and abnormal activation of the phosphatidylinositol 3-kinase/protein kinase B signaling pathway may be potential pathogenic mechanisms for the development of endometrial polyps.

Change of the vaginal microbiome with oral contraceptive therapy in women with polycystic ovary syndrome: a 6-month longitudinal cohort study.

BACKGROUND: The association between the vaginal microbiome and polycystic ovary syndrome (PCOS) is reported, but the longitudinal changes in the vaginal microbiome that accompany oral contraceptive therapy have not been described. METHODS: This cohort study included 50 PCOS patients who wanted to make their menstrual periods more regular and accepted only oral contraceptive therapy and lifestyle coaching, then they were successfully followed up for 6 months. Venous blood was collected, and follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (T), anti-Müllerian hormone (AMH), and estradiol (E2) were assayed at baseline and at months 3 and 6. Vaginal swabs were collected at baseline and at months 3 and 6. 16S rRNA genes were sequenced to identify the microbiota structure. Latent class trajectory models were used to explore the trajectory of the changes in Lactobacillus abundance. RESULTS: At 3 months, all patients reported regular periods, and the improvement lasted until 6 months. The body mass index and waist-to-hip ratio decreased with treatment (P < 0.01), and the AMH and T levels showed downward trends. We did not find a statistically significant relationship between hormone levels at the previous time point and the vaginal microbiota at subsequent time points (P > 0.05). The relative abundance of Lactobacillus increased with treatment, and trajectory analysis revealed five classes of Lactobacillus changes. Class 1, stable high level, accounted for 26%; class 2, decrease followed by increase, accounted for 18%; class 3, stable low level, accounted for 10%; class 4, increase, accounted for 20%; class 5, increase followed by decrease, accounted for 26%. Logistic models showed that compared to class 1, a higher baseline T level was associated with a reduced risk of class 2 change (odds ratio (OR) = 0.03, 95% confidence interval (CI):0.01-0.52) and class 4 change (OR = 0.10, 95% CI:0.01-0.93). CONCLUSIONS: The abundance of Lactobacilli increased with PCOS treatment; however, the trajectory was inconsistent for each individual. Evidence of the effects of female hormone levels on the vaginal microbiome is insufficient.

Oncogenic SIRT7 inhibits GATA4 transcriptional activity and activates the Wnt signaling pathway in ovarian cancer.

OBJECTIVE: Sirtuin-7 (SIRT7) is a class III histone deacetylase that plays an important role in cancer development and frequently overexpressed in carcinomas. In this study, the tumor-supporting role and underlying mechanisms of SIRT7 were characterized in ovarian cancer (OC) aggressiveness. METHODS: SIRT7 expression was examined in OC tissues and cells. Interactions among SIRT7, GATA4, Wnt signaling pathway were explored by bioinformatics tools and experimental validations. The effect of SIRT7 and GATA4 on malignant phenotypes of OC cells were examined with gain- and loss-of-function experiments. A nude mouse model of OC was developed to verify the in vitro findings. RESULTS: It was noted that SIRT7 was highly expressed in OC tissues and cells. Cell lines with higher SIRT7 expression (OVCAR-3 and OVCAR-8) were used for subsequent in vitro experiments. The experimental data indicated that silencing of SIRT7 suppressed the OC cell proliferation, colony formation, migration, and invasion, and promoted cell senescence, which could be abolished by GATA4 knockdown. Mechanistically, SIRT7 promoted deacetylation of GATA4 and consequently inhibited the transcriptional activity of GATA4. In addition, GATA4 induced OC cell senescence by inhibiting Wnt signaling pathway. Further in vivo experiments substantiated that SIRT7 knockdown or overexpressed GATA4 could effectively inhibit tumor growth of nude mice. CONCLUSION: Taken together, our findings indicated that SIRT7 enhanced development of OC by suppressing GATA4 and activating Wnt signaling pathway, suggesting the potential of SIRT7/GATA4/Wnt axis as a therapeutic target for OC.

SZB120 Exhibits Immunomodulatory Effects by Targeting eIF2α to Suppress Th17 Cell Differentiation.

IL-17-secreting Th17 cells play an important role in the pathogenesis of various inflammatory and autoimmune diseases. IL-17-targeted biologics and small molecules are becoming promising treatments for these diseases. In this study, we report that SZB120, a derivative of the natural compound 3-acetyl-ß-boswellic acid, inhibits murine Th17 cell differentiation by interacting with the α-subunit of eukaryotic initiation factor 2 (eIF2α). We showed that SZB120 directly interacts with eIF2α and contributes to serine 51 phosphorylation of eIF2α. The suppressive effect of SZB120 on Th17 cell differentiation was reversed by GSK2606414, an inhibitor of eIF2α phosphokinase. Phosphorylation of eIF2α induced by SZB120 decreased the protein expression of IκBζ, which is important for Th17 cell differentiation. Notably, interaction with eIF2α by SZB120 also impaired glucose uptake and glycolysis in T cells. In vivo, SZB120 treatment of C57BL/6 mice significantly attenuated IL-17/Th17-mediated autoimmune disease. Our study indicates that SZB120 is a promising drug candidate for IL-17/Th17-mediated inflammatory diseases.

What is behind the fear of cancer during menopausal hormone therapy in China?

PURPOSE: The application of menopausal hormone therapy (MHT) is generally restricted most likely due to limited prescriptions by doctors. Fear of cancer risk may be a critical factor. We investigated the views of Chinese obstetricians and gynecologists on the relationship between hormone therapy and cancer risk. METHODS: A self-administered web-based nationwide cross-sectional questionnaire. RESULTS: In total, 5243 medical workers responded to the questionnaire (response rate 94.5%); 4995 were certified obstetricians and gynecologists. Most were aged 36-55 years (70.9%), had > 10 years of working experience (68.5%), and worked at tertiary (34.8%) and secondary hospitals (49.1%); 70% of the clinicians were aware of the endometrial cancer risk caused by estrogen, and 20% considered progestogen to cause the same risk. Regarding breast cancer, while 67.9 and 74.8% of the clinicians viewed natural and synthetic estrogens as risk factors, respectively, only 41.7% identified the carcinogenic effect of progestins as higher than that of progesterone (26.7%). Approximately 75% of the participants believed synthetic estrogens and progestins constituted a risk for ovarian cancer (higher than the percentages for their natural counterparts); 13.0-21.1% of the respondents were worried about choriocarcinoma due to hormone treatment. Finally, 86.8% of obstetricians and gynecologists claimed to have poor knowledge regarding this field. CONCLUSION: Misconceptions and a lack of knowledge in this regard may result in the fear of cancer and could be the underlying causes of limited MHT prescriptions. We believe that scientific research, continued education, and the media all have roles to play in changing preconceived ideas regarding MHT prescriptions.

Association between polycystic ovary syndrome and the vaginal microbiome: A case-control study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. Some evidence suggests that dysbiosis of the gut microbiota could be associated with PCOS clinical parameters, but little is known for the association between vaginal microbiome and PCOS. OBJECTIVE: To determine differences in the vaginal microbiome between women with PCOS and healthy control women. RESEARCH DESIGN AND METHODS: In this case-control study, the women with newly diagnosed PCOS (n = 39) and healthy controls (n = 40) were included from the hospital and maternal and child health centre, respectively. The vaginal swabs were collected, and microbiome structures were identified by 16S rRNA gene sequencing. The screening values for potential bacteria biomarker for PCOS were assessed by receiver operating characteristic (ROC) curve method. RESULTS: There was significant difference in vaginal bacterial structures between PCOS and healthy control women. The vaginal bacterial species in the PCOS group were more diverse than the control group (Simpson index for PCOS group vs. control group: median 0.49 vs. 0.80, P = .008; Shannon index: median 1.07 vs. 0.44, P = .003; Chao1 index: median 85.12 vs. 66.13, P < .001). The relative abundance of Lactobacillus crispatus in the PCOS group was significantly lower than controls (P = .001), and the relative abundance of Mycoplasma and Prevotella was higher than controls (P < .001, P = .002, respectively). The Mycoplasma genus could be a potential biomarker for PCOS screening, as ROC analysis showed that the area under the curve (AUC) for the relative abundance of Mycoplasma was 0.958 (95% CI: 0.901-0.999). Subgroup analyses also showed these associations would not change among the women with the same BMI level and vagina cleanliness grading. CONCLUSIONS: In the vaginal microbiome, the Mycoplasma genus was associated with PCOS. Further research is required to explore causal correlations between PCOS and the vaginal microbiome.

A study on phthalate metabolites, bisphenol A and nonylphenol in the urine of Chinese women with unexplained recurrent spontaneous abortion.

Humans are widely exposed to phthalates, bisphenol A and nonylphenol owing to the ubiquitous use of these chemicals in consumer products. Increasing attention has been paid to exposure to phthalates, bisphenol A and nonylphenol because of their potential adverse effects on human fertility. A validated method was developed to investigate the three classes of environmental estrogen, mentioned above, in the urine of Chinese women of Nanjing area with unexplained recurrent spontaneous abortion. Solid-phase extraction coupled with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used. In this method, amounts of bisphenol A (BPA), nonylphenol (NP) and four phthalate metabolites, mono-n-butyl phthalate (MBP), mono-isobutyl phthalate (MiBP), mono-benzyl phthalate (MBzP) and mono-2-ethylhexyl phthalate (MEHP), along with their isotope labeled internal standards, were measured using UPLC-MS/MS operated in negative electrospray ionization multiple reaction monitoring mode. The limits of detection were 0.3ng/mL for the four phthalate metabolites, and 0.5ng/mL for bisphenol A and nonylphenol. For women with unexplained recurrent spontaneous abortion, the mean concentrations of MBP, MiBP, MBzP, MEHP, BPA and 4-n-NP were 6.52±6.04, 5.51±4.19, 0.53±0.42, 10.12±4.16, 7.13±7.42, 0.41±0.49ng/mL (mean±SD), respectively. For the control group, the mean concentrations of the corresponding analytes were 4.15±3.57, 2.96±3.30, 0.46±0.49, 6.50±2.81, 4.43±2.23,0.48±0.43ng/mL (mean±SD), respectively. Levels of MiBP and MEHP were significantly different between the two groups, using Wilcoxon rank sum tests. This method can be applied in epidemiological studies to explore the association between exposure to environmental estrogens and relevant adverse outcomes.

[Effects of estrogen replacement therapy on cognitive function of ovariectomized rats].

OBJECTIVE: To investigate the effect of estrogen replacement therapy applied in different periods to ovariectomized rats and to evaluate the cognitive function of the rats. METHODS: Totally 40 rats were ovariectomized to be postmenopausal models. They were divided into early hormone replacement therapy group (n = 10, managed by estradiol valerate at day 3 after surgery), early control group (n = 10, managed by saline at day 3 after surgery), late hormone replacement therapy (n = 10, managed by estradiol valerate at day 90 after surgery for 30 days) and late control group (n = 10, managed by saline at day 90 after surgery for 30 days). The behavior indicators of the rats were evaluated by Morris watermaze and hippocampal metabolite was detected by proton magnetic resonance spectroscopy, including N-acetylaspartate (NAA), choline containing compounds (Cho), creatine (Cr), myoinositol (mI), NAA/Cr, Cho/Cr and mI/Cr. RESULTS: (1)Navigation test: escape latency were (43 ± 13) s at the early control group, (28 ± 9) s at the early HRT group, (82 ± 26) s at the late control group and (48 ± 18) s at late HRT group. Swimming distance were (1 404 ± 238) cm at the early control group, (878 ± 354) cm at the early HRT group, (2 411 ± 818) cm at the late control group and (1 310 ± 434) cm at the late HRT group. The escape latency and swimming distance of the early and late HRT groups were significantly shorter than those at the control groups (P < 0.05). (2) Spatial probe test: the swimming time in the target quadrant of rats in the early HRT group (34.0 ± 3.0) s were longer than those in other groups (P < 0.05). (3) Proton magnetic resonance spectroscopy: NAA/Cr were 1.12 ± 0.17 at the early control group, 1.26 ± 0.12 at the early HRT group, 1.57 ± 0.21 at the late control group and 1.38 ± 0.28 at the late HRT group. The late HRT group and the late control group were higher than their early groups (F = 6.05, P = 0.040). There was no significant difference between the HRT groups and the control groups (F = 0.04, P = 0.860). mI/Cr were 0.69 ± 0.04 at the early control group, 0.46 ± 0.12 at the early HRT group, 0.70 ± 0.03 at the late control group and 0.75 ± 0.08 at the late HRT group. There were statistically significant differences of the experimental time between the early and late groups(F = 16.45, P = 0.004). The differences between the early HRT group and the early control group, and the late HRT group and the late control group were significant (F = 6.01, P = 0.040). And there was an interaction with the experimental time and HRT measures (F = 13.79, P = 0.006); early HRT can reduce the average level of mI/Cr. Cho/Cr were 0.95 ± 0.09 at the early control group, 0.80 ± 0.12 at the early HRT group, 0.87 ± 0.09 at the late control group and 0.85 ± 0.12 at the late HRT group. There was no significant difference among those groups (P > 0.05). NAA/mI: there was an interaction with the experimental time and HRT measures (F = 12.95, P = 0.007). Early HRT can elevated levels of NAA/mI, while the late results were reversed. CONCLUSION: Earlier estrogen replacement therapy may play a positive role in improving cognitive function of the ovariectomized rats.

Sex Differences in Outcomes of Hepatobiliary and Pancreatic Surgery with Accelerated Rehabilitation.

BACKGROUND: Sex, in the sense of gender, is a major social demographic characteristic that has been shown to affect health care outcomes. The concept of enhanced recovery after surgery (ERAS) is an effective perioperative management measure that can reduce the perioperative stress response in patients. However, there are few studies on the differences between male and female patients under this type of care. We aimed to analyze sex differences in clinical characteristics among patients undergoing hepatobiliary and pancreatic surgery with accelerated rehabilitation. METHODS: We enrolled patients who underwent liver, biliary tract, and gallbladder operations in the Department of Hepatobiliary and Pancreatic Surgery of Taizhou Hospital, Zhejiang Province, China, from April 2021 to July 2021. Key measures were collected for patients undergoing perioperative accelerated rehabilitation (i.e., the case group). The study group was assembled by performing 1:1 matching for age, sex, chronic disease, and type of surgery. Postoperative risk assessment, postoperative recovery indicators, and postoperative length of hospital stay (days) were compared between male and female patients. RESULTS: A total of 226 surgical patients were enrolled, including 109 male (48.23%) and 117 female patients (51.77%). The outcomes, presented as the median (min, max), were as follows: pulmonary rehabilitation risk assessment in females (1(0,3)) and males (0(0,2)), postoperative nausea and vomiting in females (2(1,3)) and males (1(0,2)), and time to first defecation in females (31(4,61)) and males (36(10,78)). Significant differences were indicated by p values < 0.05. CONCLUSION: We identified sex differences in the clinical prognosis and performance of perioperative patients undergoing hepatobiliary and pancreatic surgery with accelerated rehabilitation. The perioperative pulmonary rehabilitation risk of male patients was higher than that of female patients, and the time to first defecation was longer in male than in female patients. The incidence of nausea and vomiting in women was higher than in men.

The vaginal metabolomics profile with features of polycystic ovary syndrome: a pilot investigation in China.

Background: Polycystic ovary syndrome (PCOS) is the most common metabolic disorder and reproductive endocrine disease, posing an elevated risk to women of reproductive age. Although metabolism differences in serum, amniotic fluid and urine have been documented in PCOS, there remains a paucity of evidence for vaginal fluid. This study aimed to identify the metabolic characteristics and potential biomarkers of PCOS in Chinese women of reproductive age. Methods: We involved ten newly diagnosed PCOS women who attended gynecology at Zhongda Hospital and matched them with ten healthy controls who conducted health check-up programs at Gulou Maternal and Child Health Center in Nanjing, China from January 1st, 2019 to July 31st, 2020. Non-targeted metabolomics based on ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) was applied to differentially screen vaginal metabolites between PCOS group and healthy controls. Principal component analysis (PCA), orthogonal partial least-squares discriminant analysis (OPLS-DA) and enrichment analysis were used to observe differences, search for potential biomarkers and enrich related pathways. Results: Among the 20 participants, a total of 195 different metabolites were detected between PCOS group and healthy control group. PCOS and control groups were effectively separated by vaginal fluid. Lipids and lipid-like molecules constituted the majority of differential metabolites. Notably, dopamine exhibited an increased trend in PCOS group and emerged as the most significant differential metabolite, suggesting its potential as a biomarker for identifying PCOS. The application of UHPLC-MS/MS based vaginal metabolomics methods showed significant differences between PCOS and non-PCOS healthy control groups, especially linoleic acid metabolism disorder. Most differential metabolites were enriched in pathways associated with linoleic acid metabolism, phenylalanine metabolism, tyrosine metabolism, nicotinate and nicotinamide metabolism or arachidonic acid metabolism. Conclusions: In this pilot investigation, significant metabolomics differences could be obtained between PCOS and healthy control groups. For PCOS women of reproductive age, vaginal metabolism is a more economical, convenient and harmless alternative to provide careful personalized health diagnosis and potential targets for therapeutic intervention.

Multiple doses of SHR-1222, a sclerostin monoclonal antibody, in postmenopausal women with osteoporosis: A randomized, double-blind, placebo-controlled, dose-escalation phase 1 trial.

SHR-1222, a novel humanized monoclonal antibody targeting sclerostin, has been shown to induce bone formation and decrease bone resorption at a single dose ranging 50-400 mg in our previous phase 1 trial. This study was a randomized, double-blind, placebo-controlled, dose-escalation phase 1 trial, which further investigated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of multiple ascending doses of SHR-1222 in women with postmenopausal osteoporosis (POP). A total of 105 women with POP were enrolled and randomly assigned. Twenty-one received placebo and eighty-four received SHR-1222 sequentially (100 mg QM, n=4; 200 or 300 mg QM, n=20; and 400 or 600 mg Q2M, n=20). The most common adverse events included increased blood parathyroid hormone, increased low-density lipoprotein, increased blood alkaline phosphatase, increased blood cholesterol, back pain, and arthralgia, the majority of which were mild in severity without noticeable safety concerns. Serum SHR-1222 exposure (Cmax,ss and AUC0-tau,ss) increased in a greater than dose-proportional manner. Following multiple doses of SHR-1222, the bone formation markers (terminal propeptide of type I procollagen, bone-specific alkaline phosphatase, and osteocalcin) increased in a dose-dependent manner, whereas the bone resorption marker (ß-C-telopeptide) was downregulated. Accordingly, BMD gains in the lumbar spine, total hip, and femoral neck were observed. The maximum BMD increase from baseline at the lumbar spine was detected in the 300 mg QM cohort (14.6% vs. 0.6% in the placebo group on day 169). Six (6/83; 7.2%) subjects developed anti-SHR-1222 antibodies with no discernible effects on PKs, PDs, and safety. Thus, multiple doses of SHR-1222 showed an acceptable safety profile and dose-dependent plasma exposure in women with POP, and could improve their BMD rapidly and prominently by promoting bone formation and inhibiting bone resorption. These findings further support SHR-1222 as a potential alternative agent for the treatment of POP.

Construction of a New Dual-Responsive Nano-Drug Delivery System for Matrix Metalloproteinases and Adenosine Triphosphate in Ovarian Cancer Using Nanomicelles.

In this manuscript we constructed a dual-responsive nano-drug delivery system for matrix metalloproteinases and ATP in ovarian cancer microenvironment. The nanomicelle PCL-DNA/DOX-Peptide-PEG was prepared by intercalating doxorubicin hydrochloride between C and G base pairs of DNA double helix structure. Another ATP-responsive nanomicelle PCL-DNA/DOX-PEG was prepared. Then we analyzed the characterization of nanomicelles (particle size, potential, surface morphology, etc.) and drug loading binding and drug release behavior. In addition, the effect of nanomicelles on the viability of mouse ovarian epithelial tumor cell ID-8 was detected by CCK-8 method. CCK-8 assay detected that different concentrations of carrier had no difference on the proliferation of ID-8 cells, and the survival rate of ID-8 cells by different concentrations of DOX preparations was statistically significant and the same results were observed in cytotoxicity comparison. Confocal microscopy showed that DOX in the drug-loaded micelle group was concentrated in the nucleus, while free DOX was concentrated in the cytoplasm. ID-8 cells took up the drug-loaded micelles faster. The semi-quantitative analysis of the DOX uptake of ID-8 cells with different treatments showed extremely significant statistical differences. In conclusion, the prepared self-assembled dual-responsive nanomicelle PCL-DNA/DOX-Peptide-PEG is novel anti-tumor agent, and is expected to have good tumor tissue penetration ability with a low toxicity.

The promise of low-intensity ultrasound: A review on sonosensitizers and sonocatalysts by ultrasonic activation for bacterial killing.

Antimicrobial resistance has become one of the main public health issues in modern society. Ultrasonicantimicrobial treatment (UAT) is expected to solve the problem of antimicrobial resistance since ultrasonic treatment does not cause drug resistance during inactivation. However, the ultrasonic application is hindered due to the high energy cost. To cast more lights on the ultrasound in tandem with catalysts as a superior strategy for bacterial inactivation, the present review focuses on the UAT with the assistant of continuous development of organic sonosensitizer and inorganic sonocatalyst. With the application of these nanomaterials, the ultrasonic parameters changed from low-frequency and high-power ultrasound to high-frequency and low-power ultrasound. The review also presents the composition of sonosensitizers/sonocatalysts including organic and inorganic nanoparticles and discusses the ultrasonic activation mechanisms triggered by these catalysts. Based on the synergistic effect of ultrasound and catalysts, we discuss the importance of extracellular oxidation and intracellular oxidation in the process of bacterial inactivation. Overall, UAT combined with catalysts appears to be an effective treatment strategy that can be successfully applied in the field of medicine, environmental treatment, and food industry.

Clinical Manifestations of Polycystic Ovary Syndrome and Associations With the Vaginal Microbiome: A Cross-Sectional Based Exploratory Study.

Background: Previous studies suggest that the vaginal microbiome is associated with polycystic ovary syndrome (PCOS). However, the clinical manifestations of PCOS are heterogeneous. Whether the vaginal microbiome is related with different clinical symptoms was unknown. Materials and Methods: In this cross-sectional study, 89 female patients with PCOS admitted to Zhongda Hospital (Nanjing, China) were included. Basic demographic information, health-related behaviors, clinical manifestations and sex hormone levels were comprehensively recorded for all patients. Vaginal swabs were acquired for microbiota sequencing of the V3-V4 region of the 16S rRNA gene. Results: The prevalence of bacterial vaginitis and vulvovaginal candidiasis was 15.7% and 13.5%, respectively, within the PCOS patients, which were the most important factors affecting the vaginal microbiome (permutational multivariate analysis of variance test, R2 = 0.108, P = 0.001). The vaginal microbiome was associated with specific clinical manifestations of PCOS, including acanthosis nigricans, intermenstrual bleeding, pregnancy history, testosterone level and anti-müllerian hormone level, with P values < 0.05. The abundance of Lactobacillus crispatus was higher (P = 0.010) while that of Lactobacillus iners was lower (P = 0.036) among PCOS patients with elevated testosterone levels. Other potential bacterial biomarkers were not statistically significant after adjusting for confounding factors. No evidence of associations of other common manifestations of PCOS, such as obesity and acne, with the vaginal microbiome was obtained. Conclusion: Vaginal bacterial species among PCOS patients with variable clinical manifestations, especially differences in testosterone levels, are distinct. Further studies are essential to investigate the microbiota and molecular mechanisms underpinning this disease.

Effects of Huatan Jiangzhuo decoction on diet-induced hyperlipidemia and gene expressions in rats.

Huatan Jiangzhuo decoction (HJD) is a combination of six traditional Chinese medicines that were used for lipid metabolism-related disorders, but its efficacy and underlying mechanisms have not been explored by modern research strategies. This study aimed to investigate the therapeutic role of HJD in determining the transcriptome level. Hyperlipidemia model was established by feeding Sprague-Dawley rats with high-fat diet. Differentially expressed genes (DEGs) were detected by high-through transcriptome sequencing, followed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The total cholesterol (TC) and triglyceride (TG) levels in hyperlipidemia model rats were significantly increased, whereas high-density lipoprotein (HDL) concentration decreased when compared to normal rats, and HJD significantly downregulated TC concentrations and liver coefficient in the hyperlipidemia rats. Histology staining showed that HDJ greatly recovered the lipid accumulation in rat hepatic stellate cells and aortic arch vascular wall thickness of hyperlipidemia rats. One thousand nine hundred and thirty-six DEGs were identified in the HJD-treated hyperlipidemia rats, which were associated with various biological processes and signaling pathways such as peroxisome proliferator-activated receptors, AMP-activated Protein Kinase , and insulin signaling pathways. Quantitative reverse transcription-polymerase chain reaction further confirmed the downregulated expression of cholesterol 7-α-hydroxylase(CYP7A1), liver orphan receptor(LXRα),peroxisome proliferator-activated receptor gamma(PPARγ),andSterol Response Element-Binding Protein 1c(SREBP1c) genes in hyperlipidemia rats treated with HJD. Our data first elucidated the gene expression profile of high-fat diet-induced hyperlipidemia in rats after HJD treatment, and lipid metabolism-related genes (CYP7A1, LXRα, PPARγ, and SREBP1c) may be potentially biomarkers for HJD-alleviated hyperlipidemia.

Spike-specific circulating T follicular helper cell and cross-neutralizing antibody responses in COVID-19-convalescent individuals.

Coronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1-3 and individuals with COVID-19 have symptoms that can be asymptomatic, mild, moderate or severe4,5. In the early phase of infection, T- and B-cell counts are substantially decreased6,7; however, IgM8-11 and IgG12-14 are detectable within 14 d after symptom onset. In COVID-19-convalescent individuals, spike-specific neutralizing antibodies are variable3,15,16. No specific drug or vaccine is available for COVID-19 at the time of writing; however, patients benefit from treatment with serum from COVID-19-convalescent individuals17,18. Nevertheless, antibody responses and cross-reactivity with other coronaviruses in COVID-19-convalescent individuals are largely unknown. Here, we show that the majority of COVID-19-convalescent individuals maintained SARS-CoV-2 spike S1- and S2-specific antibodies with neutralizing activity against the SARS-CoV-2 pseudotyped virus, and that some of the antibodies cross-neutralized SARS-CoV, Middle East respiratory syndrome coronavirus or both pseudotyped viruses. Convalescent individuals who experienced severe COVID-19 showed higher neutralizing antibody titres, a faster increase in lymphocyte counts and a higher frequency of CXCR3+ T follicular help (TFH) cells compared with COVID-19-convalescent individuals who experienced non-severe disease. Circulating TFH cells were spike specific and functional, and the frequencies of CXCR3+ TFH cells were positively associated with neutralizing antibody titres in COVID-19-convalescent individuals. No individuals had detectable autoantibodies. These findings provide insights into neutralizing antibody responses in COVID-19-convalescent individuals and facilitate the treatment and vaccine development for SARS-CoV-2 infection.

Ultrasonic stimulation of the brain to enhance the release of dopamine - A potential novel treatment for Parkinson's disease.

Parkinson's disease (PD) is characterized by the decrease of dopamine (DA) production and release in the substantia nigra and striatum regions of the brain. Transcranial ultrasound has been exploited recently for neuromodulation of the brain in a number of fields. We have stimulated DA release in PC12 cells using low-intensity continuous ultrasound (0.1 W/cm2 - 0.3 W/cm2, 1 MHz), 12 h after exposure at 0.2 W/cm2, 40 s, the amount of DA content eventually increased 78.5% (p = 0.004). After 10-day ultrasonic treatment (0.3 W/cm2, 5 min/d), the DA content in the striatum of PD mice model restored to 81.07% of the control (vs 43.42% in the untreated PD mice model). In addition to this the locomotion activity was restored to the normal level after treatment. We suggest that the low intensity ultrasound-induced DA release can be attributed to a combination of neuron regeneration and improved membrane permeability produced by the mechanical force of ultrasound. Our study indicates that the application of transcranial ultrasound applied below FDA limits, could provide a candidate for relatively safe and noninvasive PD therapy through an amplification of DA levels and the stimulation of dopaminergic neuron regeneration without contrast agents.

Clinical Characteristics and Prognosis of 218 Patients With COVID-19: A Retrospective Study Based on Clinical Classification.

Background: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that has spread worldwide. Methods: This was a retrospective case series involving 218 patients admitted to three tertiary hospitals in the Loudi, Shaoyang, and Xiangtan areas of China from January 21 to June 27, 2020, who were confirmed by RT-PCR to have SARS-CoV-2. The patients' clinical characteristics, laboratory results, treatments, and prognoses based on clinical classification were recorded. Poor outcome was defined as admission to an ICU, the use of mechanical ventilation, or death. Results: The patients were classified into four clinical groups based on disease severity, namely mild (10/218, 5%), moderate (146/218, 67%), severe (24/218, 11%), or critical (14/218, 6%); 24 (11%) asymptomatic cases were also included in the study. The most common symptoms were self-reported cough (162/218, 74%), fever (145/218, 67%), sputum production (99/218, 45%), and fatigue (77/218, 35%). Among the 218 patients, 192 (88%) received lopinavir/ritonavir and interferon-alpha inhalation, and 196 (90%) patients received traditional Chinese medicine. Among the severe and critical patients, 25 (11%) were admitted to an ICU with or without mechanical ventilation, and one patient died. The presence of diabetes [relative risk (RR), 3.0; 95% CI, 1.3-6.8; p = 0.007) or other comorbidities (RR, 5.9; 95% CI, 1.9-17.8; p = 0.002) was independently associated with poor outcome. To date, 20 (9%) patients have retested positive for SARS-CoV-2 RNA after recovering and being discharged. Conclusion: The majority of patients in this case series were clinically classified as having moderate COVID-19. Older patients tended to present with greater levels of clinical severity. The prognosis for patients who were elderly or had diabetes or other chronic comorbidities was relatively poor.

Knowledge of iatrogenic premature ovarian insufficiency among Chinese obstetricians and gynaecologists: a national questionnaire survey.

BACKGROUND: With increasing cases of iatrogenic premature ovarian insufficiency (POI), more clinicians are required to counsel patients regarding the gonadotoxic effects of iatrogenic treatments. This survey aimed to explore obstetricians and gynaecologists' knowledge regarding iatrogenic POI. A national online questionnaire survey was conducted across China. Respondents were asked to select the iatrogenic condition(s) that can cause POI based on their experience and knowledge. RESULTS: Of the 5523 returned questionnaires, 4995 were analysed. Among tumour therapies causing POI, most respondents agreed that radiotherapy (73.5% of respondents) and chemotherapy (64.1%) are risk factors for POI. While only 6.5 and 7.8% of the gynaecological oncologists believed that tumour immunotherapy and tumour-targeting therapy, respectively, may cause ovarian impairment, 31.8 and 22.2% of the non-gynaecologic oncologists believed that these therapies could affect ovarian health. Most respondents believed that ovarian cystectomy (54.4%) was a risk factor for POI. In contrast, only a few respondents believed that hysterectomy with bilateral salpingectomy (39.6%) and uterine artery embolisation (33.5%) could cause ovarian impairment. Only 30.5% of respondents believed that immunosuppressants (ISs) increased the risk of POI. Views differed with experience and hospital setting. CONCLUSIONS: The knowledge of gonadal toxicity due to traditional tumour treatments is generally high among Chinese obstetricians and gynaecologists. A misunderstanding may exist in primary care hospitals and general gynaecologists regarding a link between novel tumour treatments and POI, owing to the lack of convincing evidence. Knowledge of POI caused by hysterectomy and ISs should be improved.