Population-Level Relative Effectiveness of the COVID-19 Vaccines and the Contribution of Naturally Acquired Immunity.

BACKGROUND: Immune protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be induced by natural infection or vaccination or both. Interaction between vaccine-induced immunity and naturally acquired immunity at the population level has been understudied. METHODS: We used regression models to evaluate whether the impact of coronavirus disease 2019 (COVID-19) vaccines differed across states with different levels of naturally acquired immunity from March 2021 to April 2022 in the United States. Analysis was conducted for 3 evaluation periods separately (Alpha, Delta, and Omicron waves). As a proxy for the proportion of the population with naturally acquired immunity, we used either the reported seroprevalence or the estimated proportion of the population ever infected in each state. RESULTS: COVID-19 mortality decreased as coverage of ≥1 dose increased among people ≥65 years of age, and this effect did not vary by seroprevalence or proportion of the total population ever infected. Seroprevalence and proportion ever infected were not associated with COVID-19 mortality, after controlling for vaccine coverage. These findings were consistent in all evaluation periods. CONCLUSIONS: COVID-19 vaccination was associated with a sustained reduction in mortality at state level during the Alpha, Delta, and Omicron periods. The effect did not vary by naturally acquired immunity.

The effects of hysteroscopy and laparoscopy for scar diverticulum resection and suture on blood loss, operation time and antibiotic time.

To evaluate the effect of hysteroscopy and suture on uterine scar diverticulum (CSD) after caesarean section and its influence on blood loss, operation time and antibiotic time. Eighty-nine patients with CSD were divided into observation group (n = 41 cases) and control group (n = 48 cases). Control group received laparoscopic scar diverticulum resection and suture, while the observation group received hysteroscopic resection of scar diverticulum. The operation time of the observation group was longer, while the bleeding volume and antibiotic administration time were significantly lower. The surgical treatment efficiency of the observation group (97.56%) was significantly higher. After treatment, the observation group's diverticulum repair indexes (width, depth and lower uterine muscular layer thickness) were better than those of the control group (p<.05). Hysteroscopic resection of scar diverticulum in CSD reduces intraoperative blood loss and the risk of complications, shortens time of antibiotic administration, and promotes diverticulum repair.Impact StatementWhat is already known on this subject? Uterine scar diverticulum (CSD) after caesarean section, also called postoperative uterine incision defect (PCSD), is due to poor healing of the uterine incision after caesarean section.What do the results of this study add? Hysteroscopic resection of scar diverticulum in CSD has a significant clinical effect, which can effectively reduce intraoperative blood loss and the risk of complications, shorten the time of antibiotic administration, and promote diverticulum repair.What are the implications of these findings for clinical practice and/or further research? Clinical effect of hysteroscopic resection of scar diverticulum in CSD is significant.

Severe Acute Respiratory Syndrome Coronavirus 2 Transmission in Georgia, USA, February 1-July 13, 2020.

The serial interval and effective reproduction number for coronavirus disease (COVID-19) are heterogenous, varying by demographic characteristics, region, and period. During February 1-July 13, 2020, we identified 4,080 transmission pairs in Georgia, USA, by using contact tracing information from COVID-19 cases reported to the Georgia Department of Public Health. We examined how various transmission characteristics were affected by symptoms, demographics, and period (during shelter-in-place and after subsequent reopening) and estimated the time course of reproduction numbers for all 159 Georgia counties. Transmission varied by time and place but also by persons' sex and race. The mean serial interval decreased from 5.97 days in February-April to 4.40 days in June-July. Younger adults (20-50 years of age) were involved in most transmission events occurring during or after reopening. The shelter-in-place period was not long enough to prevent sustained virus transmission in densely populated urban areas connected by major transportation links.

Interleukin 35 protects cardiomyocytes following ischemia/reperfusion-induced apoptosis via activation of mitochondrial STAT3.

Mitochondrial reactive oxygen species (mtROS)-induced apoptosis has been suggested to contribute to myocardial ischemia/reperfusion injury. Interleukin 35 (IL-35), a novel anti-inflammatory cytokine, has been shown to protect the myocardium and inhibit mtROS production. However, its effect on cardiomyocytes upon exposure to hypoxia/reoxygenation (H/R) damage has not yet been elucidated. The present study aimed to investigate the potential protective role and underlying mechanisms of IL-35 in H/R-induced mouse neonatal cardiomyocyte injury. Mouse neonatal cardiomyocytes were challenged to H/R in the presence of IL-35, and we found that IL-35 dose dependently promotes cell viability, diminishes mtROS, maintains mitochondrial membrane potential, and decreases the number of apoptotic cardiomyocytes. Meanwhile, IL-35 remarkably activates mitochondrial STAT3 (mitoSTAT3) signaling, inhibits cytochrome c release, and reduces apoptosis signaling. Furthermore, co-treatment of the cardiomyocytes with the STAT3 inhibitor AG490 abrogates the IL-35-induced cardioprotective effects. Our study identified the protective role of IL-35 in cardiomyocytes following H/R damage and revealed that IL-35 protects cardiomyocytes against mtROS-induced apoptosis through the mitoSTAT3 signaling pathway during H/R.

Correction to: L-Fucose ameliorates high-fat diet-induced obesity and hepatic steatosis in mice.

An amendment to this paper has been published and can be accessed via the original article.

Protective Effects of Hydrogen-Rich Water Against Cartilage Damage in a Rat Model of Osteoarthritis by Inhibiting Oxidative Stress, Matrix Catabolism, and Apoptosis.

BACKGROUND The aim of this study was to investigate the mechanisms underlying the potential effects of hydrogen-rich water (HW) on articular cartilage in a rat osteoarthritis (OA) model. MATERIAL AND METHODS A rat model of OA was established using the modified Hulth method, and rats were forced to exercise for 30 min every day 1 week after surgery for 7 weeks. Mankin's method was used to score the severity of OA. The animals were assigned into the OA group, OA+HW group, and sham operation group. After 8 weeks, the animals in the OA group had a Mankin score >8 points, and HW was administered into the knee joint. After 2 weeks of treatment, articular cartilage was obtained for pathological examination, consisting of hematoxylin and eosin, toluidine blue, and Hoechst staining, as well as quantitative real-time PCR and Western blot analyses. This combination of pharmacological and molecular biological analyses was performed to examine the mechanism underlying the protective effect of HW on articular cartilage. RESULTS The antioxidant effects of HW suppressed oxidative damage, which may have aided the inhibition of ECM-degrading enzymes (MMP3, MMP13, ADAMT4, and ADAMT5), the upregulation of Col II and aggrecan expression, and the downregulation of COX-2, iNOS, and NO expression. The results of HE staining indicated intra-articular treatment of HW attenuated cartilage degradation. However, Hoechst staining in the OA group indicated the nuclei of the fragmented chondrocytes were condensed compared to the sham operation group, and this effect was inhibited by HW. CONCLUSIONS HW showed a protective effect against the progression of OA in an animal model, which may have been mediated by its anti-oxidant and anti-apoptotic activities.

Overexpression of chloride channel-3 (ClC-3) is associated with human cervical carcinoma development and prognosis.

BACKGROUND: Cervical carcinoma is a major gynecological cancer and causes cancer-related deaths in worldwide, the latent pathogenesis and progress of cervical cancer is still under research. ClC-3 may be an important promoter for aggressive metastasis of malignant tumors. In this research, we explore the ClC-3 expression in cervical carcinoma and its underlying clinical significance, trying to illuminate ClC-3 probable function in the neoplasm malignant behavior, development and prognosis. METHODS: Paraffin-embedded cervical (n = 168) and lymph node (n = 100) tissue specimens were analysed by immunohistochemistry. Fresh human cervical tissue specimens (n = 165) and four human cervical cell lines were tested for ClC-3 mRNA and protein expression levels by quantitative real-time PCR and western blotting. The relationship between the expression levels of ClC-3, the pathological characteristics of the carcinoma, and the clinical prognosis were statistically analysed. RESULTS: In normal and precancerous (LSIL, HSIL) cervical tissues as well as cervical carcinoma tissues, both ClC-3 mRNA and protein expression levels increased significantly (p < 0.05). The expression level of ClC-3 was closely-related to the histological differentiation (p = 0.029), tumour staging (p = 0.016), tumour size (p = 0.039), vascular invasion (p = 0.045), interstitial infiltration depth (p = 0.012), lymphatic metastasis (p = 0.036), and HPV infection (p = 0.022). In an in vitro experiment, ClC-3 mRNA and protein were found to be overexpressed both in the HeLa and SiHa cell lines, but low expression levels were detected in the C-33A and H8 cell lines (p < 0.05). Furthermore, the high expression levels of ClC-3 was significantly correlated to poor survival in cervical carcinoma patients (Log-rank test, p = 0.046). CONCLUSIONS: These data suggest that overexpression of ClC-3 is closely associated with human cervical carcinoma progression and poor prognosis; this suggests that ClC-3 may function as a patent tumour biomarker and a latent therapeutic target for cervical carcinoma patients.

Chloride channel-3 is required for efficient tumour cell migration and invasion in human cervical squamous cell carcinoma.

OBJECTIVE: Chloride channel-3 (ClC-3) plays significant roles in various physiological and physiopathological activities, including cell migration and invasion ability. The purpose of this study was to evaluate whether ClC-3 influences the migration and invasion of cervical squamous cell carcinoma cells and its possible mechanisms. METHODS: Paraffin-embedded cervical tissues, including normal cervical tissues, cervical squamous cell carcinoma (SCC) and homologous paracancerous tissues, were collected. The cervical squamous cell carcinoma and matched paracarcinoma fresh tissues specimens were collected from 49 patients with SCC, and the normal cervical tissues were collected from 45 non-cervical squamous cell carcinoma patients. The human cervical squamous carcinoma cell line SiHa was cultured. ClC-3 expression was assessed by real-time RT-PCR, immunohistochemistry and Western blot, and the expression of phospho-PI3K/Akt/mTOR and matrix metalloproteinase-9 (MMP-9) was detected by Western blot. Small interfering RNA (siRNA) technology was used to knockdown ClC-3 expression. SiHa cell migration and invasion ability were measured using Transwell assays with or without Matrigel-coated membranes. RESULTS: ClC-3 mRNA and protein expression in SCC tissues from cervical squamous cell carcinoma patients was significantly upregulated, and no significant difference was noted between the matched paracarcinoma fresh tissue from the same patients and non-cervical cancer patients. SiHa cell migration and invasion and phospho-PI3K/Akt/mTOR and MMP-9 expression were attenuated by knocking down ClC-3 expression using ClC-3 siRNA. CONCLUSIONS: ClC-3 participates in the processes of SCC cell migration and invasion and regulates MMP-9 expression via the PI3K/Akt/mTOR signaling pathway.

L-Fucose ameliorates high-fat diet-induced obesity and hepatic steatosis in mice.

BACKGROUND: L-Fucose (Fuc), a six-deoxy hexose monosaccharide, is present endogenously in humans and animals and has a wide range of biological functions. In the present study, we aimed to examine the effect of Fuc on obesity and hepatic steatosis in mice fed a high-fat diet (HFD). METHODS: C57BL/6 mice were fed a normal chow (NC) or HFD for 18 weeks to induce obesity and fatty liver. Fuc was administered intragastrically from the 8th week to the end of the experiment (18 weeks). RESULTS: Metagenomic analysis showed that HFD altered the genomic profile of gut microbiota in the mice; specifically, expression of alpha-L-fucosidase, the gene responsible for Fuc generation, was markedly reduced in the HFD group compared with that in the NC group. Fuc treatment decreased body weight gain, fat accumulation, and hepatic triglyceride elevation in HFD-fed mice. In addition, Fuc decreased the levels of endotoxin-producing bacteria of the Desulfovibrionaceae family and restored HFD-induced enteric dysbiosis at both compositional and functional levels. CONCLUSION: Our findings suggest that Fuc might be a novel strategy to treat HFD-induced obesity and fatty liver.

Trends in incidence and mortality for ovarian cancer in China from 1990 to 2019 and its forecasted levels in 30 years.

BACKGROUND: The specific long-term trend in ovarian cancer (OC) rates in China has been rarely investigated. We aimed to estimate the temporal trends in incidence and mortality rates from 1990 to 2019 in OC and predict the next 30-year levels. Data on the incidence, mortality rates, and the number of new cases and deaths cases due to OC in the China cohort from 1990 to 2019 were retrieved from the Global Burden of Disease Study 2019. Temporal trends in incidence and mortality rates were evaluated by joinpoint regression models. The incidence and mortality rates and the estimated number of cases from 2020 to 2049 were predicted using the Bayesian age-period-cohort model. RESULTS: Consecutive increasing trends in age-standardized incidence (average annual percent change [AAPC] = 2.03; 95% confidence interval [CI], 1.90-2.16; p < 0.001) and mortality (AAPC = 1.58; 95% CI, 1.38-1.78; p < 0.001) rates in OC were observed from 1990-2019 in China. Theoretically, both the estimated age-standardized (per 100,000 women) incidence (from 4.77 in 2019 to 8.95 in 2049) and mortality (from 2.88 in 2019 to 4.03 in 2049) rates will continue to increase substantially in the coming 30 years. And the estimated number of new cases of, and deaths from OC will increase by more than 3 times between 2019 and 2049. CONCLUSIONS: The disease burden of OC in incidence and mortality has been increasing in China over the past 30 years and will be predicted to increase continuously in the coming three decades.

Factors driving norovirus transmission in long-term care facilities: A case-level analysis of 107 outbreaks.

Norovirus is the most common cause of gastroenteritis outbreaks in long-term care facilities (LTCFs) in the United States, causing a high burden of disease in both residents and staff. Understanding how case symptoms and characteristics contribute to norovirus transmission can lead to more informed outbreak control measures in LTCFs. We examined line lists for 107 norovirus outbreaks that took place in LTCFs in five U.S. states from 2015 to 2019. We estimated the individual effective reproduction number, Ri, to quantify individual case infectiousness and examined the contribution of vomiting, diarrhea, and being a resident (vs. staff) to case infectiousness. The associations between case characteristics and Ri were estimated using a multivariable, log-linear mixed model with inverse variance weighting. We found that cases with vomiting infected 1.28 (95 % CI: 1.11, 1.48) times the number of secondary cases compared to cases without vomiting, and LTCF residents infected 1.31 (95 % CI: 1.15, 1.50) times the number of secondary cases compared to staff. There was no difference in infectiousness between cases with and without diarrhea (1.07; 95 % CI: 0.90, 1.29). This suggests that vomiting, particularly by LTCF residents, was a primary driver of norovirus transmission. These results support control measures that limit exposure to vomitus during norovirus outbreaks in LTCFs.

Adipose Mesenchymal Stem Cell-Derived Exosomes Enhance PC12 Cell Function through the Activation of the PI3K/AKT Pathway.

Transplantation of mesenchymal stem cells has been considered as an auspicious treatment for repairing nerve injuries. The rat adrenal pheochromocytoma cell line (PC12) is one of the traditional models for the study of neuronal differentiation and neuroregeneration in vitro. However, the effects of adipose mesenchymal stem cell-derived exosomes (ADSC-exo) on PC12 cells remain unclear and to be elucidated. In our study, the effects of ADSC-exo on PC12 cells were investigated. ADSC-exo were isolated by ultracentrifugation and characterized by transmission electron microscopy, flow nanoanalysis, and western blot. The effects of ADSC-exo on PC12 cell proliferation, migration, apoptosis, and the protein levels were analyzed using CCK-8 assay and EdU incorporation assay, transwell migration assay and scratch wound assay, flow cytometry, and western blot, respectively. We successfully isolated and purified exosomes from ADSC supernatant and found that ADSC-exo treatment significantly promoted PC12 cell proliferation and migration, inhibited their apoptosis, and activated the PI3K/AKT pathway, while PI3K/AKT signaling repression using LY294002 exhibited the opposite effects. The results showed that ADSC-exo promoted proliferation and migration and inhibited apoptosis of PC12 through the activation of the PI3K/AKT pathway. Thus, the effect of ADSC-exo on PC12 cells may suggest ADSC-exo may be a promising therapeutic for nerve damage.

Comparison of biological characteristics of mesenchymal stem cells derived from the human umbilical cord and decidua parietalis.

Mesenchymal stem cells (MSCs) are derived from the mesoderm and have the self­renewal capacity and multi­directional differentiation potential of adult stem cells. Stem cells from different sources have different molecular and growth characteristics; therefore, the mechanisms and effects of stem cell­mediated repair and tissue regeneration may be different. The aim of the present study was to compare the biological characteristics of MSCs derived from the umbilical cord (UC­MSCs) and MSCs derived from the decidua parietalis (DP­MSCs), and to provide new evidence for the selection of seed cells in regenerative medicine. Growth curves, cell doubling times, colony formation rates, immunophenotypes, differentiation capacities and secretion­factor levels of MSCs derived from the two sources were analysed. UC­MSCs and DP­MSCs exhibited similar properties with regards to morphology, spiral growth, immunophenotype, and potential to differentiate into osteoblasts and adipocytes. For each cell type, the positive rates of the cell surface markers CD73, CD90 and CD105 were >95%, whereas CD34 and CD45 positive rates were <1%. Analyses of in vitro growth kinetics revealed shorter cell­doubling times, and higher proliferative rates and colony formation rates of UC­MSCs compared with DP­MSCs (P<0.05). The concentration of basic fibroblast growth factor in the supernatant from UC­MSCs was higher compared with that from DP­MSCs (P<0.05). However, UC­MSC supernatants exhibited lower levels of of keratinocyte growth factor, vascular endothelial growth factor and stem cell factor compared with DP­MSCs (P<0.05). In conclusion, in vitro characterization of MSCs from these tissue sources revealed a number of common biological properties. However, the results also demonstrated clear biological distinctions and suggested that UC­MSCs may have more effective application prospects.

Decreased expression of the CHD5 gene and its clinicopathological significance in breast cancer: Correlation with aberrant DNA methylation.

Chromodomain helicase DNA binding protein 5 (CHD5) has been identified as a tumor suppressor in mouse models. Downregulation of CHD5 gene expression is frequently observed in breast cancer cells and tissues. This may be explained by deletions or other mutations; however, alternative mechanisms require investigation. Therefore, the present study evaluated whether CHD5 aberrant methylation has a role in primary breast tumors. A total of 389 patients with primary breast cancer (including 252 paraffin-embedded specimens and 137 fresh-frozen samples) were enrolled in the present study. In the current study, reverse transcription-polymerase chain reaction (RT-PCR) and nested-methylation-specific PCR were used to analyze the mRNA expression and promoter methylation of CHD5 genes in a large cohort of breast cancer patients, and to investigate their associations with the clinicopathological features of tumors. CHD5 expression was significantly suppressed in breast cancer tissues compared with normal breast tissues when analyzed by RT-PCR. Furthermore, DNA methylation of CHD5 was more prevalent in breast tumors than in normal tissues. CHD5 mRNA levels correlated with the degree of CHD5 methylation in breast cancer tissues. Clinicopathological correlation analysis revealed that CHD5 promoter methylation was associated with estrogen receptor and progesterone receptor status. Thus, downregulation of CHD5, mediated by abnormal methylation, may contribute to the development and progression of breast cancer.

Protective effect of Panax quinquefolium 20(S)-protopanaxadiol saponins, isolated from Pana quinquefolium, on permanent focal cerebral ischemic injury in rats.

Oxidative stress is significant in the pathogenesis of cerebral ischemia. Panax quinquefolium 20(S)-protopanaxadiol saponins (PQDS) have been demonstrated to exhibit a variety of biological effects in the cardiovascular system as a result of their antioxidant properties. However, little is known regarding the effect of PQDS on cerebral ischemia. The purpose of this study was to investigate whether PQDS exhibited protective effects against cerebral ischemia. A model of cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in Sprague-Dawley rats. Adult male rats were randomly divided into five groups: Sham, MCAO and PQDS treatment groups at doses of 12.5, 25.0 and 50.0 mg/kg. The effects of PQDS on neurological deficits, cerebral infarct area, brain water content, and the malondialdehyde (MDA) and Ca2+ levels and Na+-K+-ATPase and superoxide dismutase (SOD) activities in the brain tissue were analyzed, and the nitric oxide (NO) content and nitric oxide synthase (NOS) activity in the serum were evaluated. Moreover, the expression of Bcl-2 was analyzed using western blotting. Pretreatment with PQDS (25.0 and 50.0 mg/kg) significantly reduced the neurological deficit score, decreased the infarcted area and decreased the brain water content from 83.09 to 80.27% (P<0.05). In addition, PQDS pretreatment decreased the NOS activity and the NO levels in the serum compared with those in the MCAO group. Furthermore, pretreatment with PQDS (25.0 and 50.0 mg/kg) significantly increased the activities of SOD and Na+-K+-ATPase and decreased the levels of Ca2+ and MDA in the brain tissue (P<0.05) compared with those in the MCAO group. Pretreatment with PQDS (25.0 and 50.0 mg/kg) also increased the protein expression level of Bcl-2 compared with that in the MCAO group. The histopathological results demonstrated the protective effect of PQDS on ischemic injury. The results indicated that PQDS has protective effects against ischemic injury in rats. The mechanism may be associated with the inhibition of oxidative stress and apoptosis.