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1.
Front Microbiol ; 15: 1363080, 2024.
Article in English | MEDLINE | ID: mdl-39027094

ABSTRACT

Background: Although numerous studies have illustrated the connection between gut microbiota and endometriosis, a conspicuous gap exists in research focusing on the pathogenesis of endometriosis at various sites and its linkage with infertility. Methods: In this study, we used a two-sample Mendelian randomization analysis to investigate the effect of gut microbiota on the development of endometriosis in different regions, including the uterus, ovary, fallopian tube, pelvic peritoneum, vagina, and rectovaginal septum, as well as the intestine. Additionally, we explored the correlation between gut microbiota and endometriosis-induced infertility. Genetic associations with gut microbes were obtained from genome-wide association study (GWAS) datasets provided by the MiBioGen consortium, whereas endometriosis-related GWAS data were sourced from the FinnGen dataset. In our analysis, single-nucleotide polymorphisms were used as instrumental variables, with the primary estimation of the causal effect performed via the inverse variance weighting method. Our sensitivity analyses incorporated heterogeneity tests, pleiotropy tests, and the leave-one-out method. Results: We identified associations at the genus level between four bacterial communities and endometriosis. Subsequently, several associations between the gut microbiota and various subtypes of endometriosis at different anatomical sites were recognized. Specifically, three genera were linked with ovarian endometriosis, six genera were associated with tubal endometriosis, four genera showed links with pelvic peritoneum endometriosis, five genera were connected with vaginal and rectovaginal septum endometriosis, and seven genera demonstrated linkages with intestinal endometriosis. Additionally, one genus was associated with adenomyosis, and three genera exhibited associations with endometriosis-induced infertility. Conclusion: Our study elucidates associations between gut microbiota and site-specific endometriosis, thereby augmenting our understanding of the pathophysiology of endometriosis. Moreover, our findings pave the way for potential therapeutic strategies targeting gut microbiota for individuals grappling with endometriosis-related infertility.

2.
Article in English | MEDLINE | ID: mdl-38551442

ABSTRACT

Background: Previous studies link overweight/obesity to reduced fertility, highlighting weight intervention as vital for better pregnancy outcomes. However, clarity on the role and efficacy of weight loss in enhancing pregnancy is inconsistent. Objective: This study aimed to assess the impact of individualized weight intervention on pregnancy among Chinese overweight/obese infertile women and explore body composition indexes influencing pregnancy outcomes. Methods: This retrospective study involved 363 overweight/obese infertile women admitted to the First Affiliated Hospital of Guangxi Medical University, Guangxi, China, from June 2017 to November 2020. Among them, 249 received personalized weight intervention (intervention group), while 114 did not (control group). Pregnancy outcomes were compared between the two groups, and changes in body composition before and after intervention were measured. Multivariate logistic regression was employed to analyze factors influencing pregnancy outcomes. Results: The intervention group exhibited significantly higher clinical pregnancy rates, natural pregnancy rates, assisted reproductive pregnancy rates, and induced ovulation (IO) pregnancy rates compared to the control group (all P < .05). Following weight intervention, there were significant decreases in body weight, body mass index (BMI), visceral fat area, and body fat (all P < .01). Logistic regression analysis identified polycystic ovary syndrome as the reason for infertility (OR=3.446, P = .016), ∆body weight %≥10% (OR=2.931, P = .014), and ∆visceral fat area% (OR=1.025, P = .047) as positive factors for a successful pregnancy. Conversely, age≥35 years old (OR=0.337, P = .001), BMI≥25 kg/m2 after intervention (OR=0.279, P < .001), and visceral fat area≥100 cm2 after intervention (OR=0.287, P = .007) were identified as negative factors. Conclusions: Individualized weight management enhances pregnancy outcomes in overweight/obese infertile women. Achieving a reduction in body weight by 10% or more, combined with effective control of visceral fat, proves important in improving pregnancy outcomes. Excess visceral fat emerges as an adverse factor impacting successful pregnancy.

3.
J Reprod Immunol ; 163: 104219, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38422807

ABSTRACT

Endometriosis is a common and frequent disease in gynecology; its etiology and pathogenesis are partially understood and still not clear. The construction of suitable animal models is beneficial for basic research related to the disease. Currently, rodents have the advantages of low cost, fast reproduction, easy rearing, and a similar endometrial structure to humans. Depending on the purpose of the experiment, different molding methods have their advantages. In this paper, we describe the traditional methods of constructing endometriosis rodent models, compare their advantages and disadvantages, and introduce newly developed rodent models, such as cell line injection models, pain models, genetically engineered mouse models, fluorescent tracer models, iron overload models, chemical induction models, and methods of constructing rodent models of different subtypes of endometriosis. Fertility and treatment of endometriosis rodent models are also described. This study provides a reference for researchers in the selection of animal models for pathogenesis and drug treatment studies.


Subject(s)
Disease Models, Animal , Endometriosis , Rodentia , Animals , Female , Humans , Mice , Rats , Endometriosis/pathology , Endometriosis/therapy , Endometriosis/immunology , Endometrium/pathology
4.
Reprod Biol Endocrinol ; 22(1): 19, 2024 Feb 03.
Article in English | MEDLINE | ID: mdl-38308329

ABSTRACT

BACKGROUND: Previous studies have suggested that oil-based contrast agents used during hysterosalpingography (HSG) in infertile patients can enhance fertility. However, limited research has investigated the effect of oil-based contrast medium specifically in individuals with endometriosis-related infertility. OBJECTIVE: This study aims to explore the impact of oil-based contrast medium on fertility outcomes in women with endometriosis-related infertility. METHODS: Conducted at the First Affiliated Hospital of Guangxi Medical University (January 2020 to June 2022), the study included 512 patients undergoing HSG. Patients were categorized into oil-based and non-oil-based groups, and after propensity score matching, demographic characteristics were compared. Main outcomes included clinical pregnancy rates, live birth rates, early miscarriage rates, and ectopic pregnancy rates. RESULTS: In our analysis, the Oil-based group showed significantly better outcomes compared to the Non-oil-based group. Specifically, the Oil-based group had higher clinical pregnancy rates (51.39% vs. 27.36%) and increased live birth rates (31.48% vs. 19.93%). This trend held true for expectant treatment, IUI, and IVF/ICSI, except for surgical treatment where no significant difference was observed. After adjusting for various factors using propensity score matching, the Non-oil-based group consistently exhibited lower clinical pregnancy rates compared to the Oil-based group. The Odds Ratio (OR) was 0.38 (95%CI: 0.27-0.55) without adjustment, 0.34 (0.22-0.51) in multivariable analysis, 0.39 (0.27-0.57) using inverse probability of treatment weighting (IPTW), and 0.22 (0.14-0.35) in propensity score matching. CONCLUSION: Oil-based contrast medium used in HSG for women with endometriosis-related infertility is associated with higher clinical pregnancy rates and live birth rates compared to Non-oil-based contrast medium.


Subject(s)
Endometriosis , Infertility, Female , Pregnancy , Humans , Female , Contrast Media , Hysterosalpingography , Endometriosis/complications , Endometriosis/diagnostic imaging , Infertility, Female/diagnostic imaging , Infertility, Female/etiology , Infertility, Female/therapy , Retrospective Studies , China/epidemiology , Fertility , Pregnancy Rate , Live Birth
5.
PLoS One ; 19(1): e0296190, 2024.
Article in English | MEDLINE | ID: mdl-38215179

ABSTRACT

Endometriosis is a multifactorial disease associated with inflammation. Vitamin D has anti-inflammatory, antiproliferative, anti-oxidative, and immunomodulatory effects. Whether vitamin D levels are correlated with endometriosis is a subject of ongoing debate. This study aimed to examine the association between endometriosis and serum vitamin D levels. From the National Health and Nutrition Examination Survey, this study examined the cross-sectional data of American women aged 20-54 years from 2001 to 2006. After adjusting for covariates, multivariable logistic regression analysis was used to assess correlations. A total of 3,232 women were included in this study. The multiple linear regression model demonstrated a negative correlation between the serum 25-hydroxyvitamin D3 (cholecalciferol) concentration and the risk of endometriosis after controlling for all confounding variables. The odds ratio was 0.73 with a 95% confidence interval of 0.54-0.97 in the adequate vitamin D level group compared with the insufficient vitamin D level group. Our results showed that endometriosis was inversely correlated with serum 25-hydroxyvitamin D3 levels. Further research is needed to establish a causal relationship and determine the potential benefits of maintaining sufficient vitamin D levels for endometriosis prevention.


Subject(s)
Endometriosis , Vitamin D Deficiency , Humans , Female , United States/epidemiology , Vitamin D , Calcifediol , Endometriosis/complications , Nutrition Surveys , Cross-Sectional Studies , Vitamins
6.
Reprod Biol Endocrinol ; 21(1): 120, 2023 Dec 12.
Article in English | MEDLINE | ID: mdl-38087312

ABSTRACT

BACKGROUND: Survival rates of young women undergoing cancer treatment have substantially improved, with a focus on post-treatment quality of life. Ovarian tissue transplantation (OTT) is a viable option to preserve fertility; however, there is no consensus on the optimal transplantation site. Most studies on OTT are nonrandomized controlled trials with limited sample sizes and uncontrolled statistical analyses, leaving the question of which transplant site yields the highest chance of achieving a live birth unanswered. OBJECTIVE: This meta-analysis aimed to assess the effect of different ovarian transplant sites on postoperative reproductive outcomes. METHODS: We adhered to the PRISMA Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Systematic searches were conducted in PubMed, Embase, Web of Science, and the Cochrane Library from inception to September 17, 2023. The inclusion criteria were as follows: (1) women who underwent OTT with a desire for future childbirth, and (2) reports of specific transplant sites and corresponding pregnancy outcomes. The exclusion criteria included the inability to isolate or extract relevant outcome data, case reports, non-original or duplicate data, and articles not written in English. RESULTS: Twelve studies (201 women) were included in the meta-analysis of cumulative live birth rates (CLBR) after OTT. The CLBR, which encompasses both spontaneous pregnancies and those achieved through assisted reproductive technology (ART) following OTT to the ovarian site, was 21% (95% CI: 6-40, I2: 52.81%, random effect). For transplantation to the pelvic site, the live birth rate was 30% (95% CI: 20-40, I2: 0.00%, fixed effect). Combining transplantation to both the pelvic and ovarian sites resulted in a live birth rate of 23% (95% CI: 11-36, I2: 0.00%, fixed effect). Notably, heterotopic OTT yielded a live birth rate of 3% (95% CI: 0-17, I2: 0.00%, fixed effect). CONCLUSION: Pregnancy outcomes were not significantly different after orthotopic ovarian transplantation, and pregnancy and live birth rates after orthotopic OTT were significantly higher than those after ectopic transplantation. REGISTRATION NUMBER: INPLASY202390008.


Subject(s)
Ovary , Quality of Life , Pregnancy , Female , Humans , Reproductive Techniques, Assisted , Pregnancy Outcome , Pregnancy, Multiple , Live Birth , Pregnancy Rate
7.
Biol Reprod ; 109(5): 736-748, 2023 Nov 15.
Article in English | MEDLINE | ID: mdl-37602667

ABSTRACT

BACKGROUND: Invasion of the endometrium by trophoblast cells is a key event during pregnancy, although the underlying mechanism remains unclear. Aquaporin 9 (AQP 9) is expressed in many eukaryotes and is associated with cell invasion. The objective of this study was to evaluate the significance of AQP9 in recurrent spontaneous abortion. METHODS: We screened the GSE22490 dataset and further differentiated aquaporin 9 expression in villi. AQP9 was evaluated as one of the key factors in abortion by injecting AQP9 overexpressed plasmid into the uterus of CD1 mice. Trophoblast cells were transfected with AQP9-overexpressing plasmid or siAQP9 to measure cell proliferation, migration, invasion, and apoptosis. Western blot was used to measure changes in the expression of invasion, epithelial-mesenchymal transformation process, and PI3K/AKT pathway. Finally, the role of AQP9 in PI3K/AKT signaling pathway was determined using the PI3K/AKT inhibitor, LY294002, and activator, 740Y-P. RESULTS: AQP9 is highly expressed in recurrent spontaneous abortion villus. Intrauterine injections of AQP9-overexpressing plasmid into CD1 mice resulted in atrophy and blackness of the gestational sac and increased the absorption rate, it is the causative factor of abortion. AQP9 upregulation inhibited the proliferation, invasion, migration, and epithelial-mesenchymal transformation process in vitro of trophoblast cells and increased cell apoptosis. The opposite result was observed after silencing AQP9. AQP9 overexpression also inhibited the PI3K/AKT pathway. LY294002 and 740Y-P partially recovered AQP9-induced trophoblast invasion and migration via the PI3K/AKT pathway. CONCLUSIONS: AQP9 reduces the invasive ability of trophoblast cells by regulating PI3K/AKT signaling pathway, participating in recurrent spontaneous abortion.


Subject(s)
Abortion, Spontaneous , Aquaporins , Peptide Fragments , Receptors, Platelet-Derived Growth Factor , Humans , Pregnancy , Female , Animals , Mice , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Trophoblasts/metabolism , Aquaporins/genetics , Aquaporins/metabolism , Cell Proliferation , Epithelial-Mesenchymal Transition , Cell Movement
8.
BMC Womens Health ; 23(1): 344, 2023 06 30.
Article in English | MEDLINE | ID: mdl-37391748

ABSTRACT

BACKGROUND: The aim of this retrospective study was to investigate whether oral antibiotics (doxycycline and metronidazole) combined with intrauterine perfusion (gentamicin and dexamethasone) are beneficial for patients with repeated implantation failure (RIF) and chronic endometritis (CE) to improve clinical pregnancy outcomes. METHODS: Patients with RIF and CE were diagnosed using hysteroscopy and histology together. A total of 42 patients were enrolled in the study. All patients received oral antibiotics (doxycycline combined with metronidazole) and 22 patients underwent intrauterine perfusion (gentamicin combined with dexamethasone) immediately after the end of oral antibiotic therapy. Pregnancy outcomes were evaluated during the first in vitro fertilization (IVF) and embryo transfer (ET) cycle. RESULTS: For the first D3 ET after treatment with oral antibiotics (doxycycline and metronidazole) combined with intrauterine perfusion (gentamicin and dexamethasone), higher embryo implantation rate (30.95% vs. 26.67%, P = 0.0308), clinical pregnancy rate (30% vs. 50%, P < 0.001), live birth rate (33.33% vs. 45.45%, P < 0.0001). No fetal malformations or ectopic pregnancies were observed. CONCLUSION: We report oral antibiotics (doxycycline and metronidazole) combined with intrauterine perfusion (gentamicin and dexamethasone) as a novel treatment for CE to improve the outcomes of successful pregnancy compared with those of oral antibiotics alone.


Subject(s)
Doxycycline , Endometritis , Female , Pregnancy , Humans , Metronidazole/therapeutic use , Pregnancy Outcome , Endometritis/drug therapy , Retrospective Studies , Perfusion , Anti-Bacterial Agents/therapeutic use , Embryo Transfer , Fertilization in Vitro , Gentamicins/therapeutic use , Chronic Disease , Embryo Implantation , Dexamethasone
9.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1025307

ABSTRACT

Objective:The purpose of quantitatively evaluating policies related to clinical specialties and exploring existing policy problems and paths to optimization is to provide a reference basis for the formulation and improvement of the policies.Methods:Text mining was conducted on the policies related to clinical specialties issued by the national and some provincial governments since the new medical reform in 2009.The PMC index model was used to construct a comprehensive evaluation system of policies containing 9 primary variables and 35 secondary variables.22 clinical specialty policies were selected for quantitative analysis.Results:Among the 22 clinical specialty policies,6 policies were good-type policies,14 were acceptable-type policies,2 were bad-type policies,and there were no excellent-type policies.The overall design of the policies related to clinical specialties is reasonable,but there is still room for improvement.Conclusion:The quality of China's clinical specialty policy text needs to be improved,and it is necessary to strengthen the top-level design,optimise the content of the objectives,focus on the balanced and sustainable development of the speciality,give full play to the role of demand-based policy tools,and enrich the incentives and constraints,in order to mobilise multi-principal participation in the construction of the clinical speciality enthusiasm.

10.
J Clin Pharm Ther ; 47(7): 870-878, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35249235

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: Reports said immunotherapy is effective for the treatment of idiopathic recurrent miscarriage (RM). Immunotherapy is invasive, and lymphocyte therapy carries some risk of infection. Oral immunosuppressants have the advantages of simple administration and convenience; however, there is no statistical analysis of whether they can improve pregnancy outcomes in patients with idiopathic RM. METHODS: Six databases were searched for studies on oral immunosuppressants and RM; 374 articles were identified. There were two oral immunosuppressants, cyclosporine A and prednisone; two studies were on cyclosporine A and three studies were on prednisone for RM. RESULTS AND DISCUSSION: In total, 554 RM patients were included in this analysis, including 357 patients who received oral immunosuppressive agents and 197 patients who received basic treatment, placebo, or no treatment. Oral administration of cyclosporine A or prednisolone increases live birth rate (OR = 3.6, 95% CI: 2.1-6.15, p < 0.00001) and ongoing pregnancy rate (OR = 8.82, 95% CI: 2.91-26.75, p = 0.0001) in patients with idiopathic RM. Drug use reduced miscarriage rate (OR = 0.21, 95% CI: 0.08-0.52, p = 0.0007); however, there was significant heterogeneity (I2  = 73%) and a moderate-to-severe risk of bias. There was no effect on premature birth rate (OR = 2.26, 95% CI: 0.96-5.31, p = 0.06). This meta-analysis cannot provide a reference for the duration of medication treatment because the selected studies had inconsistent durations. WHAT IS NEW AND CONCLUSION: We did a statistical analysis and found that oral immunosuppressants (including cyclosporine A or prednisolone) can improve pregnancy outcomes in patients with idiopathic RM, increase live birth rate and ongoing pregnancy rate, and reduce miscarriage rate.


Subject(s)
Abortion, Habitual , Pregnancy Outcome , Abortion, Habitual/drug therapy , Abortion, Habitual/etiology , Abortion, Habitual/prevention & control , Cyclosporine/therapeutic use , Female , Humans , Immunosuppressive Agents/therapeutic use , Live Birth , Prednisolone/therapeutic use , Prednisone , Pregnancy
11.
Lancet Glob Health ; 10(1): e114-e123, 2022 01.
Article in English | MEDLINE | ID: mdl-34838202

ABSTRACT

BACKGROUND: Sierra Leone's child and maternal mortality rates are among the highest in the world. However, little is known about the causes of premature mortality in the country. To rectify this, the Ministry of Health and Sanitation of Sierra Leone launched the Sierra Leone Sample Registration System (SL-SRS) of births and deaths. Here, we report cause-specific mortality from the first SL-SRS round, representing deaths from 2018 to 2020. METHODS: The Countrywide Mortality Surveillance for Action platform established the SL-SRS, which involved conducting electronic verbal autopsies in 678 randomly selected villages and urban blocks throughout the country. 61 surveyors, in teams of four or five, enrolled people and ascertained deaths of individuals younger than 70 years in 2019-20, capturing verbal autopsies on deaths from 2018 to 2020. Centrally, two trained physicians independently assigned causes of death according to the International Classification of Diseases (tenth edition). SL-SRS death proportions were applied to 5-year mortality averages from the UN World Population Prospects (2019) to derive cause-specific death totals and risks of death nationally and in four Sierra Leone regions, with comparisons made with the Western region where Freetown, the capital, is located. We compared SL-SRS results with the cause-specific mortality estimates for Sierra Leone in the 2019 WHO Global Health Estimates. FINDINGS: Between Sept 1, 2019, and Dec 15, 2020, we enrolled 343 000 people and ascertained 8374 deaths of individuals younger than 70 years. Malaria was the leading cause of death in children and adults, nationally and in each region, representing 22% of deaths under age 70 years in 2020. Other infectious diseases accounted for an additional 16% of deaths. Overall maternal mortality ratio was 510 deaths per 100 000 livebirths (95% CI 483-538), and neonatal mortality rate was 31·1 deaths per 1000 livebirths (95% CI 30·4-31·8), both among the highest rates in the world. Haemorrhage was the major cause of maternal mortality and birth asphyxia or trauma was the major cause of neonatal mortality. Excess deaths were not detected in the months of 2020 corresponding to the peak of the COVID-19 pandemic. Half of the deaths occurred in rural areas and at home. If the Northern, Eastern, and Southern regions of Sierra Leone had the lower death rates observed in the Western region, about 20 000 deaths (just over a quarter of national total deaths in people younger than 70 years) would have been avoided. WHO model-based data vastly underestimated malaria deaths and some specific causes of injury deaths, and substantially overestimated maternal mortality. INTERPRETATION: Over 60% of individuals in Sierra Leone die prematurely, before age 70 years, most from preventable or treatable causes. Nationally representative mortality surveys such as the SL-SRS are of high value in providing reliable cause-of-death information to set public health priorities and target interventions in low-income countries. FUNDING: Bill & Melinda Gates Foundation, Canadian Institutes of Health Research, Queen Elizabeth Scholarship Program.


Subject(s)
Cause of Death , Mortality, Premature , Adolescent , Adult , Aged , COVID-19 , Child , Child Mortality , Child, Preschool , Female , Humans , Infant , Infant Mortality , Infant, Newborn , Malaria/mortality , Male , Maternal Mortality , Middle Aged , Sierra Leone/epidemiology
12.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-957946

ABSTRACT

Objective:To investigate the relationship of blood lipid levels with bone mass and fracture risk in elderly patients with type 2 diabetes mellitus (T2DM).Methods:A total of 744 elderly patients with T2DM who were treated in Tangshan Second Hospital from November 2018 to May 2020 were divided into normal bone mass group, low bone mass group and osteoporosis group according to bone mass levels. The total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels in the three groups were compared, and the relationship between lipid indexes and bone mass was analyzed. The risk of fracture was calculated in the low bone mass group, and the relationship between lipid index and fracture risk was analyzed by linear regression. The blood lipid index between subjects with fracture and without fracture in osteoporosis group was compared, and the relationship between blood lipid index and fracture was analyzed by logistic regression.Results:There were significant differences in gender and age among the three groups (χ 2=38.80, F=4.94, P<0.05). The normal bone mass group had the smallest proportion of women and the youngest average age, while the osteoporosis group had the largest proportion of women and the average age. maximum. The LDL-C level in normal bone mass group was higher than those in the low bone mass group and the osteoporosis group, and LDL-C level in the low bone mass group was higher than that in the osteoporosis group ( F=3.38, P<0.05). In the low bone mass group, the risk of systemic fracture was 3.50% (2.40%, 4.10%) and hip fracture was 0.99% (0.80%, 1.20%). Linear regression showed that LDL-C and TG were positively correlated with the risk of systemic fractures in the low bone mass group (LDL-C: B=0.98, P=0.006;TG: B=0.23, P=0.024);TG was positively correlated with the risk of hip fracture in the low bone mass group ( B=0.16, P=0.002). In the osteoporosis group, the levels of HDL-C and LDL-C were lower in the patients with fractures than those without fractures ( t=3.24, P=0.001; t=2.98, P=0.003). Logistic regression analysis showed that higher HDL-C and LDL-C levels were protection factors for fracture risk in the osteoporosis group ( β=-2.73, P=0.009, OR=0.06, 95 %CI=0.04-0.10; β=-0.15, P=0.033, OR=0.83, 95 %CI=0.74-0.99). Conclusion:The relationship of serum lipid index with bone mass and fracture risk in hospitalized elderly T2DM patients is complicated, it is suggested to set individual blood lipid control targets according to the bone mass of patients.

13.
Preprint in English | medRxiv | ID: ppmedrxiv-21260872

ABSTRACT

BackgroundIndias official death totals from the COVID pandemic are widely regarded as under-reports. MethodsWe quantified all-cause excess mortality in India, comparing deaths during the peak of the first and second COVID waves (Jul-Dec 2020 and April-June 2021) with month wise deaths in 2015-19 from three sources: Civil Registration System (CRS) mortality reports from 15 states or cities with 37% of Indias population; deaths in 0.2 million health facilities; and a representative survey of 0.14 million adults about COVID deaths. ResultsDuring the first viral wave, the median excess mortality compared to CRS baseline was 22% and 41%, respectively, in included states and cities, rising to 46% and 85% during the second wave. In settings with 10 or more months of data across the two waves, the median excess mortality was 32% and 37% for states and cities, respectively. Deaths in health facilities showed a 27% excess mortality from July 2020-May 2021, reaching 120% during April-May 2021. The national survey found 3.5% of adults reported a COVID death in their household in April-June 2021, approximately doubling the 3.2% expected overall deaths. The national survey showed 29-32% excess deaths from June 1, 2020 to June 27, 2021, most of which were likely to be COVID. This translates to 3.1-3.4 million COVID deaths (including 2.5-2.8 million during April-June 2021). National extrapolations from health facility and CRS data suggest 2.7-3.3 million deaths during the year. ConclusionsIndias COVID death rate may be about 7-8 times higher than the officially reported 290/million population.

14.
Preprint in English | medRxiv | ID: ppmedrxiv-21253429

ABSTRACT

ObjectivesWe sought to understand the spread of SARS-CoV-2 infection in urban India, which has surprisingly low COVID-19 deaths. DesignCross-sectional and trend analyses of seroprevalence in self-referred test populations, and of reported cases and COVID mortality data. Participants448,518 self-referred individuals using a nationwide chain of private laboratories with central testing of SARS-CoV-2 antibodies and publicly available case and mortality data. Setting12 populous cities with nearly 92 million total population. Main outcome measuresSeropositivity trends and predictors (using a Bayesian geospatial model) and prevalence derived from mortality data and infection fatality rates (IFR). ResultsFor the whole of India, 31% of the self-referred individuals undergoing antibody testing were seropositive for SARS-CoV-2 antibodies. Seropositivity was higher in females (35%) than in males (30%) overall and in nearly every age group. In these 12 cities, seroprevalence rose from about 18% in July to 41% by December, with steeper increases at ages <20 and 20-44 years than at older ages. The "M-shaped" age pattern is consistent with intergenerational transmission. Areas of higher childhood measles vaccination in earlier years had lower seropositivity. The patterns of increase in seropositivity and in peak cases and deaths varied substantially across cities. In Delhi, death rates and cases first peaked in June and again in November; Chennai had a single peak in July. Based local IFRs and COVID deaths (adjusted for undercounts), we estimate that 43%-65% of adults above age 20 had been infected (range of mid-estimates of 12%-77%) corresponding 26 to 36 million infected adults in these cities, or an average of 9-12 infected adults per confirmed case. ConclusionEven with relatively low death rates, the large cities of India had remarkably high levels of SARS-CoV-2 infection. Vaccination strategies need to consider widespread intergenerational transmission.

15.
Neuroscience Bulletin ; (6): 353-368, 2021.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-952011

ABSTRACT

Spontaneous activity in the brain maintains an internal structured pattern that reflects the external environment, which is essential for processing information and developing perception and cognition. An essential prerequisite of spontaneous activity for perception is the ability to reverberate external information, such as by potentiation. Yet its role in the processing of potentiation in mouse superior colliculus (SC) neurons is less studied. Here, we used electrophysiological recording, optogenetics, and drug infusion methods to investigate the mechanism of potentiation in SC neurons. We found that visual experience potentiated SC neurons several minutes later in different developmental stages, and the similarity between spontaneous and visually-evoked activity increased with age. Before eye-opening, activation of retinal ganglion cells that expressed ChR2 also induced the potentiation of spontaneous activity in the mouse SC. Potentiation was dependent on stimulus number and showed feature selectivity for direction and orientation. Optogenetic activation of parvalbumin neurons in the SC attenuated the potentiation induced by visual experience. Furthermore, potentiation in SC neurons was blocked by inhibiting the glutamate transporter GLT1. These results indicated that the potentiation induced by a visual stimulus might play a key role in shaping the internal representation of the environment, and serves as a carrier for short-term memory consolidation.

16.
J Clin Invest ; 130(9): 4985-4998, 2020 09 01.
Article in English | MEDLINE | ID: mdl-32516139

ABSTRACT

The brain has evolved in an environment where food sources are scarce, and foraging for food is one of the major challenges for survival of the individual and species. Basic and clinical studies show that obesity or overnutrition leads to overwhelming changes in the brain in animals and humans. However, the exact mechanisms underlying the consequences of excessive energy intake are not well understood. Neurons expressing the neuropeptide hypocretin/orexin (Hcrt) in the lateral/perifonical hypothalamus (LH) are critical for homeostatic regulation, reward seeking, stress response, and cognitive functions. In this study, we examined adaptations in Hcrt cells regulating behavioral responses to salient stimuli in diet-induced obese mice. Our results demonstrated changes in primary cilia, synaptic transmission and plasticity, cellular responses to neurotransmitters necessary for reward seeking, and stress responses in Hcrt neurons from obese mice. Activities of neuronal networks in the LH and hippocampus were impaired as a result of decreased hypocretinergic function. The weakened Hcrt system decreased reward seeking while altering responses to acute stress (stress-coping strategy), which were reversed by selectively activating Hcrt cells with chemogenetics. Taken together, our data suggest that a deficiency in Hcrt signaling may be a common cause of behavioral changes (such as lowered arousal, weakened reward seeking, and altered stress response) in obese animals.


Subject(s)
Feeding Behavior , Hypothalamus , Nerve Net , Neurons , Obesity , Orexins , Animals , Hypothalamus/metabolism , Hypothalamus/pathology , Hypothalamus/physiopathology , Male , Mice , Mice, Transgenic , Nerve Net/metabolism , Nerve Net/pathology , Nerve Net/physiopathology , Neurons/metabolism , Neurons/pathology , Obesity/genetics , Obesity/metabolism , Obesity/pathology , Obesity/physiopathology , Orexins/genetics , Orexins/metabolism , Stress, Psychological/genetics , Stress, Psychological/metabolism , Stress, Psychological/pathology , Stress, Psychological/physiopathology
17.
Preprint in English | medRxiv | ID: ppmedrxiv-20038315

ABSTRACT

BackgroundSince December 2019, more than 100,000 coronavirus disease 2019 (COVID-19) patients have been confirmed globally based on positive viral nucleic acids with real-time reverse transcriptase-polymerase chain reaction (RT-PCR). However, the association between clinical, laboratory and CT characteristics and RT-PCR results is still unclear. We sought to examine this association in detail, especially in recovered patients. MethodsWe analysed data from 52 confirmed patients who had been discharged with COVID-19. The clinical, laboratory, and radiological data were dynamically recorded and compared with the admission and follow-up RT-PCR results. ResultsIn this cohort, 52 admitted COVID-19 patients who had confirmed positive RT-PCR results were discharged after 2 rounds of consecutively negative RT-PCR results. Compared with admission levels, CRP levels (median 4.93 mg/L [IQR: 1.78-10.20]) decreased significantly (p<0.001). and lymphocyte counts (median 1.50x109/L [IQR: 1.11-1.88]) increased obviously after obtaining negative RT-PCR results (p<0.001). Additionally, substantially improved inflammatory exudation was observed on chest CT except for 2 progressed patients. At the two-week follow-up after discharge, 7 patients had re-positive RT-PCR results, including the abovementioned 2 progressed patients. Among the 7 patients, new GGO was demonstrated in 2 patients. There were no significant differences in CPR levels or lymphocyte counts when comparing the negative and re-positive PCT results (all p >0.05). ConclusionHeterogeneity between CT features and RT-PCR results was found in COVID-19, especially in some recovered patients with negative RT-PCR results. Our study highlights that both RT-PCR and chest CT should be considered as the key determinants for the diagnosis and management of COVID-19 patients.

18.
Preprint in English | medRxiv | ID: ppmedrxiv-20031591

ABSTRACT

BackgroundSince the outbreak of the Coronavirus Disease 2019 (COVID-19) in China, respiratory manifestations of the disease have been observed. However, as a fatal comorbidity, acute myocardial injury (AMI) in COVID-19 patients has not been previously investigated in detail. We investigated the clinical characteristics of COVID-19 patients with AMI and determined the risk factors for AMI in them. MethodsWe analyzed data from 53 consecutive laboratory-confirmed and hospitalized COVID-19 patients (28 men, 25 women; age, 19-81 years). We collected information on epidemiological and demographic characteristics, clinical features, routine laboratory tests (including cardiac injury biomarkers), echocardiography, electrocardiography, imaging findings, management methods, and clinical outcomes. ResultsCardiac complications were found in 42 of the 53 (79.25%) patients: tachycardia (n=15), electrocardiography abnormities (n=11), diastolic dysfunction (n=20), elevated myocardial enzymes (n=30), and AMI (n=6). All the six AMI patients were aged >60 years; five of them had two or more underlying comorbidities (hypertension, diabetes, cardiovascular diseases, and chronic obstructive pulmonary disease). Novel coronavirus pneumonia (NCP) severity was higher in the AMI patients than in patients with non-definite AMI (p<0.001). All the AMI patients required care in intensive care unit; of them, three died, two remain hospitalized. Multivariate analyses showed that C-reactive protein (CRP) levels, NCP severity, and underlying comorbidities were the risk factors for cardiac abnormalities in COVID-19 patients. ConclusionsCardiac complications are common in COVID-19 patients. Elevated CRP levels, underlying comorbidities, and NCP severity are the main risk factors for cardiac complications in COVID-19 patients.

19.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-855989

ABSTRACT

Infectious intracranial aneurysm induced by paragonimiasis is very rare in clinic. Interventional treatment is one of the effective therapies and regular antiparasite therapy is necessary after embolization. This retrospective study summarized one case of intracranial aneurysm caused by paragonimiasis involving the medical history, laboratory examination, imaging findings and treatment strategy, and analyzed the diagnosis and treatment of the disease with literature review.

20.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-755167

ABSTRACT

Cholecystolithiasis is a common and frequently-occurring disease at home and abroad. Currently, the main therapeutic treatment is surgical cholecystectomy, especially for laparoscopic cholecys-tectomy, which benefits from less trauma and rapid recovery. However, after cholecystectomy, the original way of bile storage, concentration and excretion is changed. The relationship between these changes and digestive tract tumors has caused controversy among scholars at home and abroad. This review summarized the relationship between post-cholecystectomy and cancer of colon, bile duct, pancreas and liver, in order to provide new thinking for precise surgical treatment of gallstones.

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