The efficacy of bisphosphonates for osteoporosis in young Cushing's disease patients with biochemical remission: a retrospective cohort study.

Background: Patients with Cushing's disease (CD) often experience slow recovery of bone mineral density (BMD), and the effectiveness of anti-osteoporosis drugs in young CD patients who have achieved biochemical remission after surgery is not well understood. Therefore, we aimed to explore whether bisphosphonates could help accelerate the recovery of osteoporosis in young CD patients with remission. Methods: We retrospectively enrolled 34 young patients with CD who achieved postoperative biochemical remission. All patients suffered from osteoporosis before surgery and were divided into postoperative bisphosphonate treatment group (16 cases) and without bisphosphonate treatment group (18 cases). Clinical data, BMD (Z Value), and bone turnover markers were collected at the time of diagnosis and one year after successful tumor resection. Results: The Z values in the lumbar spine showed slight improvement in both groups at follow-up compared to baseline, but this improvement was not statistically significant. There was no significant difference observed between the two groups at follow-up. One year after operation, bone formation markers (OC and P1NP) were significantly higher than those at baseline in both groups. However, OC and P1NP in the bisphosphonate treatment group were lower than those in control group at one year follow-up. In without bisphosphonate treatment group, ß-CTX from follow-up visit was higher than that at baseline, while no significant difference was observed in the bisphosphonate treatment group before and after surgery. Conclusion: Young patients with Cushing's disease combined with osteoporosis might not benefit from bisphosphonate therapy for osteoporosis recovery in the first year after achieving biochemical remission.

Early identification of postoperative remission for thyrotropin-secreting adenomas.

OBJECTIVE: Thyrotropin-secreting adenoma (TSHoma) is a rare type of pituitary adenoma, occurring in one per million people. Little is known about TSHoma. We summarized the demographic, clinical and hormonal characteristics of TSHoma based on a single-centre experience. Moreover, we explored the predictive value of postoperative thyroid function for long-term remission. DESIGN, PATIENTS AND MEASUREMENTS: We retrospectively analysed 63 patients who were diagnosed as TSHoma and surgically treated at our hospital from January 2015 to June 2021. The preoperative clinical characteristics were analysed and compared between remission and nonremission groups. Thyroid function was measured at 1 day, 1 month, 3 months, 6 months, 12 months and over 12 months after surgery to determine whether they could predict long-term remission. RESULTS: The male to female ratio for TSHoma was 1.25. The mean age at diagnosis was 45 ± 12 years. Clinical presentation was varied, presenting with hyperthyroidism (68.25%), space-occupying effect (15.87%), amenorrhea (7.14% of female patients) and nonsymptoms (22.22%). 88.14% of patients achieved postoperative endocrinological remission. Larger tumour size and tumour invasion into cavernous sinus and suprasellar with chiasmal compression were strong predictors of lower rates of endocrinological remission. Postoperative thyroid function at 3 months was a viable diagnostic predictor for postoperative remission, especially for FT4 level with a 20.65 pmol/L cutoff. CONCLUSIONS: Tumour size and extent are major prognostic factors for remission. Postoperative thyroid function at 3 months could be used as a clinical prediction tool for long-term endocrinological remission.

Human respiratory syncytial virus subgroups A and B outbreak in a kindergarten in Zhejiang Province, China, 2023.

Background: In May-June 2023, an unprecedented outbreak of human respiratory syncytial virus (HRSV) infections occurred in a kindergarten, Zhejiang Province, China. National, provincial, and local public health officials investigated the cause of the outbreak and instituted actions to control its spread. Methods: We interviewed patients with the respiratory symptoms by questionnaire. Respiratory samples were screened for six respiratory pathogens by real-time quantitative polymerase chain reaction (RT-PCR). The confirmed cases were further sequenced of G gene to confirm the HRSV genotype. A phylogenetic tree was reconstructed by maximum likelihood method. Results: Of the 103 children in the kindergarten, 45 were classified as suspected cases, and 25 cases were confirmed by RT-PCR. All confirmed cases were identified from half of classes. 36% (9/25) were admitted to hospital, none died. The attack rate was 53.19%. The median ages of suspected and confirmed cases were 32.7 months and 35.8 months, respectively. Nine of 27 confirmed cases lived in one community. Only two-family clusters among 88 household contacts were HRSV positive. A total of 18 of the G gene were obtained from the confirmed cases. Phylogenetic analyses revealed that 16 of the sequences belonged to the HRSV B/BA9 genotype, and the other 2 sequences belonged to the HRSV A/ON1 genotype. The school were closed on June 9 and the outbreak ended on June 15. Conclusion: These findings suggest the need for an increased awareness of HRSV coinfections outbreak in the kindergarten, when HRSV resurges in the community after COVID-19 pandemic.

Estimated glucose disposal rate predicts the risk of diabetic peripheral neuropathy in type 2 diabetes: A 5-year follow-up study.

BACKGROUND: Insulin resistance is associated with chronic complications of diabetes, including diabetic peripheral neuropathy (DPN). Estimated glucose disposal rate (eGDR), calculated by the common available clinical factors, was proved to be an excellent tool to measure insulin resistance in large patient population. Few studies have explored the association between eGDR and DPN longitudinally. Therefore, we performed the current study to analyze whether eGDR could predict the risk of DPN. METHODS: In this prospective study, 366 type 2 diabetes (T2DM) subjects without DPN were enrolled from six communities in Shanghai in 2011-2014 and followed up until 2019-2020. Neuropathy was assessed by Michigan Neuropathy Screening Instrument (MSNI) at baseline and at the end of follow-up. FINDINGS: After 5.91 years, 198 of 366 participants progressed to DPN according to MNSI examination scores. The incidence of DPN in the low baseline eGDR (eGDR < 9.15) group was significantly higher than in the high baseline eGDR (eGDR ≥ 9.15) group (62.37% vs. 45.56%, p = .0013). The incidence of DPN was significantly higher in patients with sustained lower eGDR level (63.69%) compared with those with sustained higher eGDR level (35.80%). Subjects with low baseline eGDR (eGDR < 9.15) had significantly higher risk of DPN at the end of follow-up (odds ratio = 1.75), even after adjusting for other known DPN risk factors. CONCLUSIONS: The 5-year follow-up study highlights the importance of insulin resistance represented by eGDR in the development of DPN in T2DM. Diabetic patients with low eGDR are more prone to DPN and, therefore, require more intensive screening and more attention.

Diversity and composition of active and total bacteria in rhizospheric soil in response to continuous cropping years of Panax notoginseng.

The synchronous research and analysis of total and active soil microbial communities can provide insight into how these communities are impacted by continuous cropping years and pathogen infection. The diversity of total and active bacteria in rhizospheric soil of 2-year-old and 3-year-old healthy and diseased Panax notoginseng can comprehensively reveal the bacterial response characteristics in continuous cropping practice. The results showed that 4916 operational taxonomic units (OTUs) were found in the rhizospheric soil bacterial community of P. notoginseng at the DNA level, but only 2773 OTUs were found at the RNA level. The rhizospheric environment had significant effects on the active and bacterial communities, as indicated by the number of OTUs, Shannon, Chao1, Faith's phylogenetic diversity (Faith's PD), and Simpson's diversity indexes. The DNA level can better show the difference in diversity level before and after infection with root rot. The bacterial Chao1 and Faith's PD diversity indexes of 2-year-old root rot-diseased P. notoginseng rhizospheric soil (D2) were higher than that of healthy plants, while the bacterial Shannon diversity index of 3-year-old root rot-diseased P. notoginseng rhizospheric soil (D3) was the lowest in the total bacteria. Principal coordinate analysis (PCoA) illustrated that the total bacterial species composition changed markedly after root rot disease. There were significant differences in the composition of active bacterial species between the 2-year and 3-year rhizospheres. In conclusion, the total and active edaphic rhizospheric bacterial communities could provide important opportunities to understand the responses of bacteria to continuous cropping of P. notoginseng. Differential responses of total and active edaphic rhizosphere bacterial communities to continuous cropping of Panax notoginseng.

Association of IGF-1 Level with Low Bone Mass in Young Patients with Cushing's Disease.

Purpose: Few related factors of low bone mass in Cushing's disease (CD) have been identified so far, and relevant sufficient powered studies in CD patients are rare. On account of the scarcity of data, we performed a well-powered study to identify related factors associated with low bone mass in young CD patients. Methods: This retrospective study included 153 CD patients (33 males and 120 females, under the age of 50 for men and premenopausal women). Bone mineral density (BMD) of the left hip and lumbar spine was measured by dual energy X-ray absorptiometry (DEXA). In this study, low bone mass was defined when the Z score was -2.0 or lower. Results: Among those CD patients, low bone mass occurred in 74 patients (48.37%). Compared to patients with normal BMD, those patients with low bone mass had a higher level of serum cortisol at midnight (22.31 (17.95-29.62) vs. 17.80 (13.75-22.77), p=0.0006), testosterone in women (2.10 (1.33-2.89) vs. 1.54 (0.97-2.05), p=0.0012), higher portion of male (32.43% vs. 11.54%, p=0.0016) as well as hypertension (76.12% vs. 51.67%, p=0.0075), and lower IGF-1 index (0.59 (0.43-0.76) vs. 0.79 (0.60-1.02), p=0.0001). The Z score was positively associated with the IGF-1 index in both the lumbar spine (r = 0.35153, p < 0.0001) and the femoral neck (r = 0.24418, p=0.0057). The Z score in the femoral neck was negatively associated with osteocalcin (r = -0.22744, p=0.0229). Compared to the lowest tertile of the IGF-1 index (<0.5563), the patients with the highest tertile of the IGF-1 index (≥0.7993) had a lower prevalence of low bone mass (95% CI 0.02 (0.001-0.50), p=0.0002), even after adjusting for confounders such as age, gender, duration, BMI, hypertension, serum cortisol at midnight, PTH, and osteocalcin. Conclusions: The higher IGF-1 index was independently associated with lower prevalence of low bone mass in young CD patients, and IGF-1 might play an important role in the pathogenesis of CD-caused low bone mass.

The recovery time of hypothalamic-pituitary-adrenal axis after curative surgery in Cushing's disease and its related factor.

PURPOSE: Patients with Cushing's disease (CD) experienced transient central adrenal insufficiency (CAI) after successful surgery. However, the reported recovery time of hypothalamic-pituitary-adrenal (HPA) axis varied and the related factors which could affect recovery time of HPA axis had not been extensively studied. This study aimed to analyze the duration of CAI and explore the factors affecting HPA axis recovery in post-operative CD patients with biochemical remission. METHODS: Medical records of diagnosis with CD in Huashan Hospital were reviewed between 2014 and 2020. 140 patients with biochemical remission and regular follow-up after surgery were enrolled in this retrospective cohort study according to the criteria. Demographic details, clinical and biochemical information at baseline and each follow-up (within 2 years) were collected and analyzed. RESULTS: Overall, 103 patients (73.6%) recovered from transient CAI within 2 years follow-up and the median recovery time was 12 months [95% confidence intervals (CI): 10-14]. The age was younger and midnight ACTH at baseline was significantly lower, while the TT3 and FT3 levels were significantly higher in patients with recovered HPA compared to patients with persistent CAI at 2-year follow-up (p < 0.05). In persistent CAI group, more patients underwent partial hypophysectomy. TT3 at diagnosis was an independent related factor of the recovery of HPA axis, even after adjusting for gender, age, duration, surgical history, maximum tumor diameter, surgical strategy, and postoperative nadir serum cortisol level (p = 0.04, OR: 6.03, 95% CI: 1.085, 22.508). Among patients with unrecovered HPA axis at 2-year follow-up, 23 CAI patients (62%) were accompanied by multiple pituitary axis dysfunction besides HPA axis, including hypothyroidism, hypogonadism, or central diabetes insipidus. CONCLUSION: HPA axis recovered in 73.6% of CD patients within 2 years after successful surgery, and the median recovery time was 12 months. TT3 level at diagnosis was an independent related factor of postoperative recovery of HPA axis in CD patients. Moreover, patients coexisted with other hypopituitarism at 2-year follow-up had a high probability of unrecovered HPA axis.

Glycogen synthesis kinase-3ß involves in the analgesic effect of liraglutide on diabetic neuropathic pain.

AIMS: Explore whether Glycogen synthesis kinase-3ß (GSK3ß) involved in the analgesic effect of liraglutide on diabetic neuropathic pain (DNP). METHODS: DNP was induced by streptozocin (STZ) in WT and GSK3ß(S9A) mice, which carried a constitutively active form of GSK3ß. DNP mice were intracerebroventricularly injected with liraglutide 5 weeks after STZ injection. The behavior of neuropathic pain was evaluated 2 h after drugs administration. The microglial activation and the expression of NOD-like receptor protein 3 (NLRP3) in microglia in cortex were evaluated. The role of GSK3ß in the inhibitory effect of liraglutide on the NLRP3 inflammasome was explored in BV2 microglia. RESULTS: Intracerebroventricular administration of liraglutide significantly relieved neuropathic pain and inhibited the activation of cortical microglia in WT mice with DNP. But the effect of liraglutide disappeared in GSK3ß(S9A) mice. In BV2 microglia, GSK3ß inhibitor significantly suppressed NLRP3 inflammasome activation. And activating GSK3ß through GSK3ß(S9A) lentivirus significantly blocked the inhibitory effect of liraglutide on NLRP3 inflammasome in BV2 microglia. Intracerebroventricular administration of liraglutide significantly inhibited the expression of NLRP3 in cortex microglia of DNP group in WT mice but failed in GSK3ß(S9A) mice. CONCLUSION: GSK3ß involves in the analgesic effect of liraglutide on DNP through NLRP3 inflammasome in microglia.

A New Species of Nazeris Fauvel from Guangdong, China (Coleoptera, Staphylinidae, Paederinae).

A new species, Nazeris qilinshanensis Guo, Liu & Sun sp. nov. from Qilinshan, Guangdong province is described and illustrated. The external morphological characteristics and genitalia of the new species are described in detail and illustrated. The complete mitochondrial genome of N. qilinshanensis was sequenced and placed in a phylogenetic context. Phylogenetic analysis based on mitochondrial genomes showed that N. qilinshanensis forms a clade with Astenus lyonessius (Joy, 1908), within Lathrobiini.

Epidemiological characteristics of influenza outbreaks in Zhejiang Province from 2013 to 2022 / 预防医学

Objective@#To investigate the epidemiological characteristics of influenza outbreaks in Zhejiang Province from 2013 to 2022, so as to provide insights into influenza prevention and control. @*Methods@#Data pertaining to influenza outbreaks reported in Zhejiang Province from 2013 to 2022 were collected from National Influenza Surveillance System in China, including time, region, cases and pathogen types of influenza outbreaks. The temporal, spatial and pathogen distribution of influenza outbreaks were analyzed using a descriptive epidemiological method. @*Results@#A total of 577 influenza outbreaks involving 448 698 individuals were reported in Zhejiang Province from 2013 to 2022, and the overall attack rate was 5.34% (23 974 cases), with no death reported. The lowest attack rate of influenza was 0.26%, and the highest was 80.00%, with a median attack rate of 10.89% (interquartile range, 24.26%). The outbreak had the shortest duration of 1.00 day, and the longest duration of 59.00 days, with a median duration of 9.00 (interquartile range, 11.00) days. There were 387 influenza outbreaks that occurred between November and January of the following year (67.07%), and the three highest numbers of outbreaks were reported in Hangzhou City (310 outbreaks), Wenzhou City (51 outbreaks) and Jinhua City (46 outbreaks). There were 395 outbreaks reported in urban regions (68.46%), 93 in counties and townships (16.12%) and 89 in rural regions (15.42%), and influenza outbreaks predominantly occurred in primary schools (487 outbreaks, 84.40%). In addition, the types of pathogens were alternately prevalent, with influenza B virus (241 outbreaks, 41.77%) and A/H3N2 virus (232 outbreaks, 40.21%) as predominant subtypes. @* Conclusions@#Influenza outbreaks mainly occurred in winter in Zhejiang Province from 2013 to 2022, and primary schools were main places of influenza outbreaks, while influenza B virus and A/H3N2 virus were predominant subtypes. It is necessary to reinforce the surveillance and report of influenza-like illness in schools and improve the coverage of influenza vaccination to prevent influenza outbreaks.

The clinical and virological features of two children's coinfections with human adenovirus type 7 and human coronavirus-229E virus.

Objective: Human adenovirus (HAdV) coinfection with other respiratory viruses is common, but adenovirus infection combined with human coronavirus-229E (HCoV-229E) is very rare. Study design and setting: Clinical manifestations, laboratory examinations, and disease severity were compared between three groups: one coinfected with HAdV-Ad7 and HCoV-229E, one infected only with adenovirus (mono-adenovirus), and one infected only with HCoV-229E (mono-HCoV-229E). Results: From July to August 2019, there were 24 hospitalized children: two were coinfected with HAdV-Ad7 and HCoV-229E, and 21 were infected with a single adenovirus infection. Finally, one 14-year-old boy presented with a high fever, but tested negative for HAdV-Ad7 and HCoV-229E. Additionally, three adult asymptotic cases with HCoV-229E were screened. No significant difference in age was found in the coinfection and mono-adenovirus groups (11 vs. 8 years, p = 0.332). Both groups had the same incubation period (2.5 vs. 3 days, p = 0.8302), fever duration (2.5 vs. 2.9 days, p = 0.5062), and length of hospital stay (7 vs. 6.76 days, p = 0.640). No obvious differences were found in viral loads between the coinfection and mono-adenovirus groups (25.4 vs. 23.7, p = 0.570), or in the coinfection and mono-HCoV-229E groups (32.9 vs. 30.06, p = 0.067). All cases recovered and were discharged from the hospital. Conclusion: HAdV-Ad7 and HCoV-229E coinfection in healthy children may not increase the clinical severity or prolong the clinical course. The specific interaction mechanism between the viruses requires further study.

Phenylalanine impairs insulin signaling and inhibits glucose uptake through modification of IRß.

Whether amino acids act on cellular insulin signaling remains unclear, given that increased circulating amino acid levels are associated with the onset of type 2 diabetes (T2D). Here, we report that phenylalanine modifies insulin receptor beta (IRß) and inactivates insulin signaling and glucose uptake. Mice fed phenylalanine-rich chow or phenylalanine-producing aspartame or overexpressing human phenylalanyl-tRNA synthetase (hFARS) develop insulin resistance and T2D symptoms. Mechanistically, FARS phenylalanylate lysine 1057/1079 of IRß (F-K1057/1079), inactivating IRß and preventing insulin from promoting glucose uptake by cells. SIRT1 reverse F-K1057/1079 and counteract the insulin-inactivating effects of hFARS and phenylalanine. F-K1057/1079 and SIRT1 levels in white blood cells from T2D patients are positively and negatively correlated with T2D onset, respectively. Blocking F-K1057/1079 with phenylalaninol sensitizes insulin signaling and relieves T2D symptoms in hFARS-transgenic and db/db mice. These findings shed light on the activation of insulin signaling and T2D progression through inhibition of phenylalanylation.

Analysis of the effect of meteorological factors on hemorrhagic fever with renal syndrome in Taizhou City, China, 2008-2020.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is endemic in Zhejiang Province, China, while few studies have concentrated on the influence of meteorological factors on HFRS incidence in the area. METHODS: Data on HFRS and meteorological factors from January 1, 2008 to December 31, 2020 in Taizhou City, Zhejiang Province were collected. Multivariate analysis was conducted to the relationship between meteorological factors including minimum temperatures, relative humidity, and cumulative rainfall with HFRS. RESULTS: The HFRS incidence peaked in November and December and it was negatively correlated with average and highest average temperatures. Compared with median of meteorological factors, the relative risks (RR) of weekly average temperature at 12 ℃, weekly highest temperature at 18 ℃relative humidity at 40%, and cumulative rainfall at 240 mm were most significant and RRs were 1.41 (95% CI: 1.09-1.82), 1.32 (95% CI: 1.05-1.66), 2.18 (95% CI: 1.16-4.07), and 1.91 (95% CI: 1.16-2.73), respectively. Average temperature, precipitation, relative humidity had interactions on HFRS and the risk of HFRS occurrence increased with the decrease of average temperature and the increase of precipitation. CONCLUSION: Our study results are indicative of the association of environmental factors with the HFRS incidence, probable recommendation could be use of environmental factors as early warning signals for initiating the control measure and response.

Seasonality and Meteorological Factors Associated With Different Hand, Foot, and Mouth Disease: Serotype-Specific Analysis From 2010 to 2018 in Zhejiang Province, China.

Background: Hand-foot-mouth disease (HFMD) is caused by a group of enteroviruses (EVs) and has a high incidence in children; some subtypes had high mortalities in children. The subtypes of HFMD had a different incidence across seasons. Thereby, we suspect that the infection of HFMD is varied by meteorological factors. However, studies examining serotype-specific associations between meteorological factors and HFMD incidence were rare. Methods: We obtained all HFMD cases that occurred from 1 January 2010 to 31 December 2018 in Zhejiang province from the China Information System for Disease Control and Prevention (CISDCP). Daily meteorological data for Zhejiang province were provided by the China Methodological Data Sharing Service System and linked to HFMD cases based on residential addresses and dates of onset. The associations between meteorological factors and HFMDs were examined using distributed lag non-linear models (DLNMs) for each serotype. Results: Overall, the incidences of all HFMD cases were increasing in study years, while the number of severe and fatality cases were decreasing. The dominant serotypes varied by study year. The association between temperature and incidence of both CVA16 and EV71 serotypes showed an inverted U shape. The risk ratio for CVA16 was increasing when temperature is 11-25°C, reaching the maximum RR at 18°C and humidity above 77% can promote the occurrence with CVA16, and temperature between 11 and 32°C with the maximum RR at 21°C and relative humidity above 77% are risk conditions of the occurrence of HFMD associated with EV71. For other enteroviruses causing HFMD, temperature above 11°C and humidity above 76% have a risk effect. CVA16, EV71, and all enteroviruses of HFMD have a maximum effect on lag day 0, and temperature is 35, 34, and 33°C respectively, while the enteroviruses of HFMD other than EV71 and CVA16 has a maximum effect when the temperature is 33°C and the lag time is 7 days. Conclusion: This study shows that meteorological factors have an effect on the occurrence of different HFMD serotypes. Local control strategies for public health should be taken in time to prevent and reduce the risk of HFMD while the weather is getting warmer and wetter.

Improper handling of vomitus as a risk factor in the human norovirus outbreak in a kindergarten in Wuyi County, Zhejiang Province, China.

This study investigated an outbreak in a kindergarten in Wuyi County of acute gastroenteritis concerning a large number of students and teachers. We performed a case-control study, and collected information on the layout of the school, symptoms, onset time of all cases and vomiting sites. A total of 62 individuals fit the definition of probable cases; among these, there were 19 cases of laboratory-confirmed norovirus infection. Nausea and vomiting were the most common symptoms in the outbreak. Seven student norovirus patients vomited in the school. The odds ratio (OR) of norovirus illness was 15.75 times higher among teachers who handled or interacted with student vomitus without respiratory protection than compared to those without this type of exposure (OR 15.75, 95% CI 1.75-141.40). Nine samples were successfully genotyped; eight samples were norovirus GII.2[P16], one sample was norovirus GII.4 Sydney[P16]. This study revealed that improper handling of vomitus is a risk factor of norovirus infection. Therefore, more attention should be given to train school staff in knowledge of disinfection.

Glucagon-like peptide-1 receptor agonist attenuates diabetic neuropathic pain via inhibition of NOD-like receptor protein 3 inflammasome in brain microglia.

AIMS: We aimed to explore the evidence of brain microglia activation in diabetic neuropathic pain (DNP) and the effect and mechanism of glucagon-like peptide-1 receptor agonist (GLP-RA) on DNP via brain microglia. METHODS: Brain microglia activation was observed in DNP rats by positron emission tomography/computed tomography. The behavior of neuropathic pain was assessed in DNP rats after intracerebroventricular administration of GLP-1RA or microglial inhibitor minocycline. RNA sequencing was performed to explore the target of GLP-1RA on brain microglia. NOD-like receptor protein 3 (NLRP3) expression in brain microglia was evaluated in mentioned-above DNP rats, and the activation of NLRP3 inflammasome was analyzed in microglia treated with GLP-1RA. RESULTS: Microglia were activated in the cortex and thalamus of DNP rats. The thermal and mechanical allodynia were alleviated in DNP rats via intracerebroventricular administration of GLP-1RA or minocycline. And the activation of brain microglia was attenuated in DNP rats by intracerebroventricular administration of GLP-1RA. The expression of NLRP3 in brain microglia, which was found by RNA sequencing, was reduced in DNP rats by administration of GLP-1RA. Furthermore, GLP-1RA attenuated NLRP3 inflammasome activation in microglia triggered by LPS. CONCLUSION: GLP-1RA could alleviate DNP, possibly mediated by the suppression of brain microglia NLRP3 inflammasome activation.

Body fat percentage in adolescents is a better predictor of exercise effect on adiposity changes: a 4-year follow-up study.

BACKGROUND: Exercise is generally recognized as beneficial to prevent obesity; however, it is not clear which indicator can better reflect the benefits, especially in adolescents. The aim of this study was to describe the effects of exercise on body mass and fat indexes and to clarify the significance of different indexes in clinical use. METHODS: We conducted a prospective cohort study involving 1,941 freshmen from 2014, followed-up biennially until 2018. Various body mass and fat indexes, including weight, height, waist and hip circumference and body fat percentage (BFP), were measured. Physical activity and other variables were collected by questionnaire. All study participants were divided into two groups according to the frequency and intensity of exercise. RESULTS: Compared with the low frequency and intensity exercise group, the high frequency and intensity exercise group had a lower increase in BFP during the 4-year follow-up, and no significant differences were observed in the changes of other indexes between the groups. Even after adjusting, the high frequency and intensity exercise group still exhibited a higher likelihood of reducing BFP. CONCLUSIONS: High frequency and intensity exercise provides benefits for reducing BFP. No other body mass or fat indexes showed any association. BFP could be a much more sensitive indicator to detect and control obesity in adolescents.

COVID-19 Transmission Dynamics Among Close Contacts of Index Patients With COVID-19: A Population-Based Cohort Study in Zhejiang Province, China.

Importance: Much remains unknown about the transmission dynamics of COVID-19. How the severity of the index case and timing of exposure is associated with disease in close contacts of index patients with COVID-19 and clinical presentation in those developing disease is not well elucidated. Objectives: To investigate the association between the timing of exposure and development of disease among close contacts of index patients with COVID-19 and to evaluate whether the severity of the index case is associated with clinical presentation in close contacts who develop COVID-19. Design, Setting, and Participants: This study used a large, population-based cohort of 730 individuals (index patients) who received a diagnosis of COVID-19 in Zhejiang Province, China, from January 8 to July 30, 2020, along with a contact tracing surveillance program. Field workers visited 8852 close contacts of the index patients and evaluated them for COVID-19 through August 2020. A timeline was constructed to characterize different exposure periods between index patients and their contacts. Main Outcomes and Measures: The primary outcome was the attack rate of COVID-19, defined as the total number of new COVID-19 cases diagnosed among contacts of index patients divided by the total number of exposed contacts. A secondary outcome was asymptomatic clinical presentation among infected contacts. Relative risks were calculated to investigate risk factors for COVID-19 among contacts and asymptomatic clinical presentation among infected contacts. Results: Among 8852 close contacts (4679 male contacts [52.9%]; median age, 41 years [interquartile range, 28-54 years]) of 730 index patients (374 male patients [51.2%]; median age, 46 years [interquartile range, 36-56 years]), contacts were at highest risk of COVID-19 if they were exposed between 2 days before and 3 days after the index patient's symptom onset, peaking at day 0 (adjusted relative risk [ARR], 1.3; 95% CI, 1.2-1.5). Compared with being exposed to an asymptomatic index patient, the risk of COVID-19 among contacts was higher when they were exposed to index patients with mild (ARR, 4.0; 95% CI, 1.8-9.1) and moderate (ARR, 4.3; 95% CI, 1.9-9.7) cases of COVID-19. As index case severity increased, infected contacts were less likely to be asymptomatic (exposed to patient with mild COVID-19: ARR, 0.3; 95% CI, 0.1-0.9; exposed to patient with moderate COVID-19: ARR, 0.3; 95% CI, 0.1-0.8). Conclusions and Relevance: This cohort study found that individuals with COVID-19 were most infectious a few days before and after symptom onset. Infected contacts of asymptomatic index patients were less likely to present with COVID-19 symptoms, suggesting that quantity of exposure may be associated with clinical presentation in close contacts.

Decreased amino acids in the brain might contribute to the progression of diabetic neuropathic pain.

AIMS: The pathophysiological alteration of diabetic neuropathic pain (DNP) in brain is unclear. Here we aimed to explore the metabolomic characteristics of brain in rats over the progression of DNP through metabolomic analysis. METHODS: Adult rats were randomly divided into control group and DNP group. Body weight, blood glucose and behavioral assessment of neuropathic pain were measured every week after streptozotocin (STZ) injection. Finally, the brains of 2 rats from control group and 6 rats from DNP group were removed every 4 weeks after STZ injection for metabolomics analysis. RESULTS: After 4 weeks of STZ-injection, the rats with diabetes developed DNP, which was characterized as mechanical allodynia and thermal nociception. As for metabolomic analysis, differentially expressed metabolites (DE metabolites) showed a dynamic alteration over the development of DNP and affected several KEGG pathways associated with amino acid metabolism. Furthermore, the expression of l-Threonine, l-Methionine, d-Proline, l-Lysine and N-Acetyl-l-alanine were significantly decreased at all time points of DNP group. The amino acids which were precursor of analgesic neurotransmitters were downregulated over the progression of DNP, including l-tryptophan, l-histidine and l-tyrosine. CONCLUSIONS: The impairment of amino acid metabolism in brain might contribute to the progression of DNP through decreasing analgesic neurotransmitters.

Effects and interaction of meteorological factors on hemorrhagic fever with renal syndrome incidence in Huludao City, northeastern China, 2007-2018.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS), a rodent-borne disease, is a severe public health threat. Previous studies have discovered the influence of meteorological factors on HFRS incidence, while few studies have concentrated on the stratified analysis of delayed effects and interaction effects of meteorological factors on HFRS. OBJECTIVE: Huludao City is a representative area in north China that suffers from HFRS with primary transmission by Rattus norvegicus. This study aimed to evaluate the climate factors of lag, interaction, and stratified effects of meteorological factors on HFRS incidence in Huludao City. METHODS: Our researchers collected meteorological data and epidemiological data of HFRS cases in Huludao City during 2007-2018. First, a distributed lag nonlinear model (DLNM) for a maximum lag of 16 weeks was developed to assess the respective lag effect of temperature, precipitation, and humidity on HFRS incidence. We then constructed a generalized additive model (GAM) to explore the interaction effect between temperature and the other two meteorological factors on HFRS incidence and the stratified effect of meteorological factors. RESULTS: During the study period, 2751 cases of HFRS were reported in Huludao City. The incidence of HFRS showed a seasonal trend and peak times from February to May. Using the median WAT, median WTP, and median WARH as the reference, the results of DLNM showed that extremely high temperature (97.5th percentile of WAT) had significant associations with HFRS at lag week 15 (RR = 1.68, 95% CI: 1.04-2.74) and lag week 16 (RR = 2.80, 95% CI: 1.31-5.95). Under the extremely low temperature (2.5th percentile of WAT), the RRs of HFRS infection were significant at lag week 5 (RR = 1.28, 95% CI: 1.01-1.67) and lag 6 weeks (RR = 1.24, 95% CI: 1.01-1.57). The RRs of relative humidity were statistically significant at lag week 10 (RR = 1.19, 95% CI: 1.00-1.43) and lag week 11 (RR = 1.24, 95% CI: 1.02-1.50) under extremely high relative humidity (97.5th percentile of WARH); however, no statistically significance was observed under extremely low relative humidity (2.5th percentile of WARH). The RRs were significantly high when WAT was -10 degrees Celsius (RR = 1.34, 95% CI: 1.02-1.76), -9 degrees Celsius (1.37, 95% CI: 1.04-1.79), and -8 degrees Celsius (RR = 1.34, 95% CI: 1.03-1.75) at lag week 5 and more than 23 degrees Celsius after 15 weeks. Interaction and stratified analyses showed that the risk of HFRS infection reached its highest when both temperature and precipitation were at a high level. CONCLUSIONS: Our study indicates that meteorological factors, including temperature and humidity, have delayed effects on the occurrence of HFRS in the study area, and the effect of temperature can be modified by humidity and precipitation. Public health professionals should pay more attention to HFRS control when the weather conditions of high temperature with more substantial precipitation and 15 weeks after the temperature is higher than 23 degrees Celsius.