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.

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.

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.

Resistin-like molecule beta augments phenotypic modulation of human aortic smooth muscle cell triggered by high glucose.

Vascular muscle cells (VSMCs) participate in the pathophysiology of atherosclerosis. Resistin-like molecule beta (Relmß) contributes to atherosclerosis development by activating macrophage. This study aims to investigate whether Relmß regulates VSMC phenotypic modulation under high glucose environment. Human aortic vascular smooth muscle cells were cultured and treated with Relmß in the presence or absence of high glucose. VSMC phenotypic modulation was assessed by expression of related markers. The migration of VSMCs was detected by wound healing assay and transwell assay. The proliferation of VSMCs was measured using CCK-8 assay. In this study, we observed that Relmß modulated VSMC phenotypic modulation by down-regulating expression of smooth muscle α-actin (α-SMA), smooth muscle myosin heavy chain (SM-MHC), and calponin while up-regulating expression of osteopontin (OPN). Relmß increased the expression of inflammatory genes in VSMCs. Relmß also augmented VSMCs migration as well as proliferation. It is worth noting that all the effects of VSMCs were enhanced upon high glucose stimulation. The phosphorylation levels of p38MAPK and ERK1/2 were increased by co-treatment with Relmß and high glucose. The p38 MAPK pathway inhibitor RWJ64809 and pERK1/2 inhibitor PD98059 significantly inhibited the proliferation of VSMCs induced by Relmß and high glucose. Our results provide evidence that Relmß augments phenotypic modulation and migration of human aortic smooth muscle cell induced by high glucose. Relmß might be a potential target for treatment of atherosclerosis induced by hyperglycemia.

Climate factors driven typhus group rickettsiosis incidence dynamics in Xishuangbanna Dai autonomous prefecture of Yunnan province in China, 2005-2017.

BACKGROUND: Typhus group rickettsiosis (TGR), which is a neglected vector-borne infectious disease, including epidemic typhus and endemic typhus. We explored the lag effects and nonlinear association between meteorological factors and TGR incidence in Xishuangbanna Dai autonomous prefecture from 2005 to 2017, China. METHODS: A Poisson regression with a distributed lag nonlinear model (DLNM) was utilized to analyze TGR cases data and the contemporaneous meteorological data. RESULTS: A J-shaped nonlinear association between weekly mean temperature and TGR incidence was found. The cumulative exposure to weekly mean temperature indicated that the RR increased with the increment of temperature. Taking the median value as the reference, lower temperatures could decrease the risk of TGR incidence, while higher temperatures could increase the risk of TGR incidence and last for 21 weeks. We also found a reversed U-shaped nonlinear association between weekly mean precipitation and TGR incidence. Precipitation between 5 mm and 13 mm could increase the risk of TGR incidence. Taking the median value as the reference, no precipitation and lower precipitation could decrease the risk of TGR incidence, while higher precipitation could increase the risk of TGR incidence and last for 18 weeks. CONCLUSIONS: The prevention and control measures of TGR should be implemented according to climatic conditions by the local government and health departments in order to improve the efficiency.

Circulating Prolactin and Risk of Type 2 Diabetes: A Prospective Study.

Prolactin plays an important role in maintaining a normal glucose homeostasis during pregnancy and beyond. Studies investigating the association between prolactin and type 2 diabetes beyond pregnancy are rare and none is prospective. We aimed to examine whether prolactin associates with type 2 diabetes prospectively in a Chinese population. In 2009, 2,377 participants aged 40 years or older were enrolled from Shanghai, China. Among 1,596 diabetes-free participants at baseline, 1,510 completed the follow-up investigation in 2013. Participants who had a fasting plasma glucose ≥126 mg/dL and/or a 2-hour plasma glucose ≥200 mg/dL during a 75-g oral glucose tolerance test had a definite diagnosis of type 2 diabetes or received antidiabetic therapies during follow-up were classified as having type 2 diabetes. During a mean follow-up of 3.7 years, 189 new cases of type 2 diabetes were documented. After multivariate adjustment, women in the highest quartile of prolactin showed the lowest risk for diabetes compared with those in the lowest quartile (hazard ratio = 0.48, 95% confidence interval: 0.26, 0.90). However, such significant associations were not observed in men. Prolactin may be a mediator in the pathogenesis of type 2 diabetes in women; however, more studies are needed to elucidate the underlying sex-specific mechanism.

Serum lipoprotein (a) concentrations are inversely associated with T2D, prediabetes, and insulin resistance in a middle-aged and elderly Chinese population.

Lipoprotein (a) [Lp(a)], an LDL-like particle, has been proposed as a causal risk factor for CVD among general populations. Meanwhile, both serum Lp(a) and diabetes increase the risk of CVD. However, the relationship between serum Lp(a) and T2D is poorly characterized, especially in the Asian population. Therefore, we conducted a cross-sectional study in 10,122 participants aged 40 years or older in Jiading District, Shanghai, China. Our study found that the prevalence of T2D was decreased from 20.9% to 15.0% from the lowest quartile to the highest quartile of serum Lp(a) concentrations (P for trend <0.0001). Logistic regression analyses showed that the odds ratios and 95% confidence intervals of prevalent T2D for quartiles 2-4 versus quartile 1 were 0.86 (0.73-1.01), 0.88 (0.75-1.04), and 0.76 (0.64-0.90) (P for trend = 0.0002), after adjustment for traditional confounding factors. Moreover, the risks for prevalent prediabetes, insulin resistance, and hyperinsulinemia were also decreased from the lowest to the top quartile. This inverse association between serum Lp(a) and T2D was not appreciably changed after we adjusted hypoglycemic medications or excluded the subjects with hypoglycemic and/or lipid-lowering agents and/or a history of self-reported CVD.

Elevated whole blood viscosity is associated with insulin resistance and non-alcoholic fatty liver.

BACKGROUND: Accumulating evidences demonstrate that abnormalities in whole blood viscosity (WBV) have been implicated in insulin resistance which may lead to non-alcoholic fatty liver disease (NAFLD). However, epidemiological studies exploring the association between WBV and NAFLD were not available. OBJECTIVE: Our objective was to evaluate the association between WBV levels and risk of prevalent NAFLD. DESIGN: This was a cross-sectional population-based study performed in Shanghai, China. PATIENTS: A total of 8673 participants aged 40 years or older were included. MEASUREMENTS: WBV was calculated from haematocrit and plasma protein concentration, at a shear rate of 208(-1) s, by a validated equation. NAFLD was diagnosed by hepatic ultrasound after the exclusion of alcohol abuse and other liver diseases. Insulin resistance (IR) was assessed by homeostasis model assessment (HOMA-IR). RESULTS: The overall prevalence of NAFLD was 30·2% in this population. With the increase of WBV level, participants have larger waist circumference (WC), more severe insulin resistance and the prevalence of NAFLD increased significantly with elevated WBV quartiles. Compared with those in the lowest quartiles, adults in the highest quartile of WBV levels have higher prevalence of NAFLD (adjusted odds ratio 1·77, 95% confidence interval [CI] 1·48-2·13) and IR (2·72, 95% CI 2·26-3·27). CONCLUSIONS: Elevated WBV is associated with prevalence of NAFLD and IR in middle-aged and elderly Chinese population.

Low serum potassium level is associated with nonalcoholic fatty liver disease and its related metabolic disorders.

CONTEXT: Subjects with nonalcoholic fatty liver disease (NAFLD) have a high risk of developing type 2 diabetes and cardiovascular diseases. Low serum potassium concentration or low dietary potassium intake can result in metabolic disorders. OBJECTIVE: Our objective was to evaluate the association between low serum potassium level and prevalence of NAFLD in a Chinese population. DESIGN: A population-based cross-sectional study. PATIENTS: We conducted a community-based study in 8592 subjects to investigate the association of serum potassium with the risk of prevalent NAFLD. NAFLD was diagnosed by hepatic ultrasonography. RESULTS: The prevalence rate of NAFLD was 30·3% in this population and gradually decreased across serum potassium quartiles. With the reduction in serum potassium level, participants have larger waist circumference (WC) and more severe insulin resistance. The correlations hold also in multivariate linear regression analysis. In logistic regression analysis, compared with subjects in the highest quartile of serum potassium level, the adjusted odds ratios (ORs) in the lowest quartile was 1·33 [95% confidence interval (CI), 1·11-1·60] for NAFLD, 1·81 (95% CI, 1·49-2·19) for insulin resistance and 1·58 (95% CI, 1·30-1·93) for central obesity. In subgroup analysis after multiple adjustments, significant relation between serum potassium level and prevalent NAFLD was detected in women, younger subjects, those with insulin resistance and those with central obesity, respectively. CONCLUSION: Low serum potassium level significantly associated with prevalence of NAFLD in middle-aged and elderly Chinese.

Association between carotid intima-media thickness and index of central fat distribution in middle-aged and elderly Chinese.

BACKGROUND: Evidence has demonstrated that central fat distribution produces the most profound metabolic abnormalities and is associated with an increased risk of atherosclerotic cardiovascular diseases. We aimed to investigate whether the indexes of central fat distribution, including waist-to-height ratio (WHtR) and visceral fat area (VFA), were stronger risk factors of subclinical atherosclerosis than body mass index (BMI) in Chinese adults. METHODS: A total of 3381 participants aged 40 years or older without history of cardiovascular diseases (CVD) were enrolled in the present cross-sectional study from the Songnan community, Shanghai, China. Height, weight and waist circumference (WC) were measured by experienced physicians. High-resolution B-mode ultrasonography was performed to measure carotid intima-media thickness (CIMT). Regional adiposity was measured by a dual-source computed tomography (CT) scanner. RESULTS: Normal weight but central obesity group (BMI < 23 kg/m2 and WHtR > 0.5) had higher levels of systolic blood pressure (SBP), fasting plasma glucose (FPG), 2 h post-load glucose (2 h PG), Hemoglobin A1c (HbA1c), and CIMT, as well as an elevated prevalence of hypertension and diabetes compared with overweight/obesity but not central obesity group (BMI ≥ 23 kg/m2 and WHtR ≤ 0.5). In logistic regression analysis, WHtR > 0.5 was significantly and independently associated with elevated CIMT (odds ratio [OR] 1.30, 95% confidence interval [CI] 1.01-1.68, p value = 0.044). Similar association was noted for each standard deviation (SD) increase of WHtR (OR 1.25, 95% CI 1.07-1.47, p value = 0.006). Stepwise multiple linear regression analysis revealed that both WHtR and VFA were important determinants of CIMT, independent of other well-recognized risk factors (both p values < 0.01). CONCLUSIONS: WHtR and VFA were associated with CIMT, independent of BMI and conventional CVD risk factors. Given the relatively high cost and complexness of VFA measurement, WHtR could be a more convenient and appropriate measure of abdominal obesity in clinical practice.

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.

Characterization of the Metabolic Proteome of Serum From Patients With Diabetic Distal Symmetric Polyneuropathy.

AIMS: The pathophysiological of diabetic distal symmetric polyneuropathy (DSPN) remains to be elucidated and there are no diagnostic or prognostic biomarkers for the condition. In this explorative proteomic study, metabolic proteome profiling of serum in patients with/without DSPN was analyzed. We aimed to discover proteins with different abundance ranges through proximity extension assay (PEA) technology. METHODS: Temperature quantitative sensory testing (QST) and electromyography (EMG) were used to access the small- and large-fiber function of all participants, respectively. The metabolic proteome profile of serum was analyzed using PEA technology (Olink Target 96 METABOLISM panel). RESULTS: We evaluated serum from patients without DSPN (n = 27), with small-fiber neuropathy (SFN, n = 25) and with mixed small- and large-fiber neuropathy (MSLFN, n = 24). Fifteen proteins, which were especially related to immune response, insulin resistance, and lipid metabolism, were significantly different between patients without DSPN and with MSLFN. Besides, seven proteins, especially related to extracellular structure organization, were significantly different between serum from patients with SFN and with MSLFN. What's more, serum from patients without DSPN showed that three proteins, related to immune response, altered significantly compared to serum from patients with SFN. CONCLUSIONS: This was the first study that characterized the metabolic proteomic profile of serum in DSPN patients by analyzing a panel of 92 metabolic proteins using PEA technology.

Clinical characteristics and risk factors of Hepatitis E virus infection in Zhejiang Province: a multicenter case-control study.

Introduction: Hepatitis E (HE), caused by the Hepatitis E virus (HEV), is a significant cause of acute viral hepatitis globally and a major public health concern, particularly in specific high-prevalence areas in China, which have diverse transmission routes and regional differences. Identifying the primary risk factors for HE transmission is essential to develop targeted interventions for vulnerable populations. Methods: This study employed a 1:1 matched case-control methodology, using a standardized questionnaire complemented by medical records for data validation. Results: Among the 442 HE cases and 428 healthy controls, the case group had a higher prevalence of fatigue (46.21%) and loss of appetite (43.84%) compared to the control group. Furthermore, liver function indicators were significantly higher in the case group, with an average alanine aminotransferase (ALT) level of 621.94 U/L and aspartate aminotransferase (AST) level of 411.53 U/L. Severe HE patients were predominantly male, with significantly increased ALT and AST levels reaching 1443.81 U/L and 862.31 U/L respectively, along with a higher incidence of fatigue (90%) and loss of appetite (75%). Multifactorial analysis indicated that frequent dining out (OR = 2.553, 95%CI:1.686-3.868), poor hygiene conditions (OR = 3.889, 95%CI:1.399-10.807), and comorbid chronic illnesses (OR = 2.275, 95%CI:1.616-3.202) were risk factors for HE infection; conversely, good hygiene practices were protective factors against HE infection (OR = 0.698, 95%CI:0.521-0.934). Conclusion: In conclusion, HE infection in Zhejiang Province is closely associated with dietary habits and environmental hygiene, and individuals with chronic diseases or co-infections are at increased risk. This highlights the need for targeted health education to reduce the incidence of HE among these populations.

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.

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.

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.

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.

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.

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.