A 28-year-old woman presented with a 4-year history of fatigue and sleepiness and was found to have central hypothyroidism and mood disorder. The patient had normal thyroid volume and did not show any other pituitary axis involvement. Over the course of the disease, her symptom improvement matched with the free thyroxine (FT 4) rebound and the adjustment of antipsychotic medication. The patient′s grandmother had central hypothyroidism, and her mother and uncle had lowered or inappropriately normal thyroid stimulating hormone. Hence, genetic involvement was highly suspected, but whole exon sequencing did not reveal a pathogenic variant. Levothyroxine tablets were prescribed to maintain a normal median level of FT 4, and mood disorder medications were adjusted by specialists. Isolated central hypothyroidism is extremely rare, and we report this case aiming to raise awareness of this condition.

Objective: To describe the prevalence of alcohol consumption and the burden of hemorrhagic stroke and hypertensive heart disease attributed to alcohol consumption in adults aged ≥20 years in 31 provinces in China from 2005 to 2018. Methods: Data from several national representative surveys was used to estimate provincial alcohol exposure level of adults aged ≥20 years from 2005 to 2018 by using kriging interpolation and locally weighted regression methods. Global disease burden research method and data, and China's death cause surveillance data were used to calculate the population attributable fraction (PAF) of hemorrhagic stroke and hypertensive heart disease and the deaths due to alcohol consumption in men and women aged ≥20 years in 31 provinces in China. China census data of 2010 were used to calculate the attributable standardized mortality rate. Results: In 2005 and 2018, the prevalence of alcohol consumption was 58.7% (95%CI: 57.8%-59.5%) and 58.4% (95%CI: 57.6%-59.3%), respectively, in men and 17.0% (95%CI: 16.6%-17.4%) and 18.7% (95%CI:18.1%-19.3%), respectively, in women. The daily alcohol intake was 24.6 (95%CI: 23.8-25.3) g and 27.7 (95%CI: 26.8-28.7) g, respectively, in men and 6.3 (95%CI: 6.0-6.5) g and 5.3 (95%CI: 5.0-5.6) g, respectively, in women. Alcohol exposure level was higher in the provinces in central and eastern China than in western provinces. The lowest exposure level was found in northwestern provinces. From 2005 to 2018, the PAF of hemorrhagic stroke death due to alcohol consumption increased from 5.5% to 6.8%, the attributable deaths increased from 50 200 to 59 100, while the PAF of hypertensive heart disease death due to alcohol consumption increased from 7.0% to 7.7%, the attributable deaths increased from 15 200 to 29 300. The PAF of hypertensive heart disease and hemorrhagic stroke was higher in men than in women, and in central and eastern provinces than in western provinces. In 2018, the standardized mortality rates of hemorrhagic stroke and hypertensive heart disease attributed to alcohol consumption were 4.58/100 000 and 2.11/100 000, respectively. Conclusions: The prevalence of alcohol consumption in men and daily alcohol intake of drinkers were relatively high in China, especially in eastern provinces. Alcohol exposure level was lower in women than in men. Regional measures should be taken to reduce the alcohol intakes in men and current drinkers in order to reduce the health problems caused by alcohol consumption.
Adult ; Male ; Humans ; Female ; Hemorrhagic Stroke ; Hypertension/epidemiology* ; Alcohol Drinking/epidemiology* ; Heart Diseases/epidemiology* ; China/epidemiology*

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Carcinoma, Squamous Cell/pathology* ; Endometrial Hyperplasia/pathology* ; Endometrial Neoplasms/pathology* ; Endometrium/pathology* ; Female ; Humans ; Hyperplasia/pathology*

ObjectiveTo explore the effect and mechanism of Xiaojindan extract （XJD） on macrophage polarization. MethodLipopolysaccharide （LPS） and interleukin-4 （IL-4） were used to induce M1 and M2 polarization of RAW264.7 cells. The influence of 10-80 mg·L^-1 XJD on cell proliferation was detected by Cell Counting Kit-8 （CCK-8） assay. Nitric oxide （NO） and interleukin-6 （IL-6） release was explored by Griess assay and enzyme-linked immunosorbent assay （ELISA）， respectively. The mRNA expression of M1 and M2 macrophage markers was measured by real-time quantitative polymerase chain reaction （Real-time PCR）， and the CD206⁺ expression was determined by flow cytometry. The activation of phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） pathway was analyzed by western blot. Result10-80 mg·L^-1 XJD showed no marked cytotoxicity in LPS （0.5 mg·L^-1）- or IL-4 （20 μg·L^-1）-induced RAW264.7 cells. Compared with the control group， LPS significantly promoted the expression of M1 macrophage markers （P<0.01）， including increased NO and IL-6 release （P<0.01） and upregulated mRNA expression of interleukin-1β （IL-1β）， inducible nitric oxide synthase （iNOS）， cyclooxygenase-2 （COX-2） and tumor necrosis factor-α （TNF-α） （P<0.01）. Compared with LPS-induced group， 20-80 mg·L^-1 XJD decreased the release of NO and IL-6 in a dose-dependent manner （P<0.01）， and similarly 10-80 mg·L^-1 XJD suppressed the mRNA expression of IL-1β， iNOS， COX-2 and TNF-α （P<0.01）. Compared with the control group， IL-4 obviously increased the expression of M2 macrophage markers （P<0.01）， including increased CD206⁺ cell population and upregulated mRNA expression of arginine-1 （Arg-1）， interleukin-10 （IL-10）， interleukin-13 （IL-13） and transforming growth factor-β₁ （TGF-β₁）. Compared with IL-4-induced group， 10-80 mg·L^-1 XJD dose-dependently decreased CD206⁺ cell population （P<0.01） and inhibited the mRNA expression of Arg-1， IL-10， IL-13 and TGF-β₁ （P<0.01）. Western blot showed that XJD significantly downregulated the activation of PI3K/Akt pathway as compared to LPS- and IL-4-induced groups （P<0.05， P<0.01）. ConclusionXJD significantly inhibited the macrophage polarization in the LPS- and IL-4-induced RAW264.7 cells by targeting PI3K/Akt pathway.

ObjectiveTo observe the effect of asiaticoside （AC） on the expression of T helper 17 （Th17） cells and regulatory T （Treg） cells in DBA/1 mice with collagen-induced arthritis （CIA）. MethodMale SPF DBA/1 mice were randomized into six groups according to body weight： control group， CIA group， methotrexate group （MTX group， ip， 0.5 mg·kg^-1）， and AC low-， medium-， and high-dose groups （ig， 5， 15， 45 mg·kg^-1， respectively）. Modeling was performed in rats other than the control group. To be specific， they were immunized with bovine type Ⅱ collagen and complete Freund's adjuvant on the first day and with bovine type Ⅱ collagen and incomplete Freund's adjuvant on the 21^st day. Administration began on the day of the second immunization， once a day for 28 days. On the 49^th day， related tissues were collected. Then， hematoxylin-eosin （HE） staining was performed to observe the pathological changes of the joints. Immunohistochemical method was used to detect the expression of interleukin-17 （IL-17） and forkhead box protein-3 （FoxP3）， the markers of Th17 and Treg cells， respectively， immunofluorescence double staining the expression of IL-17 and FoxP3 in CD4⁺T cells of mouse joint tissue， and flow cytometry the proportions of Th17 and Treg cells in mouse lymph nodes. ResultCompared with the control group， CIA group demonstrated joint disorder， damage of articular cartilage and bone， severe bone erosion （P<0.01）， increase in stained CD4 and IL-17 and the integral absorbance （IA） （P<0.01）， decrease in stained FoxP3 and the IA （P<0.01）， rise of Th17/Treg ratio （P<0.01）， elevation of Th17 expression in mouse lymph nodes （P<0.01）， and reduction in Treg expression （P<0.01）. Compared with CIA group， MTX group and three AC groups showed normal joints， alleviated bone erosion and damage， intact and smooth joint surface， and decrease in stained IL-17 and IA （P<0.05， P<0.01）， and MTX group and AC medium-dose and high-dose groups registered decrease in stained CD4 and IA （P<0.01） and reduction in Th17/Treg ratio （P<0.05， P<0.01）. Moreover， AC medium-dose and high-dose groups showed rise in stained FoxP3 and IA （P<0.05， P<0.01）. In the lymph nodes of mice， decrease in expression of Th17 cells （P<0.05， P<0.01） and the increase in expression of Treg cells （P<0.05， P<0.01） were observed in all the three AC group. ConclusionAC can regulate Th17/Treg balance by inhibiting the expression of Th17 cells and promoting the expression of Treg cells in CIA mice.

【Objective】 To evaluate the curative effect of posterior atlantoaxial joint release and internal fixation in treating unstable craniocervical junction malformation （UCVJM）. 【Methods】 This study retrospectively enrolled 31 patients with UCVJM， who received posterior atlantoaxial joint release and internal fixation between January 2015 and December 2018. The pre- and postoperative changes of the Japanese Orthopaedic Association （JOA） scores， the cervicomedullary angle （CMA）， the atlantodental interval （ADI） and the height above the Chamberlain line of the odontoid （H） were traced to evaluate whether clinical symptoms， compression of spinal cord， horizontal and vertical dislocation of atlantoaxial were improved postoperatively. 【Results】 The average operation duration， bleeding during operation and the average days of hospitalization were （168.38±38.21）min， （147.09±59.84）mL， and （9.54±2.81） days， respectively. None of the patients had vertebral artery or spinal cord injury during operation. JOA score， ADI， H， and CMA were （11.94±1.37） points， （2.72±1.08）mm， （3.03±0.78）mm， and （145.35±8.00）° respectively on the 6th days after operation compared with the preoperative （9.94±1.26） points， （4.96±1.60）mm， （6.89±1.36） mm and （122.16±9.58）°， with statistical differences， which indicated all indexes were improved （all P<0.001）. During 6-25 months’ follow-up， there was no internal fixation looseness or displacement and JOA score was increased to （13.16±1.19） for all the patients in the last follow-up （all P<0.001）. 【Conclusion】 The posterior atlantoaxial joint release combined with internal fixation is safe and effective for patients with UCVJM.

Objective:To investigate the level of trimethylamine N-oxide (TMAO), one of gut metabolites, in patients undergoing maintenance hemodialysis (MHD) accompanied by congestive heart failure (HF) and its influencing factors.Methods:Those patients of 18-75 years old who received three or more times of hemodialysis sessions per week for three months or longer during Nov 2018 and Mar 2019 were enrolled. Those attended health checkup at the same time without obvious kidney abnormality served as non-kidney disease controls. Serum TMAO concentrations were measured using high-performance liquid chromatography electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS). The levels of TMAO were compared between patients on hemodialysis and controls, between those with heart failure and without heart failure using logrithmically transformed TMAO (lnTMAO). Linear regression analysis was performed to investigate factors influencing TMAO levels.Results:A total of 195 patients undergoing MHD and 40 controls were enrolled. Among them, 30 hemodialysis cases (15.4%) manifested as heart failure symptoms and/or left ventricular ejection fraction less than 50%. Males accounted for 67.2% in patients on hemodialysis and 37.5% in controls ( χ2=12.426, P<0.001) respectively, while the median ages in both groups were 62.0(48.0, 71.0), 45.0(33.3, 55.0) years old respectively ( Z=5.685, P<0.001). TMAO concentrations were significantly higher in patients on hemodialysis than controls [5.54(3.84, 8.91) mg/L vs 0.17(0.11, 0.30) mg/L, after log transformed, t=21.687, P<0.001]. However, there was no statistically significant difference between those with heat failure and those without in male [63.3% vs 67.9%, χ2=0.238, P=0.626], age [64.5(56.8, 71.0) years old vs 61.0(47.0, 72.0) years old, Z=0.894, P=0.372] and TMAO [5.17(3.30, 9.46) mg/L vs 5.57(3.87, 8.95) mg/L, after log transformed, t=-1.537, P=0.135]. Multivariate linear regression analysis demonstrated that in all the participants, serum urea was the main risk factor for TMAO [standardized coefficient ( SB)=0.483]. lnTMAO=0.078×[serum urea(mmol/L)]+0.001×[serum creatinine (μmol/L)]-0.002×[serum uric acid (μmol/L)]-0.003×[platelet (×10 9/L)]+0.014×[age (years old)]+0.344 (if diabetic)-1.266. While in those undergoing MHD, ultrafiltration volume had the most significant effect on TMAO levels ( SB=0.279). lnTMAO=0.249×[ultrafiltration volume(L)]+0.059×[serum albumin (g/L)]+0.008×[age (years old)-0.526 (if heart failure existed)-1.865. Conclusions:MHD patients have gut dysbiosis, while those hemodialysis patients accompanied by heart failure may have peculiar gut microbiota which induces lower serum TMAO levels than those without heart failure after adjusting for multiple related factors. Serum TMAO levels may be associated with ultrafiltration volume and nutrition status etc.

Reverse prediction and molecular docking techniques were employed to evaluate the feasibility of reniformin A(RA) as an anti-tumor leading compound. Based on the reverse prediction, network pharmacology was used to construct a "disease-compound-target-pathway" network. Thirty-nine tumor-related targets of RA were predicted, which participated in the regulation of multiple cellular activities such as apoptosis, cell cycle, and tumor metastasis, and regulated estrogen signal transduction and inflammatory response. Discovery Studio 2020 was adopted for molecular docking and toxicity prediction(TOPKAT). As revealed by the results, the binding affinity of RA with the tumor-related targets ABL1, ESR1, SRC and BCL-XL was stronger than that of oridonin(OD), while its mutagenicity, rodent carcinogenesis, and oral LD_(50) in rats were all inferior to that of OD. Furthermore, in vitro experiments were performed to confirm the anti-tumor activity of RA, and the mechanism was preliminarily discussed. The results demonstrated that RA was superior to OD in cytotoxicity, inhibition of cell colony formation, and induction of apoptosis. RA, possessing potent anti-tumor activity, is expected to be a new anti-tumor leading compound.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Lead ; Molecular Docking Simulation ; Neoplasms/genetics* ; Rats ; Signal Transduction

OBJECTIVE Programmed death ligand-1 (PD-L1) and indoleamine 2, 3-dioxygenase 1 (IDO1) are immune checkpoints which can be induced by interferon-γ(IFN-γ) in the tumor microenvironment, leading to immune escape of tumors. Myricetin (MY) is a flavonoid distributed in many edible and medicinal plants. The aim of this study is to clarify the effect and the mechanism of MY on inhibiting IFN-γ-induced PD-L1 and IDO1 in lung cancer cells. METHODS Expressions of PD-L1 and major histocompatibility complex-I (MHC-I) were evaluated by flow cytometry and Western blotting, and the expression of IDO1 was measured by Western blotting. qRT-PCR was used to detect their mRNA levels. The function of T cells was evaluated using a co-culture system consist of lung cancer cells and the Jurkat-PD-1 T cell line that overexpressing PD-1. Molecular docking analysis, Western blotting and immunofluorescence were used for mechanism study. RESULTS MY potently inhibited IFN-γ-induced PD-L1 and IDO1 expression in human lung cancer cells, while didn't show obvious effect on the expression of MHC-I. In addition, MY restored the survival, proliferation, CD69 expression and interleukin-2 (IL-2) secretion of Jurkat-PD-1 T cells suppressed by IFN-γ-treated lung cancer cells in the co-culture system. Mechanistically, IFN-γ up-regulated PD-L1 and IDO1 at the transcriptional level through the JAK-STAT-IRF1 axis, which was targeted and inhibited by MY. CONCLUSION Our research revealed a new insight into the anti-tumor effects of MY which inhibited IFN-γ-induced PD-L1 and IDO1 expression, supporting the potential of MY in anti-tumor immunotherapy.