Fluorine is a common chemical element. Excessive intake of fluoride can lead to fluorosis. Fluoride easily passes through the blood-brain barrier and accumulates in different brain regions, causing pathological changes in brain tissue. It leads to adverse effects on neuronal metabolism, enzyme, protein function, neurotransmitters, and redox homeostasis, and subsequently neuronal damage and neurodegenerative diseases in humans and experimental animals. This paper reviewed the effects and important mechanisms of fluoride on neurological function and behavior, involving mitochondrial toxicity, oxidative stress, cell apoptosis and autophagy, and activation of pro-inflammatory factors. It provided a reference for further studying the mechanisms of brain damage induced by fluorosis.

Objectives:To explore the clinicopathological characteristics and prognostic risk factors in differentiated thyroid cancer (DTC) patients with lung metastasis.Methods:Patients of differentiated thyroid cancer with lung metastasis in Tianjin Medical University Cancer Institute & Hospital were enrolled from Jan 1, 2010 to Dec 31, 2016. The clinicopathological characteristics and risk factors affecting the prognosis were analyzed retrospectively.Results:A total of 65 DTC patients with lung metastasis were collected in this study, including 56 patients with papillary thyroid carcinoma and 9 patients with follicular thyroid carcinoma; 23 patients died and 42 patients survived. Median follow-up time was 99.4 months. There were 18 males, 47 females. Age 14-73 years, median age 51.0 years. High incidence of DTC lung metastasis was 50-59 years for males and 40-49 years for females. Based on AJCC 8th edition TNM staging, there were 37 patients in stage Ⅱ (age <55 years) and 28 patients in stage Ⅳb (age ≥55 years). The number of 131Ⅰ treatments performed ranged from 1 to 13 times, with a mean of 3.9 times. Firty-five patients were with lung metastasis alone, and 10 patients with lung metastasis and distant metastasis in other organs. Eleven patients suffered from hypoparathyroidism after 131Ⅰ treatment. COX multifactorial regression analysis found that age was independent risk factor affecting prognosis, multiple organs distant metastasis and pathologic subtype were relative risk factors affecting prognosis. There was no correlation between gender, number of 131Ⅰ treatments and poor prognosis. Conclusions:DTC has a high survival even with the occurrence of lung metastasis, but the prognosis is poor when combined with multi-organ metastasis. Age and multiple organ distant metastatic are independent risk factors affecting prognosis.

Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease (ILD). It is a disease with highly heterogeneous clinical manifestations, severity and outcomes, which are associated with individual sensitivity, as well as property, dosage, duration and frequency of exposure to the antigens.The 2020 adult HP guideline reclassifies it and describes its radiographic features in detail.HP often occurs in adults, also affects the pediatric population and is one of the most common ILDs in children.The most common factors causing HP in children are avian and fungal antigens in the home environment.The diagnosis of HP is based on clear antigens, typical symptoms and characteristic radiological manifestations.The serum-specific IgG antibody, bronchoalveolar lavage fluid, and pulmonary function tests can help diagnose HP clearly, and lung histopathology is required for children whose diagnosis cannot be confirmed.Early diagnosis and adequate avoidance of antigen exposure are the keys to its treatment and prognosis.

Objective:To analyze the clinic effects of arthroscopic partial trapeziectomy and suture button suspensionplasty in the treatment of first carpometacarpal joint (CMCJ) Eaton stage II/III arthrosis.Methods:A retrospective study was conducted on a total of 15 cases (16 hands) of patients including 5 males (1 bilateral) and 10 females with CMCJ stage II/III arthrosis who underwent surgical treatment at the first affiliated hospital of Shenzhen university from January 2020 to June 2022, with mean age of 56.7±6.4 years (range, 46-75 years). The duration from pain to treatment was 7.8±3.2 months (range, 4-14 months). X-ray showed narrowing of CMCJ with osteophytes and distal radial subluxation. All the patients were treated with arthroscopic partial trapeziectomy and suture button suspensionplasty. The preoperative and last postoperative follow-up radiographs, visual analogue scale (VAS), thumb's Kapandji scores, disabilies of the arm, shoulder, and hand (DASH) scores, grip and pinch strength and time to return to work were compared.Results:All cases were followed up for 19.6±6.3 months (range, 11-36 months). The postoperative X-ray showed all the CMCJs were reduced with a normal height of first metacarpal. The mean time for patients to return to their daily activities was 18.69±3.70 d and the mean time to return to work was 24.63±4.91 d. The average VAS score decreased from 6.56±1.15 preoperatively to 1.00 (0.75, 1.25). The preoperative Kapandji's score was 8.00±0.82 and the postoperative Kapandji's score was 8.00 (7.25, 9.00). The average DASH values improved from 24.06±3.19 to 4.00 (3.00, 5.00). The were significant differences except for Kapandji score ( Z=-4.905, P<0.001; Z=-0.121, P=0.905; Z=-4.846, P<0.001). The mean grip and pinch strength showed improvement from an average of 16.4 (14.13, 18.68) kg and 1.70±0.35 kg to 26.14±3.27 kg and 3.58±0.91 kg with significant difference ( Z=-4.617, P<0.001; t=-7.669, P<0.001). Conclusion:Arthroscopic partial trapeziectomy and suture button suspensionplasty is a minimally invasive surgery for the treatment of first CMCJ Eaton stage II/III arthrosis. By this technique, the patients' existing instability and pain problems can be solved.

Objective: To investigate the current situation of using virtual simulation technology in undergraduate schools of stomatology in China, analyze the problems and put forward corresponding improvement suggestions. Methods: A questionnaire survey was conducted among 672 teachers and 3 849 students in undergraduate schools of stomatology in China. Results : 25.81% of all participants had took part in dental virtual simulation courses, and 37.80% of the participants from “Double First-Class” universities had participated in dental virtual simulation courses. 92.12% of the virtual simulation courses were established for undergraduates. "Traditional course + virtual simulation model demonstration" is the main teaching form of virtual simulation courses. Most of the participants were satisfied with the virtual simulation courses offered by their schools. At present, there are also some deficiencies in the virtual simulation courses, such as lack of teaching resources, insufficient interaction and simulation. Conclusion There is difference in the application of virtual simulation technology in undergraduate schools of stomatology in China. The virtual simulation technology is more widely used in "Double First-Class" universities than in ordinary universities. Undergraduates are the main teaching objects of virtual simulation courses. Stomatological schools in China should pay attention to the development and utilization of virtual simulation curriculum resources by cooperation, enrich the form of virtual simulation courses and strengthen the promotion and application of virtual simulation technology in stomatological education.

Objective:To observe the clinical efficacy of treating somatoform pain disorder(SPD)with electroacupuncture(EA)at the Governor and Conception Vessel points plus duloxetine.Methods:Eighty-two SPD patients were randomly allocated to an observation group and a control group,with 41 cases in each group.The control group was intervened by oral administration of duloxetine hydrochloride enteric capsules at a dose of 60 mg per time once a day;based on the medication,the observation group received additional EA treatment by selecting points from the Governor and Conception Vessels.Clinical efficacy was evaluated after 8 weeks of treatments;changes in the scores of the short-form McGill pain questionnaire(SF-MPQ),self-report symptom inventory,symptom check list-90(SCL-90),Pittsburgh sleep quality index(PSQI),and generic quality of life inventory-74(GQOLI-74)were also compared.Results:After the intervention,the observation group surpassed the control group in comparing the total effective rate(P＜0.05).The SF-MPQ score,SCL-90 somatization score,and PSQI score dropped notably in both groups after treatment,and the intra-group differences were statistically significant(P＜0.05);the three scores were significantly lower in the observation group than in the control group(P＜0.05).The GQOLI-74 score got an increase in each dimension in both groups after treatment,and the intra-group differences were also statistically significant(P＜0.05);the GQOLI-74 dimension scores were all significantly higher in the observation group than in the control group(P＜0.05).Conclusion:For patients with SPD,combining EA at the Governor and Conception Vessel points and duloxetine hydrochloride enteric capsules can markedly improve their clinical symptoms and quality of life.

Objective     To study the correlation of preoperative hemoglobin amount with venous thromboembolism (VTE) after surgical treatment of bronchiectasis and the clinical significance. Methods     A retrospective study was performed on patients with bronchiectasis who underwent surgical treatment in our center from June 2017 to November 2021. The differences in blood parameters between the VTE patients and non-VTE patients were compared. The relationship between preoperative hemoglobin and VTE was confirmed by quartile grouping and receiver operating characteristic (ROC) curve. Results     A total of 122 patients were enrolled, including 50 males and 72 females, with a mean age of 52.52±12.29 years. The overall incidence of VTE after bronchiectasis was 9.02% (11/122). Preoperative hemoglobin amount (OR=0.923, 95%CI 0.870-0.980, P=0.008) and D-dimer amount (OR=1.734, 95%CI 1.087-2.766, P=0.021) were independent influencing factors for VTE after bronchiectasis. The incidence of VTE after bronchiectasis decreased gradually with the increase of preoperative hemoglobin amount. The area under the ROC curve (AUC) of postoperative D-dimer alone was 0.757, whereas the AUC of postoperative D-dimer combined with preoperative hemoglobin amount was 0.878. Conclusion     Low preoperative hemoglobin is an independent risk factor for postoperative VTE. Postoperative D-dimer combined with preoperative hemoglobin amount has a better predictive performance compared with postoperative D-dimer alone for postoperative VTE.

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.

The clinical data of 2 children with refractory Mycoplasma pneumoniae pneumonia complicated with intracardiac thrombosis and pulmonary embolism, treated in Tianjin Children′s Hospital from July 2019 to January 2020, were analyzed retrospectively.One patient was an 8-year-old girl, who was admitted to the hospital mainly because of " fever for 5 days and cough for 2 days" . The other patient was a 7-year-old boy, who was admitted due to " intermittent fever with cough for 24 days and chest pain for 1 day" . Both children were complicated with elevated D-dimer levels and positive antiphospholipid antibody.During the treatment, right cardiac thrombosis and pulmonary embolism occurred in both cases, and the manifestations of thrombosis related symptoms were not typical.After the patients received anticoagulation treatment and thrombolytic therapy with urokinase, the cardiac thrombus dissipated and the pulmonary embolism improved.For refractory Mycoplasma pneumoniae pneumonia complicated with intracardiac thrombosis and pulmonary embolism, thrombolytic therapy can be applied to some children in addition to anticoagulant therapy.

COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development. No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections. We report herein that a macrolide antibiotic, carrimycin, potently inhibited the cytopathic effects (CPE) and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229E, OC43, and SARS-CoV-2. Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection. In support of this notion, metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA. Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.