【Objective】 Until now, most clinical and basic studies on Kashin-Beck disease (KBD) have focused on the visible deformed extremities, and there is a lack of reports concerning their spinal features, especially for the atlantoaxial joint. The purpose of this study was to determine the prevalence and radiographic features of atlantoaxial dislocation (AAD) in KBD in adult patients. 【Methods】 The prevalence and radiographic features of AAD were determined by the basic information collected, clinical symptoms, and lateral and dynamic plain radiography in 111 KBD patient and 120 non-KBD participants. In the KBD group, AAD and non-AAD patients were compared in age, gender, height, weight, BMI, smoking history, chronic history, disease duration and grade of disease so as to identify the related factors of the occurrence of AAD. 【Results】 Symptoms at the neck or neurological manifestations were present in 17.5% (21/120) in the non-KBD population and 39.6% (44/111) patients with KBD. AAD case was not detected in the non-KBD population, while in 16.2% (18/111) of KBD patients in the endemic area. The prevalence was higher in the KBD patients than in the non-KBD population, and there was a significant difference in the detection rate of AAD between the two groups (χ²=21.10, P<0.001). Plain radiography demonstrated that there were 10 (55.6%) cases with separation of the odontoid process and the other 8 (44.4%) cases with hypoplasia of odontoid process. Anterior AAD was noted in 12 (66.7%) patients and posterior AAD in 6 (33.3%) cases based on the displacement direction, while 16 (88.9%) cases were reducible and 2 (11.1%) cases were irreducible on the basis of the reducibility. Comparing the 93 patients with non-AAD KBD patients and 18 patients with AAD patients, there was no significant difference in age, sex, BMI, history of medical disease or smoking (all P>0.05). There were significant differences in height, weight, disease duration and grade of disease between AAD and non-AAD patients (all P<0.05). 【Conclusion】 KBD can cause the occurrence of atlantoaxial dislocation by inducing separation or hypoplasia of the odontoid process. This research may provide clinical evidence for screening, earlier prevention and treatment of atlantoaxial dislocation in adult KBD patients.

Objective:To systematically review the severe risk in common chronic diseases and coronavirus disease 2019 (COVID-19) cases.Methods:PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, China Biology Medicine disc, medRxiv, SSRN and ChinaXiv were searched for clinical and epidemiological studies that reported chronic diseases in patients with COVID-19. Only studies of severe COVID-19 in comparison with non-severe controls were included. The prevalence rates of chronic diseases including chronic obstructive pulmonary disease (COPD), diabetes mellitus, hypertension, malignant tumor, cardiovascular diseases, cerebrovascular disease, chronic kidney disease, and chronic liver disease were estimated. Pooled odds ratio ( OR) with 95% confidence interval ( CI) between patients with severe COVID-19 and non-severe groups were calculated. R 3.6.3 software was used for meta-analysis. Results:The search yielded 2 455 articles. A total of 19 eligible comparative studies with 4 792 patients were included in a quantitative analysis. Meta-analysis showed that there was a proportion of 55.0% (95% CI 40.0%-80.0%) male among patients with COVID-19, and the overall pooled prevalence of any chronic diseases in COVID-19 cases was 30.4% (95% CI 24.0%-37.0%). The most prevalent comorbidity was hypertension (16.9%(95% CI 14.0%-20.0%)), followed by diabetes mellitus (8.3%(95% CI 8.0%-9.0%)). The proportion of male patients with severe COVID-19 was higher than that of male patients with non-severe COVID-19 (64.4% vs 52.8%, OR=1.49, 95% CI 1.08-2.05, Z=4.63, P<0.01). The prevalence rates of COPD, cerebrovascular disease, diabetes mellitus, chronic kidney disease, hypertension, cardiovascular diseases and malignant tumor in severe COVID-19 patients were higher than those of non-severe patients ( OR=5.77, 95% CI 3.80-8.74; OR=4.47, 95% CI 2.71-7.38; OR=3.55, 95% CI 2.86-4.40; OR=3.05, 95% CI=1.76-5.28; OR=2.82, 95% CI=1.96-3.97; OR=2.39, 95% CI=1.77-3.23; OR=2.15, 95% CI 1.27-3.66, respectively, Z=8.37, 6.01, 11.60, 4.20, 5.46, 5.71, 3.12, all P<0.01). There was no significant difference in the prevalence of chronic liver disease between severe and non-severe patients ( OR=1.35, 95% CI 0.84-2.17, P=0.11). Conclusion:COVID-19 patients with chronic diseases have higher risk of developing severe disease, and the ORs from high to low are COPD, cerebrovascular disease, diabetes mellitus, chronic kidney disease, hypertension, cardiovascular diseases and malignant tumor.

OBJECTIVE: To evaluate the expression of thymidylate synthase (TS) in myoepithelial cells (MECs) of salivary adenoid tissues and explore its clinical significance. METHODS: Immunohistochemical staining EnVision method was used to detect the expression of TS, P63, Calponin, CK5/6 and S-100 in 32 salivary gland specimens, including 10 non-neoplastic and salivary inflammation specimens, 11 mixed tumor specimens, 5 basal cell carcinoma specimens and 6 adenoid cyst carcinoma specimens. The specificity and sensitivity of TS as a specific molecular marker of salivary muscle epithelial cells were evaluated in comparison with P63, Calponin, CK5/6 and S-100. RESULTS: The expression pattern of TS in all the salivary gland tissue specimens was identical with that of p63. TS and P63 both showed strong immunohistochemical expressions in MECs of salivary adenoid tissue specimens. Calponin, CK5/6, and S-100 showed cytoplasmic/membranous expressions in the MECs. In addition, TS exhibited weak or moderate cytoplasmic expression in a few salivary gland epithelial cells, cancer cells and scattered stromal cells, with negative expression in the cell nuclei. The expression of TS in the MECs of all the salivary adenoid specimens was highly consistent with those of P63, Calponin, CK5/6 and S-100 (>0.05) Except for CK5/6 expression in Salivary inflammation and Salivary gland specimens. Kappa>0.75. The specificity and sensitivity of TS as a molecular marker of MECs were both 100%. CONCLUSIONS TS is a new specific marker of MECs for differential diagnosis of salivary gland tumors.
Adenoids ; Biomarkers, Tumor ; Carcinoma, Adenoid Cystic ; Epithelial Cells ; Humans ; Salivary Gland Neoplasms ; Thymidylate Synthase

The WHO declared the coronavirus disease 2019 (COVID-19) outbreak as a public health emergency of international concern on January 30, 2020, and then a pandemic on March 11, 2020. COVID-19 affected over 200 countries and territories worldwide, with 25,541,380 confirmed cases and 852,000 deaths associated with COVID-19 globally, as of September 1, 2020. 1While facing such a public health emergency, hospitals were on the front line to deliver health care and psychological services. The early detection, diagnosis, reporting, isolation, and clinical management of patients during a public health emergency required the extensive involvement of hospitals in all aspects. The response capacity of hospitals directly determined the outcomes of the prevention and control of an outbreak. The COVID-19 pandemic has affected almost all nations and territories regardless of their development level or geographic location, although suitable risk mitigation measures differ between developing and developed countries. In low- and middle-income countries (LMICs), the consequences of the pandemic could be more complicated because incidence and mortality might be associated more with a fragile health care system and shortage of related resources. 2-3 As evidenced by the situation in Bangladesh, India, Kenya, South Africa, and other LMICs, socioeconomic status (SES) disparity was a major factor in the spread of disease, potentially leading to alarmingly insufficient preparedness and responses in dealing with the COVID-19 pandemic. 4 Conversely, the pandemic might also bring more unpredictable socioeconomic and long-term impacts in LMICs, and those with lower SES fare worse in these situations. This review aimed to summarize the responsibilities of and measures taken by hospitals in combatting the COVID-19 outbreak. Our findings are hoped to provide experiences, as well as lessons and potential implications for LMICs.

Objective: A resilient health system plays a crucial role in pandemic preparedness and response. Although the World Health Organization (WHO) has required all states parties to strengthen core capacities to respond to public health emergencies under the International Health Regulations (2005), the actions of most countries to combating coronavirus disease 2019 (COVID-19) has showed that they are not well-prepared. This cross-sectional study aimed to examine the health system resilience of selected countries and analyze their strategies and measures in response to the COVID-19 pandemic.Methods: This study selected five countries including the Iran, Japan, Republic of Korea (South Korea), the U.K., and the U.S., based on the severity of the national epidemic, the geographical location, and the development level. Cumulative number of death cases derived from WHO COVID-19 dashboard was used to measure the severity of the impact of the pandemic in each country; WHO State Parties Self-Assessment Annual Reporting (SPAR) Scores and Global Health Security (GHS) Index were applied to measure the national health system resilience; and research articles and press materials were summarized to identify the strategies and measures adopted by countries during response to COVID-19. This study applied the resilient health systems framework to analyze health system resilience in the selected countries from five dimensions, including awareness, diversity, self-regulation, integration and adaptation. Results: The SPAR Scores and GHS Index of the four developed countries, Japan, South Korea, the U.K. and the U.S. were above the global and regional averages; the SPAR Scores of Iran were above the global average while the GHI Index lain below the global average. In terms of response strategies, Japan, the U.K. and the U.S. invested more health resources in the treatment of severe patients, while South Korea and Iran had adopted a strategy of extensive testing and identification of suspected patients. In terms of specific measures, all the five countries adopted measures such as restrictions on entry and international travel, closure of schools and industries, lockdown and quarantine. Nevertheless, the effectiveness of implementing these measures varied across countries, based on the response strategies. Conclusion: Although SPAR Scores and GHS Index have evaluated the national core capacities for preparedness and response, the actions to cope with the COVID-19 pandemic has revealed the fact that most countries still do not build resilient health systems in response to public health emergencies. Health system strengthening and health security efforts should be pursued in tandem, as part of the same mutually reinforcing approach to developing resilient health systems.

OBJECTIVE: To investigate the effect of calcium channel blocker diltizem in reversing multi-drug resistance (MDR) and on metadherin expression in hepatocellular carcinoma cells and explore the molecular mechanism. METHODS: Hepatocellular carcinoma MHCC97H and 7402 cells were treated with diltiazem hydrochloride, a calcium channel blocker (0, 25, 50, 100, 200, and 400 μmol/L), for 12, 24, or 48 h. Wound healing assay was employed to assess the changes in the mobility and migration of the cells following the treatments, and the changes in the expression levels of metadherin mRNA and protein and P-gp protein were determined using RT-PCR and immunocytochemistry. RESULTS: Diltiazem hydrochloride could transiently inhibit the migration and movement of MHCC97H and 7402 cells in a time-and concentration-dependent manner ( < 0.05). Diltiazem hydrochloride at different concentrations also transiently up-regulated the expressions of metadherin mRNA and protein but did not inhibit the expression of P-gp protein in MHCC97H and 7402 cells. CONCLUSIONS Calcium channel blocker can transiently inhibit the migration of hepatocellular carcinoma cells and up-regulate the expression of metadherin mRNA and protein through a feedback mechanism, suggesting the potential risk of calcium channel blockers for promoting tumor progression during the treatment of malignant tumors.
Calcium Channel Blockers ; Carcinoma, Hepatocellular ; Cell Line, Tumor ; Diltiazem ; Humans ; Liver Neoplasms

OBJECTIVE: To generate a new strain of HBeAg transgenic mice using CRISPR/Cas9 technique. METHODS: Hepatitis B virus (HBV) HBeAg gene was cloned and inserted in the pliver-HBeAg expression frame at the site of Rosa26 gene using CRISPR/Cas9 and homologous recombination techniques to construct the pliver-HBeAg expression vector containing HBeAg gene. The linear DNA fragment containing HBeAg gene was obtained by enzyme digestion. Cas9 mRNA, gRNA and the donor vector were microinjected into fertilized eggs of C57BL/6J mice, which were then transplanted into the uterus of C57BL/6J female surrogate mice to obtain F0 generation mice. The F0 generation mice were identified by long fragment PCR to obtain F0 transgenic mice with HBeAg gene. The positive F0 generation mice were bred with wild-type C57BL/6J mice to produce the F1 mice, which were identified by PCR and sequencing. The positive F1 transgenic mice carrying HBeAg gene were backcrossed until the homozygous offspring transgenic mice were obtained. The genotypes of the offspring mice were identified. The expressions of HBeAg and HBeAb in the heterozygous and homozygous HBeAg transgenic mice were detected by automatic chemiluminescence immunoassay, immune colloidal gold technique and immunohistochemistry method. RESULTS: A total of 56 F0 mice were obtained, and 2 of them carried homologous recombined HBeAg gene. Six positive F1 mice were obtained, from which 22 homozygous and 29 heterozygous F2 generation HBeAg transgenic mice were obtained. High concentration of HBeAg protein was detected in the peripheral blood of all the positive HBeAg transgenic mice without HBeAb expression. HBeAg expression was detected in the hepatocytes of HBeAg transgenic mice. CONCLUSIONS We obtained a new strain of HBeAg transgenic mice with stable expression of HBeAg in the hepatocytes and immune tolerance to HBeAg using CRISPR/Cas9 technique, which provide a new animal model for studying HBV.
Animals ; CRISPR-Cas Systems ; Female ; Genetic Vectors ; Hepatitis B e Antigens ; genetics ; Hepatitis B virus ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic

Objective To evaluate the quality of life of patients with Kaschin-Beck disease (KBD)receiving total knee arthroplasty (TKA) before and after the operation.Methods Clinical efficacy of 25 patients with KBD who underwent TKA in Department of Orthopaedics,Shaanxi Provincial People's Hospital from January 2015 to January 2017 was prospectively analyzed.A questionnaire survey on KBD quality of life (KBDQOL)was carried out to evaluate the quality of life of the patients before,6 months and 1 year after the surgery.Results The scores of physical function,activity limit,social support,mental status and total health scores of KBDQOL in 6 months after the surgery (30.60 ± 3.73,23.24 ± 2.03,15.16 ± 1.62,18.92 ± 2.89,12.80 ± 2.57) and 1 year after the surgery (32.00 ± 3.19,23.76 ± 1.59,15.60 ± 1.29,20.16 ± 2.67,17.28 ± 3.88) were significantly higher than those of before the surgery (18.84 ± 4.94,21.04 ± 2.72,12.80 ± 2.06,13.68 ± 3.42,7.92 ± 1.93,P ＜ 0.05).However,there was no significant difference in economic scores before,6 months and 1 year after the surgery (10.68 ± 2.98,10.60 ± 2.78,10.48 ± 2.80,P ＞ 0.05).Conclusions The quality of life after TKA in patients with KBD severe knee osteoarthritis is significantly better than that before the surgery.The KBDQOL questionnaire is an appropriate tool for evaluating the quality of life in KBD patients.

Objective To study the therapeutic effects of arthroscopic debridement combined with sodium hyaluronate injection in treatment of Kashin-Beck disease with ankle arthritis.Methods Using prospective study,Kashin-Beck disease patients with ankle arthritis,who had underwent arthroscopic debridement combined with sodium hyaluronate injection,were selected as study subjects.X-ray stratification was performed based on Kellgren-Lawrence grading method,grade 1,2,3 were studied,if there were fewer patients at grade 1,then merge with grade 2.Visual analogue scale (VAS),anterior and posterior ankle activity and ankle hindfoot score were used to evaluate the effects before and 3,6,12 months after the treatment.Results Totally 33 patients were collected,VAS scores (6.9 ± 0.2,2.9 ± 0.2,2.1 ± 0.1,1.9 ± 0.1),anterior and posterior ankle activities (20.9 ± 0.6,31.5 ± 0.6,32.1 ± 0.6,34.1 ± 0.4),and ankle hindfoot scores (51.3 ± 0.5,70.8 ± 1.1,76.0 ± 0.9,77.0 ± 0.9) before and 3,6,12 months after the treatment,were compared,and the differences were statistically significant (F =267.47,703.09,756.49,P ＜ 0.01).VAS scores (7.0 ± 0.2,2.8 ± 0.2,1.7 ± 0.1,1.7 ± 0.1;7.0 ± 0.3,3.2 ± 0.3,2.8 ± 0.2,2.2 ± 0.2),anterior and posterior ankle activities (22.4 ± 0.7,32.5 ± 0.6,33.1 ± 0.6,51.3 ± 0.5;18.1 ± 0.9,29.6 ± 1.0,30.2 ± 1.0,31.4 ± 0.9),and ankle hindfoot scores (51.6 ± 0.9,70.9 ± 0.5,77.7 ± 0.9,79.1 ± 1.0;50.6 ± 0.5,65.5 ± 1.8,72.8 ± 1.4,72.9 ± 1.4) in grade 1 + grade 2,and grade 3 patients before and 3,6,12 months after the treatment,were compared,and the differences were statistically significant (F =244.80,64.04;379.94,498.83;1 393.07,159.70,P ＜ 0.01).Compared with those before the treatment,VAS scores of all,grade 1 + grade 2,and grade 3 patients in 3,6,12 months after the treatment significantly decreased,anterior and posterior ankle activities and ankle hindfoot scores significantly increased (P ＜ 0.05).Conclusion Arthroscopic debridement combined with sodium hyaluronate injection is effective in the treatment of Kashin-Beck with disease ankle arthritis.

Objective:To investigate the promotive effect of 4,5,6,7-tetrabromobenzotriazole (TBB) on the apoptosis of the human cervical cancer HeLa cells,and to clarify its effect mechanism in related signaling pathways.Methods:The human cervical cancer HeLa cells at logarithmic growth phase were divided into control group(without TBB) and experiment group(with TBB).MTT assay was used to detect the survival rate of the HeLa cells;the morphology of HeLa cells was observed under inverted microscope;Annexin Ⅴ-FITC/PI double staining and flow cytometry(FCM) were used to determine the apoptotic rates of the HeLa cells;the expression levels of apoptosis-related proteins p-Akt,Akt,Bcl-2,Bax,cleaved-caspase-3,and Pro-caspase-3 were detected by Western blotting method.Results:The MTT results showed that the survival rates of the HeLa cells in experiment group were significantly decreased(P<0.01) in a dose-dependent manner compared with control group.The apoptotic morphology of the HeLa cells in experiment group were found as cell shrinkage and karyopyknosis under inverted microscope.The Annexin Ⅴ-FITC/PI double staining and FCM results showed that the apoptotic rates of the HeLa cells in experiment group (3,6,12 and 24 h) were higher than that in control group (P<0.05 or P<0.01).The Western blotting results showed that compared with control group,the expression levels of the anti-apoptotic proteins p-Akt and Bcl-2 in HeLa cells in experiment group were decreased obviously,whereas the expression levels of the pro-apoptotic proteins Bax and cleaved-caspase-3 were increased and the expression levels of Pro-caspase-3 were decreased.Conclusion:TBB may promote the apoptosis of human cervical cancer HeLa cells by inhibiting the Akt signaling pathway.