Sjögren's syndrome （SS）， a disorder of immune system， is one of the dominant diseases treated by traditional Chinese medicine （TCM）. China Association of Chinese Medicine organized experts in the field of TCM and western medicine rheumatology and pharmacology to discuss the advantages and optimal regimens of TCM for the treatment of SS. The experts generally agreed on the low early diagnosis rate of SS and the lack of targeted therapeutic drugs. In addition， autoimmune abnormality is the key factor in the occurrence of SS and deficiency of both Qi and Yin is the core pathogenesis. SS has unique tongue manifestations， which is expected to allow for the early diagnosis and treatment with integrated traditional Chinese and western medicine. TCM has advantages in treating SS in terms of alleviating clinical symptoms and systemic involvement， individualized treatment， relieving sleep and mood disorders， preventing the occurrence in the early stage， and enhancing the effectiveness and reducing toxicity in the treatment by integrated TCM and western medicine. In general， TCM has advantages in different stages of SS. Internal and external use of TCM， acupuncture， and acupotome are all available options. The optimal regimens should be determined on the basis of pattern identification， stage of disease， and the advantages of TCM. Clinical characteristics and biomarkers of SS should be studied to classify patients， so as to design precision evidence-based TCM regimens for SS. On the basis of unique tongue manifestations of SS， models for early diagnosis and poor prognosis identification of SS should also be established to achieve early prevention and treatment and to improve the prognosis. In the future， we should vigorously carry out high-quality evidence-based medical research on the treatment of SS by TCM and integrated traditional Chinese and western medicine and develop relevant guidelines to optimize and standardize current diagnosis and treatment， thereby laying a basis for clarifying and explaining the advantages of TCM in treating SS.

Background/Aims: The increased mortality of gastric cancer (GC) is mainly attributed to the development of chemoresistance. Circular RNAs, as the novel type of biomarkers in GC, have attracted wide attention. The purpose of this study was to investigate the functional role of circ_0081143 in GC with doxorubicin (DR) resistance and its potential action mechanism. Methods: The expression of circ_0081143, miR-129-2-3p and YES proto-oncogene 1 (YES1) in GC tissues and cells was measured by quantitative real-time polymerase chain reaction. The half maximal inhibitory concentration value was calculated based on the MTT cell viability assay. Cell proliferation and apoptosis were monitored by MTT and flow cytometry assays. Transwell assays were employed to check cell migration and invasion. The protein levels of YES1 and apoptosis-related proteins were detected by western blotting. The interaction between miR-129-2-3p and circ_0081143 or YES1 was verified by dual-luciferase reporter and pull-down assays. A tumorigenicity assay was conducted to verify the role of circ_0081143 in vivo. Results: Circ_0081143 was highly expressed in DR-resistant GC tumor tissues and cells. Depletion of circ_0081143 reduced DR resistance and inhibited DR-resistant GC cell proliferation, migration and invasion. Circ_0081143 targeted miR-129-2-3p and inhibited the role of miR-129-2-3p. In addition, YES1 was a target of miR-129-2-3p, and its function was suppressed by miR-129-2-3p. Importantly, circ_0081143 positively modulated the expression of YES1 through mediating miR-129-2-3p. Circ_0081143 knockdown weakened the DR-resistant GC tumor growth in vivo. Conclusions Circ_0081143 knockdown weakened DR resistance and blocked the development of DR-resistant GC by regulating the miR-129-2-3p/YES1 axis. Our data suggest that circ_0081143 is a promising target for the treatment of GC with DR resistance.

Objective:To explore the role of N 6-methyladenosine (m6A) and its regulator METTL3 in the non-coding RNA of endometrial cancer.Methods:The expression levels of m6A and METTL3 were quantified in 20 paired carcinoma and adjacent clinical tissue samples from patients at from Jul. 2016 to Dec. 2020. HEC-1-A cell lines were constructed with METTL3 overexpression and knockdown. Western blot was used to detect the phosphorylation levels of key molecules in METTL3 and Akt/mTOR. The quantitative detection of mRNA levels were used qRT-PCR. The binding level of m6A to its receptor DGCR8 was determined by RNA immunoprecipitation.Results:The results of the m6A RNA methylation quantification kit showed that m6A (1.0±0.15) vs (1.7±0.34) ( P<0.01) and METTL3 levels were elevated in endometrial cancer cells, and METTL3 (1.0±0.13) vs (2.5±0.45) ( P<0.05) levels were elevated in endometrial cancer cells. Western blot and qRT-PCR detection of miR-17-92 cell clusters overexpressing METTL3, METTL3 overexpression significantly increased m6A modification on pri-miR-17-92 ( P<0.05) . Phosphorylation levels of AKT/mTOR pathway-related proteins were upregulated. In addition, RIP test results indicated that the binding of DGCR8 to pri-miR-17-92 was significantly facilitated. Conclusion:METTL3 modification of m6A facilitates the processing of pri-miR-1792 into the miR-17-92 clusters via m6A/DGCR8-dependent mechanism, which in turn activated the AKT/mTOR pathway.

Objective:To investigate the effect of Astragaloside Ⅳ-mediated Endothelial progenitor cells derived exosomes (EPC-Exos) on the biological function of EPC-Exos damaged by high glicose.Methods:EPCs from human umbilical cord blood were isolated and cultured in vitro. the EPC-Exos secreted by EPCs were extracted by ultracentrifugation combined with ultrafiltration, and identified by specific markers CD9, CD63 and CD81, respectively. After the cells were cultured for 24 hours with AS-IV at 100 mg/L and PBS at the same volume, the morphological characteristics of EPC-Exos were observed by transmission electron microscope. Human endothelial cells were isolated, cultured and identified in vitro. The identified endothelial cells were pretreated with 30 mmol/L glucose for 120 h and randomly divided into experimental group and control group, at the same time set the normal group. The cells were cultured for 24 hours, the effects of EPC-Exos on proliferation, adhesion, migration and angiogenesis of endothelial cells damaged by high glucose were observed by using cell counting kit-8 (CCK-8) Cell Proliferation Assay Kit, cell scratch test, adhesion assay and in vitro angiogenesis assay by Matrigel. Results:Compared with the normal group, the proliferation, migration, adhesion and tubulogenesis of human endothelial cells in the control group were significantly lower ( t=24.35, 6.80, 10.65, 9.62, P<0.05). Compared with the control group, the proliferation, adhesion, migration and tubulogenesis of human endothelial cells in the experimental group were significantly enhanced ( t=30.68, 5.99, 5.40, 8.25, P<0.05). Conclusions:EPC-Exos mediated by AS-Ⅳ can significantly improve the biological function of human endothelial cells damaged by high glucose and has the potential to modulate endothelial neovascularization in diabetic rats.

Objective:To study the efficacy and drug-related adverse reactions of long-term appli-cation of biological anti-rheumatic drugs (bDMARDs) to patients with ankylosing spondylitis (AS), and provide reference for clinical diagnosis and treatment.Methods:We retrospectively analyzed the clinical data of AS patients who were followed-up for more than 5 years in the Department of Rheumatology and Immunology of Peking University Shenzhen Hospital. The patients treated with bDMARDs alone or combined with traditional antirheumatic drugs were included as the treatment group, while those who did not receive biological or non-biological antirheumatic therapy were included as the control group. The data collected included clinical sym-ptoms, inflammatory biomarkers, imaging results, drug applications and drug-related adverse reactions, etc. The counting data were tested by χ2 test, the measurement data in normal distribution was tested by t test, and the measurement data that not normally distributed was tested by Mann-Whitney U test. Paired test was used for statistical processing before and after treatment. Results:We collected the data of 114 eligible patients, including 64 in the treatment group and 50 in the control group. There were no significant differences in baseline data between the 2 groups, including mean follow-up time, course of disease, age, sex ratio, HLA-B27 positive rate, morning stiffness duration, night pain, peripheral arthritis, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and imaging. After 5 years, patients in the treatment group had shorter morning stiffness [(3±7) min vs (26±37) min, t=4.827, P<0.01], lower nighttime pain rates [(3/64, 4.8%) vs (29/50,58.0%), χ2=38.329, P<0.01], lower ESR level [(14±14) mm/1 h vs (20±18) mm/1 h, t=2.102, P=0.038], lower CRP level [(7±8) mg/L vs (14±19) mg/L, t=2.431, P=0.017], and lower progression rate of sacroiliac arthritis [(18/64, 28.1%) vs (35/50, 70.0%), χ2=19.786, P<0.01], than the control group. The main drug-related adverse reactions in the treatment groupincluded reversible leucopenia, elevated transaminase level, redness and swelling at the injection site. Conclusion:Biologics treatment for more than 3 consecutive years can effectively control the clinical symptoms of most AS patients, reduce inflammatory indicators and delay the imaging progression of the sacroiliac joint. Without treatment, the imaging progress of the sacroiliac joint in AS patients could be 70% after 5 years.

Objective: Understanding mental health status of students with learning disabilities in Beijing to provide a basis for mental health promotion of students with learning disabilities. Methods: By means of random cluster sampling, 5 787 enrolled students in grade one and grade two of 11 public junior middle schools in Beijing were selected as the survey subjects. A self designed questionnaire was used to investigate the students’ learning disabilities and mental health status through anonymous self filling. Results: About 11.6% students self reported learning disabilities. The proportions of students with learning difficulty in mathematical reasoning and calculation were higher, 44.1% and 40.7% respectively. The reported rate of mental health problems was 38.3%. The top four of the 10 symptoms were obsessive compulsive symptoms, learning pressure, emotional instability and anxiety(2.19±0.77)(2.17±0.99)(2.09±0.90)(2.07±1.08). Compared with students without learning disabilities, students with self reported learning disabilities had poorer mental health status(OR=1.47), and learning disabilities were related to most factors of mental health. Different types of learning disabilities were associated with different mental health factors. Conclusion Mental health problems of students with learning disabilities are higher than that of students without learning disabilities. It is necessary to strengthen the mental health support for students with learning disabilities and improve their mental health.

Objective:To investigate the 2 years’ efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation.Methods:From July 2015 to June 2020, 18-75 years old patients with moderate to high-risk non muscle invasive bladder cancer (NMIBC) confirmed by pathological examination were involved. The ECOG score was 0-2. Exclusion criteria included ①immune deficiency or impairment (such as AIDS), using immunosuppressive drugs or radiotherapy, suspected allergic to BCG or epirubicin or excipients of the two drugs, fever or acute infectious diseases including active tuberculosis or receiving anti tuberculosis treatment, with severe chronic cardiovascular and cerebrovascular diseases or chronic kidney disease; ②combined with other urogenital system tumors or other organ tumors; ③combined with muscle invasive bladder urothelial carcinoma (≥T 2); ④undergoing chemotherapy, radiotherapy or immunotherapy within 4 weeks (immediate instillation after surgery not included); ⑤ pregnant or lactating women; ⑥ comfirmed or suspected bladder perforation; ⑦gross hematuria; ⑧cystitis with severe bladder irritation that may affect the evaluation; ⑨participat in other clinical trials within 3 months; ⑩alcohol or drug addiction; ?any risk factors that may increasing the risk of patients. Epirubicin 50 mg was irrigated immediately after the operation(TURBT or laser resection). The patients were randomly divided into BCG15 group, BCG19 group and epirubicin group by the ratio of 2∶2∶1, and the patients were maintained intravescical instillation for 1 year. The recurrence and adverse events of the three groups were compared. Univariate and multivariate analysis was performed to predict the risk factors of BCG irrigated therapy failure. Result:By June 15, 2020, the median follow-up duration was 22.1 months(12.1, 32.3), and there was no statistical difference between the groups ( P=0.9024). There were 274 patients enrolled in BCG19 group, 277 patients enrolled in BCG15 group and 130 patients enrolled in the epirubicin group. The drop-off rate was 16.6%(113 cases)and made no difference between groups( P=0.6222). There were no significant difference in age, gender, BMI, or ECOG score( P>0.05). During the follow-up, 116 cases was detected recurrence or progression. The recurrence rate of the three groups was 14.2% and 14.8% in BCG19 group and BCG15 group, and 27.7% in the epirubicin group. There was no difference in recurrence rate between BCG19 and BCG15 group( P=0.9464). The recurrence rate of BCG19 group was lower than that of the epirubicin group ( P=0.0017). The recurrence rate of BCG15 group was lower than that of the epirubicin group ( P=0.0020). There was no difference in the cumulative recurrence free survival rate between BCG19 and BCG15 group (95% CI0.57-1.46, P=0.7173). The cumulative recurrence free survival rate of BCG 19 group was better than that of the epirubicin group( HR=0.439, 95% CI0.26-0.74, P=0.0006), and the cumulative recurrence free survival rate of BCG15 group was better than that of the epirubicin group ( HR=0.448, 95% CI0.29-0.80, P=0.0021). The total incidence of adverse events in 19 BCG19, BCG15 and epirubicin group were 74.5%, 72.6% and 69.8% respectively. There was no difference in the incidence of adverse events between BCG19 and BCG15 group( P=0.6153). The incidence of adverse events in epirubicin group was lower than that of BCG19( P=0.0051) and BCG15( P=0.0167) groups.There was no significant difference in the incidence of serious adverse events (SAE) among the three groups ( P=0.5064). Log rank test univariate analysis and Cox risk regression model multivariate analysis showed that the history of bladder cancer recurrence( HR=6.397, 95% CI1.95-20.94, P=0.0001)was independent risk factor for BCG irrigation failure. Conclusions:The 2 years’ efficacy of intravesical instillation of domestic BCG is better than than of epirubicin with good tolerance and safety. There is no difference between BCG19 and BCG15 group. BCG doesn’t increase SAE compared with epirubicin. Recurrence status was an independent prognostic factor regarding recurrence-free survival.

Objective:To understand the function of diaphragm and analyze the clinical factors affecting the function of diaphragm by measuring twitch tracheal pressure (TwPtr) in patients with mechanical ventilation and in the weaning phase.Methods:Patients with more than 48 hours of invasive mechanical ventilation admitted to the department of critical care medicine of the First Affiliated Hospital of Guangzhou Medical University from December 2015 to March 2017 were enrolled. After the patient entered the weaning stage, TwPtr of patients was monitored by two-way non repetitive automatic respiratory trigger device, the effects of duration of mechanical ventilation, severe pulmonary infection, sedative application and chronic obstructive pulmonary disease (COPD) on weaning were analyzed.Results:A total of 62 patients were included, of which 45 were male and 17 were female. The average age was (66.8±11.7) years old. Twenty-three cases had severe pneumonia. The absolute value of TwPtr in severe pneumonia group was lower than that in non-severe pneumonia group [cmH 2O (1 cmH 2O = 0.098 kPa): 10.40±5.81 vs. 14.35±5.22, P = 0.021]. However, there was no significant difference in the duration of mechanical ventilation between the severe pneumonia group and non-severe pneumonia group [days: 26 (17, 43) vs. 15 (11, 36), P = 0.091]. In 62 patients with mechanical ventilation, there was a negative correlation between TwPtr and duration of mechanical ventilation ( r = 0.414, P = 0.002), there was also a negative correlation between the duration of mechanical ventilation and TwPtr after the assessment of diaphragm function ( r = 0.277, P = 0.039). There was a linear relationship between TwPtr and sedatives ( r = 0.220, P = 0.040), but there was no correlation between TwPtr and COPD ( r = -0.178, P = 0.166). Conclusions:For patients in the weaning stage of mechanical ventilation, severe pulmonary infection is one of the factors that affect the diaphragm dysfunction. There is a certain correlation between the diaphragm dysfunction and the use of sedatives.

Objective:To observe the long-term effects of conventional disease modifying anti-rheumatic drugs (cDMARDs) in the treatment of ankylosing spondylitis (AS) and drug-related adverse reactions, and provide reference to clinical treatment and assessment.Methods:Retrospective analysis was performed for AS patients with more than 10 years follow-up records in the Department of Rheumatology and Immunology, Peking University Shenzhen Hospital. The AS patients enrolled were treated with cDMARDs, non-steroid anti-inflammatory Drugs (NSAIDs), and glucocorticoidsonl only. The treatment group was treated continuously for at least 3 years, and the control group was untreated or treated for less than 3 months. Clinical symptoms, inflammatory indicators, imaging results and drug-related adverse reactions of all patients were collected for statistical analysis. The counting data were tested by χ2 test, the measurement data in normal distribution was tested by t test, and the measurement data that not normally distributed was tested by mann-whitney U test. Paired test was used for statistical processing before and after treatment. Results:A total of 166 eligible patients were included, including 111 in the treatment group and 55 in the control group. There were no statistical significant differences between the treatment group and the control group at baseline including the mean follow-up time, symptomatic disease course, age, sex ratio, human lymphocyte antigen (HLA)-B27 positive rate, duration of morning stiffness, pain at night, peripheral arthritis, ESR, CRP and imaging data. After 10 years, the treat-ment group had shorter morning stiffness[(8±18) vs (22±34), U=2 228, P=0.008], less nocturnal pain [(2/1.9%) vs (19/36.5%), χ2=37.037, P<0.01], lower ESR level [(14±13) vs (20±19), t=2.249, P=0.026], lower CRP level [(6±6) vs (10±11), t=2.154, P=0.033], lower incidence of peripheral arthritis [(23/20.7%) vs(25/45.5%), χ2=10.946, P=0.001] and lower sacroiliac arthritis progression rate [(28/25.2% ) vs (46/83.6%), χ2=50.922, P<0.01], and lower spinal progression rate [(8/7.2%) vs (51/92.7%), χ2=117.407, P<0.01] compared with the control group. The differences between the two groups was statistically significant. The main medications and drug proportions in the treatment group were as follows: sulfasalazine (100%), methotrexate (86.5%), NSAIDs (98.2%), glucocorticoid (78.4%) and thalidomide (62.2%). The main drug-related adverse reactions that occurred during the treatment included dizziness, abnormal menstruation, and reversible liver dysfunction. Conclusion:The combination of cDMARDs can effectively control the clinical symptoms of most AS patients, reduce inflammation indicators, delay the progression of sacroiliac joint and spinal damage, and have no serious drug-related adverse reactions. Almost all of the untreated AS patients have radiographic progression of the sacroiliac joint and spine.

OBJECTIVE: To explore the genetic basis of cerebral palsy (CP). METHODS: A pair of twins with cerebral palsy and different phenotypes were subjected to whole genome sequencing, and other 8 children with CP were subjected to whole exome sequencing. Genetic variations were screened by a self-designed filtration process in order to explore the CP-related biological pathways and genes. RESULTS: Three biological pathways related to CP were identified, which included axon guiding, transmission across chemical synapses and protein-protein interactions at synapses, and 25 susceptibility genes for CP were identified. CONCLUSION The molecular mechanism of CP has been explored, which may provide clues for development of new treatment for CP.
Cerebral Palsy ; genetics ; Child ; Genetic Testing ; Humans ; Phenotype ; Whole Exome Sequencing ; Whole Genome Sequencing