ObjectiveTo investigate the effect and underlying mechanism of the Wulao Qisun prescription on pathological new bone formation in ankylosing spondylitis （AS）. MethodsSynovial fibroblasts were isolated from the hip joints of AS patients and observed under a microscope to assess cell morphology. The cells were identified using immunofluorescence staining. The isolated AS fibroblasts were divided into blank group， low drug-containing serum group， medium drug-containing serum group， high drug-containing serum group， and positive drug group. After drug intervention， cell proliferation was measured using the cell counting kit-8 （CCK-8） assay to observe fibroblast growth and determine the optimal intervention time. Alkaline phosphatase （ALP） activity was measured using the alkaline phosphatase assay. Protein expression of osteocalcin （OCN）， osteopontin （OPN）， and runt-related transcription factor 2 （Runx2） was detected by Western blot. The mRNA expression levels of Wnt5a， β-catenin， and Dickkopf-1 （DKK-1） were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， each drug-containing serum group of Wulao Qisun prescription and the positive drug group inhibited the proliferation of AS fibroblasts and reduced ALP expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription downregulated β-catenin mRNA expression （P<0.05）. The medium and high drug-containing serum groups and the positive drug group significantly downregulated Wnt5a and β-catenin mRNA expression （P<0.05， P<0.01）， with the positive drug group showing the most pronounced effect （P<0.01）. The high drug-containing serum group and the positive drug group significantly upregulated DKK-1 mRNA expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription inhibited the expression of OPN and Runx2 proteins （P<0.05， P<0.01）， while the medium and high drug-containing serum groups and the positive drug group inhibited the expression of OCN， OPN， and Runx2 proteins （P<0.05， P<0.01）. ConclusionThe Wulao Qisun prescription can inhibit the proliferation and osteogenic differentiation of AS fibroblasts， thereby delaying the formation of pathological new bone in AS. The possible mechanism involves the regulation of Wnt/β-catenin-related gene expression， further inhibiting the transcription of downstream target genes.

Objective:To conduct a survey of the current status of education service offered to professional master's students in clinical medicine in a grade-A tertiary hospital in Chongqing, China based on the SERVQUAL model, and to discuss the problems with education service as well as measures for improvement.Methods:Based on the SERVQUAL model, a questionnaire consisting of 30 items in 5 dimensions was designed. Each item was rated for an expected score and a perceived score. Medical professional master's students in a Chongqing grade-A tertiary hospital in the first half year of 2022 were surveyed for the expected and perceived quality of education service to calculate service quality (SQ). SPSS 26.0 was used for reliability and validity analyses and descriptive statistical analyses. The results were analyzed using a two-dimensional quadrant graph.Results:A total of 263 valid questionnaires were returned, with an effective response rate of 97.77%. For both the expectation scale and the perception scale, the Cronbach's α values were >0.8, and the Kaiser-Meyer-Olkin values were >0.7, indicating good reliability and validity. The mean expected value of education service quality was 4.28, the mean perceived value was 3.96, and the mean gap value was -0.32. The SQ scores for all the items were negative, except for "provide neat suits for work". The two-dimensional quadrant analysis showed that 6 items were located in quadrant III (low-expectation and low-perception area), and 7 items were located in quadrant IV (high-expectation and low-perception area).Conclusions:The evaluation scale based on the SERVQUAL model can effectively reflect problems in postgraduate education for medical master's students, helping develop strategies to improve the quality of education service.

Ankylosing spondylitis （AS） is an inflammatory autoimmune disease with chronic low back pain as the main clinical manifestation， which mainly affects the axial joints， peripheral joints and various organs. In severe cases， the spine is stiff or deformed， which affects the quality of life and health of patients. The pathogenic factors of AS are complex， which are related to heredity， immunity and intestinal flora. The pathogenesis of AS is not clear yet. Among them， inflammatory reaction， bone destruction and heterotopic ossification are the main pathological features of AS， which play an important role in the disease process of AS. Traditional Chinese medicine has multi-target， multi-channel and multi-component pharmacological effects， which can prevent and treat AS by anti-inflammation， inhibiting bone destruction and preventing heterotopic ossification， and the clinical effect is remarkable， but there is no relevant literature report. Therefore， this review expounds the relationship between inflammatory reaction， bone destruction and heterotopic ossification and the occurrence and development of AS， and summarizes the latest research reports of traditional Chinese medicine in treating AS from anti-inflammatory， inhibiting bone destruction and preventing heterotopic ossification， aiming at providing reference and new ideas and directions for further research on the prevention and treatment of AS by traditional Chinese medicine.

Constitutively activated G proteins caused by specific mutations mediate the development of multiple malignancies. The mutated Gαq/11 are perceived as oncogenic drivers in the vast majority of uveal melanoma (UM) cases, making directly targeting Gαq/11 to be a promising strategy for combating UM. Herein, we report the optimization of imidazopiperazine derivatives as Gαq/11 inhibitors, and identified GQ262 with improved Gαq/11 inhibitory activity and drug-like properties. GQ262 efficiently blocked UM cell proliferation and migration in vitro. Analysis of the apoptosis-related proteins, extracellular signal-regulated kinase (ERK), and yes-associated protein (YAP) demonstrated that GQ262 distinctly induced UM cells apoptosis and disrupted the downstream effectors by targeting Gαq/11 directly. Significantly, GQ262 showed outstanding antitumor efficacy in vivo with good safety at the testing dose. Collectively, our findings along with the favorable pharmacokinetics of GQ262 revealed that directly targeting Gαq/11 may be an efficient strategy against uveal melanoma.

AIM: To establish a HPLC-QqQ-MS with multiple reaction monitoring (MRM) method for pharmacokinetics and tissue distribution study of ribavirin by oral and respiratory administration. METHODS: The experiment established a high-sensitivity LC-MS analytical method for the detection of ribavirin, and the linearity, specificity, recovery, accuracy, and precision were investigated. The established methods were used to investigate the pharmacokinetics and tissue distribution of the oral and respiratory administration methods. RESULTS: The concentration of drugs in the blood through respiratory tract administration is higher, and the drug absorption is faster. Respiratory tract administration C

Objective:To analyze the effects of prescription reviews of key monitored drugs using the drug regulatory platform in a district of Shanghai, and the influencing factors for the rate of unqualified prescriptions.Methods:A drug regulatory platform in a district in Shanghai began to implement prescription reviews since June 2018, extracting the reviewed prescriptions of all key monitored drugs and related information from June to December. Taking the unqualified rate of prescription in June as the baseline data, the χ2 test and the logistics regression model were used for data analysis. Results:From June to December 2018, clinical pharmacists reviewed 19 084 outpatient and emergency prescriptions and 10 607 inpatient prescriptions. The unqualified rates of outpatient and emergency prescriptions and inpatient prescriptions dropped from 16.52% and 23.28% in June to 4.45% and 13.80% in December, respectively. Logistics regression analysis showed that the rate of unqualified reviews of outpatient and emergency prescriptions was lower than that of inpatient prescriptions, and the rate of unqualified prescriptions in hospital was significantly lower than that in community health service centers; the rate of unqualified prescriptions for auxiliary drugs and nutritional drugs was significantly lower than that of antibacterial drugs.Conclusions:The prescription reviews of key monitored drugs can effectively promote the rational use of drugs. In the future, it is recommended to strengthen technical support for community health service centers and professional training for clinicians and pharmacists.

Objective To investigate the dose of docetaxel appropriate for patients with metastatic castration-resistant prostate cancer and its affects to the prognosis.Methods A retrospective analysis was performed on the clinical data of 75 patients with metastatic castration-resistant prostate cancer admitted from March 2010 to July 2016 who received docetaxel combined with prednisone chemotherapy.The patients were divided into the low-dose group (n =43,docetaxel ＜ 65 mg/m2),the middle-dose group (n =21,docetaxel 65-70 mg/m2) and the high-dose group (n =11,docetaxel ＞ 70 mg/m2).The median age in the low-dose group,middle-dose group and high-dose group was 67 (53-80),66 (56-78) and 61 (47-76) years old,respectively.Among 75 patients with bone metastasis,2 patients had no evidence of bone metastasis in the low-dose group.The lymph node metastasis was found in 26,13 and 6 cases in each group,respectively.And visceral and other metastasis were founded in 11,4 and 2 cases,respectively.The Gleason score in the low-dose group was≤7 points in 15 cases,≥8 points in 22 cases and no score in 6 cases.The Gleason score inthe middle-dose group was ≤7 points in 4 cases,≥8 points in 13 cases and no score in 4 cases.The Gleason score in the high-dose group was ≤7 points in 3 cases,≥8 points in 5 cases and no score in 3 cases.The number of patients with pain in the low-dose group,middle-dose group and high-dose group was 36,12 and 9,respectively,there were no significant differences in the above indicators (P ＞ 0.05),except age,which showed relatively more aged patients in the low-dose group,(P =0.045).Kaplan-Meier method was used to compare the overall survival (OS),progression-free survival (PFS) and the incidence of ≥CTCAE-4 grade 3 adverse reactions between the two groups.The Cox regression model was adopted to analyzed the factors that might affect patient prognosis,including the effective time of first-line endocrine therapy,hemoglobin level,ECOG score,pain score,number of cycles of chemotherapy,age,dose of docetaxel and alkaline phosphatase (ALP).Kaplan-Meier method was used to analyze the effect of dose of docetaxel on the prognosis,and log-rank method was used to test the significance of the results.Results The median OS was respectively 24.1,18.5 and 23.5 months in the low-dose group,middle-dose group and high-dose group,respectively.The median PFS was 5.3 months in all three groups,which didn't show statistically significant differences.The incidence of grade 3/4 adverse reactions in the low-dose group,middle-dose group and high-dose group was 15 cases (34.9％),8 cases (38.1％) and 5 cases (45.5％) respectively.It showed an increasing trend,but no statistically significant difference.The single factors related to OS mainly include the effective time of first-line endocrine therapy,hemoglobin level,ECOG score,pain score,number of cycles of chemotherapy,there was no significant correlation with age,docetaxel dose,ALP and PSA value.Conclusions It is common to receive lower doses of docetaxel in clinical practice for patients with metastatic castration-resistant prostate cancer in China.The efficacy of low-dose docetaxel is similar to that of high doses (standard dosage).There was no significant correlation between the OS and the actual dose of docetaxel in the tolerable range.

Objective: To investigate the relationship between physical activity (PA) and the risk of incident hypertension among population in rural areas of China. Methods: The Community Intervention of Metabolic Syndrome in China & Chinese Family Health Study (CIMIC) was conducted in 2007-2008. Data on PA, smoking, drinking, blood pressure and other variables were obtained at baseline. Then the follow-up study of incident hypertension was performed during 2012-2015. A total of 41 457 participants aged ≥18 years and free from hypertension at baseline were included in the final analyses. PA was calculated as metabolic equivalent (MET) for each participant. Cox proportional hazard models were used to explore the relationship of PA with incident hypertension according to the quartiles of PA. Results: A total of 6 780 participants developed hypertension during an average follow up of 5.8 years. The annual incidence of hypertension was 2.80%. Compared to participants in the first quartile of PA, HR (95%CI) of incident hypertension decreased with the level of PA of 0.92 (0.86, 0.99), 0.72 (0.67, 0.77) and 0.70 (0.65, 0.75) for the 2^nd, 3^rd and 4^th quartile, respectively (P_trend<0.001). In subgroup analyses, compared to the first quartile, hazards of hypertension among normotensive participants (systolic blood pressure less than 120 mmHg (1 mmHg=0.133 kPa) and diastolic blood pressure less than 80 mm Hg) in the 2^nd, 3^rd and 4^th quartile were 0.82 (0.70, 0.95), 0.73 (0.63, 0.85) and 0.78 (0.67, 0.90), respectively (P_trend=0.002). Among participants with prehypertension (systolic blood pressure from 120 to 139 mmHg and/or diastolic blood pressure from 80 to 89 mmHg), similar trend for the relationship of PA and incident hypertension was also found with HR (95%CI) of 0.94 (0.87, 1.01), 0.71 (0.65, 0.77) and 0.66 (0.61, 0.71) for the 2^nd, 3^rd and 4^th quartile, respectively (P_trend<0.001). Conclusion There was linear trend association between PA and incident hypertension. Increased PA in daily life may be a protective factor against hypertension.

Objective: To evaluate the efficacy of gastric pull-up and complex laryngotracheal flap in reconstruction for circumferencial defects after resection of hypopharyngeal and cervical esophageal cancers. Methods: A total of 163 cases (152 males, 11 females) with circumferencial defect after resection of hypopharyngeal and cervical esophageal cancers received reconstructive surgeries by gastric pull-up (42 cases) and complex laryngo-tracheal flaps (121 cases), of them 115 cases simultaneously underwent unilateral neck dissection and 20 cases had bilateral neck dissection. Postoperative radiotherapy was used in 67 cases, with a dosage of 40-60 Gy. Results: There were 127 (77.9%) cases with positive metastatic lymph nodes. Of 42 patients with gastric pull-up reconstruction, 39 cases (92.8%) recovered the function of oral swallowing after operation, and 8 cases with cervical esophageal cancer recovered the functions of oral swallowing and speech after gastroesophageal anastomosis reconstruction. There were 3 (7.1%) cases died of surgery and 8 cases with surgical complications. Reconstruction of upper digestive tract with combined laryngotracheal flap was successful in all 121 cases, with recovered oral swallowing function after operation. No patient died of surgery but 24 cases had complications, mainly pharynx skin fistula or wound infection, which were cured by conservative treatments. The 1-, 3- and 5-year survival rates for 163 patients were 69.8%, 50.5% and 34.3%, respectively. The independent factors for prognosis included T4 (P<0.001) and N+ (P=0.042). Conclusions The complex of laryngotracheal flap with pectoralis major myocutaneous flap is suitable for most advanced hypopharyngeal cancer after resection of the tumor and reconstruction of circumferencial defect. It is simple technology, low and slight complication rate. The minority is not suitable for the application of pectoralis major myocutaneous flap can be used instead of free anterolateral thigh flap. Gastric pull-up for reconstruction of upper digestive tract is suitable for most patients with cervical esophageal cancer and hypopharyngeal carcinoma invading the cervical esophagus who are not suitable for laryngotracheal flap reconstruction, with good swallowing function after surgery. However, it is prudent to choose operative indications because of serious surgical trauma and risks for complications.