Role of Wnt signaling Pathway in Diabetic Osteoporosis and Traditional Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

Diabetic osteoporosis （DOP） is a kind of bone complication caused by diabetes， which is characterized by the decrease of bone mineral density， the change of bone microstructure and the increase of bone fragility. The process of DOP is closely related to high glucose， insulin resistance， oxidative stress and other mechanisms. The Wnt/β-catenin signaling pathway plays an important role in mediating insulin resistance and bone metabolic balance in diabetes. Regulation of Wnt signal transduction promotes the expression of glycogen synthase kinase-3β（GSK-3β）phosphorylation and improves glucose and lipid metabolism. The Wnt/β-catenin signaling pathway is also an important way regulating osteocyte-driven bone remodeling， which not only plays an important regulatory role in the balance between osteoblasts and osteoclasts and improve bone metabolic homeostasis， but also promotes the expression of osteopontin， osteocalcin and type Ⅰ collagen， and improves bone proliferation and osteogenic differentiation by regulating the Wnt pathway. In recent years， the research of traditional Chinese medicine （TCM） in the prevention and treatment of DOP has gradually increased， and the exploration of TCM to interfere with the Wnt pathway to improve DOP has made some progress. This paper collects and summarizes the studies on the Wnt signaling pathway in glucose metabolism， bone metabolism and DOP worldwide in the past decade， as well as the related literature on the intervention of DOP by TCM compounds （classical and other compounds）， single Chinese medicine and TCM monomers based on the Wnt pathway， in order to provide a reference and direction for the development of new drugs for clinical prevention and treatment of DOP.

Early diagnosis of anastomotic leakage after anterior resection for rectal carcinoma / 中华普通外科杂志

Objective:To search for valuable laboratory indexes of early diagnosis of anastomotic leakage after anterior resection for rectal carcinoma.Methods:From Sep 2017 to Jan 2019, 128 patients with colorectal cancer underwent anterior rectal resection at the Department of Colorectal & Anal Surgery, the 940 Hospital of the Joint Logistics Support Force.Results:Anastomotic leakage occurred in 16 of 128 patients (12.5%). Definite diagnosis of anastomotic leakage was made on between 2nd and 9th day, postopera tively averagign (6.13±2.00) days. Tumor location was a risk factor for anastomotic leakage with the incidence significantly lower when the distance from the lower edge of the tumor to the anal margin >7 cm than when the distance ≤7 cm ( χ 2=6.022, P=0.014). The percentage of increase in peripheral blood leukocytes, neutrophils, serum interleukin-6, C-reactive protein and procalcitonin in patients 3-5 days after surgery significantly related to the occurrence of anastomotic leakage (all P<0.05). The area under the working characteristic curve of the subjects with the percentage of C-reactive protein, procalcitonin, interleukin-6, leukocytes and neutrophils from the 3rd to the 5th day after operation was greater than 0.5. Conclusion:C-reactive protein, procalcitonin, interleukin-6, leukocyte and neutrophil percentage are risk factors predicting anastomotic leakage after anterior resection of rectal cancer.

Association between anti-tissue transglutaminase antibody titers and duodenal histopathology among adults with celiac disease / 中华内科杂志

To evaluate the association between serum anti-tissue transglutaminase antibody (anti-tTG) titers and the severity of histological damage to the duodenal mucosa and to predict a possible anti-tTG cutoff value for diagnosing celiac disease (CD) and villous atrophy in the domestic population. Clinical and pathological data from 76 adult CD patients with positive anti-tTG titers and duodenal biopsy results who were treated at the People′s Hospital of Xinjiang Uygur Autonomous Region from July 2017 to January 2022 were retrospectively analyzed. The correlation between anti-tTG titers and the severity of duodenal mucosal damage was statistically assessed to predict the optimal anti-tTG titer cut-off value for diagnosing CD and villous atrophy. Of the 76 patients, 10 had underlying CD, and of the 66 patients with duodenal histopathology, four were Marsh Ⅰ, six were Marsh Ⅱ, and 56 were Marsh Ⅲa-c grade. In adults with CD, anti-tTG titers were shown to be associated with the severity of histological damage to the duodenal mucosa. When the anti-tTG level was ≥5 times the upper limit of normal (ULN), the sensitivity and specificity for diagnosing CD were 83.9% and 92.9%, respectively. When the anti-tTG titer was ≥8 times the ULN, the sensitivity and specificity for diagnosing villous atrophy were 67.9% and 90.0%, respectively. Anti-tTG levels had a strong predictive value for diagnosing CD in adults when titers exceeded 10 times the ULN. Thus, the anti-tTG cut-off value can be combined with clinical judgment to diagnose CD, limiting the use of invasive endoscopy.

Clinical and endoscopic characteristics of adult celiac disease / 中华内科杂志

Objective:The study aimed to analyze the clinical and endoscopic characteristics of adult celiac disease (CD) to provide a scientific basis for more effective CD diagnosis and treatment.Methods:In this cross-sectional study, the clinical and endoscopic data of 96 adult CD patients treated in the Department of Gastroenterology of the People′s Hospital of Xinjiang Uygur Autonomous Region from March 2016 to December 2021 were retrospectively collected and analyzed.Results:A total of 96 CD patients were diagnosed, including 33 men and 63 women. The average age was 47±14 years (range, 18-81 years). The disease occurred mainly in the age group of 31-60 years. The median course of the disease was 2.0 (0.2-40.0) years. There were 41 (42.7%) classical and 55 (57.3%) non-classical CD patients. All patients with classical CD showed chronic diarrhea, often accompanied by abdominal pain (46.3%, 19/41), abdominal distension (17.1%, 7/41), anemia (65.9%, 27/41), and chronic fatigue (48.8%, 20/41). The main manifestations of non-classical CD were chronic abdominal pain (58.2%, 32/55), abdominal distension (32.7%, 18/55), anemia (40.0%, 22/55), and osteopenia/osteoporosis (38.2%, 21/55). Compared with non-classical CD, anemia developed more frequently in classical CD, and the difference was statistically significant ( P = 0.012). The incidence of complications in CD patients was 36.5% (35/96), and the main complications were thyroid disease (19.8%, 19/96), connective tissue disease (6.2%, 6/96), and kidney disease (6.2%, 6/96). There was no significant difference between classical and non-classical CD ( P>0.05). The frequency of endoscopic manifestations in CD patients was 84.4% (81/96). Duodenal bulb endoscopy showed nodular changes (72.9%, 70/96), grooved changes (10.4%, 10/96), and focal villous atrophy (9.4%, 9/96). The main manifestations of descending endoscopy were the decrease, flattening, or disappearance of duodenal folds (43.8%, 42/96), scallop-like changes (38.5%, 37/96), and nodular changes (34.4%, 33/96). Conclusions:Adult CD patients are mostly female. CD occurred mainly in the age group of 31-60 years. The clinical manifestations were mainly those of non-classical CD. Some patients often had other autoimmune diseases. Patients with characteristic endoscopic manifestations should be warned about the possibility of developing CD. Clinicians should strengthen the understanding of CD and reduce the related rates of missed diagnosis.

Clinical study of the relationship between cellular adhesion molecules and left ventricular geometry and function in patients with obstructive sleep apnea syndrome and prehypertension / 中华超声影像学杂志

Objective:To investigate the correlations between serum E selectin, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and left ventricular geometry and function in patients with obstructive sleep apnea syndrome (OSAS) combined with prehypertension (pre-HT).Methods:A total of 462 patients with pre-HT and OSAS diagnosed by polysomnography (PSG) in the sleep monitoring unit of the Department of Respiratory and Critical Care Medicine at the First Hospital of Shanxi Medical University from July 2019 to July 2022 were restrospectively analysed, and 52 patients with pure pre-HT (pre-HT group) and 73 patients with pure OSAS (OSAS group) in the same period were selected as the control group. OSAS and pre-HT patients were divided into four groups according to left ventricular geometry: normal geometry (NG) group, concentric remodeling (CR) group, eccentric hypertrophy (EH) group and concentric hypertrophy (CH) group. The general clinical data, PSG parameters, blood biochemical parameters and left ventricular structure and function parameters were compared among the six groups. Pearson correlation and multivariate Logistic regression were used to analyze the correlation between E-selection, ICAM-1, VCAM-1, general clinical data, PSG parameters, blood biochemical parameters with left ventricular geometry and function.Results:①Serum E selectin, ICAM-1, and VCAM-1 concentrations increased sequentially from the NG, CR, and EH to CH groups, with the most significant increase in CH group (all P<0.05). In addition, there were statistically significant differences in age, body mass index (BMI), OSAS severity, neck circumference, waist circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), Glu, lowest oxygen saturation (Lowest-SaO 2), mean oxygen saturation (Mean-SaO 2), percentage of time with oxygen saturation below 90% of total sleep time (T90), left ventricular end-diastolic diameter (LVEDd), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular mass index (LVMI), relative ventricular wall thickness (RWT), left ventricular ejection fraction (LVEF), peak mitral early diastolic flow velocity/peak mitral late diastolic flow velocity (E/A), E wave deceleration time (DT), A wave duration (AD), and isovolumic relaxation time (IVRT), and overall long-axis longitudinal strain (GLS) and so on(all P<0.05). ②Pearson correlation analysis showed that E selectin was negatively correlated with LVEF, E/A, e′, E/e′, IVRT, and GLS ( r=-0.236, -0.131, -0.224, -0.215, -0.285, -0.336; all P<0.05). ICAM-1 was negatively correlated with LVEF, E, E/A, e′, IVRT, and GLS( r=-0.130, -0.129, -0.104, -0.351, -0.252, -0.259; all P<0.05). VCAM-1 was negatively correlated with E, e′, and IVRT ( r=-0.132, -0.312, -0.387; all P<0.001). ③Multifactorial logistic regression analysis showed that E selectin and VCAM-1 were independently correlated with EH (β=1.139, OR=3.124, P=0.030; β=1.288, OR=3.626, P<0.001) and with CH (β=1.178, OR=3.248, P=0.013; β=1.108, OR=3.028, P<0.001). Conclusions:E selection and VCAM-1 were independently correlated with hypertrophic left ventricular geometry, suggesting that E selectin and VCAM-1 may be involved in the process of abnormal left ventricular structure and function in patients with OSAS combined with pre-HT.

Preliminary application of a novel distraction reductor in the surgical treatment of unstable distal radius fractures with metaphyseal volar comminution / 中华创伤骨科杂志

Objective:To evaluate a novel distraction reductor in the surgical treatment of unstable distal radius fractures with metaphyseal volar comminution.Methods:From January 2019 to December 2020, 27 patients with unstable distal radius fracture complicated with metaphyseal volar comminution were treated at Department of Orthopaedics, Zhoupu Hospital Affiliated to Shanghai University of Medicine & Health Sciences. They were 6 males and 21 females, with an age of (69.4±9.4) years. All fractures were unilateral and closed, involving the right side in 17 cases and the left side in 10 cases. All patients were treated by internal fixation with an anatomical locking plate through the volar approach and the novel distraction reductor was used to reduce the fracture ends. Regular imaging examinations were performed to evaluate the reduction, maintenance and union of fractures after surgery. One year after operation, the curative efficacy was assessed by evaluation of the range of wrist motion, Disabilities of the Arm, Shoulder and Hand (DASH) score, Gartland-Werley score and Bartra radiology score.Results:All the operations went on successfully with a duration of (92.3±8.9) min. All the incisions healed primarily. The follow-up time was (15.9±2.9) months. The radial height, palmar tilt, ulnar inclination and articular surface step-off immediately after operation [(11.23±1.51) mm, 12.10°±3.44°, 20.54°±3.44°, and (0.95±0.42) mm] were not significantly lost compared with those one year after operation [(11.22±1.55) mm, 12.07°±3.44°, 20.51°±3.33°, and (0.93±0.40) mm] (all P>0.05). One year after operation, the range of wrist motion was good with dorsiflexion of 59.7°±5.5°, palm flexion of 63.0°±9.1°, pronation of 66.5°±5.5°, supination of 61.2°±5.6°, radial deviation of 22.7°±4.8°, and ulnar deviation of 30.3°±6.1°; DASH score was 13.5±5.5; Bartra radiology score was 88.6±6.5, giving an excellent and good rate of 88.9% (24/27);Gartland-Werley score was 2.7±2.1, giving an excellent and good rate of 92.6% (25/27). Follow-ups observed no poor fracture healing, internal fixation failure, tendon or nerve injury or traumatic arthritis. Conclusion:In the surgical treatment of unstable distal radius fractures with metaphyseal volar comminution, the novel distraction reductor can lead to ideal reduction of displaced fractures and effectively correct the shortening caused by volar cortex comminution to achieve satisfactory functional effects in clinic.

Intraoperative fluoroscopy on femoral tunnel placement in the treatment of professional snow sports athletes with anterior cruciate ligament injury / 中华创伤杂志

Objective:To explore the clinical outcomes of intraoperative fluoroscopy on femoral tunnel placement in treating professional snow sports athletes with anterior cruciate ligament (ACL) injury.Methods:A retrospective case series study was used to analyze the clinical data of 13 professional snow sports athletes with ACL injury treated in the National Institute of Sports Medicine, General Administration of Sport of China from January 2016 to January 2019. There were 5 males and 8 females, aged 16-27 years [(18.5±3.0)years]. Intraoperative lateral fluoroscopy combined with quadrant method was performed for the accurate femoral tunnel placement in single-bundle ACL reconstruction by using autologous hamstring tendon in all patients. KT1000 side-to-side difference (KT1000-ssd), pivot shift test, International Knee Documentation Committee (IKDC) subjective score, Lysholm score, Marx activity scale and maximum extension and flexion resistance ratio of the involved and uninvolved knee were compared before operation (or before injury) and at 3, 6, 12 and 24 months after operation. Whether returning to the field, time taken in returning to the field and re-injury were recorded at each follow-up visit. ACL graft signal intensity ratio (SIR) in MRI of the involved knee was evaluated at postoperative 24 months.Results:All patients were followed up for 24-33 months [(25.8±2.7)months]. There were 7 patients with KT1000-ssd degree I, 5 with degree II and 1 with degree III before operation, compared to 12 patients with KT1000-ssd degree 0 and 1 with degree I at 3 and 6 months after operation and 13 patients with KT1000-ssd degree 0 at 12 and 24 months after operation. The pivot shift test was grade I in 8 patients and grade II in 5 before operation, compared to 11 patients with degree 0 and 2 with degree I at 3 months after operation and 12 patients with degree 0 and 1 with degree I at 6, 12 and 24 months after operation. IKDC subjective score was (68.0±4.3)points, (84.7±7.9)points, (94.6±3.3)points and (96.5±1.8)points at postoperative 3, 6, 12 and 24 months, respectively. Six months after operation, IKDC subjective score was significantly improved compared to the preoperative (48.3±25.0)points (all P<0.01). The Lysholm score was (63.4±6.6)points, (80.1±6.5)points, (93.8±4.6)points and (96.5±2.4)points at postoperative 3, 6, 12 and 24 months, respectively. Six months after operation, the Lysholm score was significantly improved compared to the preoperative (47.5±29.4)points (all P<0.01). The Marx activity scale was (7.4±0.5)points, (13.8±0.7)points, (14.6±0.8)points and (15.0±0.7)points at postoperative 3, 6, 12 and 24 months, respectively, significantly lower than (16.0±0.0)points before the injury (all P<0.01). The maximum extension resistance ratio of the involved and uninvolved knee was 0.60±0.10, 0.85±0.08, 0.91±0.06 and 0.97±0.04 at postoperative 3, 6, 12 and 24 months, respectively. Six months after operation, the maximum extension resistance ratio of the involved and uninvolved knee was significantly increased compared to the preoperative 0.57±0.18 (all P<0.01).The maximum flexion resistance ratios of involved and uninvolved knee were 0.64±0.09, 0.82±0.06, 0.89±0.04 and 0.94±0.06 at postoperative 3, 6, 12 and 24 months, respectively. Six months after operation, the maximum flexion resistance ratio of the involved and uninvolved knee was significantly increased compared to the preoperative 0.60±0.12 (all P<0.01). Thirteen athletes returned to the field within 12 months after operation with the time taken in returning to the field ranging from 5-12 months [(8.7±1.9)months]. There was no ACL re-injury at postoperative 24 months. The ACL graft SIR in MRI of the involved knee was 1.80±0.20 at postoperative 24 months. Conclusion:Intraoperative fluoroscopy on femoral tunnel placement in the treatment of professional snow sports athletes with ACL injury can significantly improve the knee joint stability, subjective function, sports performance and muscle strength within 6 months, and can help them return to the field within 12 months, and accelerates graft healing.

The application of MOOC combined with peer mutual assistance in cardiopulmonary resuscitation teaching / 中华医学教育探索杂志

Objective:To explore the application effect of massive open online course (MOOC) combined with peer mutual assistance in cardiopulmonary resuscitation teaching.Methods:A total of 140 students in the same class of Batch 2015 were divided into the experimental group and the control group. In the teaching of cardiopulmonary resuscitation, the experimental group was based on the MOOC teaching platform, watched videos and topic tests before class, and used the peer mutual assistance in class. While the control group adopted traditional classroom teaching mode. The teaching effect of the two groups were evaluated by comparing the operation assessment scores and questionnaire survey of students' satisfaction with teaching. SPSS 22.0 was used for t-test and Chi-square test. Results:The operating assessment score of the experimental group was (82.20±2.31), and the operating assessment score of the control group was (75.80±1.72). The difference was statistically significant ( t=3.27, P<0.05). The questionnaire survey showed that the course satisfaction and learning motivation of the experimental group were better than those of the control group. In learning burden, the two groups had similar results ( P=0.739). Conclusion:MOOC combined with peer mutual assistance in cardiopulmonary resuscitation teaching can help students better master skills, improve students' course satisfaction and learning motivation, without increasing their learning burden.

Effect of Synergistic Treatment with Qingjin Huazhuo Formula （清金化浊方） on Thrombotic Events in Hospitalized Patients of Acute Exacerbation of Chronic Obstructive Pulmonary Disease with Phlegm Heat Stasis Obstructing in the Lung Syndrome： A Retrospective Cohort Study / 中医杂志

ObjectiveTo analyze the effect and possible mechanism of the synergistic treatment with Qingjin Huazhuo Formula （清金化浊方， QHF） on the occurrence of thrombotic events in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease （AECOPD） and phlegm heat stasis obstructing in the lung syndrome. MethodsIn a retrospective cohort study， 305 AECOPD inpatients with the syndrome of phlegm heat stasis obstructing in the lung were included. According to whether using QHF （the course of treatment ≥ 7 days）， they were divided into the exposure group （193 cases） and the non-exposure group （112 cases）. Totally， 109 pairs of cases were obtained by 1∶1 propensity score matching （PSM）. After matching， the occurrence of thrombotic events during hospitalization， the remission of main symptoms or signs （including cough， expectoration， wheezing， cyanosis） after 10 days （±3 days） of treatment， and the difference of the indicators including D-dimer， percentage of neutrophils （NEUT%）， C-reactive protein （CRP）， arterial partial pressure of oxygen （PaO2）， and arterial partial pressure of carbon dioxide （PaCO2） before treatment and after 10 days （±3 days） of treatment during the first auxiliary examination. ResultsAfter matching， the incidence of thrombotic events during hospitalization in the exposure group （5 cases， 4.59%） were lower than that of the non-exposure group （15 cases， 13.76%， P＜0.05）. The exposure factor that taking QHF for 7 days or above was a protective factor for thrombotic events in AECOPD hospitalized patients with phlegm heat stasis obstructing in the lung syndrome （RR = 0.333， 95% CI 0.126 to 0.885）. The remission rates of cough （100/109， 91.74%）， expectoration （103/109， 94.50%）， wheezing （102/109， 93.58%）， and cyanosis （97/109， 88.99%） in the exposure group were significantly higher than those in the non-exposure group （90/109， 82.57%； 94/109， 86.24%； 89/109， 81.65%； 86/109， 78.90%） after treatment （P＜0.05）. After treatment， the levels of D-dimer， NEUT%， CRP and PaCO2 in both groups significantly decreased （all P＜0.05）， and the level of PaO2 significantly increased （P＜0.05）. The difference of the levels of D-dimer， NEUT% and PaO2 in the exposure group before and after treatment were larger than those in the non-exposure group （P＜0.05）， while the pre-post difference of CRP and PaCO2 were not significantly different between the two groups （P＞0.05）. ConclusionThe synergistic treatment with QHF can effectively reduce the occurrence of thrombotic events， alleviate the clinical symptoms or signs such as cough， expectoration， wheezing， and cyanosis， and can improve lung function in hospita-lized patients with AECOPD and phlegm heat stasis obstructing in the lung syndrome. Its mechanism may be related to improving blood coagulation and inflammatory status.

Latent period and incubation period with associated factors of COVID-19 caused by Omicron variant / 中华预防医学杂志

Objective: To estimate the latent period and incubation period of Omicron variant infections and analyze associated factors. Methods: From January 1 to June 30, 2022, 467 infected persons and 335 confirmed cases in five local Omicron variant outbreaks in China were selected as the study subjects. The latent period and incubation period were estimated by using log-normal distribution and gamma distribution models, and the associated factors were analyzed by using the accelerated failure time model (AFT). Results: The median (Q1, Q3) age of 467 Omicron infections including 253 males (54.18%) was 26 (20, 39) years old. There were 132 asymptomatic infections (28.27%) and 335 (71.73%) symptomatic infections. The mean latent period of 467 Omicron infections was 2.65 (95%CI: 2.53-2.78) days, and 98% of infections were positive for nucleic acid detection within 6.37 (95%CI: 5.86-6.82) days after infection. The mean incubation period of 335 symptomatic infections was 3.40 (95%CI: 3.25-3.57) days, and 97% of them developed clinical symptoms within 6.80 (95%CI: 6.34-7.22) days after infection. The results of the AFT model analysis showed that compared with the group aged 18~49 years old, the latent period [exp(β)=1.36 (95%CI: 1.16-1.60), P<0.001] and incubation period [exp(β)=1.24 (95%CI: 1.07-1.45), P=0.006] of infections aged 0~17 year old were also prolonged. The latent period [exp(β)=1.38 (95%CI: 1.17-1.63), P<0.001] and the incubation period [exp(β)=1.26 (95%CI: 1.06-1.48), P=0.007] of infections aged 50 years old and above were also prolonged. Conclusion: The latent period and incubation period of most Omicron infections are within 7 days, and age may be the influencing factor of the latent period and incubation period.

Exercise promotes healthy cardiovascular aging / 生理学报

Cardiovascular disease (CVD) is an important factor threatening the health of the elderly. Aging leads to changes in the structure and function of the cardiovascular system, which increases the risk of CVD in the elderly. Cardiac aging is characterized by increased left ventricular wall thickness, increased degree of myocardial fibrosis, increased cardiac hardness, and decreased cardiac function, while vascular aging is characterized by enlarged lumen, thickened wall, and endothelial dysfunction. Promoting healthy cardiovascular aging means reducing the age-related cardiovascular dysfunction and the risks of CVD. Exercise is a crucial means for the treatment and rehabilitation of CVD. Exercise reduces the risk factors of CVD, remodels the cardiovascular structure, and increases the resistance of heart to detrimental stimulus, which promotes healthy cardiovascular aging. The improved mitochondrial function via exercise plays a key role in the health effects of exercise. In addition, exercise promotes the secretion of exerkines in various tissues and organs, which plays a role in reducing inflammation, improving metabolism, inhibiting apoptosis, etc., thus benefiting cardiovascular health. This review discusses the mechanism and potential application of exercise in promoting healthy cardiovascular aging. Exploring the specific mechanisms underlying exercise-induced cardiovascular health and formulating accurate exercise prescriptions for different populations is an important direction to promote healthy cardiovascular aging and prevent CVD.

Research progress on the biological effects of HIF-1α on follicle development and ovulation / 生理学报

Hypoxia inducible factor-1α (HIF-1α), as a hypoxia inducible factor, affects women's reproductive function by regulating the development and excretion of follicles. HIF-1α induces glycolysis and autophagy in the granule cells by promoting oocyte development, regulating the secretion of related angiogenic factors, and improving follicle maturity. In addition, HIF-1α promotes the process of luteinization of follicular vesicles, maintains luteal function, and finally completes physiological luteal atrophy through cumulative oxidative stress. Dysfunction of HIF-1α will cause a series of pathological consequences, such as angiogenesis defect, energy metabolism abnormality, excessive oxidative stress and dysregulated autophagy and apoptosis, resulting in ovulation problem and infertility. This article summarizes the previous studies on the regulation of follicle development and excretion and maintenance of luteal function and structural atrophy by HIF-1α. We also describe the effective intervention mechanism of related drugs or bioactive ingredients on follicular dysplasia and ovulation disorders through HIF-1α, in order to provide a systematic and in-depth insights for solving ovulation disorder infertility.

Professor FU Wen-bin's experience in treating "five delays and five weaknesses" in children with yang-oriented approach / 中国针灸

Professor FU Wen-bin, based on the concept of the "yang-oriented approach", identifies "yang deficiency with excess yin" as the underlying pathological mechanism of "five delays and five weaknesses" in children. He recommends a treatment model that included acupuncture, moxibustion, and rehabilitation, integrating various therapeutic methods of acupuncture, refined moxibustion, and auricular point sticking. Specific acupoints along the conception vessel, governor vessel, and bladder meridian, as well as related acupoints with tonifying effects on spleen and kidney, are selected to achieve the therapeutic goal of "promoting yang and nourishing yang simultaneously".

Research Progress of CXCR4-Targeting Radioligands for Oncologic Imaging

C-X-C motif chemokine receptor 4 (CXCR4) plays a key role in various physiological functions, such as immune processes and disease development, and can influence angiogenesis, proliferation, and distant metastasis in tumors. Recently, several radioligands, including peptides, small molecules, and nanoclusters, have been developed to target CXCR4 for diagnostic purposes, thereby providing new diagnostic strategies based on CXCR4. Herein, we focus on the recent research progress of CXCR4-targeting radioligands for tumor diagnosis. We discuss their application in the diagnosis of hematological tumors, such as lymphomas, multiple myelomas, chronic lymphocytic leukemias, and myeloproliferative tumors, as well as nonhematological tumors, including tumors of the esophagus, breast, and central nervous system. Additionally, we explored the theranostic applications of CXCR4-targeting radioligands in tumors. Targeting CXCR4 using nuclear medicine shows promise as a method for tumor diagnosis, and further research is warranted to enhance its clinical applicability.

Expression of VNN1 in Ulcerative Colitis / 胃肠病学

Background: Molecular markers associated with disease progression and prognosis of ulcerative colitis (UC) are still lacking in clinic. Aims: To investigate the expression and clinical significance of vanin 1 (VNN1) in intestinal mucosal tissue, serum and stool in patients with UC. Methods: A total of 100 UC patients and 100 healthy volunteers from Dec. 2018 to Jan. 2020 at the People's Hospital of Xinjiang Uygur Autonomous Region were recruited, and colonoscopy biopsy tissue samples, blood samples and stool samples were collected. PCR, Western blotting and immunohistochemistry were used to detect mRNA and protein expressions of VNN1 in intestinal mucosal tissue, respectively. The expression of VNN1 in serum and stool was determined by ELISA. Results: The mRNA and protein expressions of VNN1 in intestinal mucosal tissue in patients with UC were significantly higher than those in healthy controls (P0.05). Conclusions: The expressions of VNN1 in intestinal mucosal tissue and blood in UC patients are high, and can be used as a molecular marker of UC.

The hippocampal proteomics mechanism of thalidomide in Alzheimer's disease model mice induced by Aβ / 中国药理学通报

Aim To observe the effect of thalidomide on the learning and memory ability and hippocampal tissue proteome of Alzheimer's disease(AD)mice,to screen the differential proteins of thalidomide in preventing and treating AD,the pathways involved in regulation,and to explore its possible mechanism. Methods The experimental mice were randomly divided into blank control group,model group,and thalidomide high and low dose groups. The drugs were administered by gavage every day for 21 days. After the administration,Morris water maze test was used to evaluate the learning and memory abilities of the mice,HE staining and Nissl staining were used to observe the pathological tissue morphology of the mouse hippocampus,ELISA was employed to detect the mitochondrial respiratory chain enzyme complex in mouse brain,and the Label-free proteomics method was used to screen different groups of hippocampal proteome proteins. Results The results of the Morris water maze showed that compared with the model group,the escape latency time of the drug group was significantly reduced,and the number of crossing the platform significantly increased(P<0.05). Thalidomide administration could improve the morphological structure of neurons in hippocampus,and could increase the activity of the mitochondrial respiratory chain complex ,Ⅱ, and of the brain tissues of AD mice(P<0.05). A total of 4 378 differential proteins were identified,which had a significant regulatory effect on the expression of 580 proteins in hippocampus of AD mice(P<0.05). Energy metabolism may jointly participate in the regulation of neurodegeneration pathways-changes in pathways such as various diseases and Alzheimer's disease. Conclusions Thalidomide can significantly improve the learning and memory function of AD model mice induced by Aβ

Chuanxiong Rhizoma extracts prevent cholestatic liver injury by targeting H3K9ac-mediated and cholangiocyte-derived secretory protein PAI-1 and FN / 中国天然药物

Chuanxiong Rhizoma (CX, the dried rhizome of Ligusticum wallichii Franch.), a well-known traditional Chinese medicine, is clinically used for treating cardiovascular, cerebrovascular and hepatobiliary diseases. Cholestatic liver damage is one of the chronic liver diseases with limited effective therapeutic strategies. Currently, little is known about the mechanism links between CX-induced anti-cholestatic action and intercellular communication between cholangiocytes and hepatic stellate cells (HSCs). The study aimed to evaluate the hepatoprotective activity of different CX extracts including the aqueous, alkaloid, phenolic acid and phthalide extracts of CX (CXAE, CXAL, CXPA and CXPHL) and investigate the intercellular communication-related mechanisms by which the most effective extracts work on cholestatic liver injury. The active compounds of different CX extracts were identified by UPLC-MS/MS. A cholestatic liver injury mouse model induced by bile duct ligation (BDL), and transforming growth factor-β (TGF-β)-treated human intrahepatic biliary epithelial cholangiocytes (HIBECs) and HSC cell line (LX-2 cells) were used for in vivo and in vitro studies. Histological and other biological techniques were also applied. The results indicated that CXAE, CXAL and CXPHL significantly reduced ductular reaction (DR) and improved liver fibrosis in the BDL mice. Meanwhile, both CXAE and CXPHL suppressed DR in injured HIBECs and reduced collagen contraction force and the expression of fibrosis biomarkers in LX-2 cells treated with TGF-β. CXPHL suppressed the transcription and transfer of plasminogen activator inhibitor-1 (PAI-1) and fibronectin (FN) from the 'DR-like' cholangiocytes to activated HSCs. Mechanistically, the inhibition of PAI-1 and FN by CXPHL was attributed to the untight combination of the acetyltransferase KAT2A and SMAD3, followdd by the suppression of histone 3 lysine 9 acetylation (H3K9ac)-mediated transcription in cholangiocytes. In conclusion, CXPHL exerts stronger anti-cholestatic activity in vivo and in vitro than other CX extracts, and its protective effect on the intracellular communication between cholangiocytes and HSCs is achieved by reducing KAT2A/H3K9ac-mediated transcription and release of PAI-1 and FN.

Therapeutic effect of ursodeoxycholic acid-berberine supramolecular nanoparticles on ulcerative colitis based on supramolecular system induced by weak bond / 中国中药杂志

Ulcerative colitis(UC) is a recurrent, intractable inflammatory bowel disease. Coptidis Rhizoma and Bovis Calculus, serving as heat-clearing and toxin-removing drugs, have long been used in the treatment of UC. Berberine(BBR) and ursodeoxycholic acid(UDCA), the main active components of Coptidis Rhizoma and Bovis Calculus, respectively, were employed to obtain UDCA-BBR supramolecular nanoparticles by stimulated co-decocting process for enhancing the therapeutic effect on UC. As revealed by the characterization of supramolecular nanoparticles by field emission scanning electron microscopy(FE-SEM) and dynamic light scattering(DLS), the supramolecular nanoparticles were tetrahedral nanoparticles with an average particle size of 180 nm. The molecular structure was described by ultraviolet spectroscopy, fluorescence spectroscopy, infrared spectroscopy, high-resolution mass spectrometry, and hydrogen-nuclear magnetic resonance(H-NMR) spectroscopy. The results showed that the formation of the supramolecular nano-particle was attributed to the mutual electrostatic attraction and hydrophobic interaction between BBR and UDCA. Additionally, supramolecular nanoparticles were also characterized by sustained release and pH sensitivity. The acute UC model was induced by dextran sulfate sodium(DSS) in mice. It was found that supramolecular nanoparticles could effectively improve body mass reduction and colon shortening in mice with UC(P<0.001) and decrease disease activity index(DAI)(P<0.01). There were statistically significant differences between the supramolecular nanoparticles group and the mechanical mixture group(P<0.001, P<0.05). Enzyme-linked immunosorbent assay(ELISA) was used to detect the serum levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6), and the results showed that supramolecular nanoparticles could reduce serum TNF-α and IL-6 levels(P<0.001) and exhibited an obvious difference with the mechanical mixture group(P<0.01, P<0.05). Flow cytometry indicated that supramolecular nanoparticles could reduce the recruitment of neutrophils in the lamina propria of the colon(P<0.05), which was significantly different from the mechanical mixture group(P<0.05). These findings suggested that as compared with the mechanical mixture, the supramolecular nanoparticles could effectively improve the symptoms of acute UC in mice. The study provides a new research idea for the poor absorption of small molecules and the unsatisfactory therapeutic effect of traditional Chinese medicine and lays a foundation for the research on the nano-drug delivery system of traditional Chinese medicine.

Ketogenic diet improves low temperature tolerance in mice by up-regulating PPARα in the liver and brown adipose tissue / 生理学报

The aim of the present study was to investigate the effects of short-term ketogenic diet on the low temperature tolerance of mice and the involvement of peroxisome proliferator-activated receptor α (PPARα). C57BL/6J mice were divided into two groups: normal diet (WT+ND) group and ketogenic diet (WT+KD) group. After being fed with normal or ketogenic diet at room temperature for 2 d, the mice were exposed to 4 °C low temperature for 12 h. The changes in core temperature, blood glucose, blood pressure of mice under low temperature condition were detected, and the protein expression levels of PPARα and mitochondrial uncoupling protein 1 (UCP1) were detected by Western blot. PPARα knockout mice were divided into normal diet (PPARα-/-+ND) group and ketogenic diet (PPARα-/-+KD) group. After being fed with the normal or ketogenic diet at room temperature for 2 d, the mice were exposed to 4 °C low temperature for 12 h. The above indicators were also detected. The results showed that, at room temperature, the protein expression levels of PPARα and UCP1 in liver and brown adipose tissue of WT+KD group were significantly up-regulated, compared with those of WT+ND group. Under low temperature condition, compared with WT+ND, the core temperature and blood glucose of WT+KD group were increased, while mean arterial pressure was decreased; The ketogenic diet up-regulated PPARα protein expression in brown adipose tissue, as well as UCP1 protein expression in liver and brown adipose tissue of WT+KD group. Under low temperature condition, compared to WT+ND group, PPARα-/-+ND group exhibited decreased core temperature and down-regulated PPARα and UCP1 protein expression levels in liver, skeletal muscle, white and brown adipose tissue. Compared to the PPARα-/-+ND group, the PPARα-/-+KD group exhibited decreased core temperature and did not show any difference in the protein expression of UCP1 in liver, skeletal muscle, white and brown adipose tissue. These results suggest that the ketogenic diet promotes UCP1 expression by up-regulating PPARα, thus improving low temperature tolerance of mice. Therefore, short-term ketogenic diet can be used as a potential intervention to improve the low temperature tolerance.

The function and drug development progress of free fatty acid receptor 1 in chronic inflammatory diseases / 药学学报

As a member of G protein coupled-receptors superfamily, free fatty acid receptor 1 (FFAR1), is also known as GPR40, has been shown to regulate numerous pathophysiological processes in a variety of tissues and organs. The activated FFAR1 has a variety of biological functions. For instance, it can not only regulate metabolism of fatty acids and glucose, but also play an important role in immune inflammatory response, it may be a potential drug target for the treatment of various chronic inflammatory diseases. In this review, we focus on the recent researches of FFAR1's action in the regulation of pathophysiological processes, its molecular mechanism and new agonists development. At the same time, this review will take the discovery of series FFAR1 agonists as examples, and display the applied prospects of FFAR1.