Osteoporosis (OP) is a systemic skeletal disease that primarily affects the elderly population, which greatly increases the risk of fractures. Here we report that Kindlin-2 expression in adipose tissue increases during aging and high-fat diet fed and is accompanied by decreased bone mass. Kindlin-2 specific deletion (K2KO) controlled by Adipoq-Cre mice or adipose tissue-targeting AAV (AAV-Rec2-CasRx-sgK2) significantly increases bone mass. Mechanistically, Kindlin-2 promotes peroxisome proliferator-activated receptor gamma (PPARγ) activation and downstream fatty acid binding protein 4 (FABP4) expression through stabilizing fatty acid synthase (FAS), and increased FABP4 inhibits insulin expression and decreases bone mass. Kindlin-2 inhibition results in accelerated FAS degradation, decreased PPARγ activation and FABP4 expression, and therefore increased insulin expression and bone mass. Interestingly, we find that FABP4 is increased while insulin is decreased in serum of OP patients. Increased FABP4 expression through PPARγ activation by rosiglitazone reverses the high bone mass phenotype of K2KO mice. Inhibition of FAS by C75 phenocopies the high bone mass phenotype of K2KO mice. Collectively, our study establishes a novel Kindlin-2/FAS/PPARγ/FABP4/insulin axis in adipose tissue modulating bone mass and strongly indicates that FAS and Kindlin-2 are new potential targets and C75 or AAV-Rec2-CasRx-sgK2 treatment are potential strategies for OP treatment.

A total of 290 prescriptions in Treatise on Typhoid and Miscellaneous Diseases （《伤寒杂病论》） and Synopsis of the Golden Chamber （《金匮要略》） and 191 prescriptions in Prescriptionology were selected as representatives of classical prescriptions of traditional Chinese medicine （TCM）， which were translated into Chinese and Japanese. The prescription names were used as keywords for search， and the patent application data up to June 2022 were retrieved. The retrieved results underwent data cleaning and manual noise reduction. Taking the important applicants as the starting point， the key technologies were divided and indexed according to the technical improvement characteristics of classic TCM prescriptions， and the intelligence information of patent applications for classic TCM prescriptions in the two countries was deeply excavated. The differences in the patent applications and layout strategies of classic TCM prescriptions between China and Japan were further compared. This paper drew up an accurate and targeted search strategy for more accurate and comprehensive retrieval， collation， and statistics of patent data of classic TCM prescriptions of representative patent applicants in China and Japan. At the same time， this paper deeply explored the information on Chinese patent applications in Japan and compared the differences in patent application strategies and patent protection of classic TCM prescriptions and Chinese prescriptions in Japan taking the layout of classic TCM prescriptions of representative patent applicants in China and Japan as the entry point. On one hand， it can accurately grasp the current patent application status of classic TCM prescriptions in the two countries， and on the other hand， it can also provide some references for the secondary development and research， patent application， and layout of classic prescriptions of enterprises， universities， and research institutions in China.

Objective:To investigate the diagnostic value of prenatal MRI in the detection of abnormal placental cord insertions (APCIs) comparing with prenatal ultrasound and pathological examination.Methods:A retrospective data collection was conducted on 440 patients who underwent both prenatal placental ultrasound and MRI at the Foshan Women and Children Hospital from December 2013 to December 2021. Among them, 37 cases were APCIs confirmed by surgery or pathology. The prenatal placental MRI findings were analyzed and compared with prenatal ultrasound diagnosis. The diagnostic efficacy of prenatal MRI and ultrasound in diagnosing APCIs was calculated.Results:Among the 37 cases of APCIs confirmed by surgery or pathology, 17 cases had marginal cord insertion (MCI), 13 cases had velamentous cord insertion (VCI), 5 cases had vasa previa (VP), and 2 cases had VCI combined with VP. The sensitivity and specificity of ultrasound diagnosis for APCIs were 59.5% (22/37) and 97.8% (394/403), respectively. The sensitivity and specificity of MRI diagnosis for APCIs were 86.5% (32/37) and 98.5% (397/403), respectively. Among the 37 cases of APCIs, prenatal MRI missed diagnosis of 2 cases of MCI, 2 cases of VCI, and misdiagnosed 1 case of VCI as an accessory placenta. MRI identified 10 cases of APCIs missed by ultrasound, including 5 cases of MCI, 2 cases of VP, 2 cases of VCI, and 1 case of combined VCI with VP. Additionally, ultrasound misdiagnosed 4 cases of APCIs, including 2 cases of VCI misdiagnosed as MCI and 2 cases of MCI misdiagnosed as VCI.Conclusions:For APCIs complicated with abnormalities of placental location or morphology, or placental accretion spectrum disease in late pregnancy, MRI has a higher diagnostic efficacy than ultrasound.

Objective:To investigate the computed tomography (CT) examination anato-mical features and clinical significance of paraesophageal vein (PEV) in portal hypertension.Methods:The retrospective and descriptive study was conducted. The clinical data of 173 patients with portal hypertension who were admitted to the People's Hospital of Ningxia Hui Autonomous Region from January 2018 to June 2021 were collected. There were 124 males and 49 females, aged from 22 to 71 years, with a median age of 47 years. Observation indicators: (1) preoperative CT examinations; (2) surgical situations; (3) follow-up. Follow-up was conducted using outpatient examination to detect surgical effects once every 3 months within postoperative 6 months and once every 6 months after postoperative 6 months. The follow-up was up to June 2021. Measurement data with skewed distribution were represented as M(range) and count data were described as absolute numbers. Results:(1) Preoperative CT examinations. The CT detection rate of PEV in the 173 portal hyper-tension patients was 52.60%(91/173). Of 173 patients, 82 cases were negative with PEV and 91 cases were positive with PEV. Of the 91 patients who were positive with PEV, there were 46 cases with paraesophageal varices, 24 cases with thick PEV, 21 cases with thin PEV, 8 cases without esophageal varices and 83 cases accompanied with esophageal varices. Of the 83 patients who were accom-panied with esophageal varices, there were 44 cases with PEV converged alone with azygos vein or semiazygos vein, 39 cases with paraesophageal varices formed above the diaphragm confluent with esophageal varices into azygos vein. (2) Surgical situations. All the 173 patients underwent surgery successfully, including 8 cases undergoing splenectomy, 86 cases undergoing splenectomy combined with modified complete devascularization, 35 cases undergoing splenectomy combined with spontaneous gastrorenal shunt reconstructing devascularization, 41 cases undergoing splenectomy combined with PEV preserving devascularization and 3 cases undergoing splenectomy combined with PEV ring constriction. None of 173 patients had surgical relative death, 67 cases had complica-tions, including 3 cases undergoing splenectomy, 29 cases undergoing splenectomy combined with modified complete devascularization, 11 cases undergoing splenectomy combined with spontaneous gastrorenal shunt reconstructing devascularization, 23 cases undergoing splenectomy combined with PEV preserving devascularization and 1 case undergoing splenectomy combined with PEV ring constriction underwent complications. (3) Follow-up. Of the 173 patients, 159 cases were followed up for 6 to 42 months, with a median follow-up time of 28 months. In the 7 cases undergoing splenectomy who were followed up, there were 6 cases without esophageal varices and 1 case with recurrence of esophageal varices. In the 79 cases undergoing splenectomy combined with modified complete devascularization who were followed up, there were 5 cases without esophageal varices, 67 cases with mild to moderate residual of esophageal varices, 5 cases with severe residual of esophageal varices, 1 case with recurrence of esophageal varices and 1 case with recurrence of esophageal varices hemorrhage. In the 34 cases undergoing splenectomy combined with sponta-neous gastrorenal shunt reconstructing devascularization who were followed up, there were 7 cases without esophageal varices and 27 cases with mild to moderate residual of esophageal varices. In the 36 cases undergoing splenectomy combined with PEV preserving devascularization who were followed up, there were 4 cases without esophageal varices, 21 cases with mild to moderate residual of esophageal varices, 5 cases with severe residual of esophageal varices, 4 cases with recurrence of esophageal varices and 2 cases with recurrence of esophageal varices hemorrhage. In the 3 cases undergoing splenectomy combined with PEV ring constriction who were followed up, there were 2 cases with mild to moderate residual of esophageal varices, 1 case with severe residual of esophageal varices.Conclusions:The CT detection rate of PEV in portal hypertension patients is >50% and the internal diameter and distribution of blood vessels are different in patients. CT examination anatomical features of PEV can be used to guide the formula-tion of surgical methods.

Objective:To compare the efficacy of fusion and non-fusion hybrid operation with Dynesys system with the traditional fusion operation with rigid instrumentation in the patients with multi-segment lumbar degenerative disease.Methods:A total of 30 patients with multi-segment lumbar degenerative disease who were subjected to operation from January 2017 to October 2019 in Shenzhen People's Hospital were included in the study. There were 13 males and 17 females, age: 60.8±13.2 years, range: 25 to 83 years. 28 patients with two segments, 1 with three segments, and 1 with four segments. The patients were divided into two groups, i.e the hybrid operation group (13 cases, 9 males and 4 females, average age: 56.6 years, range: 25 to 83 years) versus the traditional fusion group (17 cases, 4 males and 13 females, average age: 63.9 years, range: 46 to 80 years). The main outcome measures were visual analogue scale (VAS), Oswestry disability index (ODI), range of motion (ROM), adjacent segment degeneration (ASD) and complications.Results:There were no statistically significant differences in operation data, such as operation time, intraoperative blood loss, postoperative drainage volume and length of hospitalization, between the two groups. There were no significant differences for ROM in the surgical segments between the two groups before operation (hybrid group and traditional group were 9.6°±4.9° vs. 8.9°±6.1°, t=0.341, P=0.736, respectively). However, after 12 months follow-up, the ROM disappeared in the traditional group and was partially preserved in the hybrid group, with statistically significant differences (hybrid group and traditional group were 5.4°±2.7° vs. 0°, t=9.104, P=0.001, respectively). There was a statistical difference in intervertebral disc height between the two groups at 12 months post-operation, though no statistical difference was found before operation (8.8±1.9 mm vs. 10.5±1.7 mm, t=2.927, P=0.006). There was no statistically significant difference in the intervertebral disc height of the upper adjacent vertebrae between the two groups before and after operation. There were statistically significant differences in ODI scores before operation (63.4%±11.0% vs. 71.3%±9.2%, t=2.146, P=0.041), and 12 months post-operation (17.2%±2.1% vs. 15.5%±2.3%, t=2.091, P=0.046), while no statistical difference was found in VAS scores. Conclusion:The fusion and non-fusion hybrid operation with Dynesys system has comparable clinical efficacy with the traditional fusion operation with rigid instrumentation in the treatment of multisegment lumbar degenerative disease. Meanwhile, the hybrid surgery can preserve the motion of surgical segments and provide a dynamic stability of the vertebral body. The hybrid surgery can be used as a new surgical method for multi-segment lumbar degenerative disease.

Objective:To evaluate the efficacy of comprehensive anti-cancer treatment for lung metastases after liver transplantation (LT) for hepatocellular carcinoma (HCC).Methods:From March 2012 to July 2016, A total of 36 patients with lung metastasis after LT were divided into comprehensive anti-cancer treatment group (rapamycin + radioactive I 125 seed implantation + pulmonary artery infusion chemotherapy + sorafenib, n=22) and maintenance supportive care group ( n=14). The survival profiles of two groups were evaluated. Results:No significant inter-group differences existed in preoperative basic data, tumor pathology, time of pulmonary metastatic tumor after operation and lung metastasis tumor burden.In comprehensive anti-cancer treatment group, there were partial remission ( n=3), disease stability ( n=12) and disease progression after treatment ( n=7). In maintenance supportive care group, there were disease stability ( n=3) and disease progression after treatment ( n=11). And comprehensive anti-cancer treatment was superior to maintenance supportive care ( χ2=7.901, P=0.019). The median survival time after metastasis was 23 months (95%CI: 19.68-26.32) in comprehensive anti-cancer treatment group and 7 months (95%CI: 3.33-10.67) in maintenance supportive care group; 1-year survival rate 91% and 9%, 2-year survival rate 45% and 0% and 3-year survival rate 10% and 0% respectively.The survival rate of comprehensive anti-cancer treatment group was significantly better than that of maintenance supportive care group ( P<0.001). Conclusions:Comprehensive anti-cancer treatment (rapamycin + radioactive I 125 seed implantation + pulmonary artery infusion chemotherapy + sorafenib) can improve the survival time of patients with lung metastasis after liver transplantation for HCC.

Clostridioides difficile is a key pathogen of antibiotic related diarrhea and hospital associated infection, causing several outbreaks in Europe and North Americans and resulting in severe disease burden. However, the standardized diagnostic principle and detection specifications in C. difficile infection (CDI) survey are limited in China, and the infection rate and disease burden of CDI in China are unclear. Therefore, National Institute for Communicable Disease Control and Prevention,National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, together with another 11 institutions, draft the group standard entitled "Diagnosis of Clostridium difficile infection (T/CPMA 008-2020)" of Chinese Preventive Medicine Association. Based on the principle of "legality, scientificity, advancement, and feasibility", this standard clarifies risk factors, diagnosis principles, diagnoses and differential diagnoses in order to improve the accuracy of CDI diagnosis in clinical practice, guide the surveillance for CDI, and understand the infection rate and disease burden of CDI in China .

Objective To explore the early prognosis and the risk factors of delayed graft function (DGF) of the recipients undergoing liver transplantation from donor liver with moderate-to-severe steatosis. Methods Clinical data of 475 donors and 475 recipients undergoing liver transplantation from donor liver of organ donation after citizen's death were retrospectively analyzed. According to the classification criteria of steatosis proposed by Australia National Liver Transplantation Unit (ANLTU), all recipients were divided into the S0 group (no steatosis, n=308), S1 group (mild steatosis, n=97), S2 group (moderate steatosis, n=52) and S3 group (severe steatosis, n=18), respectively. The early postoperative death and incidence of postoperative complications were statistically compared among each group. The risk factors from donors, recipients and operation leading to DGF were analyzed by univariate and multivariate logistic regression models. Results The incidence of postoperative DGF in the S2 and S3 groups was significantly higher than that in the S1 and S0 groups (all P < 0.05). The incidence of postoperative DGF in the S3 group was remarkably higher than that in the S2 group (P < 0.05). The early postoperative fatality, the incidence of primary nonfunction (PNF) of the transplant liver, postoperative bleeding, infection, biliary complications and vascular complications did not significantly differ among each group (all P > 0.05). Univariate regression analysis showed that severe steatosis of donor liver, long cold ischemia time, high model for end-stage liver disease (MELD) score and tumors of the recipients before operation were the risk factors of DGF (all P < 0.05). Multivariate logistic regression analysis demonstrated that moderate-to-severe steatosis of donor liver, cold ischemia time > 8 h and MELD score > 30 of the recipients were the independent risk factors for early postoperative DGF. Conclusions The early-stage incidence of DGF after adult liver transplantation from donor liver with moderate-to-severe steatosis is high, whereas it does not affect the early survival rate of the recipients. The selection of donor liver with moderate-to-severe steatosis should be considered in combination with cold ischemia time of the donors and MELD score of the recipients before operation, etc.

Motor timing is an important part of sensorimotor control. Previous studies have shown that beta oscillations embody the process of temporal perception in explicit timing tasks. In contrast, studies focusing on beta oscillations in implicit timing tasks are lacking. In this study, we set up an implicit motor timing task and found a modulation pattern of beta oscillations with temporal perception during movement preparation. We trained two macaques in a repetitive visually-guided reach-to-grasp task with different holding intervals. Spikes and local field potentials were recorded from microelectrode arrays in the primary motor cortex, primary somatosensory cortex, and posterior parietal cortex. We analyzed the association between beta oscillations and temporal interval in fixed-duration experiments (500 ms as the Short Group and 1500 ms as the Long Group) and random-duration experiments (500 ms to 1500 ms). The results showed that the peak beta frequencies in both experiments ranged from 15 Hz to 25 Hz. The beta power was higher during the hold period than the movement (reach and grasp) period. Further, in the fixed-duration experiments, the mean power as well as the maximum rate of change of beta power in the first 300 ms were higher in the Short Group than in the Long Group when aligned with the Center Hit event. In contrast, in the random-duration experiments, the corresponding values showed no statistical differences among groups. The peak latency of beta power was shorter in the Short Group than in the Long Group in the fixed-duration experiments, while no consistent modulation pattern was found in the random-duration experiments. These results indicate that beta oscillations can modulate with temporal interval in their power mode. The synchronization period of beta power could reflect the cognitive set maintaining working memory of the temporal structure and attention.

Objective: To explore the improvement rate of liver fibrosis in patients with chronic hepatitis B virus infection who received entecavir alone or in combination with anluohuaxianwan for 78 weeks. Methods: Patients with chronic HBV infection were randomly treated with entecavir alone or in combination with anluohuaxian for 78 weeks. Ishak fibrosis score was used for blind interpretation of liver biopsy specimens. The improvement in liver fibrosis condition before and after the treatment was compared. Student's t test and non-parametric test (Mann-Whitney U-Test and Kruskal-Wallis test) were used to analyze the measurement data. The categorical variables were analyzed by Chi-square test method and Spearman’s rank correlation coefficient was used to test bivariate associations. Results: Liver fibrosis improvement rate after 78 weeks of treatment was 36.53% (80/219) and the progression rate was 23.29% (51/219). The improvement of liver fibrosis was associated to the degree of baseline fibrosis and treatment methods (P < 0.05). The improvement rate of hepatic fibrosis in patients treated with anluohuaxianwan combined with entecavir at baseline F < 3 (54.74%, 52/95) was significantly higher than that in patients treated only with entecavir (33.33%, 16/48), P = 0.016 and the progression rate of hepatic fibrosis (13.68%, 13/95) was lower than that in patients treated alone (18.75%, 9/48), P = 0.466. In patients with baseline F < 3, the proportion of patients with improved and stable liver fibrosis in the combined treatment group (68.1%, 32/47) was higher than that in the treatment group alone (51.7%, 15/29). Conclusion Combined anluohuaxianwan and entecavir treatment can significantly improve the improvement rate of liver fibrosis in patients with chronic hepatitis B virus infection. Furthermore, it has the tendency to improve the stability rate and reduce the rate of progression of liver fibrosis.