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.

Objective:To evaluate the effect of transfusion-free techniques on the prognosis of liver transplant patients.Methods:The recipients of adult liver transplantation at Tianjin First Central Hospital from August to December 2019 were included in the clinical observation. Liver transplantation without allogeneic blood transfusion was performed through anesthesia management techniques such as acute hemodilution or phlebotomy without volume replacement,maintaining decreased baseline central venous pressure and cell saver. According to the actual results,the patients were divided into two groups: transfusion-free group( n=21) and allogeneic transfusion group( n=28). There were 13 males and 8 females aged of (56.3±11.6) years in the transfusion-free group;and there were 16 males and 12 females aged (54.3±14.2)years in the allogeneic transfusion group. The transplant recipients who had not adopted transfusion management strategy from January to July 2019 were included as control group(27 males and 13 females,aged of (58.9±14.1)years). The clinical data of patients in perioperative period were collected to compare whether there were differences in the recovery of liver function and early complications among the three groups, one-way ANOVA test, rank-sum test, and χ 2 test were used for data analysis. Results:The amount of intraoperative blood loss in both the transfusion-free group and the transfusion group was less than that in the control group((454.2±271.3)ml vs.(673.6±333.4)ml vs.(890.3±346.7)ml; q=-6.342,-5.286,both P<0.05).The duration of stay in ICU of the transfusion-free group was less than that of the transfusion group and control group((36.4±9.1)hours vs.(44.3±14.9)hours vs.(58.2±21.1)hours; q=-4.432,-3.824,both P<0.05).The mean ALT level at 7 days after operation was significantly lower in the transfusion-free group than in the control group((56.8±32.1)U/L vs.(89.6±45.6)U/L; q=-3.358, P<0.05). Conclusions:The improvement of multi-disciplinary transfusion management technology aimed at transfusion-free liver transplantation can effectively reduce intraoperative hemorrhage and help to avoid surgical transfusion. Transfusion-free liver transplantation is beneficial to the early postoperative recovery,and its long-term clinical significance is worthy of further clinical research.

Objective:To evaluate the effect of transfusion-free techniques on the prognosis of liver transplant patients.Methods:The recipients of adult liver transplantation at Tianjin First Central Hospital from August to December 2019 were included in the clinical observation. Liver transplantation without allogeneic blood transfusion was performed through anesthesia management techniques such as acute hemodilution or phlebotomy without volume replacement,maintaining decreased baseline central venous pressure and cell saver. According to the actual results,the patients were divided into two groups: transfusion-free group( n=21) and allogeneic transfusion group( n=28). There were 13 males and 8 females aged of (56.3±11.6) years in the transfusion-free group;and there were 16 males and 12 females aged (54.3±14.2)years in the allogeneic transfusion group. The transplant recipients who had not adopted transfusion management strategy from January to July 2019 were included as control group(27 males and 13 females,aged of (58.9±14.1)years). The clinical data of patients in perioperative period were collected to compare whether there were differences in the recovery of liver function and early complications among the three groups, one-way ANOVA test, rank-sum test, and χ 2 test were used for data analysis. Results:The amount of intraoperative blood loss in both the transfusion-free group and the transfusion group was less than that in the control group((454.2±271.3)ml vs.(673.6±333.4)ml vs.(890.3±346.7)ml; q=-6.342,-5.286,both P<0.05).The duration of stay in ICU of the transfusion-free group was less than that of the transfusion group and control group((36.4±9.1)hours vs.(44.3±14.9)hours vs.(58.2±21.1)hours; q=-4.432,-3.824,both P<0.05).The mean ALT level at 7 days after operation was significantly lower in the transfusion-free group than in the control group((56.8±32.1)U/L vs.(89.6±45.6)U/L; q=-3.358, P<0.05). Conclusions:The improvement of multi-disciplinary transfusion management technology aimed at transfusion-free liver transplantation can effectively reduce intraoperative hemorrhage and help to avoid surgical transfusion. Transfusion-free liver transplantation is beneficial to the early postoperative recovery,and its long-term clinical significance is worthy of further clinical research.

Objective To study the efficacy and safety of percutaneous transhepatic one-step biliary fistulation (PTOBF) with rigid cholangioscopic lithotripsy for treatment of complicated hepatolithiasis under the ultrasonic navigation technique.Methods In this retrospective study,PTOBF lithotripsy surgery was performed in 94 patients with hepatolithiasis under general anesthesia with tracheal intubation,and with percutaneous transhepatic puncture of targeted bile duct under ultrasonic navigation in The First Affiliated Hospital of Guangzhou Medical University.Biliary expanders were used along a guidewire to expand the sinus gradually until 14Fr to establish a fistulous channel.Lithotripsy was then performed through the channel by rigid cholangioscopy.The operation-related data were collected and analyzed,including puncture and fistula establishment success ratio,complication rate,intraoperative blood loss,residual and recurrence hepatolithiasis rates.Results 94 patients (total 122 patient-times) underwent PTOBF lithotripsy.There was no perioperative mortality.The overall puncture success rate was 100％,and the fistula/puncture rate was 97.5％ (119/122).In 118 patients success was achieved in 2 time (96.7％).The complication rate was 9.6％ (9/94).The average intraoperation blood loss were (24.9 ± 21.3)ml.The residual calculus rate after therapy was 13.8％ (13/94).All patients were followed-up for a period that ranged between 18 and 30 months.The recurrence rate was 14.9％ (14/94).Conclusions Ultrasonic navigation technique plays an important role in bile duct puncture,sinus expansion and rigid cholangioscopic lithotripsy for treatment of complicated hepatolithiasis.PTOBF lithotripsy is a safe and effective procedure,which provides a new way in mini-invasive treatment for hepatolithiasis.It is worth generalizing.

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.

Objective To compare the therapeutic effects between three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) in patients with stage Ⅱ/Ⅲ esophageal cancer and investigate the prognostic factors.Methods Medical record of 2 132 patients with stage Ⅱ/Ⅲ esophageal cancer who underwent definitive radiotherapy with/without chemotherapy in 10 hospitals from January 2002 to December 2016 from were retrospectively analyzed.Among these patients,37.9％ of them were aged ≥ 70 years,33.9％ with neck and upper esophageal tumors and 66.1％ with middle and lower esophageal and borderline tumors.The median gross tumor volume (GTV) and lymph node gross tumor volume (GTVnd) was 41.6 cm3.Among them,32％ were stage Ⅱ] and 68％ were stage Ⅲ.A total of 723 patients received 3DCRT and 1 409 cases received IMRT.Patients received an equivalent dose in 2 Gy (EQD2) ≥ 60 Gy accounted for 86.1％,and 41.1％ of them received concurrent chemoradiotherapy.Results The median follow-up time was 60.8 months.The 1-,3-and 5-year overall survival (OS) of all patients was 73.9％,41.7％ and 32.6％,and the 1-,3-and 5-year progression-free survival (PFS) was 62.2％,37.3％ and 32％,respectively.Multivariate analysis demonstrated that age,primary tumor location,clinical stage,tumor target volume,EQD2 and concurrent chemoradiotherapy were the independent prognostic factors for OS.Age,primary tumor location,clinical stage,tumor target volume and EQD2 were the independent prognostic factors for PFS.The OS and PFS did not significantly differ among the low-risk,low-/moderate-risk,moderate-/high-risk and high-risk groups according to age≥70 years,tumor diameter＞5 cm,tumor volume ≥41.6 cm3 and stage Ⅲ (P＜0.001).After the propensity score matching (PSM) method,neither 3DCRT nor IMRT yielded significant advantages in OS or PFS (P=0.971;P=0.658).However,IMRT tended to yield survival benefits in low-risk patients (P=0.125).Conclusions Both 3DCRT and IMRT yield relatively high OS rate in patients with stage Ⅱ/Ⅲ esophageal cancer.The prognosis model established in this investigation can properly predict the survival of patients.Low-risk patients tend to obtain survival benefits from IMRT.

Objective To investigate the relationship between disrupted corticospinal tract (CST) and motor recovery after stroke by using diffusion tensor tracking (DTT). Methods From March, 2012 to June, 2013, 15 chronic stroke patients with left subcortical lesions and 15 age- and sex- matched healthy subjects were performed diffusion tensor imaging (DTI) examination. The CST was tracked by DTT technique, and the damaged values of the CST caused by the stroke lesions were quantified using a CST template generated from healthy controls. Furthermore, the correlations of the damaged values of the CST with Fugl-Meyer Assessment (FMA) were performed. Results The range of the damaged values of CST in stroke patients was 0.00% to 29.6%. There were very strong negative correlation between the damaged values of the CST and FMA scores (the wrist, r = -0.660; hand, r = -0.813; wrist plus hand, r = -0.795, respectively, P < 0.01). It also showed strong negative correlation between the damaged values of the CST and FMA scores (upper limb, r = -0.614; upper limb plus lower limb, r = -0.563, respectively, P < 0.05). Whereas, there was no correlation between the damaged values of the CST and FMA scores of lower limb (r = -0.270, P = 0.331). In addition, the lesion volumes of stroke and FMA scores were not significantly correlated (P > 0.05). Conclusion The severity of motor deficit after stroke was closely related to the overlap of lesions with CST. The damaged values of the CST based on DTT may be used as a potential biomarker to assess motor impairments of upper limbs, especially hand and wrist in stroke patients.

Objective: Hepatitis B surface antigen (HBsAg) loss is seldom achieved with nucleos(t)ide analog (NA) therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon (Peg-IFN) alfa-2a. We assessed HBsAg loss with 48- and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA. Methods: Hepatitis B e antigen (HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA < 200 IU/mL with previous adefovir, lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48 (n = 153) or 96 weeks (n = 150). The primary endpoint of this study was HBsAg loss at end of treatment. The ClinicalTrials.gov identifier is NCT01464281. Results: At the end of 48 and 96 weeks' treatment, 14.4% (22/153) and 20.7% (31/150) of patients, respectively, who switched from NA to Peg-IFN alfa-2a cleared HBsAg. Rates were similar irrespective of prior NA or baseline HBeAg seroconversion. Among those who cleared HBsAg by the end of 48 and 96 weeks' treatment, 77.8% (14/18) and 71.4% (20/28), respectively, sustained HBsAg loss for a further 48 weeks. Baseline HBsAg < 1 500 IU/mL and week 24 HBsAg < 200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48- and 96-week treatment (51.4% and 58.7%, respectively). Importantly, extending treatment from 48 to 96 weeks enabled 48.3% (14/29) more patients to achieve HBsAg loss. Conclusion Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a. HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks, although the differences in our study cohort were not statistically significant. Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.

Objective To analyze the clinical value of transforaminal endoscopic minimally invasive surgery for the treatment of recurrent lumbar disc herniation.Methods Strictly included in the criteria,47 patients diagnosed with recurrent lumbar disc herniation who was treated unsuccessfully with conservative treatment were selected from our department from May 2011 to December 2015.There were 31 males and 16 females,with an average age of 43.45 ±3.37 years old (29-62 years old).There were L3,4 section in 4 cases,L4,5 section in 32 cases,and L5S1 section in 11 cases.The interval between the first operation and the reoperation was between 10 and 185 months,with an average of 49 months.In the first operation,there were 11 cases of posterior intervertebral disc endoscopy (MED) surgery,and 36 cases of decompression of vertebral disc nucleus pulposus surgery.Take a prone position under local anesthesia percutaneous puncture intervertebral foramen in the endoscopic minimally invasive surgery,intraoperative decompression of vertebral canal and nerve root canal,removal of intervertebral disc nucleus pulposus tissue,explore and release nerve root.The Oswestry disability index (ODI),visual analogue scale (VAS) and improved Macnab standard were used to assess the efficacy of the operation.Operation segments intervertebral height change,lumbar power X-ray slice of intervertebral Angle was measured according to preoperative and last follow-up of lumbar lateral X-ray observation,and lumbar spine motion (the range of motion,ROM) was calculated.Results All cases were successfully performed,no open surgery,and all cases were followed up.The average surgical blood volume was 10.3± 2.7 ml,the operation time was 63.5±11.6 min,no nerve root injury,dural injury,cerebrospinal fluid leakage,muscle strength decline,secondary obstruction,lumbar instability or other serious complications occurred.The follow-up time was from 18 to 52 months,with an average of 35.5±5.1 months.The preoperative ODI 51.35± 15.29 decreased to 3.31 ±2.17 at the last postoperative follow-up,the preoperative VAS score 8.11 ± 1.05 decreased to (1.03± 0.81) at the last postoperative follow-up,and the difference was statistically significant (P ＜ 0.05).As to the last follow-up evaluation of curative effect,according to the modified MacNab method,the fine rate was 87.2％;At the time of the last follow-up,surgery intervertebral disc height of front and rear section before and after surgery had no significant differences (P ＞ 0.05),the motion of operation segmental lumbar (the range of motion,ROM) had no significant difference (P ＞ 0.05).Conclusion Under the premise of strict control of surgical indications,the clinical efficacy of minimally invasive surgery for the treatment of recurrent lumbar disc herniation is reliable.The transforaminal approach does not affect the stability of the spine.The operation has the advantages of small trauma,fewer complications,and is safe and effective.

Objective: To investigate the efficacy and safety of the new investigational drug pegylated interferon α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 µg/week) combined with ribavirin in the treatment of patients with genotype 1/6 chronic hepatitis C (CHC), with standard-dose Peg-IFN-α-2a combined with ribavirin as a positive control. Methods: A multicenter, randomized, open-label, and positive-controlled phase III clinical trial was performed. Eligible patients with genotype 1/6 CHC were screened out and randomly divided into Peg-IFN-α-2b(Y shape, 40kD) group and Peg-IFN-α-2a group at a ratio of 2:1. The patients in both groups were given oral ribavirin for 48 weeks in addition and then followed up for 24 weeks after drug withdrawal. Abbott Real Time HCV Genotype II was used to determine HCV genotype, and Cobas TaqMan quantitative real-time PCR was used to measure HCV RNA level at 0, 4, 12, 24, 48, and 72 weeks. Adverse events were recorded in detail. The primary efficacy endpoint was sustained virological response (SVR), and a non-inferiority test was also performed. Results: A total of 561 patients with genotype 1/6 CHC were enrolled, among whom 529 received treatment; 90.9% of these patients had genotype 1 CHC. The data of the full analysis set showed that SVR rate was 69.80% (95% CI 65.00%-74.60%) in the trial group and 74.16% (95% CI 67.73%-80.59%) in the control group (P = 0.297 0). The data of the per protocol set (PPS) showed that SVR rate was 80.63% (95% CI 76.04%-85.23%) in the trial group and 81.33% (95% CI 75.10%-87.57%) in the control group (P = 0.849 8), and the 95% CI of rate difference conformed to the non-inferiority standard. The analysis of the PPS population showed that of all subjects, 47.9% achieved rapid virologic response, with a positive predictive value of 93.8%. The incidence rate of adverse events was 96.30% in the trial group and 94.94% in the control group, and the incidence rate of serious adverse events was 5.13% in the trail group and 5.06% in the control group. Conclusion In the regimen of Peg-IFN-α combined with ribavirin for the treatment of genotype 1/6 CHC, the new investigational drug Peg-IFN-α-2b(Y shape, 40 kD) has comparable clinical effect and safety to the control drug Peg-IFN-α-2a.