Purpose To investigate the effect of MYD88 gene overexpression on the proliferation and apoptosis of human diffuse large B cell lymphoma(DLBCL)cells,and to prelimi-narily explore the mechanism of MYD88 gene action.Methods PEGFP-C2-MYD88 overexpressing MYD88 L265P gene was transfected into DLBCL cells by plasmid transfection.The exper-iment was divided into blank control group,negative control group and MYD88 L265P overexpression group.The fluores-cence expression of MYD88 L265P after overexpression was ob-served under inverted fluorescence microscope.RT-PCR and Western blot were used to detect the mRNA and protein expres-sion of MYD88 L265P,IRAK4,NF-κB and BCL2 in DLBCL cells before and after overexpression of MYD88 L265.CCK8 method was used to detect DLBCL cells proliferation and Ho-echst staining was used to detect DLBCL cells apoptosis.Re-sults After overexpression of MYD88 L265P,compared with the blank control group(0.670 4±0.017 5)and the negative control group(0.715 3±0.019 6),the MYD88L265P overex-pression group(1.157 2±0.010 2)increased significantly,with statistical significance(all P＜0.05).After overexpression of MYD88 L265P,compared with the blank control group(0.69 ±0.04)and the negative control group(0.81±0.07),the MYD88L265P overexpression group(0.48±0.05)was signifi-cantly decreased,with statistical significance(all P＜0.05).After overexpression of MYD88 L265P,compared with the blank control group(mRNA:1.0158±0.0115,0.987 3±0.010 2,1.007 6±0.015 3,protein:0.183 4±0.058 9,0.096 8± 0.015 7,0.147 5±0.0418)and negative control group(mR-NA:0.9132±0.0098,1.0032±0.0156,0.9327± 0.011 2,protein:0.187 9±0.042 3,0.088 9±0.0513,0.134 8±0.050 1),the mRNA(3.243 2±0.013 6,2.976 6 ±0.0213,1.585 9±0.019 8)and protein expressions(0.452 7±0.052 4,0.218 9±0.047 5,0.301 4±0.059 8)of IRAK4,NF-κB and anti-apoptosis protein BCL2 in MYD88L265P overexpression group were significantly increased,which was statistically significant(all P＜0.05).Conclusion After overexpression of MYD88 L265P,the apoptosis rate of DLBCL cells decreased and the cell proliferation rate increased.The mechanism may be related to the mutation of MYD88 L265P gene,activation and amplification of NF-κB pathway,and pro-motion of the overexpression of antiapoptotic protein BCL2.

BACKGROUND:After the internal fixation of cannulated screws in femoral neck fractures,because the affected limb is often unable to bear weight in the short term and the implants with high stiffness have a stress shielding effect on the fracture end,it is easy to cause osteoporosis of the affected limb and changes in the biomechanical distribution of the proximal femur,the incidence of osteonecrosis of the femoral head is high after surgery.At present,few studies have been conducted on the biomechanical effects of osteoporosis at the proximal end of the femur occurring after femoral neck fracture surgery on femoral neck fracture treated with cannulated screws. OBJECTIVE:Using finite element analysis,to investigate the biomechanical effects of osteoporosis occurring after femoral neck fracture surgery on femoral neck fracture treated with cannulated screws and explore the role of biomechanical factors in osteonecrosis of the femoral head. METHODS:Based on the obtained CT scan data of the femur in a patient with a femoral neck fracture,a proximal femoral model for internal fixation for femoral neck fracture was established by Mimics 19.0,3-Matic,UG 11.0,Hypermesh 14.0,and Abaqus software.One finite element model of the proximal femur without osteoporosis and three finite element models of the proximal femur with osteoporosis were analyzed using Abaqus software.The stress,contact pressure,displacement peak and cloud map under different components of the four models were measured and analyzed,and the internal stress changes and distribution of the femoral head were compared and analyzed. RESULTS AND CONCLUSION:The stresses and contact pressures of the femoral head and lower anterior cannulated screws varied more with the degree of osteoporosis.The peak displacement of the four models increased slowly with the degree of osteoporosis.By one-way analysis of variance,there was no significant effect of the degree of osteoporosis on the peak stress,contact pressure,and displacement of the different components.The internal stress distribution of the femoral head changed with the degree of osteoporosis.Changes in the biomechanical environment of the proximal femur have an important impact on osteonecrosis of the femoral head.

Objective To optimize the preparation process of hydroxysafflor yellow A(HSYA)nanoparticle and conduct in vitro release evaluation.Methods HSYA nanoparticles were prepared with PLGA as carrier by modified compound emulsion method.The optimal preparation process of the experiment was selected by Plackett-Burman and Box-Behnken response surface method.The nanoparticles were characterized by using particle size analyzer,TEM scanning electron microscope,Fourier transform infrared spectroscopy(FT-IR),X-ray diffraction(XRD).Frozen(4℃)storage stability,stability in physiological medium,lyophilized protective agent and in vitro release rate were investigated.Results The optimal process prescription of nanoparticle is as follow:pH value is 6.95,the dosage is 2.8 mg,and carrier dosage is 18.2 mg.The size of nanoparticles obtained at optimum condition is(176.4±1.29)nm,the polydiseperse index(PDI)is 0.152±0.014,the Zeta potential is(-17.6±0.46)mV,the encapsulation rate is(78.5±0.49)％,drug loading is(7.3±0.07)％.These nanoparticles showed round and good dispersion.Good stability in 4℃ storage environment and different physiological media of nanoparticles were observed.The best lyophilized protective agent was 1％glucose and the in vitro release rate of nanoparticles at 48 hours was 85％.Conclusion The optimization method is reasonable and reliable.The obtained nanoparticles have good stability and sustained-release effect.The in vitro release behavior conformed to first-order kinetic model.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Humans ; East Asian People ; Surveys and Questionnaires ; Vitiligo/epidemiology*

Objective: To examine the correlation between frailty and lifestyle factors among middle-aged and elderly populations, so as to provide insights into the management of frailty among middle-aged and elderly populations. Methods : Middle-aged and elderly residents at ages of 45 ot 69 years were recruited using the convenient sampling method from seven townships in Changxing County of Zhejiang Province from 2019 to 2020. The demographic characteristics and lifestyle factors were collected using questionnaires, and the frailty was measured using the Chinese version of Tilburg Frailty Indicator ( TFI ). Factors affecting frailty were identified among middle-aged and elderly populations using the multivariable logistic regression model. Results: A total of 7 170 residents were surveyed, including 2 780 males ( 38.77% ) and 4 390 females ( 61.23% ), which had a median age of 56 (interquartile range, 10) years. The median frailty score was 2 (interquartile range, 3 ) among the study subjects, and the median frailty score was 2 ( interquartile range, 2 ) among residents at ages of 45 to 59 years, and 2 (interquartile range, 3) among residents at ages of 60 to 69 years. The overall detection of frailty was 16.07%, and the detection of frailty was 13.52% among subjects at ages of 45 to 59 years and 21.01% among subjects at ages of 60 to 69 years. Multivariable logistic regression analysis identified physical activity ( OR=0.826, 95%CI: 0.719-0.949 ) and sleep quality ( OR: 3.376-11.493, 95%CI: 2.907-15.808 ) as factors affecting frailty among middle-aged and elderly residents. Following age stratification, physical activity ( OR=0.817, 95%CI: 0.681-0.981 ) and sleep quality ( OR: 3.076-11.566, 95%CI: 2.518-18.216 ) as factors affecting frailty among subjects at ages of 45 to 59 years, while sleep quality ( OR: 3.777-11.827, 95%CI: 3.002-18.547 ) significantly correlated with frailty among residents at ages of 60 to 69 years. Conclusion Physical activity and sleep quality are associated with the risk of frailty among middle-aged and elderly populations.

Objective: To investigate the effect of early-stage training combined with the ultrashort wave therapy on the functional recovery of rats after a spinal cord injury, and to observe the expression of aquaporin protein-4 (AQP-4) and glial fibrillary acidic protein (GFAP). Methods: Fifty female Sprague-Dawley rats had spinal cord injury (SCI) induced using the modified Allen′s method. After successful modeling, 40 were randomly divided into a sham operation group, a control group, an ultrashort wave group, a treadmill group and a combined group, each of 8. Motor function in their hind limbs was evaluated 4 weeks after the operation using BBB scoring. GFAP and AQP-4 immunohistochemical staining were used to determine the integral optical density (IOD) of the protein expression. Results: The average BBB score of the sham operation group was 21, while the other four groups averages were all less than 1 on the 1st day after the operation. They gradually increased with time, and by 4 weeks the increases were significant. Compared with the control group at the same time point, the average BBB scores of the treadmill and the combined groups were significantly higher. Compared with the ultrashort wave group, the average BBB score of the treadmill group was higher after 4 weeks, and the combined group′s average was significantly higher at 2, 3 and 4 weeks after the operation. Four weeks after the SCI modeling, the average AQP-4 IOD and GFAP IOD levels of the ultrashort wave group, the treadmill group and the combined group were lower than that of the control group, while the average AQP-4 and GFAP IOD levels of the combined group were significantly lower than those of the ultrashort wave group. Compared with the treadmill group, the combined group had a significantly lower average GFAP level. Conclusions Both treadmill training and ultrashort wave treatment promote motor function recovery after a spinal cord injury. The mechanism may be related to downregulation of AQP-4 and GFAP expression at the injured site. Combining the two treatments gives better effects.

OBJECTIVE: To review the development of adult and pediatric liver transplantation in Tianjin First Center Hospital, and to enhance academic exchanges, improve technological innovation, and jointly promote the progress and maturity in the field of liver transplantation. METHODS: The development of liver transplantation in Tianjin First Center Hospital was analyzed. The clinical data of adult and pediatric liver transplantation from September 1998 to September 2018 were collected. The important events and technological innovation achievements of liver transplantation during the 20 years were summarized. RESULTS: The first clinical liver transplantation was attempted in Tianjin First Central Hospital in April 1980. The first long-term survival adult liver transplantation in China was completed in 1994 (11 years survival after the operation). The specialized team of liver transplantation was formally established in September 1998. The 20-year clinical exploration and progress reflected the characteristics of era changes and technological innovation during the rapid development of liver transplantation in China. Our center performed liver re-transplantation in January 1999, reduced-size pediatric liver transplantation in August 2000. In May 2001, we organized the formulation for the preventive and treatment plan for hepatitis B recurrence after liver transplantation. We performed combined liver and kidney transplantation in July 2002, split liver transplantation (SLT) in April 2004, the first domino liver transplantation (DLT) in August 2005. Pediatric living donor liver transplantation (LDLT) was initiated in October 2006, adult LDLT was carried out in August 2007. In September 2007, the first living donor combined liver and kidney transplantation from the same donor in Asia was performed. The first domino+living donor double grafts liver transplantation in the world was performed in January 2009. In March 2011, we performed laparoscopically assisted right hepatic lobe liver transplantation (LDLT) with middle hepatic vein. In May 2014, living donor laparoscopic left lateral lobe procurement was successfully established. In April 2016, simultaneous liver, pancreas and kidney multi-organ transplantation was completed. Domino donor-auxiliary liver transplantation was performed in February 2017. In December 2017, extracorporeal membrane oxygenation (ECMO)-supported liver transplantation in a patient with severe pulmonary hypertension was successfully completed. Liver transplantation combined with partial splenectomy was established in April 2018. Cross-domino liver transplantation (hypersensitive kidney transplantation with auxiliary liver transplantation+pediatric liver transplantation) was performed in May 2018. During the 20 years, the team has performed or assisted other centers in Beijing, Shanghai, Guangzhou and Shenzhen to carry out more than 10 000 cases of liver transplantations. A total of 7 043 cases of various types of liver transplantation were performed in the single center of the hospital (6 005 adult liver transplantations and 1 038 pediatric liver transplantations). Concerning adult liver transplantation, the cumulative 1-year, 3-year and 5-year survival rate from September 1998 to March 2003 were 83.1%, 73.0% and 69.0%, from April 2003 to March 2009 were 85.3%, 76.2% and 72.1% and from April 2009 to September 2018 were 87.5%, 79.2% and 75.1%, respectively. The cumulative 1-year, 3-year and 5-year survival rate for pediatric liver transplantation were 93.5%, 92.2% and 90.2%, respectively. The nucleoside (acid) analogue combined with low dose hepatitis B immunoglobulin (HBIG) was developed to prevent the recurrence of hepatitis B after liver transplantation, this plan has reduced the recurrence rate of hepatitis B and the 5-year re-infection rate of hepatitis B virus (HBV) after liver transplantation significantly. The risk assessment system for tumor recurrence after liver transplantation was established and individual treatment method was established based on this assessment system. Continuous exploration and improvement of liver transplantation for liver cancer, liver re-transplantation, liver transplantation with portal vein thrombosis, SLT, DLT and multi-organ combined transplantation have significantly improved the clinical efficacy of patients and the post-operative survival rate. CONCLUSIONS The liver transplantation team of Tianjin First Center Hospital has carried out a scientific and technological exploration on the key problems and technical difficulties of clinical liver transplantation. This work strongly has initiated and promoted the rapid development of liver transplantation in China. The restrictive barrier of hepatitis B recurrence after liver transplantation has been overcome. The risk prevention and control system of tumor recurrence after liver transplantation has been established. A series of innovative achievements that can be popularized have been achieved in the field of complex liver transplantation and expansion of donor liver source. The iterative progress and sustainable development of liver transplantation have been realized.
China ; Humans ; Liver Transplantation

Objective To explore the effect of primary exchange reamed nailing (ERN) and augmentation compression plating (ACP) combined with autogenous bone grafting (ABG) on health-related quality of life in patients with dystrophic or atrophic nonunion of femoral shaft after intramedullary nailing. Methods The study used a prospective study method. Sixty- two patients with femoral shaft nonunion after intramedullary nailing from August 2010 to October 2016 were selected, and the patients were divided into ERN group (group A, 32 cases) and ACP group (group B, 30 cases) by random digits table method. In group A, isthmus nonunion was in 18 cases (56.2％), and non-isthmus nonunion in 14 cases (43.8％); in group B, isthmus nonunion was in 16 cases (53.3％), and non-isthmus nonunion in 14 cases (46.7％ ). The health- related quality of life was compared between 2 groups, including physical component summary (PCS) and mental component summary (MCS) in the- 12- item short form health survey (SF- 12), brief pain inventory- severity (BPI- S) and brief pain inventory- interference (BPI- I). Results Fifty-four patients were followed-up for more than 1 year, and the mean follow-up time was 18.3 (13 to 37) months. All patients successfully achieved bone union, and the mean time was 5.8 (4 to 8) months. Significant improvements in terms of SF-12 PCS and SF-12 MCS score were noted after operation for patients with isthmus nonunion in both groups (t=3.148, 2.156, 2.456 and 2.559; P < 0.05), but there were no significant differences before and after operation in group A with non-isthmus nonunion (P >0.05). At the last follow-up, SF-12 PCS and SF-12 MCS in group B were significantly improved compared with those in group A: (45.2 ± 5.8) scores vs. (33.6 ± 4.7) scores and (48.8 ± 6.5) scores vs. (39.4 ± 5.6) scores, and there were statistical difference (P<0.05); SF-12 BPI-S and BPI-I showed obvious relief: (4.6 ± 2.1) scores vs. (6.2 ± 2.5) scores and (5.2 ± 1.9) scores vs. (6.8 ± 2.7) scores, and there were statistical differences (P<0.05); however there were no statistical difference in SF-12 PCS, SF-12 MCS, BPI-S and BPI- I between 2 groups (P>0.05). Conclusions Compared with ERN combined with ABG, ACP combined with ABG can significantly improve the quality of life in patients with dystrophic or atrophic nonunion of femoral shaft after intramedullary nailing. It has greater advantage on the improvement of health-related quality of life, especially for patients with non-isthmus nonunion.

Objective To evaluate the clinical efficacy of single ilioinguinal approach combined with screwing for treatment of complex acetabular fractures.Methods Twenty-six patients with complex acetabular fracture were treated by single ilioinguinal approach combined with screwing from May 2015 to April 2017 at Department of Orthopaedics,Hospital of Traditional Chinese Medicine,Xinjiang Medical University.They were 17 men and 9 women,aged from 31 to 69 years (average,54 years).By the Judet-Letournel classification,there were 9 anterior + posterior hemitransverse fractures,13 double-column fractures and 4 T-type fractures.They were treated by pilot surgical plan based on preoperative CT reconstruction,disinfection at floating position for the standby posterior approach,single ilioinguinal approach for standard reduction,followed by intraoperative fixation with lag screws,posterior column screws,or acetabular screws.Operation time,intraoperative blood loss and complications were documented.Fracture reduction was assessed postoperatively using the modified Matta system for X-rays.The function of affected hip was evaluated using Harris hip score at the last Follow-ups.Results The 26 patients were followed up for 6 to 24 months (average,11 months).Their operation time averaged 210 min and intraoperative blood loss 600 mL.The postoperative modified Matta scores showed that 14 cases obtained excellent anatomic reduction,9 good anatomic reduction,one poor anatomic reduction,and 2 articular outline reduction.Fracture union was achieved in all after an average time of 2.3 months.Their Harris hip scores at the last Follow-ups ranged from 70 to 86 points,averaging 80 points.The function of affected hip was excellent in 13 cases,good in 6,fair in 4 and poor in 3,giving an excellent to good rate of 73.1％ (19/26).Postoperatively,deep venous thrombosis of lower extremity was found in 3 patients,injury to the lateral femoral cutaneous nerve in 5,and incision complication in one.No re-displacement of the fracture occurred.Conclusion In treatment of complex acetabular fractures,single ilioinguinal approach combined with screwing can lead to a high rate of fine reduction,limited complications,a low displacement risk,and good clinical efficacy.