Objective To systematically summarize the published literature on the genetic variants associated with nonalcoholic fatty liver disease(NAFLD). Methods Literature from Web of Science,PubMed,and Embase between January 1980 and September 2022 was systematically searched.Meta-analyses of the genetic variants were conducted using at least five data sources.The epidemiologic credibility of the significant associations was graded using the Venice criteria. Results Based on literature screening,399 eligible studies were included,comprising 381 candidate gene association,16 genome-wide association,and 2 whole-exome sequencing studies.We identified 465 genetic variants in 173 genes in candidate gene association studies,and 25 genetic variants in 17 genes were included in the meta-analysis.The meta-analysis identified 11 variants in 10 genes that were significantly associated with NAFLD,with cumulative epidemiological evidence of an association graded as strong for two variants in two genes(HFE,TNF),moderate for four variants in three genes(TM6SF2,GCKR,and ADIPOQ),and weak for five variants in five genes(MBOAT7,PEMT,PNPLA3,LEPR,and MTHFR). Conclusion This study identified six variants in five genes that had moderate to strong evidence of an association with NAFLD,which may help understand the genetic architecture of NAFLD risk.

Objective:To establish a high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of voliconazole (VRC), posaconazole (PCZ), and linazolam (LNZ) in human serum.Methods:This study is a methodological validation by LC-MS/MS. The blood concentration results of VRC, PCZ, and LNZ in our hospital′s anti-infection patients were collected. Voriconazole, Posaconazole, and Linezolid were accurately weighed and prepared. Linezolid-[2H3] was used as the internal standard. After gradient elution on the ACE PFP column, the residuals were analyzed by LC-MS/MS in the positive electrospray ionization mode and multiple reaction monitor (MRM) mode. The method′s linearity, precision, lower limit of detection, and recovery rate were validated according to standard guidelines.Results:The linear correlation coefficient ( r) of the standard curve was above 0.99 ( r>0.99). The linear range of VRC and PCZ were 0.10 mg/L~10.00 mg/L, and the lower limit of detection were 0.01 mg/L. The linear range of LNZ was 0.50 mg/L~50.00 mg/L, and the lower limit of detection was 0.05 mg/L. The recoveries of VRC, PCZ and LNZ were 90.96%-103.18%, 91.84%-99.17%, and 97.04%-100.41%, respectively. Intra-and inter-batch precision (% CV) for VRC were less than 8.30%. Intra-and inter-batch precision (% CV) for PCZ was less than 9.78%. Intra-and inter-batch precision (% CV) for LNZ was less than 7.14%. Drug concentrations in 155 cases of VRC, 44 cases of PCZ, and 59 cases of LNZ were detected. Conclusion:We have established an LC-MS/MS method for the rapid, accurate, highly specific determination of VRC, PCZ, and LNZ concentrations in human serum. This method is suitable for analyzing large clinical sample sets.

  Objective  To understand the current status of surgical treatment for hemophilia osteoarthropathy (HO) in China.  Methods  Using an online questionnaire, select domestic hospitals that partici-pated in the compilation of the 'Guideline for perioperative management of hemophilia patients undergoing orthopaedic surgery in China ', in addition to members of the National Joint Surgery Group, and the Orthopedic Branch of the Chinese Medical Association for targeted investigation and analysis.  Results  A total of 17 domestic hospitals were included, all of which were general hospitals. Hospitals that started HO surgery treatment before 2000 accounted for 35.29%. A total of 3057 surgical cases of HO were reported by those hospitals. The most commonly performed surgical procedures were hip and knee joint replacement. The most commonly used coagulation factor replacement regimen was recombinant coagulation factor preparation. Ten hospitals reported finding patients with transfusion-related infectious diseases. Bleeding and hematoma formation were the most frequently reported surgical complications. Excessive length of hospital stay and high economic costs were the most frequently reported problems.  Conclusions  Surgical treatment for HO in 17 hospitals is mainly carried out in some large comprehensive medical centers in the eastern region. Compared with the patient base, the popularity and number of surgeries are still relatively insufficient. It is necessary to further standardize the treatment system by standardizing factor replacement and strengthening rehabilitation to improve surgical treatment outcomes.

The limited coverage of soft tissue and complex biomechanical factors make resection and reconstruction of distal tibial tumors extremely challenging. Megaprosthesis can provide good mechanical strength for tumor en bloc resection, but there are many postoperative complications, and the problems of insufficient soft tissue coverage and postoperative ankle instability must be solved. The development of three-dimensional digital technology may provide a new treatment strategy for distal tibial reconstruction. Compared to ankle joint preservation endoprostheses, the rapid osseointegration effect of three dimensional-printed megaprosthesis with ankle arthrodesis provides better ankle joint stability and postoperative function. In addition, the three dimensional-printed megaprosthesis may improve complications such as insufficient soft tissue coverage and talus collapse by reducing the circumference of the prosthesis and matching it with the talus through personalized design. Of course, there are few research reports on distal tibial prostheses, and the safety of three dimensional-printed megaprosthesis with ankle arthrodesis needs to be confirmed through extensive long-term follow-up studies. The selection of proximal and distal fixation methods for prostheses needs to be explored in future research.

The limited coverage of soft tissue and complex biomechanical factors make resection and reconstruction of distal tibial tumors extremely challenging. Megaprosthesis can provide good mechanical strength for tumor en bloc resection, but there are many postoperative complications, and the problems of insufficient soft tissue coverage and postoperative ankle instability must be solved. The development of three-dimensional digital technology may provide a new treatment strategy for distal tibial reconstruction. Compared to ankle joint preservation endoprostheses, the rapid osseointegration effect of three dimensional-printed megaprosthesis with ankle arthrodesis provides better ankle joint stability and postoperative function. In addition, the three dimensional-printed megaprosthesis may improve complications such as insufficient soft tissue coverage and talus collapse by reducing the circumference of the prosthesis and matching it with the talus through personalized design. Of course, there are few research reports on distal tibial prostheses, and the safety of three dimensional-printed megaprosthesis with ankle arthrodesis needs to be confirmed through extensive long-term follow-up studies. The selection of proximal and distal fixation methods for prostheses needs to be explored in future research.

Objective To investigate a reasonable threshold of total bilirubin for the diagnosis of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), and to realize accurate early diagnosis. Methods A retrospective analysis was performed for the clinical data of 1232 patients with HBV-ACLF who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from September 2008 to September 2018, and according to the baseline serum level of total bilirubin (TBil), the patients were divided into group A (TBil < 205.2 μmol/L) and group B (TBil ≥205.2 μmol/L). the two groups were compared in terms of clinical features and 28-day, 90-day, 1-year, and 3-year survival. The t -test or the Mann-Whitney U rank sum test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to analyze survival rate, and the log-rank test was used for comparison. Results There were significant differences between the two groups in age( t =3.188, P =0.001) male sex( χ 2 =33.833, P < 0.001), liver failure classification( χ 2 =39.987, P < 0.001), white blood cell count( Z =6.586, P < 0.001), hemoglobin( Z =4.272, P < 0.001), platelet count( Z =3.680, P < 0.001), creatinine( Z =4.505, P < 0.001), total cholesterol( Z =8.644, P < 0.001), Na( Z =2.335, P =0.020), albumin( Z =2.592, P =0.010), HBV DNA( Z =3.703, P < 0.001), Model for End-Stage Liver Disease score( Z =11.828, P < 0.001), and MELD-Na score( Z =8.410, P < 0.001). At baseline, there were significant differences in the incidence rates of ascites and gastrointestinal bleeding between the two groups ( χ 2 =12.036、4.342, P < 0.05). Infection was the most common new-onset complication within 28 days, followed by hepatic encephalopathy, and there was a significant difference in the incidence rate of infection between the two groups ( χ 2 =5.294, P < 0.05). The 28-day transplant-free mortality rate was 21.2% in group A and 29.5% in group B( HR =1.473[95% CI : 1.151~1.886], P =0.005), which was consistent with the clinical feature of a high short-term mortality rate (> 15%) in patients with acute-on-chronic liver failure (ACLF). Although there was a difference in long-term mortality rate between the two groups, there was no significant increase in transplant-free mortality rate after 90 days in either group. Conclusion Under the premise of international normalized ratio ≥1.5, it is not recommended to increase the threshold of TBil to 205.2 μmol/L in the diagnostic criteria for HBV-ACLF, so as to ensure the early diagnosis of more ACLF patients and bring more opportunities for treatment and cure.

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Objective To evaluate the effect of Lejours' procedure in the treatment of breast prolapse.Methods From July 2014 to July 2018,the Second People's Hospital of Guangdong Prov ince accepted 36 female patients with breast prolapse and correction failure,aged 25 42 years,with an average age of 32.1 years.According to the preoperative design,the pedicel epidermis,the redundant skin,the prosthesis and capsule were removed,and the mammary flap was fixed on the fascia of pectoralis major muscle,and the nipple and areola were fixed and sutured layer by layer.Results In 36 cases,the shape of breast was improved,the scar of incision was smaller,and the color of scar became lighter with time.There were no serious complications such as nipple and areola necrosis.The breast was straight and round after operation.After 6-24 months follow-up,one patient had delayed wound healing and received repeated dressing changes for 7 days.Conclusions The design of the op eration is simple,with little scar,few complications and good long term effect.The shape of the breast after repair is round and straight,which can be used as one of the feasible operation methods for the repair of breast ptosis.

Prostate cancer (PCa) patients who progress to metastatic castration-resistant PCa (mCRPC) mostly have poor outcomes due to the lack of effective therapies. Our recent study established the orphan nuclear receptor ROR

BACKGROUND: Specific bone-targeting drug delivery system is very important in the treatment of bone-related diseases. Development of nanotechnology provides a good platform and a new thought for preparation of specific bone-targeting nanoscale drug delivery system. OBJECTIVE: To review the current development and future prospects of specific bone-targeting drug delivery systems. METHODS: A computer-based online search of PubMed, Web of Science, and Medline databases was performed to retrieve studies regarding active targeting drug delivery system and nanoscale drug delivery system published between March 2014 and March 2019 with the search terms “Bone target therapy, Nanoparticles, Drug delivery system”. RESULTS AND CONCLUSION: The targeting group is an important component of the specific bone-targeting drug delivery system and it determines the targeting efficiency of the drug delivery system. Targeting bone tissue, osteoblasts, osteoblasts, and bone marrow mesenchymal stem cells have their own advantages and disadvantages. Specific bone-targeting nanoscale drug delivery systems have been widely used in various bone diseases, such as metastatic osteoporosis, osteomyelitis, multiple myeloma, osteosarcoma, and bone metastases. Specific bone-targeting drug delivery systems have advantages and challenges. Although many basic studies have shown good results of specific bone-targeting drug delivery systems in vivo, little is reported on successful clinical transformation of bone-targeting groups-modified nanoscale drug delivery systems.