OBJECTIVE: To explore clinical effect of arthroscopy-assisted rotator cuff tendon transfer in treating irreparable rotator cuff tears (IRCT). METHODS: From May 2015 to May 2018, 23 patients with unrepairable rotator cuff tears were treated with arthroscopy-assisted rotator cuff tendon transfer, and 21 patients were followed up finally, including 8 males and 13 females, aged from 48 to 82 years old with an average of(64.3±9.1) years old;the courses of disease ranged from 6 to 36 months with an average of (14.0±6.4) months. American Rotator and Elbow Surgeons Score(ASES) and Constant-Murley score were used to evaluate clinical efficacy before surgery and at the latest follow-up. RESULTS: All 21 patients were followed up for 36 to 54 months with an average of (39.4±4.4) months. Axillary incision of 1 patient was redness, swelling and exudation after surgery, which healed after 3 weeks of dressing change, and exudate culture was negative. At the latest follow-up, MRI showed partial tearing of the metastatic tendon in 2 patients, but pain and movement of the affected shoulder were still better than before surgery. ASES increased from preoperative (41.0±9.6) scores to the latest follow-up (75.6±14.0) scores, and had statistical difference (t=10.50, P<0.01). Constant-Murley score increased from (49.8±7.1) scores before operation to (67.5±11.6) scores at the latest follow-up (t=11.27, P<0.01). CONCLUSION Arthroscopic assisted latissimus dorsalis tendon transposition restores physiological and anatomical structure of glenohumeral joint by reconstructing balance of horizontal and vertical couples of shoulder joint, thus achieving the stability of the shoulder joint, relieving shoulder pain and improving shoulder joint function.
Male ; Female ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Rotator Cuff Injuries/surgery* ; Superficial Back Muscles ; Rotator Cuff ; Treatment Outcome ; Shoulder Joint/surgery* ; Tendon Transfer ; Arthroscopy ; Range of Motion, Articular/physiology*

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.

Objective: To identify the internal nasal valve (INV) and to evaluate its key parameters in the established 3D models of nasal cavity space via Mimics from CT images, in order to provide evidence for quantitative diagnosis of nasal valve compromise. Methods: A total of 32 Han adults without nasal diseases who underwent maxillofacial CT test in Shanghai Ninth People's Hospital from January 2015 to December 2018 were retrospectively recruited, including 16 males and 16 females, with the age ranged from 20 to 80 years (50% age<50 years old). Maxillofacial CT images were used to create 3D model of nasal cavity space. The INV was identified and the following parameters were measured: the angle between the INV and the nasal bone (θ_INV-B), unilateral cross-sectional area of the INV (A_INV-R, A_INV-L), total cross-sectional area of the INV (A_INV), unilateral height of the INV (H_INV-R, H_INV-L), unilateral nasal valve angle (α_INV-R, α_INV-L), and the sum of nasal valve angle (α_INV). The A_INV in our study was compared with the results of the previously adopted planes (Plane_C, perpendicular to the hard palate and Plane_B, plane perpendicular to the nasal bone). The parameters above were compared among genders, age and race groups. SPSS 26 and GraphPad Prism 9 software were used for statistical analysis and mapping of data. Results: The A_INV in our study was (214.87±52.94) mm², which was significantly less than that of Plane_C (254.97±47.80) mm² and Plane_B (226.07±57.36) mm². The measured parameters were as follows: θ_INV-B was (82.07±7.06)°; A_INV-R was (112.66±31.39) mm²; A_INV-L was (102.21±27.14) mm²; A_INV was (214.87±52.94) mm²; H_INV-R was (24.87±4.62) mm; H_INV-L was (24.35±4.86) mm; α_INV-R was (20.48±2.99)°; α_INV-L was (19.65±3.82)°; α_INV was (40.13±6.24)°. The A_INV-R was larger than A_INV-L (t=2.33, P<0.05); The H_INV, A_INV-R, A_INV-L and A_INV of males were more than those of females (t value was 5.77, 3.21, 2.91 and 3.52, respectively, all P<0.01). The A_INV of the young group (<50 years) was larger than that of the old group (t=2.83, P<0.01); The θ_INV-B was different between the Han people and the Caucasian (t=2.92,P<0.01). The α_INV of the Han people was larger than that of Caucasians (Z=-6.92, P<0.01), but the H_INV was smaller (Z=-3.89, P<0.01). Conclusion: The A_INV carried out in 3D models of nasal cavity space is significantly smaller than that obtained by the previous methods of CT evaluation. INV static parameters differ among genders, age and race groups.
Adult ; Female ; Humans ; Male ; Young Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Nasal Cavity/diagnostic imaging* ; Retrospective Studies ; China ; Nose ; Nasal Bone

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.
Humans ; Anti-Bacterial Agents/therapeutic use* ; China ; Drug Monitoring/methods* ; Polymyxin B ; Practice Guidelines as Topic

Chemical investigation of the culture extract of an endophytic Penicillium citrinum from Dendrobium officinale, afforded nine citrinin derivatives (1-9) and one peptide-polyketide hybrid GKK1032B (10). The structures of these compounds were determined by spectroscopic methods. The absolute configurations of 1 and 2 were determined for the first time by calculation of electronic circular dichroism (ECD) data. Among them, GKK1032B (10) showed significant cytotoxicity against human osteosarcoma cell line MG63 with an IC₅₀ value of 3.49 μmol·L^-1, and a primary mechanistic study revealed that it induced the apoptosis of MG63 cellsvia caspase pathway activation.
Apoptosis ; Bone Neoplasms ; Caspases ; Humans ; Osteosarcoma/drug therapy* ; Penicillium

LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
Animals ; Cell Differentiation ; Embryo, Mammalian/metabolism* ; Embryonic Development ; Mice ; Pluripotent Stem Cells/metabolism* ; RNA, Messenger/genetics* ; RNA, Ribosomal ; RNA-Binding Proteins/metabolism* ; Transcription Factors/metabolism* ; Zygote/metabolism*

Aortic Valve/surgery* ; Aortic Valve Stenosis/surgery* ; China/epidemiology* ; Heart Valve Prosthesis Implantation ; Humans ; Severity of Illness Index ; Treatment Outcome

Animals ; Diabetes Mellitus, Experimental/drug therapy* ; Fibrosis/prevention & control* ; Hyperglycemia/prevention & control* ; Hypoglycemic Agents/pharmacology* ; Inflammation/prevention & control* ; Male ; Rats ; Rats, Sprague-Dawley ; Stilbenes/pharmacology*

BACKGROUND: Psoriasis is a chronic inflammatory skin disease, affecting about 0.6% of the Chinese population. Many patients are not well controlled by conventional treatments, thus there is need for new treatment regimens. In this study, we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis. METHODS: This study was a 52-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 trial. A sub-population of study participants (≥18 years) of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab, or placebo. The co-primary endpoints were psoriasis area severity index (PASI) 75 and Investigator's Global Assessment (IGA) 0/1 at Week 12. RESULTS: A total of 441 Chinese patients were enrolled in this study. Co-primary outcomes were achieved; 300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75 (97.7% and 87.2% vs. 3.7%, respectively; P < 0.001), and IGA 0/1 (82.3% and 69.7% vs. 2.7%; P < 0.001) at Week 12. Treatment efficacy was maintained until Week 52. There was no increase in overall adverse events with secukinumab relative to placebo throughout the 52-week period. CONCLUSION: Secukinumab is highly effective and well tolerated in Chinese patients with moderate to severe plaque psoriasis. TRIAL REGISTRATION ClinicalTrials.gov, NCT03066609; https://clinicaltrials.gov/ct2/show/record/NCT03066609.
Antibodies, Monoclonal/therapeutic use* ; Antibodies, Monoclonal, Humanized ; China ; Double-Blind Method ; Humans ; Psoriasis/drug therapy* ; Severity of Illness Index ; Treatment Outcome

Objective: To investigate the incidence of postoperative pancreatic fistula (POPF) and its risk factors after radical gastrectomy. Methods: The prospective study was conducted. The clinicopathological data of 2 089 patients who underwent radical gastrectomy in 22 medical centers between December 2017 and November 2018 were collected, including 380 in the Zhongshan Hospital of Fudan University, 351 in the Renji Hospital of Shanghai Jiaotong University School of Medicine, 130 in the Ruijin Hospital of Shanghai Jiaotong University School of Medicine, 139 in the Peking University Cancer Hospital, 128 in the Fujian Provincial Cancer Hospital, 114 in the First Hospital Affiliated to Army Medical University, 104 in the First Affiliated Hospital of Nanchang University, 104 in the Affiliated Hospital of Qinghai University, 103 in the Weifang People′s Hospital, 102 in the Fujian Medical University Union Hospital, 99 in the First Affiliated Hospital of Air Force Medical University, 97 in the Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine, 60 in the Hangzhou First People′s Hospital Affiliated to Zhejiang University School of Medicine, 48 in the Fudan University Shanghai Cancer Center, 29 in the First Affiliated Hospital of Xi′an Jiaotong University, 26 in the Lishui Municipal Central Hospital, 26 in the Guangdong Provincial People′s Hospital, 23 in the Jiangsu Province Hospital, 13 in the First Affiliated Hospital of Sun Yat-Sen University, 7 in the Second Hospital of Jilin University, 4 in the First Affiliated Hospital of Xinjiang Medical University, 2 in the Beijing Chao-Yang Hospital of Capital Medical University. Observation indicators: (1) the incidence of POPF after radical gastrectomy; (2) treatment of grade B POPF after radical gastrectomy; (3) analysis of clinicopathological data; (4) analysis of surgical data; (5) risk factors for grade B POPF after radical gastrectomy. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was analyzed using ANOVA. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Univariate analysis was conducted using the t test or chi-square test based on data excluding missing data of clinico-pathological and surgical data. Multivariate analysis was conducted using the Logistic regression model based on factors with P<0.20 in univariate analysis. Results: There were 2 089 patients screened for eligibility, including 1 512 males, 576 females and 1 without sex information, aged (62±11)years. The body mass index (BMI) was (23±3)kg/m². (1) The incidence of POPF after radical gastrectomy: the total incidence rate of POPF in the 2 089 patients was 20.728%(433/2 089). The incidence rates of biochemical fistula, grade B pancreatic fistula, and grade C pancreatic fistula were 19.627%(410/2 089), 1.101%(23/2 089), 0, respectively. (2) Treatment of grade B POPF after radical gastrectomy: 2 of 23 patients with grade B POPF after radical gastrectomy had drainage tube placed for more than 21 days and received anti-infective therapy. Four of 23 patients with grade B POPF after radical gastrectomy had ascites detected by imaging examination, of which 2 received peritoneal drainage guided by ultrasound, 1 received failed puncture drainage, 1 received no puncture drainage, and they were given anti-infective therapy. Eleven of 23 patients with grade B POPF after radical gastrectomy had no ascites detected by imaging examinations, and they were given anti-infective therapy and inhibitors of pancreas secretion for clinical manifestation as fever or elevated white blood cells. Six patients with no typical clinical manifestations were given somatostatin to inhibite pancreas secretion and prolonged duration of abdominal drainage tube placement (with a median time of 7 days). All the 23 patients recovered well after treatment, without reoperation. (3) Analysis of clinicopathological data: for the 2 089 patients, BMI, cases with or without neoadjuvant therapy were (23±3)kg/m^2, 1 487, 160 of patients without pancreatic fistula, (23±3)kg/m^2, 386, 22 of patients with biochemical fistula, and (24±3)kg/m^2, 22, 1 of patents with grade B pancreatic fistula, showing significant differences between the three groups (F=5.787, χ²=8.269, P<0.05). (4) Analysis of surgical data: for the 2 089 patients, cases with open surgery, laparoscopic assisted surgery, totally laparoscopic surgery (surgical method), cases with D₁ lymph lode dissection, D₂ lymph lode dissection, and other lymph lode dissection (range of lymph lode dissection), cases with no omentectomy, partial omentectomy, and total omentectomy (range of omentectomy), cases with no usage of energy facility, usage of CUSA, LigaSure, LigaSure+ CUSA as energy facility, cases with or without biological glue, the number of lymph node dissection were 737, 624, 292, 24, 1 580, 51, 418, 834, 381, 63, 1 530, 23, 16, 1 431, 201, 33±14 of patients without pancreatic fistula, 146, 189, 74, 11, 389, 9, 110, 171, 128, 35, 359, 6, 9, 378, 31, 31±14 of patients with biochemical fistula, and 14, 5, 4, 0, 20, 3, 6, 13, 4, 2, 18, 1, 2, 22, 1, 37±16 of patients with grade B pancreatic fistula, showing significant differences between the three groups (χ²=15.578, 9.397, 15.023, 28.245, 8.359, F=4.945, P<0.05). (5) Risk factors for grade B POPF after radical gastrectomy: results of univariate analysis showed that usage of energy facility was a related factor for grade B POPF after radical gastrectomy (χ²=9.914, P<0.05). Results of multivariate analysis showed that laparoscopic assisted surgery, combined evisceration, application of LigaSure + CUSA, the number of lymph lode dissection were independent factors for for grade B POPF after radical gastrectomy (odds ratio=0.168, 3.922, 9.250, 1.030, 95% confidence interval: 0.036-0.789, 1.031-14.919, 1.036-82.602, 1.001-1.059, P<0.05). Conclusions The incidence of grade B POPF after radical gastrectomy is relatively low. Laparoscopic assisted surgery, combined evisceration, application of LigaSure + CUSA, and the number of lymph lode dissection are independent risk factors for grade B POPF. Trial Registration: This study was registrated at ClinicalTrial.gov in United States with the registration number of NCT03391687.