BACKGROUND:Currently,there have been studies on the regulatory mechanism of lncRNA\miRNA\mRNA co-expression network on the occurrence and development of osteoarthritis.Our research group has screened qualified NONHSAT248596.1 and miR-146a-5p through the database in the previous stage,but the corresponding in vivo experiments to verify the above regulatory mechanisms are still lacking. OBJECTIVE:To explore the role of NONHSAT248596.1 in regulating competitive endogenous RNA of miR-146a-5p in cartilage degeneration mediated by stromal cell derived factor type 1/chemokine receptor 4 axis in vivo. METHODS:The models of osteoarthritis were established in 36 New Zealand rabbits by injecting stromal cell derived factor 1 solution into the knee joint of the right hind limb.According to the random number table method,they were divided into four groups.lncRNA group,miRNA group,ceRNA group and control group were injected with lentivirus vector overexpressing NONHSAT248596.1,lentivirus vector overexpressing miR-146a-5p,lentivirus vector overexpressing miR-146a-5p+NONHSAT248596.1 and empty lentivirus vector into the molded knee joint,respectively.At 4,8 and 12 weeks of modeling,cartilage tissues and subchondral bone tissues of the knee joint were taken for relevant detection. RESULTS AND CONCLUSION:Hematoxylin-eosin staining and safranin fast green staining showed different degrees of degeneration in the four groups.At 4 weeks,the cartilage tissue of the lncRNA group showed swelling of chondrocytes,loss of cell polarity,destruction of extracellular matrix,surface erosion,fracture formation and partial or full layer loss of cartilage tissue.The degree of cartilage injury was gradually aggravated with time.The progression of articular cartilage inflammation in the miRNA group was the slowest among the four groups.qRT-PCR showed that at the same time point,mRNA expression levels of NONHSAT248596.1,chemokine receptor 4,matrix metalloproteinase 3,matrix metalloproteinase 9 and matrix metalloproteinase 13 in cartilage tissue of the lncRNA group were higher than those of the other three groups(P＜0.05).The mRNA expression levels of miR-146a-5p,aggrecan and type Ⅱ collagen were lower than those of the other three groups(P＜0.05).The mRNA expression levels of NONHSAT248596.1,chemokine receptor 4,matrix metalloproteinase 3,matrix metalloproteinase 9 and matrix metalloproteinase 13 in the miRNA group were lower than those in the ceRNA group and control group at 8 and 12 weeks after the model construction(P＜0.05).The mRNA expressions of miR-146a-5p,aggrecan and type Ⅱ collagen were higher than those of the ceRNA group and control group(P＜0.05).Western blot assay showed that at the same time point,the expression levels of aggrecan and type Ⅱ collagen in cartilage tissue of the lncRNA group were always lower than those of the other three groups(P＜0.05).The expression levels of aggrecan and type Ⅱ collagen in cartilage tissue of the miRNA group at 8 and 12 weeks after modeling were higher than those of the ceRNA group and control group(P＜0.05).The results showed that miR-146a-5p,as the target of NONHSAT248596.1,could be inhibited by the effect of its ceRNA.After acting on miR-146a-5p,NONHSAT248596.1 regulates the stromal cell derived factor type 1/chemokine receptor 4 axis to affect the expression of matrix metalloprotein,type Ⅱ collagen,and aggrecan in osteoarthritis chondrocytes,resulting in the degradation of extracellular matrix and the loss of proteoglycan.

The purpose of this study was to explore transrectal ultrasound (TRUS) findings of prostate cancer (PCa) guided by multiparametric magnetic resonance imaging (mpMRI) and to improve the Prostate Imaging Reporting and Data System (PI-RADS) system for avoiding unnecessary mpMRI-guided targeted biopsy (TB). From January 2018 to October 2019, fusion mpMRI and TRUS-guided biopsies were performed in 162 consecutive patients. The study included 188 suspicious lesions on mpMRI in 156 patients, all of whom underwent mpMRI-TRUS fusion imaging-guided TB and 12-core transperineal systematic biopsy (SB). Univariate analyses were performed to investigate the relationship between TRUS features and PCa. Then, logistic regression analysis with generalized estimating equations was performed to determine the independent predictors of PCa and obtain the fitted probability of PCa. The detection rates of PCa based on TB alone, SB alone, and combined SB and TB were 55.9% (105 of 188), 52.6% (82 of 156), and 62.8% (98 of 156), respectively. The significant predictors of PCa on TRUS were hypoechogenicity (odds ratio [OR]: 9.595, P = 0.002), taller-than-wide shape (OR: 3.539, P = 0.022), asymmetric vascular structures (OR: 3.728, P = 0.031), close proximity to capsule (OR: 3.473, P = 0.040), and irregular margins (OR: 3.843, P = 0.041). We propose subgrouping PI-RADS score 3 into categories 3a, 3b, 3c, and 3d based on different numbers of TRUS predictors, as the creation of PI-RADS 3a (no suspicious ultrasound features) could avoid 16.7% of mpMRI-guided TBs. Risk stratification of PCa with mpMRI-TRUS fusion imaging-directed ultrasound features could avoid unnecessary mpMRI-TBs.
Male ; Humans ; Prostatic Neoplasms/pathology* ; Multiparametric Magnetic Resonance Imaging ; Magnetic Resonance Imaging/methods* ; Prostate/pathology* ; Image-Guided Biopsy/methods*

Although there is guidance from different regulatory agencies, there are opportunities to bring greater consistency and stronger applicability to address the practical issues of establishing and operating a data monitoring committee (DMC) for clinical studies of Chinese medicine. We names it as a Chinese Medicine Data Monitoring Committee (CMDMC). A panel composed of clinical and statistical experts shared their experience and thoughts on the important aspects of CMDMCs. Subsequently, a community standard on CMDMCs (T/CACM 1323-2019) was issued by the China Association of Chinese Medicine on September 12, 2019. This paper summarizes the key content of this standard to help the sponsors of clinical studies establish and operate CMDMCs, which will further develop the scientific integrity and quality of clinical studies.

Anemia, Hemolytic, Congenital ; Humans ; Ion Channels/genetics* ; Mutation

BACKGROUNDDecoy receptor 3 (DcR3) is a protein with anti-apoptotic effect that belongs to the tumor necrosis factor receptor superfamily. DcR3 is highly expressed in a variety of malignant tumors including cholangiocarcinoma and its expression was found to be related to the clinical stage, the invasion, and the metastasis of the tumor. This in vitro study aimed to investigate the effect of downregulated expression of DcR3 on cell viability, cell apoptosis, and cell cycle in cholangiocarcinoma cell line TFK-1.

METHODSThree different cell lines were cultured: human cholangiocarcinoma TFK-1, human biliary epithelial carcinoma HuCCT-1, and human cholangiocarcinoma RBE. The cholangiocarcinoma cell line with the highest expression of DcR3 was selected for further investigation. The expression of DcR3 was silenced/knocked down by transfection with DcR3-siRNA in the selected cell line. Various biological phenotype parameters such as cell viability, apoptosis, and cell cycle were observed.

RESULTSThe mRNA and protein levels of DcR3 were measured in the three cell lines, and TFK-1 was selected. After the treatment with DcR3-siRNA for 48 h, DcR3 mRNA and protein expression in the treatment group were 38.45% (P < 0.01) and 48.03% (P < 0.05) of that of the control, respectively. It was found that the cell viability decreased to 61.87% of the control group (P < 0.01) after the downregulation of DcR3 in cholangiocarcinoma cell line TFK-1 by transfection with DcR3-siRNA, while the percentage of apoptotic cells was 2.98 times as compared with the control group (P < 0.05). Compared with the control group the ratio of G0/G1increased, and the ratio of G2/M decreased in the treatment group. However, the differences were not statistically significant.

CONCLUSIONSThe effect of DcR3 on the growth and apoptosis of cholangiocarcinoma has been demonstrated. DcR3 is not only a predictive marker for malignant tumor but it is also likely to be a potential target for cancer gene therapy. Further studies should focus on exploring the binding ligand of DcR3, the signaling pathway involved, and the molecular mechanism for the regulation of DcR3 expression in cholangiocarcinoma.

Objective To observe and analyze the clinical outcomes of perfluoropropane (C3 Fs) injection and laser photocoagulation on myopic foveoschisis.Methods A total of 14 patients (18 eyes) diagnosed as myopic foveoschisis were enrolled in this retrospective study.All patients received intraocular tamponade of 0.5-0.7 mL C3 F8,and after 1 week,underwent macular photocoagulation.These patients were given the best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) examination for central foveal thickness (CFT) and maximal macular thickness (MMT) before and after treatment.Results OCT examination showed that the mean CFT decreased significantly from (494.00 ±454.80) iμm before treatment to (193.61 ± 97.42) μm at the last follow-up,with statistical significance (P =0.01),and the mean MMT decreased from (687.33 ± 385.15)pμn to (331.06 ± 109.31)μm at the same duration,approaching significant difference (P =0.001).The foveoschisis healed completely and partially in 14 eyes at the last follow-up,the mean CFT decreased significantly from (567.36 ±493.01) μm before treatment to (171.43 ± 90.84) μm after treatment,with statistical significance (P =0.006),and the mean MMT decreased from (744.14 ± 417.38)μm to (303.86 ± 8.62)prn at the same duration,approaching significant difference (P =0.002).Patients' BCVA before treatment was (0.94 ± 0.39) logMAR,of which 13 eyes had BCVA ＜ 0.6 logMAR,and increased to (0.92 ± 0.36) logMAR at the last follow-up,with no significant difference (P =0.78).The foveoschisis healed completely and partially in 14 eyes,and the BCVA was (1.04 ± 0.37) logMAR before treatment,up to (0.90 ± 0.34) logMAR after treatment,and the difference was not statistically significant (P =0.16).At the last follow-up,the vision of 4 eyes was increased by 2 lines and above,and unchanged in 10 eyes.All patients had no visual symptoms such as dark spots and no increase in intraocular pressure after treatment.Conclusion Intraocular C3 F8 tamponade and macular photocoagulation can be an satisfying alternative treatment for patients with myopic foveoschisis.

OBJECTIVELaparoscopic colorectal surgery is a skill-dependent procedure. The present study aims to analyze the learning curve of a properly trained surgeon, with basic laparoscopic techniques, to become skillful in performing laparoscopic colorectal operations.

METHODSA series of non-selective, consecutive 189 cases of laparoscopic colorectal surgery were accomplished, from December 2009 to February 2012, by one surgeon with years of skilled technique in laparoscopic cholecystectomy, rich experience in assisting laparoscopic colorectal surgery, and experience of approximately 180 procedures of gastric and colorectal surgery annually. 170 out of 189 procedures were radical operations for colorectal neoplasma, including right colectomies in 28 cases, left colectomies in 5 cases, sigmoidectomies in 28 cases, high Dixon procedures in 45 cases, low Dixon (total mesorectal excision, TME) procedures in 41 cases and Miles procedure in 23 cases. 19 other patients underwent combined procedures for multi-primary tumors or inflammatory enteritis. All these procedures were analyzed according to time span (the earlier half and later half) in respect to length of surgery, intraoperative blood loss, number of lymph nodes retrieved, intraoperative events and postoperative complications.

RESULTSFor radical right colectomy, the D2 dissection conducted in the earlier phase (n = 8) had the similar length of surgery, more blood loss and less LN retrieval, compared with the D3 dissection conducted in recent phase (n = 20). The earlier performed high Dixon procedures (n = 22) consumed longer time than the later procedures (n = 23) consumed, but with similar blood loss and LN retrieval. Low Dixon (TME) procedures showed significant differences in length of surgery and blood loss relative to time span. Recently performed simoidectomy and Miles procedures showed a trend of shorter time consumed compared with earlier performed procedures. Conversion ratio to open surgery was 1.05%. Adverse effects occurred in 8 cases of surgeries, including intestinal injury (3/189), insufficient distal margin (2/189), intraoperative bleeding (2/189) and vaginal injury (1/76). There was no operative death. Chief complications included urinary retention 5.82%, ileus 4.76%, anastomotic leak 4.24%, perineal infection 23.08% (6/26), wound dehiscence 2.65%, gastrointestinal bleeding 1.59%, peritoneal infection 1.06%. Surgery for distal rectum tended to have more complications, such as urinary retention, anastomotic leak and perineal infection. The later performed low Dixon procedures produced insignificantly fewer anastomotic leaks than those in the earlier phase.

CONCLUSIONSFor a trained surgeon with basic laparoscopic techniques, there are at least 15 - 25 cases of different procedures needed for him/her to become skilled to perform laparoscopic surgery. The learning curve should also depend on the annual number of colorectal surgeries.

Aged ; Colonic Diseases ; surgery ; Colorectal Neoplasms ; surgery ; Colorectal Surgery ; methods ; Female ; Humans ; Laparoscopy ; methods ; Learning Curve ; Male ; Middle Aged ; Postoperative Complications ; epidemiology ; Treatment Outcome

OBJECTIVETo determine the prevalence of urolithiasis in young children fed infant formula (IF) contaminated with melamine, and the association between IF consumption and urolithiasis.

DESIGNA total of 2 733 children < or = 3 years of age on September 1, 2008 in two townships of Gansu Province, China were studied. Cases of urolithiasis were diagnosed by ultrasonography. Milk product consumption was determined by their caregivers. Remaining IF samples were tested for melamine and cyanuric acid.

RESULTSOf 2 733 eligible children in the two townships, 2 186 (80%) were enrolled in our study. Overall, 16.6% (362) of 2 186 children had urolithiasis. The prevalence was 24.6% in children exclusively fed Sanlu brand IF, 9.7% in those fed other IF, and 8.5% in those fed exclusively on other milk products. For children exclusively breast-fed, no urolithiasis was found (P < 0.05). The prevalence of urolithiasis was 11.4% in children fed 400 g of Sanlu IF, rising to 37.5% in children fed over 25 600 g. Of 48 Sanlu IF samples, 91.7% contained melamine (median = 1 800 ppm; range = 45-4 700) and 66.7% contained cyanuric acid (median = 1.2 ppm; range = 0.4-6.3). Melamine was also detected in 22.2% of 36 other brand IF (median = 27.5 ppm, range = 4-50).

CONCLUSIONSUrolithiasis was associated with melamine-contaminated IF. Although one product caused most morbidity, other milk products may have also contributed to the outbreak.

Child, Preschool ; Data Collection ; Food Contamination ; Humans ; Infant Food ; analysis ; Triazines ; toxicity ; Urolithiasis ; chemically induced

OBJECTIVETo evaluate the ASES, Constant and HSS score systems and their significance on postoperative function of the shoulder.

METHODSTotally 172 cases of proximal humeral fracture of five affiliated hospital from September 2004 to September 2008 were analyzed. All the functional outcome of the involved shoulder were evaluated by ASES, Constant, HSS score and patient self score. The correlations and agreement of three shoulder scales were analyzed with Pearson correlation test and Bland-Altman plot in different age groups and fracture types.

RESULTS(1) The Constant score were lower than other two scores in the same age group and fracture type (F = 13.62 and 4.80, P < 0.05). (2) The correlations between three shoulder scales: ASES and Constant (r = 0.754, P = 0.0003), ASES and HSS (r = 0.755, P = 0.0001), Constant and HSS (r = 0.858, P = 0.0002). The correlations between three shoulder scales and patient self evaluation: ASES (r = 0.602, P = 0.0002), Constant (r = 0.705, P = 0.0001), HSS (r = 0.663, P = 0.0037). The Bland-Altman plot shows three shoulder scales have good agreement. (3)The correlation between Constant score and patient self evaluation decreased in the elder group and severe fracture type.

CONCLUSIONSASES, Constant, HSS shoulder score systems are all fit to evaluate the functional outcome of the shoulder, they have good correlation and agreement. Constant score in recommended for its high correlation coefficient with patient self evaluation score. However, its age bias must be paid attention in clinical practice. ASES shoulder score can be used in remote follow-up.

Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Postoperative Period ; Retrospective Studies ; Shoulder Fractures ; physiopathology ; surgery ; Shoulder Joint ; physiopathology ; Trauma Severity Indices ; Young Adult