[Clinical management of thrombocytopenia in cirrhosis].

Thrombocytopenia is one of the common complications of cirrhotic patients, which can induce an increasing bleeding risk and closely correlate with bleeding following invasive procedures. Consequently, how to respond to thrombocytopenia is crucial for improving the prognosis of patients with cirrhosis. This article reviews the main mechanisms of cirrhosis concurrent with thrombocytopenia, as well as the corresponding clinical management strategies.

[Epidemiology, clinical characteristics and treatment in 278 patients with coronavirus disease 2019 in Guangzhou].

Objective: To retrospective analyze the epidemiology, clinical characteristics, treatment and prognosis in patients with coronavirus disease 2019 (COVID-19). Methods: A total of 278 patients with COVID-19 admitted to Guangzhou Eighth People's Hospital from January 20 to February 10, 2020 were selected. The general demographic data, epidemiological data, clinical symptoms, laboratory examinations, lung CT imaging, treatment and prognosis were analyzed. Results: There were 130 male patients (46.8%) and 148 females (53.2%) with age (48.1±17.0) years and 88.8% patients between 20-69 years. Two hundred and thirty-six (84.9%) patients had comorbidities. Two hundred and eleven cases (75.9%) were common type. The in-hospital mortality was 0.4% (1/278). The majority (201, 72.3%) were imported cases mainly from Wuhan (89, 44.3%). The most common clinical manifestations were fever (70.9%) and dry cough (61.5%). In some patients, hemoglobin (10.4%), platelets (12.6%) and albumin (55.4%) were lower than the normal range. Other biochemical tests according to liver and function were normal, while lactic dehydrogenase (LDH) was elevated in 61 patients (21.9%), creatine kinase increased in 26 patients (9.4%). Prolonged activated partial thromboplastin time (APTT) was seen in 52 patients (18.7%), D-dimer higher than normal in 140 patients (50.4%), while 117 patients (42.1%) had elevated high-sensitivity C-reactive protein. Typical CT manifestations included single or multiple ground glass shadows especially in lung periphery in early disease which infiltrated and enlarged during progressive stage. Diffuse consolidation with multiple patchy density in severe/critical cases and even "white lung" presented in a few patients. Two hundred and forty-two patients (87.1%) received one or more antiviral agents, 242 (87.1%) combined with antibacterials, 191 (68.7%) with oxygen therapy. There were 198 patients (71.2%) treated with traditional Chinese medicine. Conclusions: COVID-19 could attack patients in all ages with majority of common type and low mortality rate. Clinical manifestations involve multiple organs or systems. Progression of the disease results in critical status which should be paid much attention.

[Effectiveness and safety of sofosbuvir/velpatasvir combination ± ribavirin in the treatment of Chinese adults with chronic hepatitis C virus infection].

Objective: To understand the effectiveness and safety sofosbuvir/velpatasvir (SOF/VEL) combination ±ribavirin in the treatment of chronic hepatitis C virus (HCV) infection in China. Methods: A total of 96 Chinese adults with chronic HCV infection who were treated with SOF/VEL combination ± ribavirin for 12 weeks between July 2018 and February 2020 were selected. HCV RNA, routine blood test, liver, kidney and coagulation function, abdominal Color Doppler ultrasound or CT and liver stiffness were detected at baseline, 4 weeks of treatment, end of treatment and 12 weeks of follow-up. Adverse events and laboratory abnormalities during the treatment were recorded. A t-test was used to compare the measurement data between the two groups, and the analysis of variance was used for multiple group comparison. Results: A total of 93 cases (96.9%) achieved sustained virological response (SVR12), of which 3 cases had relapsed. 88 cases (91.7%, 88/96) had achieved rapid virological response (RVR). 96 cases (100%) had achieved virological response by the end of treatment (EOT). In patients with decompensated liver cirrhosis, the average baseline Child-Pugh score and Model for End-Stage Liver Disease score was 7.4±1.0, and 11.4±1.7, respectively. Among them, 12 cases of the SOF/VEL combined with RBV treatment had achieved SVR12 (100%) at 12 weeks, while only 3 of the 5 cases of single-tablet regimen of SOF/VEL had achieved SVR12 (60%). There was no significant difference between creatinine levels and baseline during or 12 weeks after treatment. The incidence of adverse events in patients with chronic hepatitis C and compensated cirrhosis was 6.3% (5/79), while that in patients with decompensated cirrhosis was 35.3% (6/17). The most common adverse events were hyperbilirubinemia, fatigue and anemia. There were no serious adverse events, deaths or discontinuation of treatment due to adverse events. Conclusion: SOF/VEL combination ± ribavirin in the treatment of various common genotypes of chronic hepatitis C, compensated cirrhosis, decompensated cirrhosis and hepatocellular carcinoma has higher SVR12 in China, and the tolerance and safety are good.

[Real-world study of paritaprevir/ritonavir-ombitasvir combined with dasabuvir for the treatment of chronic hepatitis C 1b genotype infection in China].

Objective: To evaluate the real-world safety and curative effect of ombitasvir combined with dasabuvir for the treatment of chronic hepatitis C 1b genotype infection in non-cirrhotic or compensated cirrhotic patients. Methods: A real-world research method was adopted, and the research was conducted at three medical centers of mainland China. Non- cirrhotic or compensated cirrhotic patients with HCV genotype 1b infection who were initially treated with IFN/PEG-IFN-alpha combined with ribavirin, and ombitasvir combined with dasabuvir for 8 or 12 weeks were taken. Sustained virological response (SVR) and the incidence of adverse events during treatment and follow-up were evaluated after 12 weeks of drug withdrawal at OBV/PTV/r 25/150/100mg once daily and DSV 250mg, twice daily. Median and range were used for description of non-normally distributed data. Results: 80 cases of GT1b were included in this study. Of these 88.8% (71/80) were newly diagnosed, 12.5% (10/80) were compensated cirrhotic, 97.5% (78/80) received 12 weeks treatment, and 2.5% (2/80) received 8 weeks treatment. The rate of HCV RNA negative at EOT (end of treatment) was 100% (64/64). A total of 67 patients completed the treatment within 12 weeks, and 43 patients returned to the hospital for further consultations, and SVR12 was 100%(43/43). No patient discontinued the drugs because of an adverse event during treatment. Conclusion: In the real world, Ombitasvir combined with dasabuvir for the treatment of chronic hepatitis C 1b genotype infection in China has 100% rates of EOT and SVR12 with well- tolerability and safety.

[A phase II, single-arm, open-label, multicenter clinical study to evaluate the efficacy and safety of sofosbuvir combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection].

Objective: To evaluate the efficacy and safety of sofosbuvir (Nanjing Zhengda Tianqing Pharmaceutical Co., Ltd.) combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection. Methods: Treatment-naïve or treatment experienced genotype 2 chronic hepatitis C patients from sixteen research centers of China were screened. All subjects received once-daily dose of sofosbuvir (400 mg) combined with ribavirin (body weight < 75 kg, 1 000 mg/day, 400 mg in the morning and 600 mg in the evening; body weight > 75 kg, 1 200 mg/d, 600 mg in the morning and 600 mg in the evening) for 12 weeks. Patients were followed-up for a period of 12 weeks after discontinuation of treatment. Continuous variables were expressed as mean ± standard deviation. The proportion of subjects with virologic response at different follow-up time points and 95% confidence intervals were estimated by maximum likelihood ratio and Clopper-Pearson interval. Results: 132 cases with genotype 2 chronic hepatitis C virus infection from sixteen research centers of China were included, 12 cases of whom were associated with cirrhosis, and the remaining 120 cases were not associated with cirrhosis. One hundred and thirty-one cases completed the study, and one patient lost to follow-up at week 4 after the end of treatment. The sustained virological response rate was 96.2% (95% confidence interval: 92.37% - 99.16%) after 12 weeks of drug withdrawal. Virological relapse occurred in four cases. Of the 132 subjects enrolled in the study, 119 (90.2%) reported 617 adverse events during treatment, of which 359 (76.5%) were TEAE related to sofosbuvir and/or ribavirin. There were nine TEAEs of grade 3 and above, and six cases (4.5%) of them had six severe adverse events. Only one serious adverse event was associated with sofosbuvir and ribavirin (unstable angina pectoris). There were no adverse events leading to drug discontinuation or death. Conclusion: Sofosbuvir combined with ribavirin has a high SVR rate in the treatment of genotype 2 chronic hepatitis C virus infection, and most of the adverse events occurred were mild with acceptable safety profile.

[A clinical study of antiviral therapy for patients with compensated hepatitis C cirrhosis].

Objective: To investigate the effect of antiviral therapy on the progression of liver cirrhosis and related predictive factors through a retrospective analysis of patients with compensated hepatitis C cirrhosis. Methods: The patients with compensated hepatitis C cirrhosis who were treated in our hospital from 2004 to 2015 were divided into sustained virologic response (SVR) group, non-SVR (NSVR) group, and untreated group. The baseline features of patients with or without liver cirrhosis were compared to identify the predictive factors for the progression of liver cirrhosis. The changes in platelet count, spleen sizes, Model for End-Stage Liver Disease (MELD) score, Sequential Organ Failure Assessment (SOFA) score, and Child-Turotte-Pugh (CTP) score were analyzed, and the incidence rate of liver cancer was compared between groups. A one-way analysis of variance, the Kruskal-wallis H test, the two-independent-sample t test, the chi-square test, and a multivariate logistic regression analysis were used for data analysis based on data type. Results: A total of 89 patients with compensated liver cirrhosis were enrolled, among whom 42 received the antiviral treatment with interferon and ribavirin (30 were treated with pegylated interferon-α and 12 were treated with ordinary interferon) and 47 did not receive any antiviral therapy. Among the patients who received the antiviral treatment with interferon and ribavirin, 20 achieved SVR and 22 did not achieve SVR. Compared with baseline values, platelet count in the SVR group and the NSVR group was increased by (44.93 ± 32.66)×10(9)/L and (9.73 ± 28.83)×10(9)/L, respectively, and platelet count in the untreated group was reduced by (19.76 ± 54.5)×10(9)/L; the three groups had a significant change in platelet count (F = 14.731, P < 0.001). Spleen size was reduced by 0.91 ± 1.09 cm in the SVR group and increased by 0.20±0.84 cm and 1.11 ± 1.69 cm in the NSVR group and the untreated group, respectively; the three groups had a significant change in spleen size (F = 14.943, P < 0.001). The three groups had no significant changes in MELD, SOFA, and CTP scores (P > 0.05). One patient (5.00%) in the SVR group, 5 (22.73%) in the NSVR group, and 6 (12.77%) in the untreated group progressed to liver cancer (χ (2) = 13.787, P = 0.001). The univariate analysis showed that SVR, HCV RNA, total bilirubin, and albumin were predictive factors for disease progression, and the multiple logistic regression analysis demonstrated that SVR and total bilirubin were predictive factors for disease progression. Conclusion: Interferon combined with ribavirin has a marked clinical effect in the treatment of compensated hepatitis C cirrhosis with good short- and long-term efficacy.

Preoperative computed tomography-guided hook-wire positioning of pulmonary nodules.

This study aimed to analyze the clinical application value of computed tomography (CT)-guided hook-wire positioning before thoracoscopic surgery. Eighty-four patients who had received a thoracoscopic wedge resection of pulmonary nodules between January and December 2013 were selected. Group A consisted of 38 cases where the hook-wire positioning technique was not used, and the positioning approaches were intraoperative observation and palpation. Group B consisted of 46 cases where the hook-wire positioning technique was used. The diameter of each nodule was less than 2 cm, and all patients underwent the operation within 2 h of invasive positioning. The evaluation indexes included positioning success rate, positioning-related complications, and rate of conversion to thoracotomy. In Group A, nine patients (23.68%) underwent conversion to thoracotomy; in Group B, three patients (6.52%) did. This difference was statistically significant (P < 0.05). The average operation duration was 118 ± 21 min in Group A and 53 ± 18 min in Group B. The difference between both groups was statistically significant (P < 0.05). The average length of hospital stay of patients who underwent conversion to thoracotomy was 8.7 ± 2.2 days, and of patients who underwent thoracoscopic pulmonary wedge resection was 4.5 ± 1.6 days. This difference was statistically significant (P < 0.05). Therefore, CT-guided hook-wire positioning of pulmonary nodules before thoracoscopic surgery has clinical application value. It helps to accurately locate the pulmonary nodules, effectively lowers the rate of conversion to thoracotomy, and reduces the operation duration.

Efficacy and safety of HSK3486 for the induction and maintenance of general anesthesia in elective surgical patients: a multicenter, randomized, open-label, propofol-controlled phase 2 clinical trial.

OBJECTIVE: To evaluate the efficacy and safety of HSK3486 for the induction and maintenance of general anesthesia in elective surgical patients, but excluding emergency, cardiothoracic, cerebral and endoscopic sinus cases. PATIENTS AND METHODS: A total of 40 eligible patients were randomly assigned to HSK3486 (n = 30) or propofol (n = 10) dosage groups in a ratio of 3:1. Drugs were administered as a bolus injection of 0.4 mg/kg (HSK3486) or 2.0 mg/kg (propofol) for induction, followed by maintenance infusion with the same anesthetic. An additional 6 non-randomized patients received propofol (2.0 mg/kg) for induction and were given HSK3486 for maintenance. RESULTS: The primary efficacy endpoint - the success rate of anesthesia maintenance - was 100% in the 3 arms. The secondary efficacy endpoints included times from discontinuation of HSK3486 or propofol maintenance to full alertness, respiratory recovery, extubation and reaching the goal of the Aldrete score. Also, the proportion of patients who constantly maintained BIS40-60 or those with a period of BIS40-60 during maintenance anesthesia showed no significant difference in the HSK3486 and propofol groups (all p > 0.05). Patients who received HSK3486 exhibited a higher satisfaction score from anesthesiologists during the induction period (p = 0.024). The occurrence and types of treatment-emergent adverse events were similar among the 3 arms, both with a severity of grade 1 or 2. Drug-related hypotension occurred in 14 (46.7%) and 7 (70.0%) patients treated with HSK3486 and propofol, respectively. CONCLUSIONS: HSK3486 exhibited good efficacy for the induction and maintenance of general anesthesia and was well tolerated by patients who underwent elective surgery.

Long noncoding RNA ROR promotes proliferation and invasion of colorectal cancer by inhibiting tumor suppressor gene NF2 through interacting with miR-223-3p.

OBJECTIVE: Colorectal cancer is one of the most common cancers in the world. LncRNA ROR, is a tumor oncogene associated with various human cancers. However, the role of ROR in colorectal cancer cells still remains unknown. The aim of this study was to measure the expression level of ROR and clarify its biological functions in colorectal cancer cells. MATERIALS AND METHODS: The expression level of ROR in colorectal cancer cells was detected using qRT-PCR. We performed CCK8 assay, colony formation assay, cell migration and invasion assays to evaluate the effects of ROR on cell proliferation, migration and invasion of colorectal cancer cells. Then, transfection of ROR, ROR inhibitor, miRNA-223-3p-mimics and miRNA-223-3p-inhibitor, qRT-PCR, and luciferase reporter assay were used to explore the molecular mechanisms. RESULTS: In the present study, Lnc-ROR was highly expressed in colorectal cancers compared with adjacent non-cancerous normal tissues. And the expression level of ROR was also increased in colorectal cancer cells (p < 0.05). CCK8 assay and invasion assay suggested that ROR can promote cell proliferation and invasion. The luciferase reporter assay showed ROR acted as sponge and directly competed with miRNA-223-3p, then decreasing the expression of tumor suppressor gene NF2. CONCLUSIONS: The findings of this study first revealed that ROR was upregulated in colorectal cancer cells and can promote cell proliferation and invasion by inhibiting tumor suppressor gene NF2 through interacting with miR-223-3p.

[Effect of Cordyceps sinesis on T-lymphocyte subsets in chronic renal failure].

Synchronous measurements of renal function and T-cell subsets were taken in 51 cases of chronic renal failure (CRF) patients. Cordyceps sinesis 3-5 g/d was given to 28 out of these 51 patients, which was considered as follow-up group. The results were stated as follows: (1) Obvious decrease of OKT3, OKT4, OKT4/OKT8 was found in CRF (P < 0.01). (2) OKT4 and OKT4/OKT8 were proportional to plasma albumin and Hb levels (P < 0.05). (3) After administration of Cordyceps sinesis, improvement of renal function and OKT4, OKT4/OKT8 were confirmed. This study indicated that cellular immune function was decreased in CRF. Administration of Cordyceps sinesis might improve their renal function and as the same time enhance the cellular immune function in CRF.

Effects of laminin blended with chitosan on axon guidance on patterned substrates.

Axon guidance is a crucial consideration in the design of tissue scaffolds used to promote nerve regeneration. Here we investigate the combined use of laminin (a putative axon adhesion and guidance molecule) and chitosan (a leading candidate base material for the construction of scaffolds) for promoting axon guidance in cultured adult dorsal root ganglion (DRG) neurons. Using a dispensing-based rapid prototyping (DBRP) technique, two-dimensional grid patterns were created by dispensing chitosan or laminin-blended chitosan substrate strands oriented in orthogonal directions. In vitro experiments illustrated DRG neurites on these patterns preferentially grew upon and followed the laminin-blended chitosan pathways. These results suggest that an orientation of neurite growth can be achieved in an artificially patterned substrate by creating selectively biofunctional pathways. The DBRP technique may provide improved strategies for the use of biofunctional pathways in the design of three-dimensional scaffolds for guidance of nerve repair.

Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China.

A novel coronavirus (SCoV) is the etiological agent of severe acute respiratory syndrome (SARS). SCoV-like viruses were isolated from Himalayan palm civets found in a live-animal market in Guangdong, China. Evidence of virus infection was also detected in other animals (including a raccoon dog, Nyctereutes procyonoides) and in humans working at the same market. All the animal isolates retain a 29-nucleotide sequence that is not found in most human isolates. The detection of SCoV-like viruses in small, live wild mammals in a retail market indicates a route of interspecies transmission, although the natural reservoir is not known.