[Establishment of a prognostic nomogram and discussion on optimal treatment for cervical adenocarcinoma:a retrospective study based on SEER database and Chinese single-center data].

Objective: To establish and validate a predicting nomogram for cervical adenocarcinoma based on surveillance, epidemiology and end results (SEER) database and Chinese single-center data, and to explore the optimal treatment for cervical adenocarcinoma. Methods: This study selected 2 478 cervical adenocarcinoma patients from the SEER database as the training cohort, and 195 cervical adenocarcinoma patients from Cancer Hospital of Dalian University of Technology, Liaouing Cancer Hospital and Institute as an external validation cohort. Clinicopathological information and follow-up data of the two cohorts were collected. The radiotherapy group was defined as receiving comprehensive treatment based on concurrent chemoradiotherapy after initial diagnosis, while the surgery group was defined as receiving comprehensive treatment based on radical surgery. Log-rank test and cox regression were used to evaluate factors affecting the prognosis of cervical adenocarcinoma patients. A nomogram was drawn to predict the 3-year and 5-year overall survival rates of cervical adenocarcinoma patients, and then internal validation of the training cohort from SEER database and external validation of the hospital cohort were conducted. Results: (1) In the SEER database training cohort, there were 385 patients (15.54%, 385/2 478) in the radiotherapy group and 2 093 patients (84.46%, 2 093/2 478) in the surgery group. Overall survival time of the radiotherapy group was (55.8±51.3) months, while that of the surgery roup was (94.4±61.7) months, the difference between the two groups was statistically significant (χ2=256.44, P<0.001). Log-rank test showed that age, marital status, maximum of tumor diameters, pathological grade, International Federation of Gynecology and Obstetrics (FIGO) stage, and treatments were all significant factors affecting the overall survival time of cervical adenocarcinoma patients (all P<0.001). Multivariate Cox regression analysis showed that elder (>50 years old), single status, huge tumors (>4 cm), high pathological grades (G2, G3), and advanced FIGO stages (≥Ⅱa2 stage) were independent risk factors for the overall survival time of cervical adenocarcinoma patients (all P<0.05); compared with radiotherapy, surgery was a protective factor for the prognosis of cervical adenocarcinoma patients (HR=0.619, 95%CI: 0.494-0.777; P<0.001). Further analysis of locally advanced stage and Ⅲc stage of patients showed that surgery was a protective factor for the prognosis of cervical adenocarcinoma patients with a maximum tumor diameter >4 to <6 cm (HR=0.414, 95%CI: 0.182-0.942; P=0.036) in locally advanced stage and Ⅲc T1 to T2 stage (HR=0.473, 95%CI: 0.307-0.728; P=0.001). (2) The external validation cohort consisted of 39 patients (20.00%, 39/195) in the radiotherapy group and 156 patients (80.00%, 156/195) in the surgery group. The overall survival time of patients in the radiotherapy group was (51.7±34.3) months, while that of the surgery group was (63.1±26.6) months (χ2=28.41, P<0.001). Further analysis was conducted on locally advanced stage and Ⅲc stage patients, and multivariate Cox regression analysis was performed after propensity score matching, which showed that surgery was a protective factor for the prognosis of cervical adenocarcinoma patients with a maximum tumor diameter >4 to <6 cm in locally advanced stage (HR=0.141, 95%CI: 0.023-0.843; P=0.032) and Ⅲc T1 to T2 stage (HR=0.184, 95%CI: 0.036-0.947; P=0.043). (3) Establishment and internal and external validation of nomogram: based on the six factors screened out by the multivariate Cox regression model, the nomogram was developed to predict the prognosis of cervical adenocarcinoma patients. The consistency index of the internal and external validation were 0.801 and 0.766, respectively, and the calibration curves matched well with the ideal fitting line. Conclusions: The key to the treatment of cervical adenocarcinoma is to prioritize radical surgery for patients with conditions for radical tumor resection. Compared with concurrent chemoradiotherapy, patients with locally advanced stages (Ⅰb3, Ⅱa2), and Ⅲc (T1, T2) stages cervical adenocarcinoma could benefit from comprehensive treatment based on radical surgery. The nomogram of this study has been validated internally and externally, and show good survival prediction efficacy for cervical adenocarcinoma patients.

[Progress and implementing of novel surgical concepts and techniques in patients with resectable gastric cancer liver metastasis].

In recent years, advances in surgical techniques and evolving concepts have significantly improved treatment strategies and prognosis for patients with gastric cancer liver metastases. In particular, patients diagnosed with initially resectable gastric cancer liver metastases shows marked improvement in survival. Despite variations in the definition of initially resectable gastric cancer liver metastases among different consensus and guidelines, surgical resection and hepatic physiotherapy are increasingly crucial components of comprehensive treatment. Meanwhile, the advancement of the multidisciplinary team model for diagnosis and treatment, along with the evolution of minimally invasive surgical concepts, offers patients increasingly personalized and less intrusive therapeutic alternatives. According to the Chinese Consensus Classification System for Gastric Cancer Liver Metastasis, the optimal clinical pathway for patients initially diagnosed with resectable gastric cancer liver metastasis involves precise categorization, guided selection of surgical approaches and physiotherapy using the multidisciplinary team model, and consideration of molecular classification. However, the refinement and confirmation of these clinical strategies is still required through high-quality clinical trials.

[Comparison of the efficacy of different surgical strategies in the treatment of patients with initially resectable gastric cancer liver metastases].

Objective: To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM). Methods: This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging (M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results: (1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95%CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference (P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options (HR=1.98, 95%CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients' prognosis (HR=2.01, 95%CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors (HR=2.84, 95%CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver (HR=2.06, 95%CI 1.19 to 3.57, P=0.010). Conclusions: In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

[Interpretation of the limit values of iodide in the "Standards for Drinking Water Quality（GB5749-2022）" in China].

The Drinking Water Sanitation Standard (GB 5749-2022) has been officially promulgated and implemented, with the iodide listed as a new reference indicator for water quality. This study interprets the distribution of iodine in environmental media, the impact of water iodine on health, the significance of establishing iodide standard limits, and the use of iodide standard limits, in order to provide a scientific basis for the application of iodide standard limits in this revised standard.

[Advances and controversies of statins application in prevention and treatment of hepatocellular carcinoma].

Statins, as lipid-regulating drugs, have been widely used in the treatment for hyperlipidemia and the primary and secondary prevention of cardio-cerebrovascular diseases. Hepatocellular carcinoma (HCC) is a serious burden of liver disease in China with poor prognosis, thus effective adjuvant drug used for HCC treatment has attracted much attention. Statins can suppress tumor growth, decrease the risk of tumorigenesis and postoperative recurrence of HCC, extend the survival time and improve the therapeutic effect of other treatment, therefore might increase the benefit obtained by the HCC patients. Statins also can impact the expression of MAPK/ERK signaling pathway, promote the apoptosis of malignant cells and ameliorate the HCC risk of hepatitis B virus infected patients. Statins not only prevents the HCC, but also has part therapeutic effect on the different stage of HCC. Although it can't replace the operation, radiofrequency ablation, molecular targeted treatment and immunotherapy currently, statins may be a potential adjuvant drug to provide clinical benefit for HCC patients. The advancement of statins application in the prevention and treatment of HCC has attracted more attention recently, however, discussion and controversy also existed about whether it can eventually become an adjuvant therapy for HCC. The purpose of this paper is to summarize and comment on the new development and disputes of statins application in the prevention and treatment of HCC in recent years, to provide help for the future clinical practice.

[Application of latent class model in genetic association between ARID1A low-frequency variants and primary liver cancer].

Objective: To analyze the association between low-frequency variants of ARID1A gene and primary liver cancer using latent category model. Methods: The low-frequency variants of ARID1A gene was combined according to different functional areas, and the combined variables were analyzed by using the latent class model to obtain the latent variables. Then the logistic regression was used to analyze the association between low-frequency variants of ARID1A gene and primary liver cancer. Results: The low-frequency variants of ARID1A gene were divided into three categories by the latent class model. The class 1 was mainly unmutated population, the proportion was 94.2% (2 454/2 603). The class 2 was mainly transcriptional regulatory domain mutation, take 4.8% (124/2 603). The class 3 was dominantly exon mutation, about 1.0% (27/2 603). Using class 1 as a reference, it was found that mutations in the transcriptional regulatory domain could reduce the risk of liver cancer (OR=0.601, 95% CI=0.364-0.992, P=0.046). Conclusion: The latent class model can identify low-frequency variants of gene associated with liver cancer and can be extended to more genetic association studies of low-frequency variants related to complex diseases.

[Immune cells role and their new potential therapeutic targets in the pathogenesis of alcoholic liver disease].

The key factors driving the pathogenesis of alcoholic liver disease are still not fully understood. At present, it is believed that the direct toxic effects of ethanol and its intermediate metabolite acetaldehyde can cause oxidative stress, mitochondrial damage, adipogenesis, malnutrition, intestinal endotoxin leakage, etc., thereby participating in the occurrence and progression of alcoholic liver disease. Among the many pathogenic factors that have been revealed, the immunological mechanism plays an important role. Therefore, the role of immune cells and inflammatory mediators has attracted much attention. This article reviews and summarizes the new progress of specific immune cell mechanisms involved in innate and adaptive immune response during the formation and development of alcoholic liver disease, and proposes potential therapeutic targets and clinical trials of related new drugs, which may improve the re-recognition of molecular mechanism and treatment expectation in clinical practice.

[Aldehyde dehydrogenase with hepatocellular carcinoma].

Acetaldehyde dehydrogenase 2 (ALDH2) is a key enzyme in liver acetaldehyde metabolism (product of ethanol metabolism). Globally, about 8% of the population and about 30% to 40% of the East Asian population carry defective genes that encode no / low activity ALDH2. Recently, many studies have focused on the relationship between ALDH and viral hepatitis, alcoholic liver disease, liver fibrosis and liver cancer. Importantly, ALDH2 expression is closely related to the risk, pathogenesis and prognosis of liver cancer, so it can be used as a potential therapeutic target. This article summarizes and reviews the new progress and new research directions of this field.

[The therapeutic effect of carnosine combined with dexamethasone in the lung injury of seawater-drowning].

Objective: To explore the therapeutic effect of carnosine and dexamethasone in lung injury caused by seawater drowning. Methods: The in vitro experiments with A549 cells were divided into 5 groups: blank control group (C), seawater injury group (S), seawater injury+dexamethasone treatment group (S+D), seawater injury+carnosine treatment group (S+C), seawater injury dexamethasone and carnosine combined therapy(S+D+C) group. The optimal therapeutic dose of drugs for the treatment of seawater drowning lung injury was tested in vitro. Based on the optimal dose, the levels of TNF-α and IL-6 in each group at different time points were detected at the cell level by ELISA. The level of apoptosis was detected by flow cytometry. The in vivo experiments with SD rats were randomly divided into 5 groups (n=8 each): blank control group (RC),seawater drowning injury group (RS),seawater drowning injury+dexamethasone treatment group (RSD),seawater drowning injury+carnosine treatment group (RSC),seawater drowning injury+dexamethasone+carnosine combined treatment group (RSDC). The animal model with seawater inhalation acute lung injury was made by intratracheal infusion (4 ml/kg). The pathological changes of the lungs were observed. The expression of superoxide dismutase (SOD) in each group was detected by Western blot. Results: The results of in vitro experiments showed significant increase of apoptosis after seawater injury. The normal cell rate in group C was 98.3% while the apoptosis rate was 1.7%. The normal cell in group S was 18.8%, and the apoptosis rate was 81% (P<0.01). TNF-α and IL-6 levels in group S increased to 180.25 ng/L and 61.56 ng/L, respectively, which were statistically significant compared with group C (P<0.01). After drug protection, apoptosis was reduced in S+D group, S+C group and S+D+C group, with apoptosis rates of 65.4%, 70.9% and 42.6%, respectively. The contents of TNF-α and IL-6 also decreased in the S+D+C group (P<0.01). The results of in vivo experiments showed obvious lung injury and disordered lung tissue structures in the RS group at 4 h after modeling. There was hemorrhage in the pulmonary interstitium and a large number of inflammatory cells. Results of western blot showed that the expression of SOD increased in the RS group. Compared with RS group, the treatment alleviated acute lung injury and decreased the expression level of SOD in RSD, RSC and RSDC groups (P<0.01). Conclusion: Dexamethasone and carnosine reduced the influence of seawater inhalation on the lung in the rat model. The positive effect of combination of these two drugs on lung injury caused by seawater inhalation was stronger than a single drug.

[Utility of the type 3 portable monitor for the diagnosis of patients with obstructive sleep apnea].

Objective: To evaluate the utility of a portable monitor at home for diagnosis of obstructive sleep apnea (OSA) in Chinese adults. Methods: Eighty nine patients suspected of OSA underwent overnight, unattended home sleep apnea testing (HSAT) with a portable monitor (Nox-T3, Nox Medical Inc. Iceland)followed by an in-laboratory polysomnogram (PSG) with simultaneous portable monitor (PM) recording within one week. PSG and PM recorder were scored according to recommended guidelines by independent technicians. The correlation between PSG apnea hypopnea index (AHI) and PM respiratory disturbance index (RDI) were evaluated. Results: Sleep testing showed RDI was (30.0±20.9) events/h on HSAT, and (33.4±22.4) events/h on in-laboratory PM recording. Apnea-hypopnea index (AHI) on PSG was (35.1±23.7) events/h. There was significantly statistical difference among the three group (P<0.001). Both RDI on HSAT and RDI on in-laboratory PM correlated significantly with AHI on PSG (r=0.877, P<0.001 and r=0.962, P<0.001, respectively). Bland-Altman analysis of AHI on PSG versus RDI on HSAT showed a mean difference of 4.4 events/h; limits of agreement was -17.6 to 26.5 events/h. Closer agreements were present when comparing the simultaneous recordings, with AHI on PSG versus RDI on in-laboratory PM showing a mean difference of 1.4 events/h, and limits of agreement was -11.3 to 14.2 events/h. Based on a threshold of AHI≥5 events/h, RDI on HSAT had 98.8% sensitivity, 40.0% specificity. Using an AHI ≥ 15 events/h, RDI on HSAT had 91.5% sensitivity, 76.5% specificity. Conclusion: Type 3 PM has a good diagnostic value for adult OSA patients and there is close agreement between the Type 3 portable monitor and PSG.

[Incidence of depressive disorders and related independent risk factors in patients with chronic hepatitis C].

Objective: To investigate the incidence and related independent risk factors of depression in treatment-naïve Han ethnic Chinese patients with chronic hepatitis C. Methods: Nine hundred and ninety-seven Han Chinese patients with confirmed chronic HCV infection were enrolled. Beck's depression inventory scale was used to assess depression score. Patients were divided into two groups according to the score: score≥17, depression group (16.85%, 168/997); score <17, no depression group (83.15%, 829/997). Multivariate logistic regression was used to analyze independent risk factors related with the onset of depression in patients with chronic hepatitis C. Results: There was a statistically significant difference between the two groups in terms of gender distribution, marital status, education level, income level and smoking status (P < 0.05). Independent risk factors were female [odds ratio (OR) = 3.85; 95% CI: 2.28-6.50, P = 0.001], decompensated cirrhosis [OR = 2.31; 95% CI: 1.20-4.48, P = 0.013], unmarried [OR = 2.01; 95% CI: 1.12-3.60, P = 0.019], separated [OR = 17.39; 95% CI: 1.64-184.47, P = 0.018], divorced [OR = 3.82; 95% CI: 1.36-10.74, P = 0.011], without higher education [OR = 2.04; 95% CI: 1.22-3.42, P = 0.007], low income [OR = 3.94; 95% CI: 1.38-11.28, P = 0.011], middle income [OR = 2.96; 95% CI: 1.02-8.62, P = 0.047], uninterrupted smoking [OR = 3.67; 95% CI: 2.13-6.31, P = 0.001], and previously smoked [OR = 3.33, 95% CI: 1.66-6.68, P = 0.001]. Conclusion: The incidence of depression in patients with chronic hepatitis C is relatively high. The independent risk factors related with depression include female, unmarried, separated, and divorced, without higher education, low and middle-income level, smoking and disease progression to decompensated cirrhosis, but no significant correlation between hepatitis C virus genotypes and viral load.

[Respiratory pathogen spectrum in pulmonary exacerbation of bronchiectasis in adults and its association with disease severity].

Objective: To determine the pattern of respiratory pathogens at bronchiectasis exacerbation and its associations with disease severity. Methods: A total of 119 steady-state bronchiectasis patients [42 males, 77 females, age range 19 to 74 years, mean age (45±14)years], diagnosed by a compatible history combined with evidence of bronchial dilatation on high-resolution computed tomography (HRCT), were recruited prospectively from out-patient clinics in the First Affiliated Hospital of Guangzhou Medical University between September 2012 and March 2013. A comprehensive history taking, radiologic appearance, spirometry, sputum bacterial culture and 16 respiratory viruses in nasopharyngeal swabs and sputum samples by PCR assays were collected at steady-state bronchiectasis. All bronchiectasis patients were followed up one year and assessed for bacteriology, virology and systemic inflammatory indices [including white blood cell, C-reactive protein (CRP), interleukin-6, 8 and tumor necrosis factor-α] during bronchiectasis exacerbation. Results: Fifty-eight bronchiectasis patients [20 males, 38 females, age range 19 to 74 years, mean age (44±14) years] reported 100 exacerbations (1 to 5 exacerbation events per patient) during one year follow-up. Respiratory viruses were found more frequently in sputum and nasal swab during exacerbation [35.0% (35/100) and 39% (39/100)] than those during steady-state in bronchiectasis [sputum: 13.8% (8/58), nasal swab: 8.6% (5/58)] (χ(2)=8.33,χ(2)=13.51; respectively, all P<0.05). The rate of bacterial detection during exacerbation in sputum was 56% (56/100), which was not significantly different compared with those at steady-state (35/58, 60.3%;χ(2)=0.284, P=0.59). Of these respiratory infections, viral-bacterial co-infection accounted for 30% exacerbation events. The most common bacteria and viruses during exacerbation in mild bronchiectasis (n=18, with 25 exacerbation events) were Haemophilus parainfluenzae (4 cases) in sputum and influenza A in nasal swab or sputum (4 cases), respectively. In patients with moderate (n=17, with 29 exacerbation events)-severe bronchiectasis (n=23, with 46 exacerbation events), pseudomonas aeruginosa was the most common bacteria in sputum (35 cases), and the most common respiratory viruses were rhinovirus in nasal swab or sputum (11 cases). In these 100 exacerbation events, patients with bacterial and viral co-infection, pure bacteria infection, pure virus infection, no bacteria and virus infection accounted for 30, 29, 16 and 25 exacerbation events, respectively. And patients with co-infection had higher serum CRP (45±23) mg/L and IL-8 [9.0 (4.4-15.5) ng/L] (F=23.32, F=9.81,respectively; all P<0.05), and increased risk of hospitalization (30% vs. 0] compared with those in non-infectious group(χ(2)=9.0, P=0.003). Conclusions: Pseudomonas aeruginosa, rhinovirus and influenza A were common causative agents of exacerbation in bronchiectasis.In patients with moderate-severe bronchiectasis, pseudomonas aeruginosa was the most common bacterium in sputum, and the most common respiratory virus was rhinovirus in nasal swab or sputum, compared to Haemophilus parainfluenzae in sputum and influenza A in nasal swab or sputum in mild bronchiectasis. Patients with co-infection had more severe systemic inflammatory response and higher risk of hospitalization during exacerbation.

[Effect of Anluohuaxianwan on the expression of matrix metalloproteinases and their inhibitors in rat liver with fibrosis].

Objective: To investigate the effect of anluohuaxianwan (ALHXW) using rat model of carbon tetrachloride (CCl(4)) induced liver fibrosis on the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Methods: Thirty-six male Wistar rats were randomly assigned into control, model and treatment groups. Rats in the model and treatment groups were injected intraperitoneally with 40% CCl(4) (2 ml/kg), and the control group were given isotonic saline twice a week for six weeks. Meanwhile, the treatment group were gavaged with ALHXW solution daily (concentration 0.15 g/ml, 9.9 ml/kg) for 6 weeks, while the control and model groups were given isotonic saline once a day for 6 weeks. Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured at the end of third and sixth week. At the end of six weeks, liver tissues were harvested for histopathological evaluation and the detection of mRNA and protein expression levels of MMP-2/13 and TIMP-1/2. According to different data, LSD method, parametric (one-way ANOVA) and non-parametric tests (Kruskal-Wallis H-test and Mann-Whitney U test) were used for statistical analysis. Results: Compared with the model group, ALHXW markedly alleviated liver injury in the treatment group, and thereby improved the general state of rats, liver and spleen morphological characteristics, and ALT and AST levels. Histopathological examination demonstrated that the extent of liver fibrosis was improved (2.75 ± 0.75 vs. 3.55 ± 0.69, P = 0.015) in the treatment group as compared with the model group. The mRNA and protein expression levels of MMP-13 in the treatment group were significantly higher than that of the model group (mRNA: 10.50 ± 7.64 vs. 4.40 ± 2.97, P = 0.029. Protein: 1.15 ± 0.09 vs. 0.78 ± 0.21, P = 0.016), whereas the mRNA and protein expression levels of MMP-2, TIMP-1/2 in the treatment group were significantly lower than that of the model group (mRNA: 4.55 ± 3.29 vs. 7.83 ± 4.19, P = 0.048; 1.66 ± 0.73 vs. 3.69 ± 2.78, P = 0.023; 2.25 ± 1.16 vs. 3.41 ± 1.51, P = 0.049; respectively. Protein: 0.44 ± 0.11 vs. 0.65 ± 0.05, P = 0.03; 0.69 ± 0.06 vs. 1.07 ± 0.21, P = 0.016; 0.46 ± 0.09 vs. 0.81 ± 0.13, P = 0.003; respectively). Conclusion: ALHXW exerts anti-liver fibrosis effects mainly by improving liver function, inhibiting the activation of hepatic stellate cells, enhancing the expression of MMP-13, and inhibiting the expression of MMP-2 and TIMP-1/2.

[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.

Exposure Duration Is a Determinant of the Effect of Sinusoidal Electromagnetic Fields on Peak Bone Mass of Young Rats.

We proposed a three-step strategy to obtain the optimal therapeutic parameters, which is composed of large-scale screening at cellular level, verification in animal experiments, and confirmation by a clinical trial. The objective of the current study was to test the feasibility of our strategy. Newborn rat calvarial osteoblasts were treated by 50 Hz 1.8 mT sinusoidal electromagnetic fields (SEMFs) with 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 h/days, respectively. The osteogenic differentiation and maturation of the osteoblast were assayed and compared to obtain the optimal duration. One-month-old growing rats were then treated by the same SEMFs with 0.5, 1.5, and 2.5 h/days, respectively, and the peak bone mass was analyzed after 2 months. It was found that the optimal exposure duration to promote the osteogenic differentiation and maturation of osteoblasts was 1.5 h/days, judging by the increasing degrees of ALP activity, calcified nodules formed, the gene and protein expression levels of Runx-2, BMP-2, and Col-I, as well as the expression levels of signaling proteins of the BMP-2/Smad1/5/8 pathway. The highest increase of peak bone mass after 2 months was also obtained by 1.5 h/days, judging by the results of X-ray dual-energy absorptiometry, mechanical property analysis, micro-CT scanning, and serum bone turnover marker examinations. The above results indicated that exposure duration is a determinant for the therapeutic effect of EMFs, and the optimal therapeutic effects only can be obtained by the optimal exposure duration.

[Glucocorticoids and liver diseases].

Glucocorticoids is a type of steroid hormone secreted from zona fasciculata of adrenal cortex.As an immune and inflammatory inhibitor, glucocorticoids has been used to treat many kinds of diseases.T cell response plays a crucial role in the pathogenesis of liver diseases. However, the role of glucocorticoids in the mechanism and treatment of liver disease in current clinical practice is controversial. This paper summarizes the progress of glucocorticoid use for the treatment of liver diseases in recent years. References will be provided for how to grasp the indications,application timing and proper dosage of glucocorticoids in liver diseases.

[Application of direct antiviral drugs in special patients with HCV infection].

Patients with HCV infection can develop decompensated cirrhosis, hepatocellular carcinoma (HCC), even liver failure. As a result, efficient antiviral treatment is very essential to prevent HCV-related disease progression. Newly developed direct-acting antiviral agents (DAAs) have shown safety profile, favorable tolerability, and relatively short duration, which provide an opportunity to expand the number of patients who can be treated for HCV infection. There is a need for further clinical observation and summaries for DAAs in a real world. In the era of DAAs, special patients with HCV infection still get lots of attention from doctors. This review aims at the application of DAAs in patients with HCV infection, combined with chronic kidney diseases, hepatocellular carcinoma, HBV/HCV co-infection, HIV/HCV co-infection, post liver transplantation, pregnancy, children, lymphoma and retreatment.

[Comparison of the short-term and long-term outcome between robotic gastrectomy and laparoscopic gastrectomy: a propensity score matching analysis].

Objective: To compare the short-term and long-term outcome between robotic gastrectomy and laparoscopic gastrectomy. Methods: The clinical data of 517 patients who had received robotic gastectomy and laparoscopic gastrectomy between December 2011 and December 2013 at Department of General Surgery, Chinese People's Liberation Army General Hospital was collected. After propensity score matching, 70 patients in robotic gastectomy and 70 patients in laparoscopic gastectomy were identified. Perioperative outcome and overall survival were compared between the two groups using t test, χ(2) test, Kaplan-Meier curve and Log-rank test, respectively. Prognosis factors were analyzed by Cox's proportional hazards regression. Results: There were comparable baseline characteristics between patients in robotic group (RG) and those in laparoscopic group (LG). The conversion rate for RG and LG were 5.7% and 4.3% respectively (P=1.000). Compared with LG, RG had similar lymph node retrieval (25.5±7.2 vs. 24.5±8.3, t=0.770, P=0.443) and less blood loss ((147.0±96.8) ml vs. (188.0±111.2) ml, t=-2.326, P=0.021). There were also similar complications (χ(2)=0.233, P=0.629) and severity of complications (W=70.500, P=0.053). Although there tended to be early mobility, early flatus and less hospital stay for patients in RG group, the difference between RG and LG was not statistically significant. The 3-year survival rate was 72.9% and 60.0% for patients in RG and patients in LG (P=0.578). Multivariable analysis revealed gender (HR=2.529, 95% CI: 1.042 to 6.140, P=0.040), neoadjuvant chemotherapy (HR=0.272, 95% CI: 0.104 to 0.710, P=0.008) and vascular invasion (HR=2.135, 95% CI: 1.027 to 4.438, P=0.042) were independent prognostic factors. Conclusion: Compared with laparoscopic gastrectomy, robotic gastectomy could achieve similar short-term and long-term outcomes.

Effect of electroacupuncture on the cervicospinal P2X7 receptor/fractalkine/CX3CR1 signaling pathway in a rat neck-incision pain model.

Increasing evidence supports that acupuncture intervention is an effective approach for intraoperative and postoperative pain. Neuron-microglia crosstalk, mediated by the purinergic P2X7 receptor (R)/fractalkine/CX3CR1 cascade in the spinal cord dorsal horn, plays a pivotal role in pain processing. However, its involvement in the analgesic effect of electroacupuncture (EA) remains unclear. In this study, a rat neck-incision pain model was established by making a longitudinal incision along the midline of the neck and subsequent repeated mechanical stimulation. EA stimulation was applied to bilateral LI18, LI4-PC6, or ST36-GB34. The thermal pain threshold, cervicospinal ATP concentration, expression levels of purinergic P2XR and P2YR subunits mRNAs, and fractalkine, CX3CR1 and p38 MAPK proteins, were detected separately. The neck incision induced strong thermal hyperalgesia and upregulation of spinal ATP within 48 h. No significant change was found in thermal hyperalgesia after a single session of EA intervention. However, a single session of EA dramatically enhanced the neck incision-induced upregulation of ATP and upregulated the expression of P2X7R, which was reversed by two sessions of EA. Two sessions of EA at bilateral LI18 or LI4-PC6 attenuated hyperalgesia significantly, accompanied with downregulation of P2X7R/fractalkine/ CX3CR1 signaling after three sessions of EA. EA stimulation of LI18 or LI4-PC6 alleviates thermal hyperalgesia in neck-incision pain rats, which may be associated with its effects in regulating the neck incision-induced increase of ATP and P2X7R and subsequently suppressing fractalkine/CX3CR1 signaling in the cervical spinal cord.

Primary cilium is required for the stimulating effect of icaritin on osteogenic differentiation and mineralization of osteoblasts in vitro.

OBJECTIVE: Icaritin, one effective metabolite of Herba Epimedii-derived flavonoid icariin, has a strong osteogenic activity. However, its action mechanism remains unclear. Since primary cilia have been shown to play a pivotal role in regulating the osteogenesis, we hypothesized primary cilia are indispensable in mediating icaritin osteogenic effect. MATERIALS AND METHODS: Primary rat calvarial osteoblasts were transfected with siRNA1 targeting intraflagellar transport protein 88 (IFT88), a protein required for ciliogenesis, to prevent formation of primary cilium and were treated with 10-6 M icaritin. RESULTS: Alkaline phosphatase (ALP) activity was significantly increased after 3 days in cells transfected with scrambled siRNA control and treated by icaritin (SC+I group) compared to cells transfected with scrambled siRNA control only (SC group). ALP activity after IFT88 siRNA1 transfection and icaritin treatment (siRNA1+I group) was significantly lower than that of SC+I group. Formation of ALP positively stained colonies after 6 days, osteocalcin secretion after 9 days and formation of calcified nodules after 12 days displayed a similar tendency among the three groups. mRNA expression of osteogenesis-related genes ALP, BMP-2, COL1α, RUNX-2 and OSX after 24 h was significantly increased in SC+I group, but was not different with SC group in siRNA1+I group. Protein levels of BMP-2, COL1α, RUNX-2 and OSX after 48 h showed the similar tendency with gene expression. CONCLUSION: Primary cilia are important in mediating icaritin-stimulated osteogenic differentiation and may be a novel target for pharmacological therapies for bone loss.