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Objective: To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) followed by hepatic arterial infusion chemotherapy (HAIC) combined with TKI drugs and PD-1 inhibitors as the first-line treatment for advanced hepatocellular carcinoma (HCC)., Methods: We retrospectively analyzed the data of 70 patients with advanced HCC treated in the Department of Oncology of Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine between July, 2020 and June, 2023. 23 of the patients received TACE combined with HAIC and TKI (TACE+HAIC+ TKI group) and 47 received TACE combined with HAIC, PD-1 inhibitors and TKI (TACE+HAIC+PD-1+TKI group). The clinical characteristics, laboratory test results, efficacy, outcomes and adverse events of the patients were compared between the two groups., Results: The TACE+HAIC+TKI and TACE+HAIC+PD-1+TKI groups had significantly different objective remission rates (ORR; 60.87% vs 36.17%, P =0.031), comparable disease control rates (95.65% vs 93.62%, P =0.068), and different median progression-free survival (PFS) time (10.2 vs 11.8 months, P =0.003) and median overall survival (OS) time (15.7 vs 19.5 months, P =0.035). After propensity score matching (PSM), the median PFS and OS time of the two groups was 10.1 vs 14.5 months ( P = 0.024) and 14.2 vs 21.2 months ( P =0.221), respectively. The 1-year PFS rates of the 2 groups were 24.0% vs 52.2%, and the 1-, 2-and 3-year OS rates were 72.3% vs 93.1%, 23.9% vs 63.8%, and 23.9% vs 36.5%, respectively. The incidence of proteinuria was significantly higher in TACE+HAIC+PD-1+TKI group than in TACE+HAIC+TKI group (21.28% vs 0, P =0.025), but the incidences of grade 3-4 treatment-related adverse events were all similar between the two groups., Conclusion: The first-line treatment with TACE+HAIC+PD-1+TKI is safe and effective for advanced HCC and can significantly prolong the survival of the patients.

Objective: This study aims to compare the antiviral treatment similarities and differences in the population covered by the 2024 version of the World Health Organization's (WHO) hepatitis B prevention and treatment guidelines and the current Chinese hepatitis B prevention and treatment guidelines, so as to explore their impact on the indications for antiviral therapy in Chinese patients with chronic hepatitis B (CHB). Methods: The information of patients with chronic hepatitis B virus infection who did not receive antiviral treatment was collected through the registration database of the China Clinical Research Platform for Hepatitis B Elimination. Descriptive statistics were conducted on the demographic, blood, biochemical, and virological levels of patients according to the treatment recommendations of the two versions of the guidelines. The Mann-Whitney U test and χ2 test were used to compare the differences and proportional distribution of the treatment populations covered by the two guidelines. The χ2 test was used to analyze the coverage rate of different antiviral treatment indications. Results: A total of 21,134 CHB patients without antiviral treatment were enrolled. 69.4% of patients met the 2024 versions of the WHO guidelines' recommendations. 85.0% of patients met the current Chinese hepatitis B prevention and treatment guidelines. The WHO guidelines for antiviral therapy indications were met in younger patients with higher levels of ALT, AST, and APRI scores, as well as greater proportion of patients with higher viral loads (P<0.001). The WHO guidelines recommended a cut-off value of APRI>0.5, which raised the proportion of patients on antiviral therapy from 6.6% to 30.9%. 45.7% of patients met the antiviral indications for HBV DNA >2000 IU/ml with abnormal transaminase (ALT>30 U/L for males and ALT>19 U/L for females). The reduced APRI diagnostic cut-off value and ALT treatment threshold had further increased the treatment coverage rate by 91.6% in patients with chronic HBV infection in line with the 2024 versions of WHO guidelines. Conclusion: The reduction of the APRI diagnostic cut-off value and the ALT treatment threshold, based on the current hepatitis B guidelines of China, will further improve the treatment coverage of CHB patients.

The global chronic hepatitis B (CHB) guidelines have gradually expanded treatment indications in order to accelerate the elimination and improve the treatment rate of hepatitis B virus (HBV) infection. This article analyzes the new treatment concepts for chronic hepatitis B at home and abroad from two aspects: expanding treatment by paying more attention to the long-term prognosis of the disease and maximizing the use of existing drugs in order to achieve the early goal of the World Health Organization's of eliminating viral hepatitis by 2030.

A coupling system of ultrasonic composite iron-carbon activated persulfate (US/PS/Fe-C) was built to treat a triphenylmethane derivative, crystal violet (CV). The results revealed that US/PS/Fe-C ternary system had a good coupling effect. The structure and surface morphology of commercial Fe-C and self-made Fe-C catalysts were analyzed using an X-ray diffractometer (XRD) and scanning electron microscope (SEM), respectively. Finally, commercial Fe-C was used to study the effects of different factors on the CV of US/PS/Fe-C ternary coupling degradation, and the optimum conditions were as follows:PDS concentration 2 mmol·L -1 , iron-carbon catalyst 1 g·L -1 , pH without adjustment, and the removal rate of 15 mg·L -1 CV reached 90% after 30 min. To explore the effects of anions and cations on the system, it was observed that Mg 2+ and NO 3 - had almost no effect on the treatment of the system, and Mn 2+ , Cl - , and CO 3 2- had a certain effect on the treatment of the system, whereas Fe 2+ could promote the reaction at low concentration and inhibit the reaction at high concentration. By adding different quenchants, it was concluded that there were four types of active substances: 1 O 2 , SO 4 - ·,·O 2 - , and·OH.

Through the analysis of PAC module faults in two GE Signa HDxt 1.5 T MRI cases, the fault performance was analyzed. According to the working principle of PAC module, the fault was analyzed and processed, and then the suspicious fault parts were located and repaired to make the equipment run normally. Finally, the operating principles of PAC module in terms of power supply, signal transmission and data transmission were summarized to facilitate the subsequent quickly and find out fault points for maintenance accurately.

Objective: To investigate the clinical features and long-term prognosis of primary biliary cholangitis (PBC) in patients with past hepatitis B virus (HBV) infection. Methods: 353 cases with PBC who visited the Liver Disease Center of Beijing Friendship Hospital Affiliated to Capital Medical University between January 2000 and January 2018 were retrospectively analyzed and were divided into the past HBV infection group (156 cases) and the no HBV infection group (197 cases). The two groups' baseline clinical features were compared. Ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, and long-term liver transplantation-free survival rate were compared through outpatient and telephone follow-up. Results: PBC with past HBV infection had a significantly reduced female proportion compared to the no HBV infection group (91.9% vs. 79.5%, P = 0.001). However, there were no statistically significant differences in age, biochemical indices, immunological indicators, platelet count, cirrhosis proportion, and others. Ursodeoxycholic acid biochemical response rate was reduced in patients with past HBV infection at the end of one year of treatment, but the difference was not statistically significant (65.8% vs. 78.2%, P = 0.068). In addition, there were no statistically significant differences between the GLOBE score (0.57 vs. 0.59, P = 0.26) and UK-PBC 5-year (2.87% vs. 2.87%, P = 0.38), 10-year (9.29% vs. 8.2%, P = 0.39) and 15-year liver transplantation rates (16.6% vs. 14.73%, P = 0.39). Lastly, the overall 5-year liver transplantation-free survival rate had no statistically significant difference between the two groups of patients (86.4% vs. 87.5%, P = 0.796). Conclusion: Primary biliary cholangitis had no discernible effect in terms of age at onset, biochemical indices, immunological indicators, cirrhosis proportion, ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, or overall liver transplantation-free survival rate in patients with past hepatitis B virus infections.

A normal liver can develop cirrhosis through long-term and repeated stimulation from various etiologies. Histological manifestations like the collapse of hepatic lobular structure (including microvascular structure) and the formation of pseudolobules can lead to portal hypertension and even decompensated cirrhosis. More and more evidence suggests that effective etiological treatment can not only delay but also reverse the progression of cirrhosis. The mechanism of cirrhosis reversal mainly includes the degradation of extracellular matrix, hepatocyte regeneration, and hepatic lobular remodeling. The "gold standard" for the evaluation of cirrhosis reversal at present is still a liver biopsy. Therefore, the histopathological evaluation of cirrhosis reversal is very important for determining the disease's prognosis, efficacy, and mechanism of exploration.

Objective: To understand ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China. Methods: Patients with chronic HBV infection:demographic, virologic, hematologic, blood biochemistry, and antiviral treatment data were extracted from the China Registry of Hepatitis B (CR-HepB) database between 2012 and 2022 for descriptive statistics and change trend analysis. Multiple group comparisons were conducted using the Kruskal Wallis H test, while counting data was compared between groups using χ (2) test. Results: A total of 180 012 patients with chronic HBV infection were included, with a median age of 40 years old, and a male proportion accounting for 60.2%. The HBeAg positive rate was 43.3%. Over time, the median age of new patients each year increased from 39 to 47 years, while the HBeAg positive rate decreased from 51.3% to 32.8%. The initial diagnosis of patients was mainly CHB (71.4%), followed by hepatitis B cirrhosis (11.8%), inactive HBsAg carrier status (10.6%), and chronic HBV carrier status (6.2%). Among the newly registered patients every year from 2012 to 2022, the proportion of hepatitis B cirrhosis remained stable, but after 2019, the proportion of CHB increased and the proportion of other diagnoses decreased. The proportion of patients with cirrhosis increased with age in different age groups, with 3.5%, 19.3%, and 30.4% in the < 40, 40-69, and≥70 age groups, respectively. The proportion of women in patients with cirrhosis also increased with age, from 16.1% in those < 30 years old to 44.3% in those≥80 years old. From 2012 to 2022, the proportion of patients receiving first-line nucleos(t)ide analog antiviral treatment increased year by year, from 51.0% in 2012-2013 to 99.8% in 2022. Conclusion: The CR-HepB registration data reflect the changes in clinical characteristics and antiviral treatment patterns in patients with chronic HBV infection in China over the past ten years and can thus provide a reference to promote hepatitis B diagnosis and treatment practice, as well as scientific research.

Objective: To investigate the effect of electroacupuncture on osteoarthritis in rats and explore the possible mechanism., Methods: Thirty SD rats were randomly divided into osteoarthritis model group, electro-acupuncture group and control group ( n =10), and in the former two groups, early osteoarthritis was induced using a modified DMM surgical modeling method. After successful modeling, the rats in the electro-acupuncture group were treated with electro-acupuncture at bilateral "Housanli" and "Anterior knee point". Behavioral tests of the rats were performed and scored using the LequesneMG scale. Subchondral bone degeneration was observed in each group, and serum levels of IL-1β, ADAMTS-7, MMP-3 and COMP were measured using ELISA. The mRNA and protein expressions of IL-1β, Wnt-7B, β-catenin, ADAMTS-7, and MMP-3 in the cartilage tissue of the knee joints were detected using RT-PCR and Western blotting., Results: In behavioral tests, the rats in the model and electroacupuncture groups had significantly higher LequesneMG scores after modeling than those in the control group ( P < 0.05). After 20 days of treatment, LequesneMG scores were significantly lowered in rats in the electroacupuncture as compared with the model rats ( P < 0.05). Imaging examination revealed obvious subchondral bone damage in both the electroacupuncture group and the model group, but the damages were significantly milder with former group. Compared with the model rats, the rats receiving electroacupuncture had significantly lower serum levels of IL-1β, ADAMTS-7, MMP-3 and COMP ( P < 0.05) with also lower expressions of IL-1β, Wnt-7B, β-catenin, ADAMTS-7 and MMP-3 in the cartilage tissues at both the mRNA and protein levels ( P < 0.05)., Conclusion: Electroacupuncture can alleviate joint pain and improve subchondral bone damage in rats with osteoarthritis by reducing IL-1β levels in the joint cartilage tissue and serum to alleviate joint inflammation and by reducing such cytokines as ADAMTS-7 and MMP-3 via regulating the Wnt-7B/β-catenin signaling pathway.

Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association update the guidelines for the prevention and treatment of chronic hepatitis B (version 2022) in 2022. The latest guidelines recommend more extensive screening and more active antiviral treating for hepatitis B virus infection. This article interprets the essential updates in the guidelines to help deepen understanding and better guide the clinical practice.

Patients with HBeAg-positive and negative chronic hepatitis B (CHB) have different immunological states and disease progression. Hence, the previously recommended antiviral therapy strategies for the two are different. In recent years, the antiviral indications have gradually eased, and the treatment goal has began to pursue clinical cure, as experts and scholars have gradually attached importance to the potential risk of disease progression in hepatitis B patients. Antiviral treatment strategies are gradually becoming uniform for patients with HBeAg-positive and negative. However, among them, HBeAg-negative patients can be combined with HBsAg quantification and other indicators to further screen the clinically cured dominant population in order to formulate the next treatment strategy.

Objective: To compare oxytocin combined with ergometrine with oxytocin alone in terms of primary prophylaxis for postpartum hemorrhage (PPH) at the time of cesarean section (CS). Methods: This was a multicenter double-blind randomized controlled interventional study comparing ergometrine combined with oxytocin and oxytocin alone administered at CS. From December 2018 to November 2019, a total of 298 parturients were enrolled in 16 hospitals nationwide. They were randomly divided into experimental group (ergometrine intra-myometrial injection following oxytocin intravenously; 148 cases) and control group (oxytocin intra-myometrial injection following oxytocin intravenously; 150 cases) according to 1∶1 random allocation. The following indexes were compared between the two groups: (1) main index: blood loss 2 hours (h) after delivery; (2) secondary indicators: postpartum blood loss at 6 h and 24 h, placental retention time, incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution; (3) safety indicators: nausea, vomiting, dizziness and other adverse reactions, and blood pressure at each time point of administration. Results: (1) The blood loss at 2 h after delivery in the experimental group [(402±18) ml] was less than that in the control group [(505±18) ml], and the difference was statistically significant ( P <0.05). (2) The blood loss at 6 h and 24 h after delivery in the experimental group were less than those in the control group, and the differences were statistically significant (all P <0.05). There were no significant differences between the two groups in the incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution (all P >0.05). (3) Adverse reactions occurred in 2 cases (1.4%, 2/148) in the experimental group and 1 case (0.7%, 1/150) in the control group. There was no significant difference between the two groups ( P >0.05). The systolic blood pressure within 2.0 h and diastolic blood pressure within 1.5 h of drug administration in the experimental group were higher than those in the control group, and the differences were statistically significant ( P <0.05), but the blood pressure of the two groups were in the normal range. Conclusion: The use of ergometrine injection in CS could reduce the amount of PPH, which is safe and feasible.

The Chinese Society of Hepatology, Chinese Medical Association published "Expert Opinions on Expanding Antiviral Therapy for Chronic Hepatitis B" in 2022, with a focus on "active screening of the existing patients, paying attention to the potential risk of disease progression, and active intervening of the low level viremia," and recommended that specific actions be taken to further optimize the expanding screening, widening the antiviral indications, and scale up the diagnosis and treatment of low level viremia.

Hepatic fibrosis is a response to various types of hepatic injury, which can lead to cirrhosis and its complications. In recent years, in patients with viral hepatitis, nonalcoholic steatohepatitis, alcoholic liver disease, autoimmune liver disease and others the fibrosis or even early cirrhosis can be regressed if the etiology are controlled. Liver biopsy is still the gold standard for assessing fibrosis reversal, but non-invasive methods such as transient elastography hold great promise due to the ease to use for dynamic monitoring. Mechanisms of hepatic fibrosis reversal include extracellular matrix degradation, hepatocyte regeneration, and vascular remodeling. Presently, novel agents targeting the steps of fibrosis are urgently need for achieving regression of liver fibrosis.

Objective: Our study aims to determine histological regression and clinical improvement after long-term antiviral therapy in hepatitis B virus-related cirrhosis patients. Methods: Treatment-naïve chronic hepatitis B patients with histologically or clinically diagnosed liver cirrhosis were enrolled. Liver biopsies were performed after 5 years entecavir-based antiviral treatment. Patients were followed up every 6 months. Cirrhosis regression was evaluated based on Metavir system and P-I-R score. Clinical improvement was evaluated before and after the long-term treatment. Kruskal Wallis test and Wilcoxon signed-rank test were used for continuous variables, Fisher's exact test was used for categorical variables and multivariate analysis was performed using logistic regression analysis. Results: Totals of 73 patients with HBV-related liver cirrhosis were enrolled. Among them, 30 (41.1%) patients were biopsy proved liver cirrhosis and the remaining 43 (58.9%) cirrhotic patients were diagnosed by clinical features. Based on Metavir system and P-I-R score, 72.6% (53/73) patients attained histological regression. Furthermore, 30.1% (22/73) were defined as significant regression (Metavir decrease ≥2 stage), 42.5% (31/73) were mild regression (Metavir decrease 1 stage or predominantly regressive by P-I-R system if still cirrhosis after treatment) and 27.4% (20/73) were the non-regression. Compared to levels of clinical characteristics at baseline, HBV DNA, ALT, AST, liver stiffness(decreased from 12.7 to 6.4 kPa in significant regression, from 18.1 to 7.3 kPa in mild regression and from 21.4 to 11.2 kPa in non-regression)and Ishak-HAI score significantly decreased after 5 years of anti-HBV treatment, while serum levels of platelets and albumin improved remarkably ( P <0.05). In multivariate analysis, only the pre-treatment liver stiffness level was associated with significant regression ( OR =0.887, 95% CI : 0.802-0.981, P =0.020). Conclusions: After long-term antiviral therapy, patients with HBV-related cirrhosis are easily to attain improvements in clinical parameters, while a certain percentage of these patients still cannot achieve histological reversal.

Objective: To clarify the effect and related factors of antiviral therapy on the change of esophageal varices in patients with hepatitis B virus-related cirrhosis. Methods: Fifty-two cases with hepatitis B virus-related cirrhosis who underwent endoscopy before and after antiviral therapy were selected from prospective cohorts. Patients were divided into three groups: no, mild, and moderate-severe based on the degree of esophageal varices. The changes in the severity of esophageal varices in each group were compared after antiviral therapy. Clinical characteristics (platelet, liver and kidney function, liver stiffness, and virological response) of patients with different regressions were analyzed. Measurement data were analyzed by independent sample t-test, one-way ANOVA, Mann-Whitney U test and Kruskal-Wallis H test, and Chi-Square test was used for count data. Results: All patients received entecavir-based antiviral therapy. The median treatment time was 3.1 (2.5-4.4) years. The proportion of patients without esophageal varices increased from 30.8% to 51.9%, the proportion of mild esophageal varices decreased from 40.4% to 30.8%, and the proportion of patients with moderate-to-severe esophageal varices decreased from 28.8% to 17.3% ( χ 2 =14.067, P =0.001). A total of 40.4% of patients had esophageal varices regression, and 13.5% had esophageal varices progression. The progression rate was significantly higher in patients with moderate-severe esophageal varices than patients with mild and no esophageal varices ( χ 2 =28.126, P <0.001), and 60.0% of patients with moderate-severe esophageal varices still remained in moderate-severe state after antiviral treatment. Baseline platelet count and 5-year mean change rates were significantly lower in patients with progressive moderate-to-severe esophageal varices than in those without progression (+3.3% vs . +34.1%, Z =7.00, P =0.027). Conclusion: After effective antiviral treatment, 40.4% of patients with hepatitis B virus-related cirrhosis combined with esophageal varices has obtained esophageal varices regression, but those with moderate to severe esophageal varices still have a considerable risk of progression while receiving mono antiviral treatment only. Thrombocytopenia and without significant improving are the clinical signs of progression risk after receiving antiviral treatment.

Liver have complex functions with a high workload. Various liver diseases are the result of the interaction of diverse genetic and environmental factors. Moreover, other systemic diseases may also affect liver, producing corresponding manifestations, such as abnormal liver function tests, portal vein or hepatic vein thrombosis, portal hypertension, hepatosplenomegaly and liver space-occupying lesions. Therefore, it is extremely important for hepatologists to have an in-depth understanding of other systemic diseases of hepatic manifestations, especially hematologic, connective tissue, endocrine, and circulatory, in order to improve the level of clinical diagnosis and treatment.

Objective: To analyze the clinical characteristics, treatment response, and prognosis of newly diagnosed symptomatic multiple myeloma (MM) patients with systemic light chain amyloidosis (AL) . Methods: The clinical data of 160 patients with newly diagnosed MM treated at the First Affiliated Hospital of Soochow University from January 1, 2017 to October 31, 2018, were retrospectively analyzed. According to the histopathological biopsy results of bone marrow, skin, and other tissues, the patients were divided into two groups according to whether amyloidosis was combined or not, namely, the MM+AL group and the MM group. The clinical characteristics and treatment responses of the two groups were compared. Results: Among the 160 patients with newly diagnosed MM, there were 42 cases in the MM+AL group and 118 cases in the MM group. In terms of clinical features, the involved light chain and non-involved light chain (dFLC) in the MM+AL group was significantly higher than that in the MM group ( P =0.039) . After induction treatment, the MM+AL group had a higher overall response rate (85.7% vs 79.7%, P <0.05) and higher excellent partial response (76.2% vs 55.1%, P <0.05) . After a median follow-up of 26 (0.25-41) months, there was no significant difference in the progression free survival and overall survival (OS) between the two groups ( P >0.05) . The OS of patients in autologous hematopoietic stem cell transplantation group was better than that in non transplantation group ( P <0.05) .The prognosis of patients with cardiac involvement in the MM+AL group was significantly worse than that in the MM group and MM+AL group without cardiac involvement ( P <0.001) , with a median OS of only 13 months. Conclusion: The differential diagnosis between the MM+AL and MM groups requires histopathology, particularly for patients with significantly increased dFLC. The overall remission rate of patients in MM+AL group after 4 courses of induction chemotherapy was higher than that in MM group. The prognosis of patients with cardiac involvement in MM+AL group was poor.

Objective: To investigate the clinical features, diagnosis,treatment and prognosis of children with acute lymphoblastic leukemia complicated with mucormycosis, and to improve the understanding of the disease. Methods: The clinical data of 3 children with acute lymphoblastic leukemia (ALL) complicated with mucormycosis treated at the First Affiliated Hospital of Zhengzhou University between October 2020 and January 2021 were analyzed retrospectively. Literature search and review covered the China national knowledge infrastructure, Wanfang database and Pubmed using the keywords of "acute lymphoblastic leukemia" and "mucormycosis" up to June 2021. Results: Case 1, a 12-year-old boy, was diagnosed with ALL, developed fever and chest pain during induction therapy. The Metagenomic next-generation sequencing (mNGS) testing of alveolar perfusion fluid suggested infection with Rhizopus oryzae. Amphotericin B combined with posaconazole was applied and amphotericin B was removed after improvement. Bone destruction was indicated by CT. Amphotericin B was applied again. Case 2, a 4-year-old boy, with a history of pallor and tetter, was diagnosed with ALL. He developed cough and fever during induction therapy. mNGS of blood suggested infection with Rhizomucor pusillus. Amphotericin B combined with voriconazole was applied, but the situation was not significantly improved. The disseminated infection occurred. Amphotericin B combined with posaconazole was applied and vacuum sealing drainage was performed. Case 3, a 2-year-old girl, was diagnosed with ALL, developed fever and cough during induction therapy. Rhizomucor pusillus was indicated by mNGS. Amphotericin B combined with posaconazole was used, and posaconazole was stopped after improvement. Follow-up until June 2021, the condition of the 3 children improved. There was no recurrent Mucor infection, and the primary hematopathy was in complete remission. According to the literature, 7 reports were found in Chinese journals, while 17 reports were found in English literature, 25 cases have been reported. Among a total of 28 children, 11 cases rhino-orbito-cerebral mucormycosis, four pulmonary mucormycosis, 2 cutaneous mucormycosis, 2 gastrointestinal mucormycosis and 9 disseminated mucormycosis. There were 17 cases developed infection during induction chemotherapy, 8 cases during maintenance therapy, 3 cases after hematopoietic stem cell transplantation. Voriconazole was used in 15 cases; 19 cases were treated with combined surgery, 7 cases were treated with drugs only, 2 cases were untreated; 21 cases showed improvement after treatment. Death occurred in seven cases. Conclusions: ALL complicated with mucormycosis often occurs in the stage of induction therapy. The clinical features lacked specificity, mNGS can help find the pathogen and provide evidence for diagnosis. Surgical treatment also could be combined when necessary, which is helpful to improve the prognosis.

Objectives: Residual ventricular septal defect (VSD) after congenital heart disease (CHD) is one of the major postoperative complications in cardiac surgery. At present, the commonly used clinical treatment methods for this complication are reoperation to redo surgical repair with cardiopulmonary bypass (CPB) and percutaneous transcatheter device closure, but these 2 methods have their own advantages and disadvantages. Transthoracic punctural closure of residual VSD is a feasible, safe, and novel technique for patients with residual VSD, which avoids not only the risk of difficulties in reoperation under another CPB due to thoracic adhesion, but also the risk of radiation exposure. Moreover, the operation is easier to handle due to short and direct operation path. This study aims to explore the role and value of echocardiography in transthoracic punctural closure of postoperative residual VSD of CHD., Methods: A total of 25 patients, who were admitted in the Department of Cardiovascular Surgery, Second Xiangya Hospital, Central South University and accepted transthoracic punctural closure of postoperative residual VSD, were collected. The morphology of the residual VSD and the distance from tricuspid valve and aortic valve were assessed by trans-esophageal echocardiography (TEE) preoperatively, and the location of the punctural point and the direction of puncture were determined. The establishment of delivery track and releasing of occluder device were accurately guided by TEE intraoperatively. The position and morphology of the occluder device, residual shunt, aortic regurgitaion, and outflow obstruction were required close attention in immediately postoperative evaluation. If any dislocation or residual shunt was found, adjustments were needed immediately. Follow-ups were performed at 3-5 days, 1 month, 3 months, 6 months, and 1 year after operation. Occluder location, residual shunt, valvular function, and other complications were observed by transthoracic echocardiography (TTE) to assess the effect of the closure by occluder. Ventricular size and cardiac function were determined to evaluate the state of ventricular remodeling. In addition, cardiac rhythm was monitored by ECG periodically., Results: Of the 25 patients underwent transthoracic punctural closure of postoperative residual VSD, except 1 double outlet right ventricle (DORV) and 1 tetralogy of fallot (TOF) postoperative patients failured and immediately received a thoracotomy surgery with CPB due to excessive size of residual defect and the irregular morphology, the rest 23 patients were successfully closed by the occluders (92.0%). Among the 23 occluders (diameters range from 5 mm to 10 mm), membrane symmetrical VSD occluders were applied to 17 cases, small-waist-large-edge VSD occluder was applied to 1 case, and eccentric VSD occluders were applied to 5 cases. TEE, applied immediately after occlusion, showed the satisfactory position and the shaping of the occluders. There were no residual shunts, no cardiac tamponade, no thrombosis and outflow obstruction. Two patients had small amounts of pericardial effusion. No newly emerging valve reflux was observed. After 3-48 months of observation, there was no device displacement, newly emerging valve reflux, and residual shunt. One case had incomplete right bundle branch block., Conclusions: Guided by TEE, transthoracic punctural closure of postoperative residual ventricular septal defect of CHD is safe and effective. This procedure has broadened the indications for the minimally invasive treatment of CHD and improved the technical system of the minimally invasive treatment of CHD. TEE which can provide accurate diagnosis and guide the whole process plays a decisive role in this operation technique.

Low-level viremia after antiviral therapy has gradually attracted attention due to its relation to liver fibrosis progression, hepatocellular carcinoma occurrence and long-term survival rate reduction in patients with chronic hepatitis B. In addition, it should be used as a risk factor for intervention during antiviral therapy in order to achieve complete virological response and improve the long-term prognosis of patients.

Long term antiviral therapy with nucleos(ti)ide analogues could suppress HBV viral load thereby prevent the progression to cirrhosis and hepatocellular carcinoma. Interferon-based therapy could result in sustained virological response in a fair proportion of patients and even HBsAg loss in a small proportion of them. Novel therapies aiming at functional cure (loss of HBsAg) are under active development. Among the categories of many, HBV core protein inhibitors are safe and could suppress the HBV DNA and HBV RNA, but only with modest effect on the level of HBsAg; silencing of HBV mRNA by siRNA or antisense oligonucleotides could produce meaningful and sustainable declining in HBsAg levels; immune modulators with different mode of action showed modest effect on the reduction of HBsAg, but with noticeable adverse event (especially transaminase flares) related to the mode of action. Novel clinical trial design on the combination or sequential use of innovative molecules will ultimately lead to the functional cure of CHB in the near future.

Objective: To evaluate the effect of rosmarinic acid (RA) on mitophagy and hypertrophy of cardiomyocytes exposed to high glucose (HG)., Methods: Rat cardiomyocytes (H9c2) exposed to HG (25 mmol/L) were treated with 50 μmol/L RA or with both RA treatment and Parkin siRNA transfection, with the cells cultured in normal glucose (5.5 mmol/L) and HG as the controls. The expressions of PINK1, Parkin and LC3II/LC3I in the cells were detected by Western blotting. The formation of mitochondrial autophagosomes was observed by transmission electron microscope. Flow cytometry was employed to detect the level of reactive oxygen species (ROS) and apoptotic rate of the cells. The activities of respiratory chain complex enzymes were measured by spectrophotometry. Fluorescence enzyme labeling and 3 H-leucine labeling were used for determining the level of membrane potential and protein synthesis rate, respectively. The cell surface area was observed by light microscopy., Results: RA treatment significantly increased the expression levels of PINK1, Parkin and LC3-II/I ( P < 0.05), promoted the formation of mitochondrail autophagosome, inhibited the production of reactive oxygen species ( P < 0.05), restored the activities of mitochondrial respiratory chain complex enzymes and mitochondrial membrane potential ( P < 0.05), inhibited apoptosis ( P < 0.05), and reduced the cell surface area and protein synthesis rate of H9c2 cells induced by HG exposure ( P < 0.05). The protective effects of RA against HG-induced oxidative stress and cardiomyocyte hypertrophy was obviously blocked by inhibition of mitophagy mediated by transfection with Parkin siRNA ( P < 0.05)., Conclusions: RA can protect rat cardiomyocytes against oxidative stress injury and cardiomyocyte hypertrophy induced by HG by activating Parkin-mediated mitophagy.

The rational clinical examination is important. The authors raised the concept of "medical imaging clinical appropriateness (MICA) " to meet the medical need in clinic (for diagnosis or assessment of a kind of disease or syndrome), which means radiologists and clinicians work together to carefully evaluate the necessity and rationality of an examination according to evidence of evidence-based medicine, expertise, experience, and patient's willing.The necessity is prerequisite, the rationality is the core, the evaluation of evidence is the basis, the application of evidence-based medicine is the important method. This work will provide us a series of criteria in the format of guidelines, providing evidence of rational examination for clinicians. Based on hard working and cooperation between radiologists and clinicians, we will establish the system of MICA in China, standardizing medical process, promoting rationalization, optimizing medical resources allocation and usage.

The research and development of innovative drugs targeting the clinical cure of chronic hepatitis B has become active in recent years. In the clinical trials of new drugs for hepatitis B, the use of new design concepts, new methods, and new technologies to evaluate the efficacy of innovative drugs is expected to shorten the clinical research process of candidate new drugs and reduce the cost of new drug development. However, the new designs such as seamless adaptive design and master plan design have few practical applications in clinical trials of innovative hepatitis B drugs. This article will focus on the methodological factors in the design of phase II/III clinical trials of innovative hepatitis B drugs, and introduce the key points of the new clinical trial design in order to provide methodological references for the development of innovative hepatitis B drugs.

The research and development of chronic hepatitis B (CHB) therapeutic drugs has been undergoing rapid development in recent years in order to achieve the World Health Organization's goal of eliminating viral hepatitis as a major public health threat by 2030. The focus of early stage clinical trials (including the first human trial) is the selection of subjects, study design, dose selection, administration method, dose escalation, monitoring, observation and reporting procedures for adverse events/reactions (tolerability evaluation), and criteria for subjects to continue and discontinue administration. Therefore, quantitative pharmacology knowledge is required to analyze the relationship between in vivo drug exposure, efficacy and adverse reactions, and the inclusion of exploratory indicators such as HBV RNA, hepatitis B virus core-related antigen (HBcrAg), etc., to analyze the mechanism and target of innovative drugs and the efficacy of cccDNA in anti-hepatocytes. On the other hand, Phase II-III clinical trials prioritize the optimal dose, efficacy and safety indicators to verify the efficacy and safety of new drugs in a wider range of subjects. This paper refers to the relevant domestic and foreign literature, combined with the author's practical experience in early clinical research, and then briefly introduces the clinical issues that should be paid attention to in the design of clinical trials of CHB innovative drugs.

Objective: To describe the current status of registration and design characteristics of clinical trials of new drugs for curing hepatitis B through domestic and foreign websites, so as to provide references for the follow-up clinical trials of new hepatitis B drugs. Methods: A search was conducted on the US Clinical Trials Database and the Chinese Clinical Trial Registry Center. The search date was from the establishment of the database to May 26, 2020, and the registration trials of new drugs for curing hepatitis B at home and abroad were included. Two researchers independently searched and screened the literature and extracted the data. Results: A total of 106 registered clinical trials of new drugs for curing hepatitis B were included (94 English registration websites and 12 Chinese registration websites), and the number of registrations had increased year by year. Among them, the proportion of therapeutic vaccines and core protein inhibitors were the highest, accounting for 27.4% ( n = 29) and 22.6% ( n = 24), respectively. The vast majority of clinical trials ( n = 96, 90.6%) were in the early stages (Phase I and II). The subjects in phase I clinical trial were mainly healthy people and treated CHB patients, while the subjects in phase II clinical trial were mainly CHB patients who had achieved viral suppression after initial or post-treatment. The main evaluation indicators of Phase I clinical trials were the safety and tolerability of new drugs. The main evaluation indicators in about half of Phase II clinical trials were HBsAg negative conversion/quantitative decline. Overall, the number of clinical trials with the new design was small, accounting for 3.8% (4 / 106). There were relatively few trials of new drugs for curing hepatitis B on domestic registration websites, and the information provided was incomplete. Conclusion: The number of clinical trials of new hepatitis B drugs at home and abroad is increasing year by year, but most of them are in phase I and II, with few adopting new designs. In addition, the information integrity of the domestic website registration center needs to be improved.

An anoxic membrane bioreactor-microalgae membrane reactor coupling system (anoxic MBR-MMR) was used to deal with mariculture wastewater. Pre-anoxic MBR was used for the degradation of organic matter, NO 3 - -N and NO 2 - -N, and the released NH 4 + -N entered MMR for microalgae growth and was removed. Meanwhile, the treatment efficiency and the microalgae recovery were studied, and the membrane fouling behavior was investigated. After running for 91 days, the removal rates of the system toward NO 3 - -N and NH 4 + -N were stable at above 90.0% and 88.0%, respectively. Furthermore, the average removal rates of PO 4 3- -P and TOC were 49.4% and 84.7%, respectively. Under the condition that the microalgae were harvested continuously, the biomass can be stably operated at an average concentration of 9×10 7 cells·mL -1 and good removal efficiency and resource utilization could be achieved. Through infrared spectrum and three-dimensional fluorescence spectrum analysis, the main substances causing membrane fouling in MMR were tryptophan proteins and humic acids. The membrane fouling in MMR was lighter than that in anoxic MBR.

Objective: To investigate the alteration in Golgi and blood-brain barrier after cerebral hemorrhage in SD rats, and to evaluate the effect of butylphthalide on blood-brain barrier. 
 Methods: Sprague-Dawley rats were randomly distributed into 4 groups: a control group, a sham group, an intracerebral hemorrhage (ICH) group, and a butylphthalide group. Brain tissue was collected at 48 h after the blood brain barrier permeability was examined. Western blotting and real-time polymerase chain reaction (real-time PCR) were conducted to explore the change of GM130, Cdc42 and tight junction protein and mRNA expression in rat brain after ICH. Immunohistochemistry (IHC) was performed to explore the distribution of ZO-1 and Occludin in the cerebral vascular endothelial cells around the hematoma.
 Results: The Evans blue (EB) extravasation in the ICH group were much greater than that in the sham group (P<0.05). Butylphthalide treatment significantly decreased Evans blue extravasation compared to the ICH group (P<0.05). Results of Western blotting and real-time PCR showed that GM130, Cdc42, ZO-1/Occludin were decreased (P<0.05). The intervention of butylphthalide significantly upregulated the expressions of Cdc42 as well as ZO-1/Occludin (P<0.05), but exerted no effect on GM130 (P<0.05). Immunofluorescent staining showed that GM130 was co-localized with Cdc42 and administration of butylphthalide improved the expression of Cdc42 around the hematoma without affecting the expression of GM130. IHC showed that expressions of occludin and ZO-1 around the hematoma were significantly decreased in the ICH group (P<0.05), whereas butylphthalide treatment elevated the expressions of ZO-1 and occludin around the hematoma compared with the ICH group (P<0.05).
 Conclusion: Morphology of Golgi apparatus is altered and the blood-brain barrier is destroyed after ICH. The application of butylphthalide can alleviate neurological impairment and blood-brain barrier disruption, which is related to the up-regulation of Cdc42, but not GM130.

Hereditary hemochromatosis is a kind of hereditary metabolic liver disorders. It is caused by mutations in genes related to hemochromatosis, which leads to over deposition of iron in the liver, pancreas, skin, hypophysis, gonad and other organs and tissues of the whole body and is manifested as cirrhosis, diabetes, skin pigmentation, and low libido. Physicians of our country have inadequate understanding and familiarity with this disorder. Both the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases have issued guidelines for the diagnosis and treatment of hemochromatosis, but these two guidelines are complicated and difficult for Chinese clinical physician to comprehend. In 2018, Hepatology International published therapeutic recommendations in HFE hemochromatosis for p.Cys282Tyr homozygous genotype developed by Hemochromatosis International, these recommendations were objective, simple, and practical. We believe the above-mentioned guideline is understandable and helpful for clinicians and patients without medical education background. Therefore, herein the recommendations are translated into Chinese language, with a view to being able to be clinical work guide for the majority of Chinese hepatologists.

Liver cirrhosis is the end stage of chronic liver disease and as the disease progresses to decompensated stage cirrhosis, the mortality rate of patients' increases significantly. The goal of controlling the etiology or treatment in decompensated stage cirrhosis is to improve the liver function of patients, stabilize the disease condition or reverse decompensation, reduce the recurrence of decompensated events and reduce the mortality rate. However, presently, there are few studies on the reversal of cirrhotic decompensation/ re-compensation. Moreover, the effect of prophylactic treatment on re-compensation, evaluation indicators and duration of re-compensation, structure of hepatic lobules and whether microvessels can be reconstructed are unclear, so require further research.

Objective: Portal vein thrombosis (PVT) is a rare and severe clinical manifestation of antiphospholipid syndrome (APS), as well as a predictor of poor prognosis. This study was conducted to explore the clinical features and risk factors of PVT in APS patients. Methods: A total of 123 APS patients diagnosed from 2012 to 2019 were retrospectively enrolled. The diagnosis of PVT was made according to the 2009 American College of Liver Diseases (AASLD) criteria. Clinical and laboratory data were collected. A multivariate (MV) logistic regression model was constructed using a stepwise forward selection procedure among those candidate univariables with P values<0.10. Results: A total of 28 cases with PVT, and 95 control cases without PVT were finally enrolled.The 28 APS-PVT patients included 5 males and 23 females with age range from 17 to 63 years. Clinical manifestations included acute thrombosis in 8 patients, chronic thrombosis in 16, and 4 with portal vein spongiform. As to the involved vessels, single portal vein thrombosis was seen in 20 patients, portal combined with superior mesenteric vein (SMV) and splenic vein in one patient, portal plus SMV in 4 and only SMV in 3 patients. Other manifestations were portal hypertension (16/28), esophageal varices (13/28), spleen infarction (7/28) and gastrointestinal bleeding (4/28). Two antiphospholipid antibodies were positive in 13 cases. Triple positive antibodies were seen in 7 cases. Multivariate logistic regression analysis showed that disease duration less than 0.5 years ( OR= 72.74, 95 %CI 7.50-705.45, P< 0.001), hypoalbuminemia ( OR= 356.45, 95 %CI 19.19-6 620.14, P< 0.001), and elevated erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) ( OR= 14.41, 95 %CI 1.49-139.20, P< 0.001) were independent risk factors for PVT in APS. Conclusion: PVT is usually misdiagnosed due to insidious onset. Short disease duration, hypoalbuminemia and elevated ESR/CRP are risk factors for PVT in APS. Better understanding, early diagnosis and treatment will improve the clinical outcome.

Achieving HBV DNA negative transformation and HBsAg clearance with effective antiviral therapy can reduce the incidence of HCC, but some patients are still at risk of developing HCC. Therefore, screening high-risk patients for close monitoring is essential to reduce the incidence of HCC. This paper reviews the occurrence of HCC, risk factors and risk prediction models of HBV DNA negative transformation and HBsAg clearance, and provides a basis for screening and follow-up management of high-risk group of HCC with chronic hepatitis B.

Cream formula has been mostly used to treat deficiency syndrome. Currently,it has been used to recuperate the body,promote health against aging,and prevent and treat chronic disease. In modern medicine,there are only treatment concepts and methods of diseases,but lack of concepts of " deficiency syndrome" and " restoring deficiency". The concepts of " deficiency syndrome" and " restoring deficiency" could effectively supplement and improve the diagnosis and treatment scheme of some modern diseases. Refractory heart failure,dilated cardiomyopathy,ischemic cardiomyopathy,and valvular heart disease belong to the traditional category of " consumptive disease". The cream formula with the efficacy of restoring deficiency can not only alleviate symptoms and improve the quality of life,but also improve the structure and function of the heart,reduce the dosage of diuretics and the number of hospitalizations,and achieve the purpose of secondary prevention in the treatment of severe heart failure,dilated cardiomyopathy,ischemic cardiomyopathy and valvular heart disease. The cream formula for treating chronic heart failure include Shenqi Pills,Zhenwu Decoction,Yougui Pills,Wuling Powder,Linggui Zhugan Decoction,Danggui Shaoyao Powder,Lizhong Decoction,Buzhong Yiqi Decoction,Guipi Decoction,Yupingfeng Powder,Guizhi Decoction. Long-term administration of cream formula could not only resist aging,but also play an irreplaceable role in the secondary prevention of acute and critical diseases.

In order to treat mariculture wastewater, the pollutant removal performance and membrane fouling characteristics of a microalgae membrane reactor were investigated using Platymonas helgolandica tsingtaoensis . After 60 days of operation, the total nitrogen (TN) and total phosphorus (TP) removal efficiency of the reactor were 73.6% and 77.9%, respectively, and the removal rates of TN and TP reached 15 g·(m 3 ·d) -1 and 2.8 g·(m 3 ·d) -1 . The microalgae in the reactor could be enriched rapidly, with a maximum growth rate of 53.3 mg·(L·d) -1 and a maximum biomass of 1.4 g·L -1 . The microalgae in the reactor were harvested on day 18 and day 36; harvesting did not affect the nitrogen and phosphorus removal efficiency of the reactor. To some extent, the membrane fouling phenomenon was alleviated. The increase in the microalgae biomass would significantly increase the pollutant content of the membrane. The three-dimensional excitation-emission matrix (EEM) spectra results confirmed that tryptophan-like substances and aromatic proteins had a significant effect on membrane fouling.

Objective: To explore the clinical early-middle stage clinical effect of percutaneous spinal endoscopic with the technique of Broad Easy Immediate Surgery(BEIS) for lumbar spinal stenosis., Methods: The clinical data of 57 patients with lumbar spinal stenosis treated by surgery from June 2015 to June 2016 were retrospectively analyzed, including 32 cases treated by percutaneous spinal endoscopic with the technique of BEIS (minimally invasive group) and 25 cases by posterior approach of lumbar pedicle screws internal fixation and intervertebral disc excision with bone graft fusion surgery (open surgery group). The pre-operative general data such as age, Body Mass Index (BMI) and etc. were analysed and compared. The operation time, intraoperative blood loss, hospitalization time of the two groups were analyzed. Visual analogue score(VAS), Oswestry Disability Index(ODI), Japanese Orthopedic Association Score(JOA) of preoperative and at 1 week, 1 month, 3 months, 6 months after surgery were used to evaluate the clinical outcome of the two group., Results: All the operations were successful and all the patients recovered smoothly without severe complications, all the wounds got good healing. The pain of the lumbar and lower limb had been improved after surgery. All the patients were followed up more than 6 months with an average of(10.65±3.38) months. There was no significant difference in general data such as age, BMI, and etc. between two groups( P >0.05). There were significant differences in VAS, ODI between two groups at 1 week, 1, 3, 6 months after surgery( P <0.05). The postoperative lumbar pain of the minimally invasive group had been better improved than the open surgery group. However, there was no significant difference in JOA between two groups at 1 week, 1, 3, 6 months after surgery( P >0.05). Intraoperative blood loss and hospitalization time of minimally invasive group was less than that of open surgery group., Conclusions: BEIS technique has the advantage of less trauma, less bleeding for lumbar stenosis when compared to open surgery. It can better alleviate the postoperative local lumbar pain, and early-middle clinical effect is equivalent to open surgery, so it can be used as a safe and effective surgical treatment for lumbar spinal stenosis., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2019 by the China Journal of Orthopaedics and Traumatology Press.)

Hepatolenticular degeneration (HLD) is an autosomal recessive inherited disorder of copper metabolism. The mutations in the ATP7B gene on chromosome 13 leads to the functional defect of ATP7B, which produces pathological deposits of copper in liver, brain, cornea and kidney, with diverse clinical manifestations in various forms of liver disease, nervous system disease and corneal disease (Kayser-Fleischer rings). Early diagnosis and proper treatment can improve the prognosis of hepatolenticular degeneration. Conversely, it may progress to end-stage liver disease or severe motor dysfunction, which seriously affects patient quality of life.

Objective: To investigate the consequences of the thickness of ganglion cell layer (GCL) and visual field defect of non-functional pituitary adenoma with chiasm compression. Methods: A case control study. The study included 40 (80 eyes) non-functional pituitary adenoma patients in Peking Union Medical College Hospital from March 2015 to February 2017. Twenty patients (no visual field defect group, 40 eyes) of them were detected to be chiasm compressed or touched by the adenoma with no visual field defect detected, and the other 20 patients (visual field defect group, 40 eyes) were the sex-and-age matched pituitary adenoma patients with bitemporal heminopsia. This study also included 20 (control group, 40 eyes) sex-and-age matched healthy controls. The para-papillary retinal nerve fiber layer (RNFL) thickness in 6 quadrants including nasal, temporal, nasal superior, temporal superior, nasal inferior and temporal inferior as well as the macular GCL thickness and ganglion cell-inner plexiform layer (GCIPL) thickness in 4 quadrants including nasal superior, nasal inferior, temporal superior and temporal inferior were measured. The non-parametric test was used to compare the RNFL, GCL and GCIPL thickness among the three groups. Results: The mean age among the three groups was (46±10) years and the difference among the three groups was not significant ( P= 0.88). The sex ratio of the three groups was 9∶11 (male∶female) and the difference among the three groups was not significant. The mean axial length among the three groups was (23.22±0.90) mm and the difference among the three groups was not significant ( P= 0.51). The thickness of para-papillary RNFL of temporal superior, temporal, nasal superior, nasal, nasal inferior quadrants and whole circumference was significantly thinner in the visual field defect group than the control group [(129.88±28.64) μm, (63.63±26.84) μm, (88.08±32.16) μm, (50.68±19.99) μm, (92.48±25.06) μm, and (85.00±20.65) μm vs . (141.10±18.95) μm, (79.12±16.78) μm, (113.68±21.28) μm, (69.67±14.23) μm, (117.80±31.32) μm, and (102.80±9.68) μm, t= 2.26, 3.06, 4.14, 4.84, 4.25, 4.88, all P< 0.05]. In the nasal quadrant, the para-papillary RNFL of the no visual field defect group was significantly thinner compared with the control group [(61.45±9.83) μm vs . (69.67±14.23) μm, t= 2.97, P< 0.05]. The total GCL thickness was (30.48±5.42) μm in the visual field defect group, (31.35±2.77) μm in the no visual field defect group, thinner than that in the control group [(33.32±2.92) μm, t= 2.92, 3.62; both P< 0.05]. The total GCIPL thickness showed no significant difference among the three groups ( P= 0.07). In the superior and inferior temporal quadrants, the GCL and GCIPL thickness showed no significant difference among the three groups (all P> 0.05). In the superior and inferior nasal quadrants, the GCL thickness was (29.41±5.97) μm, and (28.47±5.13) μm in the visual field defect group, (31.15±3.27) μm and (30.61±2.96) μm in the no visual field defect group, and (34.23±3.16) μm and (32.97±2.78) μm in the control group. The GCL thickness in the nasal quadrant was thinner in the visual field defect group ( t= 4.45, 4.82)and the no visual field defect group( t= 4.23, 3.63) than in the control group (all P< 0.01). However, no significant difference in GCL thickness was detected between the visual field defect group and the no visual field defect group (both P> 0.05). In the superior and inferior nasal quadrants, the GCIPL thickness was (54.06±10.50) μm and (51.77±9.18) μm in the visual field defect group, (58.03±4.00) μm and (56.23±5.37) μm in the no visual field defect group, and (62.26±7.11) μm and (59.39±6.64) μm in the control group. The GCIPL thickness was thinner in the nasal quadrant in the visual field defect group than in the control group ( t= 3.95, 4.20, both P< 0.01). Only in the Superior nasal quadrant, the GCIPL was significantly thinner in the no visual field defect group than the control group ( t= 3.25, P< 0.01). Conclusion: The optic GCL may get thinner in pituitary nonfunctional adenoma with chiasm compression patients without the RNFL layer thinning and visual field defect. (Chin J Ophthalmol, 2019, 55: 186 - 194) .

Inherited metabolic liver disease is a kind of metabolic disorders caused by the interactions between host and environmental factors because of genetic defects. The incidence of inherited metabolic liver disease is low and its clinical manifestations are complex and diverse, which initiates difficulties in clinical diagnosis. In addition, hereditary hemochromatosis and Wilson's disease are common types of metabolic abnormalities, often seem in clinical practice, and early diagnosis and treatment can improve the prognosis. Benign recurrent intrahepatic cholestasis in cholestatic liver disease is a benign phenotype of progressive familial intrahepatic cholestasis and progressive familial intrahepatic cholestasis type 3 can progress to adulthood with a poor outcome. The incidence of Gilbert's syndrome is higher in congenital metabolic diseases, and the prognosis is good in absence of special treatment but most importantly, it should be differentiated from Crigler-Najjar syndrome and Dubin-Johnson syndrome. Presently the general characteristic of inherited metabolic liver disease in Chinese population is still vague.

Sellar malignant tumors are uncommon and usually reported as metastatic diseases from breast or lung cancers. Spindle cell carcinoma (SCC) is a rare malignancy and has been found in breast,oral cavity,lungs,kidneys,and hepatobiliary pancreatic system but not in sellar region. We report here the first case of isolated sellar SCC with aggressive features in Peking Union Medical College Hospital. This patient was referred to our hospital on September 9,2015 and discharged on October 16,2015. We described the clinical manifestations,imaging findings,and pathological features of this rare disease.

The application of classic formulas from Shanghan Zabing Lun has a long history in treatment of dysmenorrhea. However, the understanding on how to use classic formula in treatment of dysmenorrhea is still insufficient in the traditional Chinese medicine (TCM), mainly limited to syndrome differentiation and the formula-syndrome correlation. The treatment method of syndrome differentiation is flexible and changeable, but the process is tedious and difficult to copy. In addition, its experience is not easy to summarize and pass on, and it is difficult for beginners to comprehend the essence. Formula-syndrome correlation method is accurate, quick acting, but subjective, too mechanical, and will have obvious side effects in case of prescription mistakes. For complex diseases or when suffering from a variety of diseases, the efficacy of formula-syndrome correlation method is not so obvious. By analyzing the advantages and limitations of these two methods, the author has created a four-dimensional therapy which combines the advantages of these two, from four dimensions including disease differentiation, syndromes differentiation, time differentiation, and constitution differentiation in clinical application for dysmenorrheal. Its clinical curative effect is satisfactory. Four-dimensional therapy is a way of thinking, to guide clinicians for accurate diagnosis and precisely choosing drugs; meanwhile, the personalized health guidance is given according to different constitutions and different seasons, which also has certain significance to treat the undiseased., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

This study explored a strategy of replacing the surface stabilizer of cetyltrimethylammonium bromide (CTAB) on the tag surface with bovine serum albumin (BSA) and developed a BSA coated Au@4-nitrothiophenol(NT)@Ag internal surface-enhanced Raman scattering (SERS) tag Au@NT@Ag@BSA. The Au@NT@Ag@BSA tag retained the monodispersity and high sensitivity of the original tag, while significantly improving the signal stability and biocompatibility. Furthermore, labeling and Raman spectroscopic imaging of SMMC7721 lung cancer cells were realized by the incubation of the cells with the Au@NT@Ag@BSA SERS tags. The results demonstrated that the proposed Au@NT@Ag@BSA internal SERS tags had good potential for in vivo imaging applications.

Hepatitis B core antibody (anti-HBc) targets viral core protein and is produced in patients with hepatitis B virus (HBV) infection, and seroconversion occurs in the early stage of infection and often lasts for a lifetime. Qualitative detection of anti-HBc has been used in clinical practice for many years, while the clinical significance of its quantitative level remains unclear. A novel anti-HBc immunoassay based on double-antigen sandwich ELISA has been developed in recent years and lays a foundation for illustrating the change in the quantitative level of anti-HBc (qAnti-HBc) in HBV infection and its clinical significance. Several recent studies have revealed that qAnti-HBc is associated with the degree of hepatitis activity and response to pharmacotherapy and may become an important basis for selecting antiviral drugs, optimizing therapeutic regimen, and predicting treatment outcome.

Objective: To investigate the methods for qualitative pathological assessment of dynamic changes in liver fibrosis/cirrhosis after antiviral therapy in patients with chronic hepatitis B (CHB), since antiviral therapy can partially reverse liver fibrosis and cirrhosis caused by hepatitis B and semi-quantitative, rather than qualitative, pathological assessment is often used for the research on liver fibrosis regression. Methods: Previously untreated CHB patients with liver fibrosis and cirrhosis were enrolled, and liver biopsy was performed before treatment and at 78 weeks after the antiviral therapy based on entecavir. The follow-up assessment was performed once every half a year. Based on the proportion of different types of fibrous septum, we put forward the new qualitative criteria called P-I-R classification (predominantly progressive, predominantly regressive, and indeterminate) for evaluating dynamic changes in liver fibrosis. This classification or Ishak fibrosis stage was used to evaluate the change in liver fibrosis after treatment and Ishak liver inflammation score was used to evaluate the change in liver inflammation after treatment. Results: A total of 112 CHB patients who underwent liver biopsy before and after treatment were enrolled, and among these patients, 71 with an Ishak stage of ≥3 and qualified results of live biopsy were included in the final analysis. Based on the P-I-R classification, 58% (41/71) were classified as predominantly progressive, 29% (21/71) were classified as indeterminate, and 13% (9/71) were classified as predominantly regressive; there were no significant differences between the three groups in alanine aminotransferase, aspartate aminotransferase, albumin, HBeAg positive rate, HBV DNA, and liver stiffness ( P < 0.05). After treatment, the proportion of predominantly progressive, indeterminate, or predominantly regressive patients changed to 11% (8/71), 11% (8/71), and 78% (55/71), respectively. Among the 35 patients who had no change in Ishak stage after treatment, 72% (25/35) were classified as predominantly regressive and had certain reductions in the Laennec score, percentage of collagen area, and liver stiffness. Conclusion: This new P-I-R classification can be used to assess the dynamic changes in liver fibrosis after antiviral therapy in CHB patients.

Various chronic liver diseases may progress to liver fibrosis or liver cirrhosis. Assessment of the degree of liver fibrosis helps with clinical decision-making, prognosis prediction, and evaluation of therapeutic effect, and therefore, accurate diagnosis and evaluation of the degree of liver fibrosis is a research hotspot at present. The advances in the diagnosis of liver fibrosis in recent years include the publication of international consensuses and guidelines, evaluation of the outcome of liver fibrosis after antiviral therapy, development of the diagnosis of liver fibrosis in patients with non-viral hepatitis, and constant update of noninvasive diagnostic techniques.

Objective: To investigate the efficacy and safety of the new investigational drug pegylated interferon α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 µg/week) combined with ribavirin in the treatment of patients with genotype 1/6 chronic hepatitis C (CHC), with standard-dose Peg-IFN-α-2a combined with ribavirin as a positive control. Methods: A multicenter, randomized, open-label, and positive-controlled phase III clinical trial was performed. Eligible patients with genotype 1/6 CHC were screened out and randomly divided into Peg-IFN-α-2b(Y shape, 40kD) group and Peg-IFN-α-2a group at a ratio of 2:1. The patients in both groups were given oral ribavirin for 48 weeks in addition and then followed up for 24 weeks after drug withdrawal. Abbott Real Time HCV Genotype II was used to determine HCV genotype, and Cobas TaqMan quantitative real-time PCR was used to measure HCV RNA level at 0, 4, 12, 24, 48, and 72 weeks. Adverse events were recorded in detail. The primary efficacy endpoint was sustained virological response (SVR), and a non-inferiority test was also performed. Results: A total of 561 patients with genotype 1/6 CHC were enrolled, among whom 529 received treatment; 90.9% of these patients had genotype 1 CHC. The data of the full analysis set showed that SVR rate was 69.80% (95% CI 65.00%-74.60%) in the trial group and 74.16% (95% CI 67.73%-80.59%) in the control group ( P = 0.297 0). The data of the per protocol set (PPS) showed that SVR rate was 80.63% (95% CI 76.04%-85.23%) in the trial group and 81.33% (95% CI 75.10%-87.57%) in the control group ( P = 0.849 8), and the 95% CI of rate difference conformed to the non-inferiority standard. The analysis of the PPS population showed that of all subjects, 47.9% achieved rapid virologic response, with a positive predictive value of 93.8%. The incidence rate of adverse events was 96.30% in the trial group and 94.94% in the control group, and the incidence rate of serious adverse events was 5.13% in the trail group and 5.06% in the control group. Conclusion: In the regimen of Peg-IFN-α combined with ribavirin for the treatment of genotype 1/6 CHC, the new investigational drug Peg-IFN-α-2b(Y shape, 40 kD) has comparable clinical effect and safety to the control drug Peg-IFN-α-2a.

Withdrawal of nucleos(t)ide analogues in chronic hepatitis B patients has always been a clinical problem for scholars and patients. Many studies showed that the withdrawal of nucleos(t)ide analogues often leads to a high recurrence rate in clinical practice. The factors such as age, baseline HBV DNA load, time of drug consolidation therapy, and HBsAg level are associated with recurrence after withdrawal of nucleos(t)ide analogues. In addition, there are many studies on safety after withdrawal of nucleos(t)ide analogues and response to retreatment after recurrence. This article reviews the research advances in the aspects mentioned above.