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.
Humans ; Hepatitis B, Chronic/drug therapy* ; Hepatitis B/drug therapy* ; Hepatitis B virus ; Antiviral Agents/therapeutic use* ; Gastroenterology

Objective:To investigate the expression and clinical significance of endostatin (ES) and angiostatin (AS) in pterygium.Methods:From January 2016 to December 2018, 60 cases (60 eyes) of pterygium tissue and 60 cases (60 eyes) of normal human conjunctival tissue were selected from the eye surgery of Traditional Chinese Medicine Hospital of Yiwu.HE staining was used to observe the morphological changes of pterygium and normal conjunctival tissue.Western blot was used to measure ES and AS protein levels in the tissues of pterygium group and control group.Results:HE staining showed that in the normal bulbar conjunctival tissue, the stromal layer was connective tissue and the epithelial layer was columnar epithelium; in the pterygium, the basal layer had a large number of new blood vessels, fibroblasts, collagen fibers, and inflammatory cells infiltrated around the blood vessels; the epithelium showed different degrees of hyperplasia.The protein levels of ES and AS in pterygium tissues[(0.35±0.12), (0.62±0.17)] were higher than those in the control group [(0.13±0.08), (0.16±0.09)]( t=11.816, 18.524, P=0.000, 0.000). The protein levels of ES and AS in the pterygium tissues of the recurrent group [(0.63±0.15), (0.87±0.21)] were higher than those in the initial group [(0.22±0.11), (0.45±0.16)]( t=17.073, 12.323, P=0.000, 0.000). There was positive correlation between ES and AS in pterygium ( r=0.571, P=0.000). Conclusion:The levels of ES and AS in pterygium tissue are increased, and ES and AS may be involved in the occurrence and recurrence of pterygium.

Heparin and heparan sulfate are a class of glycosaminoglycans for clinical anticoagulation. Heparosan N-sulfate-glucuronate 5-epimerase (C5, EC 5.1.3.17) is a critical modifying enzyme in the synthesis of heparin and heparan sulfate, and catalyzes the inversion of carboxyl group at position 5 on D-glucuronic acid (D-GlcA) of N-sulfoheparosan to form L-iduronic acid (L-IdoA). In this study, the heparin C5 epimerase gene Glce from zebrafish was expressed and molecularly modified in Escherichia coli. After comparing three expression vectors of pET-20b (+), pET-28a (+) and pCold Ⅲ, C5 activity reached the highest ((1 873.61±5.42) U/L) with the vector pCold Ⅲ. Then we fused the solution-promoting label SET2 at the N-terminal for increasing the soluble expression of C5. As a result, the soluble protein expression was increased by 50% compared with the control, and the enzyme activity reached (2 409±6.43) U/L. Based on this, site-directed mutations near the substrate binding pocket were performed through rational design, the optimal mutant (V153R) enzyme activity and specific enzyme activity were (5 804±5.63) U/L and (145.1±2.33) U/mg, respectively 2.41-fold and 2.28-fold of the original enzyme. Modification and expression optimization of heparin C5 epimerase has laid the foundation for heparin enzymatic catalytic biosynthesis.
Animals ; Carbohydrate Epimerases ; biosynthesis ; chemistry ; genetics ; Escherichia coli ; Gene Expression ; Heparin ; metabolism ; Heparitin Sulfate ; metabolism ; Iduronic Acid ; metabolism ; Zebrafish Proteins ; biosynthesis ; chemistry ; genetics

Objective:To explore the clinical characteristics and establish a corresponding prognostic scoring model in patients with early-stage clinical features of hepatitis B-induced acute-on-chronic liver failure (HBV-ACLF).Methods:Clinical characteristics of 725 cases with hepatitis B-related acute-on-chronic hepatic dysfunction (HBV-ACHD) were retrospectively analyzed using Chinese group on the study of severe hepatitis B (COSSH). The independent risk factors associated with 90-day prognosis to establish a prognostic scoring model was analyzed by multivariate Cox regression, and was validated by 500 internal and 390 external HBV-ACHD patients.Results:Among 725 cases with HBV-ACHD, 76.8% were male, 96.8% had cirrhosis base,66.5% had complications of ascites, 4.1% had coagulation failure in respect to organ failure, and 9.2% had 90-day mortality rate. Multivariate Cox regression analysis showed that TBil, WBC and ALP were the best predictors of 90-day mortality rate in HBV-ACHD patients. The established scoring model was COSS-HACHADs = 0.75 × ln(WBC) + 0.57 × ln(TBil)-0.94 × ln(ALP) +10. The area under the receiver operating characteristic curve (AUROC) of subjects was significantly higher than MELD, MELD-Na, CTP and CLIF-C ADs( P < 0.05). An analysis of 500 and 390 cases of internal random selection group and external group had similar verified results. Conclusion:HBV-ACHD patients are a group of people with decompensated cirrhosis combined with small number of organ failure, and the 90-day mortality rate is 9.2%. COSSH-ACHDs have a higher predictive effect on HBV-ACHD patients' 90-day prognosis, and thus provide evidence-based medicine for early clinical diagnosis and treatment.

Objective: To study the effect of pranoprofen combined with 0.3% hyaluronic acid sodium eye drops on dry eye after cataract surgery. Methods: From July 2016 to June 2018, 80 patients with dry eye after cataract surgery in the Traditional Chinese Medicine Hospital of Yiwu were selected study objects, and they were randomly divided into control group and observation group by double blind random assignment method, with 40 cases in each group.The control group was treated with pranoprofen eye drops alone, while the observation group was treated with pranoprofen eye drops combined with 0.3% hyaluronic acid sodium eye drops.The lacrimal gland secretion, corneal fluorescein staining (FL) and corneal rupture time (BUT) were observed before and after treatment in the two groups.The improvement of dry eye symptoms, ocular surface signs score and life satisfaction were observed in the two groups. Results: There were no statistically significant differences in lacrimal gland secretion test, FL and BUT test before treatment between the two groups (all P>0.05). The lacrimal gland secretion test, BUT and FL in the control group were (6.44±0.32)mm/5 min, (1.60±0.45), (4.31±0.23)s, respectively, which in the observation group were (9.03±0.86)mm/5 min, (0.66±0.25), (5.20±0.33)s, respectively, the differences were statistically significant(t=17.79, 11.43, 13.59, all P<0.05). In the control group, significant improvement in dry eye symptoms observed in 26 cases, slightly improved in 9 cases, no improvement in 5 cases, which in the observation group were 32 cases, 8 cases, 0 case, and there was statistically significant difference between the two groups (Z=0.342, P=0.006). Ocular surface signs analysis: before treatment, the score of the control group was (3.61±1.33)points, which of the observation group was (3.65±1.27)points, the difference was not statistically significant (P=0.051); after treatment, the score of the control group was (1.97±1.21)points, which of the observation group was (1.32±0.91)points, the difference was statistically significant (t=4.673, P=0.003). Life satisfaction score: after 1, 2 and 3 weeks of treatment, the control group was (20.62±3.17)points, (22.35±2.17)points, (29.16±3.19)points respectively, and the observation group was (23.32±2.16)points, (27.41±2.51)points, (33.11±4.15)points respectively, the differences are statistically significant between the two groups(t=6.29, 8.34, 6.31, P=0.002, 0.005, 0.013). Conclusion Pranoprofen combined with hyaluronic acid sodium eye drops has significant effect in the treatment of dry eye after cataract surgery.

Objective: To evaluate the efficacy and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) 25/150/100 mg once daily and dasabuvir (DSV) 250 mg twice daily combined with ribavirin in adult patients of Mainland China with chronic HCV genotype 1b infection and compensated cirrhosis. Methods: An open-label, multicenter, phase 3 clinical trial study was conducted in mainland China, Taiwan, and South Korea. Adult patients with compensated cirrhosis (Metavir score =F4) who were newly diagnosed and treated for hepatitis C virus genotype 1b infection with ombitasvir/paritaprevir/ritonavir and dasabuvir combined with ribavirin for 12 weeks were included. Assessed SVR rate of patients obtained at 12 and 24 weeks after drug withdrawal. Efficacy and safety were evaluated in patients who received at least one time study drugs. Results: A total of 63 patients from mainland China were enrolled, 62 of whom (98.4%) had a baseline Child-Pugh score of 5 points. The overall rate of SVR12 and SVR24 in patients was 100% (95% CI: 94.3% to 100.0%). Most of the adverse events that occurred were mild. The incidence of common (≥10%) adverse events and laboratory abnormalities included elevated total bilirubin (36.5%), weakness (19.0%), elevated unconjugated bilirubin (19.0%) and conjugated bilirubin (17.5%), and anemia (14.3%). Three cases (4.8%) of patients experienced Grade ≥ 3 adverse events that were considered by the investigators to be unrelated to the study drug. None patients had adverse events leading to premature drug withdrawal. Conclusion Mainland Chinese patients with chronic HCV genotype 1b infection and compensated cirrhosis who were treated with OBV/PTV/r plus DSV combined with RBV for 12 weeks achieved 100 % SVR at 12 and 24 weeks after drug withdrawal. Tolerability and safety were good, and majority of adverse events were mild.

Objective: To evaluate the safety and efficacy of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) 25/150/100 mg once daily combined with dasabuvir 250mg, twice daily in non-cirrhotic Chinese adult patients with newly diagnosed and treated chronic HCV genotype 1b infection. Methods: A randomized, double-blind, placebo-controlled, multicenter phase 3 clinical trial was conducted in mainland China, Korea, and Taiwan.Safety and efficacy of OBV/PTV/r plus DSV administered for 12 weeks were evaluated in a newly diagnosed and treated (interferon alpha /pegylated interferon alpha) and ribavirin non-cirrhotic adults with chronic HCVgenotype 1b infection. Patients randomly received OBV/PTV/r plus DSV for 12 weeks (Group A), or placebo for 12 weeks (Group B) followed by an open-label phase of OBV/PTV/r plus DSV for 12 weeks. Sustained response (SVR12) rate obtained at 12 weeks and (SVR24) 24 weeks after discontinuation of treatment, and the incidence of adverse events and laboratory abnormalities after double-blind and open-label phase treatment were assessed. Results: A total of 410 cases of Chinese patients were included and randomly assigned to group A and B (with 205 cases in each group) in a 1:1 ratio. The rates of SVR12 and SVR24 were 99% (95% CI: 94.8% - 99.8%) in the newly diagnosed patients in group A (205 patients) and the rates of SVR12 and SVR24 were 100% in treated patients (95% CI: 96.3% - 100%). Different baseline characteristics had no effect on SVR12 and SVR24 rates. Most of the adverse events occurred were mild, asymptomatic, and≥ 3 laboratory abnormalities during treatment were rare, including elevation of alanine aminotransferase (2 cases in double-blind stage A group), aspartate aminotransferase (Double-blind stage A (3 cases) and total bilirubin (1 case in open-label phase B group); however, those mild adverse events could be recovered after drug withdrawal or discontinuation. only1 person discontinued drugs due to adverse events (Group B, open-label phase). Conclusion The 12 weeks treatment course of OBV/PTV/r combined with DSV produced 99% ~ 100% rates of SVR12 and SVR24 in non-cirrhotic Asian adult patients with newly diagnosed and treated chronic HCV genotype 1b infection, and the tolerance and safety were good.

Objective To study the association between blood glucose control and mild cognitive impairment (MCI) in patients with diabetes mellitus and small-artery occlusion (SAO).Methods A screening study of cognitive impairment was conducted in the 676 patients diagnosed with SAO who had been treated at Department of Neurology,Huanhu Hospital from January 2010 through June 2017.They were divided into a normal cognition group (n=629) and an MCI group (n=47) according to the screening results.They were also divided into 4 groups according to their history of diabetes and levels of hemoglobin Alc:normal blood glucose group (n=398),stringent goals group (n=59),general goals group (n=46) and goals-not-met group (n=173).The differences were compared in terms of Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment Scale (MoCA) scores between the normal blood glucose,stringent goals,general goals and goals-not-met groups.We also analyzed the general clinical data and risk factors between the normal cognition and MCI groups.Variables of confounders that were identified as significant were entered into logistic regression.Results There were significant differences in MMSE and MoCA scores between the 4 groups (P＜0.05).Between the normal cognition and MCI groups,significant differences were found in proportion of smokers,blood glucose level and severity of stroke (P＜0.05).Logistic regression analysis showed that compared with the normal blood glucose group the incidence of MCI was 2.707-fold higher in the stringent goals group (OR=2.707,95％ CI:1.035～7.083,P=0.042),2.963-fold higher in the general goals group (OR=2.963,95％ CI:1.064～8.277,P=0.038) and 2.604-fold higher in the goals-not-met group (OR=2.604,95％ CI:1.269～5.341,P=0.009).Conclusions MCI is more likely to occur in acute phase in patients with diabetes and SAO stroke.The patients can benefit from joint managements of diabetes,stroke and cognitive dysfunction in clinical practice.

OBJECTIVETo evaluate the efficacy and safety of anagrelide in essential thrombocythemia (ET).

METHODSPatients who diagnosed as ET according to the World Health Organization classification were enrolled. Each patient was assigned to take anagrelide hydrochloride capsule or hydroxyurea tablet by random 1∶1 ratio. Dose of anagrelide started at 2 mg/d, then increased gradually and the maximum dose was 10 mg/d until the platelet counts dropped to (100-400) × 10⁹/L, one month later gradually reduced to maintain dose. The dose of hydroxyurea was 1000 mg/d at beginning, then increased gradually, when platelet counts dropped to (100-400)×10⁹/L and kept for one month, reduced to maintain dose as 10 mg·kg⁻¹·d⁻¹. The observation period was 12 weeks.

RESULTSA total of 222 patients were enrolled in seventeen centers (including 113 patients treated with anagrelide and 109 with hydroxyurea). Therapy efficacy can be evaluated in 198 patients (including 97 patients administered with anagrelide and 101 with hydroxyurea). At 12th weeks of therapy, the hematologic remission rate was 87.63% (85/97) in anagrelide group and 88.12% (89/107) in hydroxyurea group, the differences between the two groups were not significant (P=0.173). Treatment with anagrelide lowered the platelet counts by a median of 393 (362-1 339) × 10⁹/L from a median of 827 (562-1657) × 109/L at the beginning of the observation to 400(127-1130)×10⁹/L after 12 weeks (P<0.001), which were similar to the treatment result of hydroxyurea by a median drop of 398 (597-1846)× 10⁹/L (P=0.982). The median time to achieving response of anagrelide group was 7 (3-14) days, superior to that of hydroxyurea for 21 (14-28) significantly (P=0.003). Frequency of anagrelide related adverse events was 65.49 % (74/113), including cardiopalmus (36.28% ), headache (21.24% ), fatigue (14.16% ) and dizzy (11.50% ).

CONCLUSIONAnagrelide was effective in patients with ET which had similar hematologic remission rate to hydroxyurea and could take effect more quickly than hydroxyurea. Incidence of adverse events was undifferentiated between anagrelide and hydroxyurea, but anagrelide treatment had tolerable adverse effects and no hematologic toxicity.

Humans ; Hydroxyurea ; administration & dosage ; therapeutic use ; Platelet Aggregation Inhibitors ; administration & dosage ; therapeutic use ; Platelet Count ; Quinazolines ; administration & dosage ; therapeutic use ; Thrombocythemia, Essential ; drug therapy ; Treatment Outcome

Objective To investigate the relationship between various stages of chronic hepatitis B virus (HBV) infection and lipid metabolism and its influencing factors.Methods Seventy-two cases of chronic hepatitis B (CHB),40 cases of liver cirrhosis and 17 cases of hepatocellular carcinoma (HCC) were enrolled.One-way ANOVA analyses were used to compare age,gender,liver function,lipid metabolism,and HBV DNA levels of each group.Pearson correlation analysis was used to study the correlation between HBV DNA and lipid metabolism.Binary Logistic regression analyses were performed to explore the risk factors of cirrhosis and HCC in patients with CHB.Results Differences of age,alanine aminotransferase (ALT),albumin (Alb),triglyceride (TG),and cholesterol(CHO) among the three groups (CHB group,cirrhosis group and HCC group) were statistically significant (all P＜0.05).TG levels in cirrhosis and HCC groups were (-0.061± 0.234)lg mmol/L and (-0.061±0.253) lg mmol/L,respectively,which were both significantly lower than that of the CHB group (0.116±0.182) lg mmol/L (F=11.466,P=0.000).CHO level in cirrhosis group was (0.460±0.333) lg mmol/L,which was lower than that in CHB group (0.586±0.101) lg mmol/L (F=4.892,P=0.009).The HBV DNA levels inversely correlated with TG and CHO levels in CHB group (r=-0.266,P=0.024; r=-0.309,P=0.008,respectively).The HBV DNA levels of cirrhosis and HCC patients positively correlated with ALT levels (r=0.355,P =0.007).Old age (OR=1.096,95％CI:1.025-1.172),low Alb (OR=0.000,95％CI:0.000-0.000),and low levels of ALT (OR=0.128,95％CI:0.026-0.641) were risk factors for development of cirrhosis and HCC in CHB patients (all P＜0.05).Conclusions With the progression of liver injuries,TG and CHO levels are reduced.Further studies of correlation between risk factors for the development of cirrhosis and HCC and lipid metabolism in CHB patients are needed.