[Efficacy and safety of different doses of antiviral agents in the treatment of herpes zoster: a meta-analysis].

Objective: To systematically evaluate the efficacy and safety of different doses of antiviral drugs in the treatment of herpes zoster. Methods: PubMed, EMBASE, Cochrane Library, VIP, CNKI and WanFang database up to April 9, 2022 were searched. Two reviewers selected the studies according to inclusion and exclusion criteria, and the Cochrane bias risk assessment tool was used for quality evaluation. Data were analyzed by Revman 5.4 software for meta-analysis. The qualitative data used relative risk (RR) as the effect index, and the quantitative data used mean difference (MD) as the effect index. The point estimates and 95%CI of each effect were given. Results: Fourteen randomized controlled trials with 1 831 patients were included in the study. Compared with the 200 mg acyclovir with five times a day, the 800 mg can improve the effective rate, shorten the blister stopping time (MD=-1.29, 95%CI:-1.62- -0.96, P<0.001), relieve the pain faster (MD=-2.73, 95%CI:-4.37- -1.09, P=0.001), shorten the scabbing time (MD=-2.42, 95%CI:-2.96- -1.89, P<0.001) without increasing the adverse reaction rate (RR=1.64, 95%CI:0.80-3.36, P=0.17); Compared with the 300 mg valaciclovir with twice daily, the 900-1 000 mg valaciclovir with three times a day can improve the effective rate(RR=1.17, 95%CI:1.04-1.32, P=0.007), shorten the blister stopping time (MD=-1.53, 95%CI:-2.54- -0.51, P=0.003), relieve the pain faster (MD=-1.04, 95%CI:-1.30- -0.77, P<0.001), shorten the scabbing time (MD=-1.78, 95%CI:-2.80- -0.76, P<0.001), reduce the incidence of postherpetic neuralgia(RR=0.28, 95%CI:0.15-0.52, P<0.001) without increasing the adverse reaction rate (RR=1.47, 95%CI:0.93-2.32, P=0.10); In immunocompromised patients, compared with 1 000 mg valaciclovir with three times a day, 2 000 mg cannot significantly improve the treatment efficacy. There was no significant difference among the efficacy of 250 mg, 500 mg and 750 mg famciclovir, three times a day, in the treatment of herpes zoster. Conclusion: The 800 mg acyclovir with five times a day; 900-1 000 mg valaciclovir and 250 mg famciclovir with three times a day, are better choices in the treatment of herpes zoster.

[Clinical characteristics of 114 patients with iridocorneal endothelial syndrome].

Objective: To investigate the clinical features in patients with iridocorneal endothelial (ICE) syndrome. Methods: A retrospective case series study. Data of clinical manifestations of patients with ICE syndrome including clinical subtypes, presenting visual acuity, clinical features and secondary glaucoma were collected from January 2014 to May 2020 in the Eye Hospital, School of Ophthalmology and Optometry, Wenzhou Medical University. The Wald's Chi-square test of generalized estimating equations was performed to analyze the differences in three clinical subtypes. Results: A total of 127 eyes of 114 subjects (64 females and 50 males) were included. Mean±SD age at presentation was (49±13) years. There were 53 patients (46.5%) with Chandler's syndrome (CS), 36 patients (31.6%) with progressive iris atrophy (PIA), 24 patients (21.0%) with Cogan-Reese syndrome (CRS) and one patient (0.9%) with an undetermined subtype. And 101 patients (88.6%) had uniocular ICE syndrome. Approximately 81.7% (49/60), 56.1% (23/41) and 41.7% (10/24) of eyes presented visual acuity <0.3 in patients with CS, PIA and CRS, respectively. Corneal edema was most common in CS (52.5%, 32/61), followed by PIA (29.3%, 12/41) and CRS (20.8%, 5/24). Corectopia was found in 95.8% (23/24) of eyes with CRS, 95.1% (39/41) of eyes with PIA and 78.7% (48/61) of eyes with CS. Polycoria was observed in 29.3% (12/41) of eyes with PIA, 3.3% (2/61) of eyes with CS and 8.3% (2/24) of eyes with CRS. Ectropion uvea was most common in CRS (54.2%, 13/24), followed by 16.4% (10/61) in CS and 12.2% (5/41) in PIA. Glaucoma was found in 94 eyes (74.0%, 94/127). Among them, 60.7% (37/61) of CS, 80.5% (33/41) of PIA and 95.8% (23/24) of CRS had secondary glaucoma. The difference of presenting visual acuity, corneal edema, corectopia, polycoria, ectropion uveae and secondary glaucoma in three clinical subtypes all had statistical significance (Wald χ2=13.87, 10.77, 965.78, 11.45, 15.00, 222.04; all P<0.05). And 86.2% of eyes (81/94) had glaucoma surgeries and 41 eyes (43.6%, 41/94) had the intraocular pressure well controlled with various interventions. Conclusions: ICE syndrome is mostly uniocular and more common in middle-aged patients. CS is the most common clinical subtype with poor presenting visual acuity. About 3/4 of eyes have secondary glaucoma, and the majority of them require surgical interventions, but prognoses are discouraging.

[Prognostic factors affecting the success of conversion chemotherapy in patients with unresectable liver metastases from initially colorectal cancer].

Objective: To investigate the factors affecting the success of conversion therapy in patients with initially unresectable colorectal cancer liver metastases (CRLM) in order to provide evidence-based medical evidence for formulating individualized treatment strategies for patients. Methods: A retrospective case-control study was used in this study. Clinical data of 232 patients with initially unresectable CRLM receiving first-line systemic treatment in Sun Yat-sen University Cancer Center from January 2013 to January 2020 were collected, including 98 patients of successful conversion and 134 patients of failed conversion as control. Conversion therapy scheme: 38 patients received FOLFOXIRI regimen chemotherapy (irinotecan, oxaliplatin, calcium folinate and fluorouracil), 152 patients received FOLFOX regimen (oxaliplatin, calcium folinate and fluorouracil), 19 patients received FOLRIRI regimen (irinotecan, calcium folinate and fluorouracil), 23 patients received systemic chemotherapy combined with fluorouridine hepatic artery infusion chemotherapy; 168 patients received targeted therapy, including 68 of bevacizumab and 100 of cetuximab. Logistics analysis was used to compare the factors affecting the success of conversion therapy. The Kaplan-Meier method was used to calculate progression-free survival (PFS), and the Log-rank test was used for survival comparison. Results: Among 232 patients, 98 patients had successful conversions and 134 patients had failed conversions with a successful conversion rate of 42.2%, meanwhile 30 patients underwent simple hepatectomy and 68 underwent hepatectomy combined with intraoperative radiofrequency ablation. After first-line chemotherapy, 111 patients (47.8%) were partial remission, 57 patients (24.6%) were stable disease, and 64 patients (27.6%) were progression disease. During the median follow-up of 18.8 (1.0-87.9) months, 148 patients were dead or with tumor progression. The median PFS time of patients with successful conversion was longer than that of patients with failed conversion (31.0 months vs. 9.9 months, P<0.001). Univariate analysis found that the bilobar distribution of liver tumors (P=0.003), elevated baseline carcinoembryonic antigen (CEA) levels (P=0.024), tumor invasion of the portal vein (P=0.001), number of metastatic tumor>8 (P<0.001), non-FOLFOXIRI (P=0.005), and no targeted therapy (P=0.038) were high risk factors for the failed conversion therapy. The results of multivariate logistics analysis indicated that the number of metastatic tumor >8 (OR=2.422, 95%CI: 1.291-4.544, P=0.006), portal vein invasion (OR=2.727, 95%CI: 1.237-4.170, P=0.008) were the independent risk factors for failed conversion therapy, while FOLFOXIRI regimen (OR=0.300, 95%CI: 0.135-0.666, P=0.003) and targeted drugs (OR=0.411, 95%CI: 0.209-0.809, P=0.010) were independent protective factors for successful conversion therapy. Conclusions: The number of metastatic tumor and portal vein invasion are key factors that affect the outcomes of conversion therapy for initially unresectable CRLM. If a patient can tolerate chemotherapy, a combination program of three-drug and targeted therapy is preferred for the active conversion therapy.

Intervention effects of four exercise modalities on nonalcoholic fatty liver disease: a systematic review and Bayesian network meta-analysis.

OBJECTIVE: This study aimed to evaluate the effect of four exercise modalities on patients with nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: Databases of CNKI, Wanfang, VIP, Web of Science, PubMed, Cochrane Library, Medline, and Embase were searched for relevant studies. The literature search was restricted to those published between January 2010 and June 2021. Randomized controlled trials of exercise interventions on NAFLD were collected. Data were presented as statistical graphics using ADDIS 1.16.5 and R-Studio 4.1. RESULTS: Seventeen controlled studies analyzing 1627 patients with NAFLD were included. Patients were divided into the control group (n=688), aerobic training group (AT, n=554), resistance training group (RT, n=232), high-intensity interval training group (HIIT, n=53), and aerobic training with resistance training group (AT+RT, n=100). Results of the statistical analysis showed that the combined exercise intervention had the most significant effect on the total serum cholesterol of patients' mean difference [MD=0.47(0.23, 0.73), p<0.05]. Levels of alanine aminotransferase and aspartate aminotransferase were improved, but no significant difference was found in their levels in the four groups of exercise intervention. The intervention effect of the four exercises on blood lipid and liver enzymes in patients with NAFLD was in the order of AT+RT > HIIT > RT > AT > control. CONCLUSIONS: Exercise interventions are recommended as stand-alone or adjunctive therapy. For patients with NAFLD who can tolerate various exercises, priority should be given to AT+RT exercise 4-5 times per week. The exercise intensity should be 50%-70% of the maximum heart rate and performed for >3 months to improve the effectiveness of the exercise supervision intervention.

[A meta-analysis of prevalence of diabetic retinopathy in China].

Objective: To analyze and summarize the prevalence of diabetic retinopathy (DR) in China, and provide scientific evidence for its prevention and intervention. Methods: Literature search of PubMed, Web of Science, Embase, Wanfangdata, Vip and CNKI between 1990 and 2020 was performed to retrieve epidemiological studies of DR in China. The total prevalence of DR was analyzed by performing a meta-analysis, and the prevalences of DR in different regions and age groups were also evaluated by subgroup analyses. Results: A total of 40 studies were enrolled. The total sample size of the general population was 282 620, and the total number of diabetic patients was 47 022. The prevalence of DR in the general population and diabetic patients was 1.7% (95%CI: 1.4%-2.0%) and 22.4% (95% CI: 18.8%-26.1%), respectively. The highest prevalence of DR was found in patients aged 50-59 years (22.1%). Among the diabetic population, the prevalence of DR was high in North (27.7%) and Northeast China (23.7%), but the East China had the largest estimated number of DR patients (4 971 000). Moreover, the prevalence of DR in rural areas (34.0%) was higher than that in urban areas (18.7%). Conclusions: The prevalence of DR is high in Chinese diabetic population, and there are differences among regions and age subgroups. The results of the current meta-analysis emphasize the necessity of DR screening for diabetic population, especially in rural areas.

[Clinical features and gene mutation analysis of patients with Niemann-Pick disease type C].

Objective: To analyze the clinical manifestations, therapeutic efficacy, prognosis and characteristics of NPC1 mutation in Chinese patients with Niemann-Pick disease type C(NPC). Methods: Ten unrelated Chinese NPC patients were diagnosed by NPC1 mutation analysis from July 2013 to February 2017 in Beijing Tian Tan Hospital of Capital Medical University. Clinical data of 10 cases were analyzed retrospectively which included clinical manifestations, laboratory results and NPC1 gene mutation features, and a series of follow-up were carried out about therapeutic efficacy and prognosis. Results: Ten patients suffering from NPC included 5 males and 5 females, aged from 42 days to 14 years when they presented to Tian Tan Hospital. According to their age of neurological onset, 4 were in early infantile period, 2 in late infantile period, 2 in juvenile periods, and the other 2 cases in neonatal period. They all presented with splenomegaly, 5 of 10 accompanied with hepatomegaly. Two cases of neonatal subtype presented mainly with delayed neonatal cholestatic jaundice and hepatosplenomegaly, accompanied with decreased muscle tone and slight psychomotor retardation. The other 8 cases presented with severe neurological involvement, such as progressive encephalopathy, ataxia and language impairment, 4 with dystonia, 3 with decreased muscle tension, 5 with vertical supranuclear gaze palsy, 5 with gelastic cataplexy, and 4 with epilepsy. Eight of 9 cases presented with foam cells in their bone marrow. Head MRI showed diffuse cerebral atrophy in 8 cases, thin corpus callosum in 2 cases, and brain white matter abnormal signals in 2 cases. Among 10 cases, 18 different mutations of NPC1 allelic genes were identified including 11 reported mutations, 3 novel missense mutations: c. 3683T>C (p.Met1128Thr), c.1926G>C (p.Met642Iie) and c. 3006C>G (p.Phe1002Leu), 2 novel nonsense mutation: c. 1142G>A(p.Trp381Ter ) and c. 3229C>T(p.Arg1077Ter), 1 novel minimal deletion mutation: c. 1385-1386del, and 1 novel intron mutation: c. 1757+ 5G>A. In 5 cases, the symptom of gelastic cataplexy was alleviated by imipramine, and the convulsion was relieved by valproate in 2 cases, by carbamazepine in 1 case at the beginning of seizure. During the 25 (3-66) months of follow-up, 4 cases died, the others' neurological symptoms were deteriorated progressively. Conclusions: The NPC1 gene mutation were high heterozygous in this group, and 7 novel mutations enriched the gene mutation spectrum of NPC1. The neurological manifestations were complicated in patients with NPC, and the symptomatology would be different according to their onset age of neurological symptoms. There might be effective symptomatic treatment for gelastic cataplexy by imipramine and for convulsion by valproate or carbamazepine.

[Study on the expression of epidermal growth factor receptor protein during benzo(a)pyrene induced carcinogenesis].

Objective: To explore the expression of epidermal growth factor receptor(EGFR) protein during benzo(a)pyrene (BaP) induced carcinogenesis. Methods: This study, we firstly utilized immunofluorescence assay and Western-blot to examine EGFR expression of the BaP which was constructed previously by project team induced malignant transformation human bronchial epithelial cell (BTC) and the control (16HBE cell). Then, we selected 36 healthy SD rats, divided into two groups according to simple random method, 18 rats each group. The constructed rat lung neoplasm model induced by pulmonary injection of BaP (10 mg/ml of BaP solution in 0.2 ml corn oil), contrast group use 0.2 ml corn oil, lung tissue was collected and the EGFR expression of lung tissue was detected by immunofluorescence assay and Western blot. T analysis was used to test the different of EGFR between two groups. Results: Immunofluorescence analysis showed that the EGFR expression in BTC was significantly higher than 16HBE cell. Meanwhile, Western blot also was used to confirmed this result, the relative expression of EGFR protein in the rats of the model group the control group were 1.04±0.13 and 2.32±0.12, respectively, and the difference was statistically significance (t=12.39, P<0.001). In vivo, well-defined tumor was found in the rat with pulmonary injection of BaP, and the lung showed diffuse alveolar septal thickening, alveolar wall destruction and pulmonary alveoli fusion, which suggested that the rat lung neoplasm model was constructive successfully. Furthermore, we found the EGFR expression of lung was increased dramatically in the rat lung neoplasm model by immunofluorescence detection and Western blot. The relative expression of EGFR protein in the rats of the model group the control group were 0.21±0.03 and 1.30±0.07, respectively, and the difference was statistically significance (t=12.84, P<0.001). Conclusion: Expression of EGFR protein was increased during BaP carcinogenesis, and EGFR may play an important role in the carcinogenesis of BaP.

Downregulation of MACC1 expression enhances cisplatin sensitivity in SKOV-3/DDP cells.

The aim of this study was to investigate the correlation between MACC1 expression and resistance to cisplatin (DDP) in DDP-resistant human epithelial ovarian cancer SKOV-3 cells (SKOV-3/DDP). MACC1 mRNA and protein expression levels in SKOV-3 and SKOV-3/DDP cells were detected by reverse transcriptase polymerase chain reaction and western blot. The SKOV-3/DDP cells were divided into 5 groups: control, shVect (transfected with p-super-EGFP-1 plasmid), pshMACC1 (transfected with psuper-EGFP-shMACC1 plasmid), PD (pretreated with 20 µM PD98059), and combined (transfected with psuper-EGFP-shMACC1 plasmid and pretreated with 20 µM PD98059) groups. Cisplatin sensitivity and cell apoptosis in SKOV-3/DDP cells were assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry. ERK1/2 and p-ERK1/2 expression was determined by western blot. MACC1 mRNA and protein expression levels in SKOV-3/DDP cells were 2.66 ± 0.54 and 1.95 ± 0.45 times those seen in SKOV-3 cells (P < 0.05). Cisplatin sensitivity of pshMACC1 group was much higher than that in the control and shVect groups. Cisplatin-induced cell apoptosis rates increased significantly in the pshMACC1, PD, and combined groups, compared to the control and shVect groups. Moreover, the apoptosis rate was the highest in the combined group among the 5 groups (IC50 = 20.836 ± 0.629 µM). p-ERK1/2 expression decreased significantly in the pshMACC1, PD, and combined groups (this decrease was the most obvious in the combined group). In conclusion, downregulation of MACC1 expression could enhance cisplatin sensitivity and decrease drug resistance in SKOV- 3/DDP cells.

The relationship between the internal oxidation-reduction system and fetal distress on pregnant patients with intrahepatic cholestasis.

OBJECTIVE: To discuss the relationship between the internal oxidation-reduction system and fetal distress in pregnant patients with intrahepatic cholestasis in order to provide a new basis for clinical treatment and research. PATIENTS AND METHODS: From March 2012 to March 2015, eighty patients with intrahepatic cholestasis of pregnancy (ICP) were selected and divided into two groups: the distressed group (n = 31) and non-distressed group (n = 49). We compared the two groups for differences in MDA, SOD, NO level, GSH level, venous blood and total bile acid level. The relevance of the oxidation-reduction system indicators and the venous blood and total bile acid levels, as well as the differences in the delivery outcome and fetal distress, were compared between the two groups. RESULTS: The serum MDA level of the distressed group was higher than the non-distressed group while the SOD, NO, and GSH levels were lower than the non-distressed group. All differences were statistically significant (p < 0.05). Both the venous blood and total bile acid levels in the distressed group were higher than the non-distressed group and were statistically significant (p < 0.05). Based on Pearson's analysis, MDA was positively associated with the venous blood and total bile acid levels while SOD, NO and GSH levels were negatively associated with it. All differences were statistically significant (p < 0.05). The death rate of cesarean section and perinatal infant in the distressed group were higher than that of the non-distressed group. The proportion of mild and severe asphyxia was higher than the non-distressed group. However, the neonatal weight of the distressed group was lower. All differences were statistically significant (p < 0.05). CONCLUSIONS: The internal oxidation-reduction system indicators of pregnant patients with intrahepatic cholestasis, which are MDA, SOD, NO and GSH levels, may contribute to the occurrence of fetal distress.

Antiviral activity and mode of action of extracts from neem seed kernel against duck plague virus in vitro1.

Four fractions obtained from alcohol extracts of neem (Azadirachta indica) seed kernel by column chromatography were investigated for antivirus activity against the duck plague virus (DPV) in vitro. Duck embryo fibroblasts (DEF) infected with DPV were treated with the neem seed kernel extracts, and the effect of antivirus was judged by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide colorimetric method assay and direct immunofluorescence assay. The mode of action was tested by the plaque reduction assay. The results showed that fractions 1 to 3 were inactive. The median inhibitory concentration (IC(50)) of fraction 4 was 10.9 µg/mL and inhibited the virus protein expression in the direct immunofluorescence assay. In the plaque reduction assay, fraction 4 could significantly reduce the number of plaques compared with the negative control (P < 0.01) in all modes of action. This study indicated that the fourth fraction obtained from neem seed kernel could improve the viability of infected cells, and reduce the cytopathic effects caused by DPV and the amount of the virus protein expressed in virus-infected cells. The antiviral activity works in the whole process of virus infecting the normal cells.

Improving the numerical stability of the MAGIC model.

MAGIC is one of the most widely used models for forecasting long-term acidification. The model's code, however, has been experiencing numerical instability, though this might not be widely known to the public users. The major instability comes from the analytical solution to two cubic equations for calculating SO4(2-) concentration and the exchangeable fraction of Al on the soils. The mathematical algorithm for calculating the concentration of SO4(2-) from a quadratic equation is also found unstable. This paper is aimed at improving the instability above through proved numerical algorithms.