Validez de herramientas diagnósticas en pacientes pediátricos hospitalizados con diagnóstico presuntivo de dengue en un Hospital de Referencia de Paraguay / Validity of diagnostic tools in pediatric patients hospitalized with a presumptive diagnosis of dengue in a Reference Hospital in Paraguay

Introducción: El dengue es la enfermedad arboviral más común en los seres humanos. Un diagnóstico temprano y preciso del dengue puede respaldar el manejo clínico, la vigilancia y el control de la enfermedad y es fundamental, por ello en el diagnóstico del dengue es importante contar con pautas clínicas y epidemiológicas que permitan la identificación oportuna y una conducta terapéutica adecuada. Objetivos: Evaluar la validez de herramientas diagnósticas en pacientes pediátricos hospitalizados con diagnóstico presuntivo de dengue en un Hospital de Referencia de Paraguay durante los años de 2012 a 2020. Materiales y métodos: Estudio analítico de tipo observacional, retrospectivo correspondientes a pacientes pediátricos (0 a 18 años) internados en el Hospital de Referencia de Paraguay el periodo enero 2012 a julio 2020 con diagnostico presuntivo de dengue al ingreso. Se realizó́ un análisis bivariado relacionando las frecuencias de 20 grupos de criterios diagnósticos combinados y 3 criterios diagnósticos aislados (OMS 2009, nexo epidemiológico y antigenemia NS1 para dengue) con el gold standard de diagnóstico que fue la conversión serológica. Resultados: Participaron del estudio 342 sujetos. EL 44% tenía edad escolar y 70% tenía 5 años o más. El 52,76% (191) fueron masculinos. Se encontraron desnutrición y sobrepeso en el 13% y 2%, respectivamente. La combinación de proteína C reactiva con plaquetopenia se encontró́ en 0.45% de los pacientes sin dengue y en el 6% de los pacientes con diagnóstico final de dengue (p=0.004). Conclusión: Este resultado aporta la alternativa de uso de una combinación sencilla de exámenes de laboratorio que puede replicarse en salas de urgencias como en salas de internación en un primer contacto con pacientes febriles con sospecha de fiebre dengue.

Introduction: Dengue is the most common arboviral disease in humans. An early and accurate diagnosis of dengue can support the clinical management, surveillance and control of the disease and is essential, therefore in the diagnosis of dengue it is important to have clinical and epidemiological guidelines that allow timely identification and appropriate therapeutic conduct. Objectives: To evaluate the validity of diagnostic tools in pediatric patients hospitalized with a presumptive diagnosis of dengue in a Reference Hospital in Paraguay during the years 2012 to 2020. Materials and methods: Analytical study of case and control type, observational, longitudinal, retrospective corresponding to pediatric patients (0 to 18 years) admitted to the Reference Hospital of Paraguay from January 2012 to July 2020 with a presumptive diagnosis of dengue at income. A bivariate analysis was performed relating the frequencies of 20 groups of combined diagnostic criteria and 3 isolated diagnostic criteria (WHO 2009, epidemiological link and NS1 antigenemia for dengue) with the gold standard of diagnosis, which was serological conversion. Results: 342 subjects participated in the study. 44% were school age and 70% were 5 years old or older. 52.76% (191) were male. Malnutrition and overweight were found in 13% and 2%, respectively. The combination of C-reactive protein with thrombocytopenia was found in 0.45% of patients without dengue and in 6% of patients with a final diagnosis of dengue (p=0.004). Conclusion: This result provides the alternative of using a simple combination of laboratory tests that can be replicated in emergency rooms and inpatient wards in a first contact with febrile patients with suspected dengue fever.

Renal deficit and associated factors in children born with low birth weight / Déficit renal e fatores associados em crianças nascidas com baixo peso

ABSTRACT Introduction: Kidney problems may be due to low birth weight alone or may occur in association with other conditions. The objective this study was to evaluate the association between maternal and birth characteristics, anthropometric measurements, and kidney function deficit in low birth weight infants. Methods: Cross-sectional study with children who were born weighing < 2500 grams and were under outpatient follow-up. Maternal factors investigated were prenatal care and presence of hypertension, diabetes, and infection during pregnancy. The children's variables were sex, gestational age, birth weight, Apgar score, use of nephrotoxic medications, age, body weight at the time of evaluation, height, and serum creatinine and cystatin C dosages. The glomerular filtration rate (GFR) was estimated with the combined Zapittelli equation. Multivariate logistic regression model was used for identification of associated factors, with renal function deficit (GFR < 60 mL/min/1.73 m2) as the dependent variable. Results: Of the 154 children evaluated, 34.42% had kidney function deficit. Most of them had a gestational age > 32 weeks (56.6%), a mean birth weight of 1439.7 grams, and mean estimated GFR of 46.9 ± 9.3 mL/min/1.73 m2. There was a significant association of GFR < 60 mL/min/1.73 m2 with children's current weight and use of nephrotoxic drugs. Discussion: Children born with low birth weight had a high prevalence of kidney function deficit and current normal weight was a protective factor while the use of nephrotoxic drugs during perinatal period increased the chance of kidney deficit. These findings reinforce the need to evaluate the kidney function in these children, especially those who use nephrotoxic drugs.

RESUMO Introdução: Problemas renais podem ser devido apenas ao baixo peso ao nascer ou podem ocorrer em associação com outras condições. O objetivo deste estudo foi avaliar a associação entre características maternas e de nascimento, medidas antropométricas e déficit da função renal em bebês de baixo peso ao nascer. Métodos: Estudo transversal com crianças que nasceram com peso < 2500 gramas e estavam sob acompanhamento ambulatorial. Os fatores maternos investigados foram cuidados pré-natal e presença de hipertensão, diabetes e infecção durante a gravidez. As variáveis das crianças foram sexo, idade gestacional, peso ao nascer, índice Apgar, uso de medicamentos nefrotóxicos, idade, peso corporal no momento da avaliação, altura e dosagens séricas de creatinina e cistatina C. A taxa de filtração glomerular (TFG) foi estimada com a equação combinada de Zapittelli. Utilizou-se um modelo de regressão logística multivariada para identificação de fatores associados, com déficit da função renal (TFG < 60 mL/min/1,73 m2) como variável dependente. Resultados: Das 154 crianças avaliadas, 34,42% apresentaram déficit da função renal. A maioria tinha idade gestacional > 32 semanas (56,6%), peso médio ao nascer de 1439,7 gramas, e TFG média estimada de 46,9 ± 9,3 mL/min/1,73 m2. Houve uma associação significativa da TFG < 60 mL/min/1,73 m2 com o peso atual das crianças e o uso de medicamentos nefrotóxicos. Discussão: Crianças nascidas com baixo peso apresentaram alta prevalência de déficit da função renal e o peso atual normal foi um fator de proteção, enquanto o uso de medicamentos nefrotóxicos durante o período perinatal aumentou a chance de déficit renal. Estes achados reforçam a necessidade de avaliar a função renal destas crianças, especialmente aquelas que usam medicamentos nefrotóxicos.

Endotoxin test by recombinant Factor C for 0.9% sodium chloride injection

Endotoxin contamination is a threat to the safety of pharmaceutical products, especially parenteral drugs. Any sterile and/or pyrogen-free pharmaceutical product requires regulatory specifications to ensure safe patient use. This study covers the performance evaluation study of an endotoxin quantitation commercial kit by recombinant Factor C (rFC), Endozyme II® Go, for 0.9% sodium chloride injection. The samples were spiked with endotoxin solutions between 0.0005 and 10 EU/mL and tested by the rFC kit to evaluate precision, accuracy, detection and quantification limits, linearity, and robustness. Each of the six points was assayed at least five times.The relative standard deviation for precision testing ranged from 1.9 to 8.3%. The recovery accuracy values of endotoxin were between 61% and 125% for the range from 0.005 to 10 EU/mL. The results demonstrated that the rFC method allows endotoxin quantification with accuracy, precision, specificity, and linearity for the range of 0.005 and 10 EU/mL for 0.9% sodium chloride injection. (AU)

A contaminação por endotoxinas é uma ameaça à segurança dos produtos farmacêuticos, especialmente dos medicamentos parenterais. Qualquer produto farmacêutico estéril e/ou livre de pirogênios requer especificações regulatórias para garantir a segurança de uso para o paciente. Este estudo abrange o estudo de avaliação de desempenho empregando o kit comercial Endozyme II® Go para quantificação de endotoxina, por Fator C recombinante (FCr), em amostras de cloreto de sódio 0,9% para uso parenteral. As amostras foram fortificadas com cinco concentrações distintas de soluções de endotoxina na faixa entre 0,0005 e 10 UE/mL. Cada um dos cinco níveis foi testado pelo menos cinco vezes para avaliação dos critérios de precisão, exatidão, limites de detecção e quantificação, linearidade e robustez. O desvio padrão relativo para os testes de precisão variou de 1,9 a 8,3%. Os valores de recuperação de endotoxina para o parâmetro exatidão estiveram compreendidos entre 61% e 125%. Os resultados demonstraram que o método por FCr permite a quantificação de endotoxinas com exatidão, precisão, especificidade e linearidade para a faixa de 0,005 e 10 UE/mL em amostras de cloreto de sódio 0,9% para uso parenteral. (AU)

O-arm navigation versus C-arm navigation for guiding percutaneous long sacroiliac screws placement in treatment of Denis type Ⅱ sacral fractures / 中国修复重建外科杂志

OBJECTIVE@#To compare the effectiveness of O-arm navigation and C-arm navigation for guiding percutaneous long sacroiliac screws in treatment of Denis type Ⅱ sacral fractures.@*METHODS@#A retrospective study was conducted on clinical data of the 46 patients with Denis type Ⅱ sacral fractures between April 2021 and October 2022. Among them, 19 patients underwent O-arm navigation assisted percutaneous long sacroiliac screw fixation (O-arm navigation group), and 27 patients underwent C-arm navigation assisted percutaneous long sacroiliac screw fixation (C-arm navigation group). There was no significant difference in gender, age, causes of injuries, Tile classification of pelvic fractures, combined injury, the interval from injury to operation between the two groups ( P>0.05). The intraoperative preparation time, the placement time of each screw, the fluoroscopy time of each screw during placement, screw position accuracy, the quality of fracture reduction, and fracture healing time were recorded and compared, postoperative complications were observed. Pelvic function was evaluated by Majeed score at last follow-up.@*RESULTS@#All operations were completed successfully, and all incisions healed by first intention. Compared to the C-arm navigation group, the O-arm navigation group had shorter intraoperative preparation time, placement time of each screw, and fluoroscopy time, with significant differences ( P<0.05). There was no significant difference in screw position accuracy and the quality of fracture reduction ( P>0.05). There was no nerve or vascular injury during screw placed in the two groups. All patients in both groups were followed up, with the follow-up time of 6-21 months (mean, 12.0 months). Imaging re-examination showed that both groups achieved bony healing, and there was no significant difference in fracture healing time between the two groups ( P>0.05). During follow-up, there was no postoperative complications, such as screw loosening and breaking or loss of fracture reduction. At last follow-up, there was no significant difference in pelvic function between the two groups ( P>0.05).@*CONCLUSION@#Compared with the C-arm navigation, the O-arm navigation assisted percutaneous long sacroiliac screws for the treatment of Denis typeⅡsacral fractures can significantly shorten the intraoperative preparation time, screw placement time, and fluoroscopy time, improve the accuracy of screw placement, and obtain clearer navigation images.

Effects of C3435T polymorphism in ABCB1 gene on lipid-lowering efficacy of statins：a meta-analysis / 中国药房

OBJECTIVE To systematically evaluate the effects of C3435T polymorphism in ABCB1 gene on lipid-lowering efficacy of statins. METHODS Retrieved from PubMed， Web of Science， the Cochrane Library， CNKI and VIP， the cohort studies on the use of statins were collected from the inception to November 1， 2023. After literature screening， data extraction and quality evaluation， meta-analysis was performed by using RevMan 5.4 software. RESULTS A total of 11 literature involving 1 575 patients were included. The results showed that under the dominant genetic model， the reduction of low-density lipoprotein cholesterol （LDL-C） [MD＝－1.87， 95%CI （－3.62， －0.13）， P＝0.04]， total cholesterol （TC） [MD＝－1.42， 95%CI （－2.80， －0.04）， P＝0.04] in patients with CT+TT genotype was significantly higher than CC genotype. There was no significant difference in the increase of high-density lipoprotein cholesterol （HDL-C） [MD＝－0.65， 95%CI （－2.48， 1.18）， P＝0.49] or the decrease of triglyceride （TG） [MD＝－0.05， 95%CI （－2.94， 2.84）， P＝0.97] between patients with CT+TT genotype and CC genotype. Under the recessive genetic model， the reduction of TC [MD＝2.26， 95%CI （0.97， 3.56）， P＝0.000 6] and the increase of HDL-C [MD＝2.38， 95%CI （0.42， 4.35）， P＝0.02] in patients with TT genotype were significantly higher than CC+ CT genotype. There was no significant difference in the reduction of LDL-C [MD＝1.53， 95%CI （－0.10， 3.15）， P＝0.07] or TG [MD＝0.06， 95%CI （－2.98， 3.10）， P＝0.97] between CC+CT genotype and TT genotype. Under the additive genetic model， the reduction of TC [MD＝2.98， 95%CI （1.27， 4.69）， P＝0.000 6] and LDL-C [MD＝2.84， 95%CI （0.67， 5.01）， P＝0.01] in patients with TT genotype were significantly higher than CC genotype. There was no significant difference in the increase of HDL-C [MD＝2.40， 95%CI （－0.17， 4.97）， P＝0.07] or the decrease of TG [MD＝0.97， 95%CI 　　 （－2.93， 4.87）， P＝0.63] between patients with TT genotype and CC genotype. CONCLUSIONS The reduction of LDL-C and TC in patients with dyslipidemia treated with statins may be related to the heterozygous and homozygous mutation of C3435T in ABCB1 gene， and the reduction of LDL-C and TC in patients with CT or TT genotype is more obvious， compared with patients with CC genotype. The elevation of HDL-C may be related to homozygous mutation， and the effect of HDL-C elevation may be more obvious in patients with TT genotype， compared with CC+CT genotype. However， the change of TG may not be related to the C3435T polymorphism in ABCB1 gene.

Efficacy of C3F8 versus silicone oil tamponade in highly myopic macular hole retinal detachment / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the outcome of C3F8 versus silicone oil tamponade after pars plana vitrectomy(PPV)and inverted internal limiting membrane(ILM)for the treatment of highly myopic macular hole retinal detachment(MHRD).METHODS: Retrospective clinical study. Totally 45 patients(45 eyes)with highly myopic MHRD who visited our hospital between January 2019 and August 2022 were selected as the research subjects. The patients were divided into two groups according to different intraocular tamponade agents: C3F8(22 eyes)and silicone oil(23 eyes)groups. All patients underwent conventional three-incision PPV, ILM was tamped, a venous blood clot was placed on the tamped ILM, and 15% C3F8 and silicone oil were used as tamponade, respectively. The best corrected visual acuity(BCVA), multifocal electroretinogram(mfERG), the closure of the macular hole, retinal reattachment and the complications were observed.RESULTS: The macular hole closure rate was 77% in the C3F8 group and 83% in the silicone oil group, respectively(P&#x003E;0.05), and retinal reattachment rates were 95% and 96%, respectively(P&#x003E;0.05). The visual acuity of the two groups significantly improved, which was 0.99±0.34 and 1.22±0.37, respectively, and the C3F8 group was better than that of the silicone oil group(t=-2.156, P=0.037). After operation, the response density of the first ring of P1 wave in the first order kernel in mfERG was 114.27±26.37 nV/deg2 for the C3F8 group and 98.08±24.36 nV/deg2 for the silicone oil group, and the response density of the second ring of P1 wave was 80.45±14.94 nV/deg2 for the C3F8 group and 67.73±15.33 nV/deg2 for the silicone oil group, all of which were significantly higher compared to pre-operation [the response density of the first ring of P1 wave: 58.13±13.96 nV/deg2 for the C3F8 group and 55.30±10.48 nV/deg2 for the silicone oil group, the response density of the second ring of P1 wave: 51.18±8.19 nV/deg2 for the C3F8 group and 47.43±11.97 nV/deg2 for the silicone oil group](all P&#x003C;0.05). It was found that the response density of the first ring of P1 wave was lower in the silicone oil group than in the C3F8 group(P&#x003C;0.05). There was no statistically significant difference in the incidence of complications between the two groups(P&#x003E;0.05).CONCLUSION: Silicone oil tamponade or C3F8 tamponade after PPV combined with ILM can both promote retinal reattachment and macular hole closure in patients with MHRD, and the C3F8 tamponade was superior to silicone oil in visual function recovery.

Therapeutic effect of Xiayuxue decoction on a mouse model of nonalcoholic fatty liver disease induced by high-fat diet and its mechanism / 临床肝胆病杂志

ObjectiveTo investigate the mechanism of action of Xiayuxue decoction in inhibiting nonalcoholic fatty liver disease （NAFLD） induced by high-fat diet in mice by regulating nucleotide binding oligomerization domain like receptor containing pyrin domain protein 6 （NLRP6）. MethodsA total of 15 male C57BL/6 mice were randomly divided into low-fat diet （LFD） group， high-fat diet （HFD） group， and Xiayuxue decoction-HFD group （XYXD group）， with 5 mice in each group. Liver function parameters （alanine aminotransferase ［ALT］ and aspartate aminotransferase ［AST］） and blood lipid metabolic indicators （triglycerides ［TG］ and total cholesterol ［TC］） were measured； HE staining and oil red O staining were performed for liver tissue to observe histomorpholoty and lipid droplet deposition； quantitative real-time PCR was used to measure the expression levels of inflammatory factors （tumor necrosis factor-α ［TNF-α］， interleukin-1β ［IL-1β］， interleukin-18 ［IL-18］， and NLRP6） in liver tissue； Western blot was used to measure the protein expression levels of NLRP6， nuclear factor-kappa B （NF-κB）， and NF-κB p65； immunohistochemistry was used to measure the expression of NLRP6 and CD68. Mouse Raw264.7 cells were treated with palmitic acid （PA）， lipopolysaccharide， and serum containing Xiayuxue decoction to observe inflammation. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the LFD group， the HFD group had significant increases in the serum levels of ALT， AST， TC， and TG （all P<0.05）. Liver histopathological examination showed that the HFD group had marked hepatic steatosis and a signficant increase in NAS score （P<0.05）， and quantitative real-time PCR showed significant increases in the inflammatory factors such as IL1β and IL-18 and a significant reduction in the expression of NLRP6 （all P<0.05）. Immunohistochemistry showed that the expression of NLRP6 showed a similar trend as that of the macrophage marker CD68. Western blot showed that after the downregulation of NLRP6 expression， there was a significant increase in phosphorylated NF-κB p65 （P<0.05）. Compared with the HFD group， Xiayuxue decoction effectively improved liver inflammation， upregulated the expression of NLRP6， and downregulated phosphorylated NF-κB p65 in HFD mice （all P<0.05）. After Raw264.7 cells were treated with PA， NLRP6 was downregulated to promote the progression of inflammation （P<0.05）， and treatment with Xiayuxue decoction could upregulate NLRP6 and inhibit inflammation NF-κB （P<0.05）. ConclusionXiayuxue decoction can effectively improve hepatic steatosis and liver inflammation in a mouse model of NAFLD， possibly by regulating NLRP6/NF-κB to alleviate macrophage activation.

Protective effect of Genistein against nonalcoholic fatty liver disease in ovariectomized mice and its mechanism / 临床肝胆病杂志

ObjectiveTo investigate the protective effect of Genistein against nonalcoholic fatty liver disease （NAFLD） in ovariectomized （OVX） mice and its mechanism. MethodsA total of 40 female C57BL/6 mice， aged 6 weeks， were used to establish an OVX mouse model， and then they were randomly divided into blank group， 4-week model group， 6-week model group， 8-week model group， and 10-week model group， with 8 mice in each group. Under the same environmental conditions， the mice were given high-fat diet for modeling， and pathological examination showed that NAFLD was successfully induced by 10-week high-fat diet. Another 40 female C57BL/6 mice， aged 6 weeks， were randomly divided into blank group， sham operation group （Sham group）， OVX group， OVX+L-Genistein （4 mg/kg body weight） group， and OVX+H-Genistein （8 mg/kg body weight） group. The mice in the Sham group were given the same procedure of OVX， without the ligation of the ovarian artery and the resection of the ovary. The mice in the blank group were given normal diet， and those in the other groups were given high-fat diet. Genistein was dissolved in DMSO， and the mice in the Sham group and the OVX group were treated with solvent solution alone by gavage， once a day for 10 consecutive weeks. Body weight and visceral index were recorded， and the mice were sacrificed to collect serum and liver tissue. Kits were used to measure the activity of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） and the serum levels of triglyceride （TG） and total cholesterol （TC）， and HE staining and oil red O staining were used to observe liver histopathology； Western blot was used to measure the protein expression levels of sterol regulatory element-binding protein 1c （SREBP-1c） and peroxisome proliferator-activated receptor alpha （PPARα） associated with lipid metabolism in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the Dunnett-t test was used for further comparison between two groups. ResultsAfter 10 weeks of high-fat diet， the OVX+L-Genistein group and the OVX+H-Genistein group had significantly lower body weight， liver index， and liver tissue weight （all P<0.05）. In addition， Genistein significantly downregulated the serum levels of TC and TG （P<0.05） and reduced the activities of serum AST and ALT （P<0.05）. HE and oil red O staining showed that compared with the OVX group， the OVX+L-Genistein group and the OVX+H-Genistein group had a significant reduction in the accumulation of lipid droplets. Western blot showed that after Genistein intervention， there was a significant reduction in the protein expression level of SREBP-1c and a significant increase in the protein expression level of PPARα （P<0.05）. ConclusionGenistein exerts a protective effect against NAFLD in OVX mice possibly by regulating the expression of SREBP-1c and PPARα， thereby promoting fatty acid oxidation and inhibiting liver lipid synthesis.

Association of polymorphisms of the acetyl-coA acetyltransferase 1 gene and the melatonin receptor 1B gene with the susceptibility to nonalcoholic fatty liver disease / 临床肝胆病杂志

ObjectiveTo investigate the association of the polymorphisms of the acetyl-CoA acetyltransferase 1 （ACAT1） gene and the melatonin receptor 1B （MTNR1B） gene with the susceptibility to nonalcoholic fatty liver disease （NAFLD）. MethodsA total of 164 healthy controls and 228 NAFLD patients were enrolled in this study. PCR and sequencing methods were used to determine the genotypes of the polymorphisms of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus， and fasting venous blood samples were collected for biochemical analysis. The t-test was used for comparison of normally distributed continuous data between groups， and the non-parametric Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups； the chi-square test was used for comparison of categorical data between groups. ResultsThere were no significant differences between the NAFLD group and the healthy control group in the genotype distribution of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus （all P>0.05）. The carriers of AA genotype at the rs1044925 locus of the ACAT1 gene had a significantly higher level of low-density lipoprotein than the carriers of C allele （Z=-2.08， P=0.04）， and the carriers of G allele at the rs10830963 locus of the MTNR1B gene had a significantly higher level of fasting blood glucose than the carriers of CC genotype （Z=-3.01， P<0.01）. ConclusionThe polymorphisms of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus were not associated with the susceptibility to NAFLD. The rs1044925 locus of the ACAT1 gene and the rs10830963 locus of the MTNR1B gene are associated with the levels of low-density lipoprotein and fasting blood glucose， respectively.

Management of hepatitis C in children and pregnant women / 临床肝胆病杂志

Hepatitis C virus infection is a global public health issue， and the emergence of direct-acting antiviral agents has brought revolutionary breakthroughs in the treatment of hepatitis C patients. Although direct-acting antiviral agents have a marked therapeutic effect in adult patients， there are still many challenges in the treatment of special populations such as pregnant women， infants， young children， and adolescents. This article reviews the current status of antiviral therapy for these special populations with hepatitis C and the problems that need to be solved， in order to provide reference and guidance for clinical workers.

Current status of hepatitis C virus infection and progress in its elimination in China / 临床肝胆病杂志

Hepatitis C virus （HCV） can develop into liver cirrhosis or hepatocellular carcinoma， imposing a heavy burden on the patient’s family and the society. Hepatitis C is one of the major public threats for humans， and eliminating hepatitis C is a common goal of all humans. Direct-acting antiviral agents （DAAs） are currently a relatively safe treatment regimen for hepatitis C that can reach a relatively high cure rate and can target different HCV genotypes， making it possible to eliminate HCV infection. China actively promotes the clinical application of DAAs， accelerates drug approval， improves the accessibility of DAAs， and strengthens population intervention. National Medical Insurance Administration has gradually included DAAs in the national medical insurance directory， providing strong support for eliminating HCV infection. In response to the WHO’s goal of eliminating viral hepatitis as a public health hazard by 2030， China has successively released national strategic plans and action plans in recent years， making significant achievements in HCV infection elimination， forming a joint prevention and control system across multiple sectors of the society， and ultimately achieving the goal of eliminating HCV infection. With a focus on the current status of HCV infection in China and prominent prevention and control strategies， this article analyzes and summarizes the practical process of the prevention， control， and micro-elimination of HCV infection， in order to provide a policy reference for carrying out HCV elimination in China and help to achieve the goal of comprehensive elimination of HCV infection.

miR-3612 regulates the malignant biological behaviors of hepatocellular carcinoma cells via targeting SEMA4C / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨miR-3612靶向信号素（SEMA）4C对肝细胞癌细胞增殖与侵袭能力的影响。方法: 收集2020年5月至2021年9月间在皖南医学院第一附属医院弋矶山医院手术切除的肝细胞肝癌的40对癌组织和相应癌旁组织，常规培养肝细胞癌Hep3B和Huh7细胞，将其分为对照组、miR-3612 mimics-NC组、miR-3612 mimics组、miR-3612 inhibitor-NC组、miR-3612 inhibitor组、si-NC组、si-SEMA4C组、mimics-NC+pcDNA-NC组、miR-3612 mimics+pcDNA-NC组和miR-3612 mimics+pcDNA-SEMA4C组，用转染试剂将相应的核酸和质粒转染各组细胞。qPCR法检测miR-3612和SEMA4C mRNA在肝细胞癌组织和Hep3B和Huh7细胞中的表达，双荧光素酶报告基因实验和免疫共沉淀（RIP）实验验证miR-3612与SEMA4C的结合及调控关系，qPCR法和WB法检测转染后各组Hep3B和Huh7细胞中miR-3612、SEMA4C mRNA和蛋白的表达，CCK-8法、细胞划痕实验和Transwell小室实验分别检测各组Hep3B和Huh7细胞的增殖、迁移和侵袭能力。结果: miR-3612在肝细胞癌组织和Hep3B和Huh7细胞中呈低表达（P<0.001），而SEMA4C则呈高表达（P<0.001），过表达miR-3612可抑制Hep3B和Huh7细胞的增殖、迁移、侵袭和vimentin、SEMA4C蛋白的表达，促进E-cadherin蛋白的表达（P<0.05或P<0.01或P<0.001），敲低miR-3612则促进Hep3B和Huh7细胞的增殖、迁移、侵袭和SEMA4C蛋白的表达（P<0.05或P<0.01或P<0.001）。双荧光素酶报告基因实验和RIP实验证实miR-3612与SEMA4C可直接结合（P<0.001），miR-3612与SEMA4C的表达呈负相关也间接证明了这一点（P<0.001）。敲减SEMA4C能明显抑制Hep3B、Huh7细胞的增殖、侵袭和迁移能力（P<0.05或P<0.01或P<0.001），过表达SEMA4C可逆转过表达miR-3612对Hep3B和Huh7细胞增殖、迁移、侵袭和EMT的抑制作用（P<0.05或P<0.01或P<0.001）。结论: miR-3612通过调控SEMA4C表达影响Hep3B和Huh7细胞的恶性生物学行为，miR-3612有望成为临床肝细胞癌治疗的潜在靶点。

Establishment and observation of a mouse model of cytokine release syndrome induced by recombinant mouse IFN-γ adenovirus / 中国肿瘤生物治疗杂志

@#目的：通过向C57Bl/6J小鼠腹腔注射IFN-γ腺病毒（Ad-mIFN-γ）建立细胞因子释放综合征（CRS）的动物模型。方法：构建Ad-mIFN-γ及对照Ad-lacZ腺病毒载体，分别以MOI=100体外转染小鼠腹腔巨噬细胞，流式细胞术检测其对细胞mIFN-γ分泌的影响。将40只雌性C57Bl/6J小鼠按随机数字表法分为对照组、载体对照组、病毒低、中、高剂量组（每组8只），分别向各组小鼠腹腔注射PBS（200 μL）、Ad-lacZ（2×107 PFU/只）、Ad-mIFN-γ（5×106 PFU/只）、Ad-mIFN-γ（1.5×107 PFU/只）和Ad-mIFN-γ（2×107 PFU /只）。每日观测小鼠的体质量及生存情况；第3天时采用流式细胞术检测小鼠外周血和脾内单核细胞（CD11b+）、巨噬细胞（CD11b+/CD86+）比例，免疫荧光染色法检测脾内CD11b+的单核细胞比例；第9天时采用流式细胞术检测小鼠血清中细胞因子的分泌水平；第14天，采用颈椎脱臼法处死小鼠，H-E染色法观察小鼠肝、脾、肺和肾的病理和组织学变化。结果： Ad-mIFN-γ体外感染小鼠腹腔巨噬细胞，在第3天检测到巨噬细胞分泌mIFN-γ达到峰值（118.34±2.90）pg/mL，并在一周内持续高分泌mIFN-γ，Ad-lacZ对照组IFN-γ分泌水平较低后，第3天时为（0.17±0.08）pg/mL。小鼠腹腔注射Ad-mIFN-γ后，在14 d内病毒低、中剂量组无小鼠死亡，病毒高剂量组小鼠体质量持续减轻（P<0.001）；第3天，病毒高剂量组小鼠外周血和脾组织内单核细胞、巨噬细胞比例较对照组和中剂量组均显著增加（P<0.05或P<0.01）；第9天，病毒低、中、高剂量组小鼠血清中mIFN-γ、IL-6、单核细胞趋化蛋白-1（MCP-1）、IL-1、TNF-α等细胞因子的水平均显著升高（P<0.001）；10 d内病毒高剂量组小鼠死亡率达100%。组织病理检测可见病毒高剂量组小鼠的肝、脾、肺、肾组织有明显损伤。结论： Ad-mIFN-γ体外感染小鼠原代腹腔巨噬细胞后，可以快速分泌mIFN-γ；腹腔注射高剂量（2×107 PFU/只）Ad-mIFN-γ导致小鼠出现CRS典型表现，可作为CAR-T细胞治疗诱发CRS的动物模型。

Construction of recombinant adenovirus expression vector of avian reovirus σC protein and its effect on proliferation of hepatocellular carcinoma cells / 中国生物制品学杂志

@#Objective To construct the recombinant adenovirus vector pAd-σC for the expression of avian reovirus(ARV)aC protein and to detect its effects on the proliferation of hepatocellular carcinoma cells,in order to build up a basis for the development of novel anti-tumor vaccines.Methods The recombinant shuttle vector pShuttle-σC was constructed by PCR amplification of ARV σC gene,and then transformed into competent BJ5183 cells containing the adenovirus vector pAdessy-1.The recombi-nant adenovirus vector pAd-σC was obtained by homologous recombination,and the virus was packaged in HEK293 cells.The virus titer was measured by TCID_(50),the expression of σC protein was determined by Western blot and ELISA,and the effect of virus on the proliferation of human hepatocellular carcinoma cells SMMC7721 was detected by CCK-8 assay.Results The recombinant shuttle vector pShuttle-σC was confirmed to be constructed correctly by double enzyme digestion and sequen-cing,and the recombinant adenovirus vector pAd-σC was constructed correctly as identified by colony PCR.σC protein was successfully expressed in hepatocellular carcinoma cells SMMC7721.The recombinant adenovirus Ad-σC had a titer of 10~(7.5)/0.1 mL,which inhibited the proliferation of hepatocellular carcinoma cells SMMC7721.Conclusion The recombinant adenovirus vector pAd-trC containing ARV σC gene was successfully constructed,and its inhibitory effect on tumor cell proliferation was preliminarily analyzed,which lays a foundation for revealing the molecular mechanism of ARV oncolytic effect and further developing novel anti-tumor biological preparation.

Effect of human umbilical cord mesenchymal stem cells in treatment of mice with liver fibrosis and its mechanism / 临床肝胆病杂志

ObjectiveTo investigate the effect of human umbilical cord mesenchymal stem cells （hUCMSCs） in the treatment of mice with liver fibrosis and its mechanism. MethodsA total of 18 specific pathogen-free C57BL/6 mice， aged 6 weeks， were selected and divided into control group （n=6）， carbon tetrachloride （CCl4） model group （CCl4 group， n=6）， and hUCMSCs treatment group （MSC group， n=6） using a random number table. The mice in the CCl4 group and the MSC group were given intraperitoneal injection of CCl4 solution to establish a mouse model of liver fibrosis， while those in the control group were injected with the same dose of corn oil， and the mice in the MSC group were injected with hUCMSCs via the caudal vein during the injection of CCl4. At the end of week 8， mouse serum was collected， and the mice were sacrificed to collect and fix the liver. Enzyme-linked immunosorbent assay was used to measure the levels of inflammatory factors； an automatic biochemical detector was used to measure liver function parameters； HE staining， Masson staining， Sirius Red staining， and α-SMA immunofluorescence assay were used to evaluate liver fibrosis. Hepatic stellate cells （HSCs） stimulated by TGF-β were co-cultured with hUCMSCs in the medium with or without chitinase-3 like-protein-1 （CHI3L1）， and Western blot was used to measure the expression levels of proteins. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the Dunnett’s t-test was used for further comparison between two groups. ResultsMasson staining and Sirius Red staining showed that the CCl4 group had a significantly higher degree of fibrosis than the control group （both P<0.05）， and the MSC group had significant alleviation of fibrosis compared with the CCl4 group （both P<0.05）. Compared with the control group， the CCl4 group had significant increases in the levels of interleukin-1β， interleukin-6 （IL-6）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， and alkaline phosphatase （ALP） （all P<0.05）， and compared with the CCl4 group， the MSC group had significant reductions in the levels of IL-6， AST， ALT， and ALP （all P<0.05）. The CCl4 group had significantly higher expression levels of CHI3L1 and α-SMA than the control group and the MSC group （all P<0.05）. The cell culture experiment showed that the MSC+HSC group had a significantly higher expression level of Bax than the HSC group and the MSC+CHI3L1 group （both P<0.05）， suggesting that CHI3L1 reversed the pro-apoptotic effect of MSC on activated HSCs. ConclusionThis study shows that hUCMSCs can improve liver fibrosis in mice， possibly by inhibiting CHI3L1 to promote the apoptosis of HSCs.

Role and mechanism of action of Yinchenhao Decoction in inhibiting ferroptosis of hepatocytes in mice with autoimmune hepatitis / 临床肝胆病杂志

ObjectiveTo investigate the role and mechanism of action of Yinchenhao Decoction in inhibiting ferroptosis of hepatocytes in mice with autoimmune hepatitis. MethodsA total of 18 specific pathogen-free female C57BL/6 mice were selected and divided into normal group， model group， and treatment group using a random number table， with 6 mice in each group. The mice in the model group and the treatment group were injected with concanavalin A （Con A） via the caudal vein to establish a mouse model of autoimmune hepatitis， and those in the normal group were injected with normal saline. The mice in the treatment group were given prophylactic treatment with Yinchenhao Decoction （4.68 g crude drug/kg） by gavage at 14 days before modeling， and Con A was injected after the last gavage. The levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， interferon gamma （IFN-γ）， tumor necrosis factor-α （TNF-α）， iron ion， glutathione （GSH）， reactive oxygen species （ROS）， adenosine triphosphate （ATP）， and malondialdehyde （MDA） were measured； liver index and spleen index were calculated； the expression levels of GPX4 and SLC7A11 were measured； liver histopathological changes were compared between groups. A one-way analysis of variance was used for comparison of normally distributed continuous data between three groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the normal group， the model group had significant increases in liver index， spleen index， ALT， AST， IFN-γ， TNF-α， iron ion， ROS and MDA （all P<0.05） and significant reductions in the content of GSH and ATP and the protein expression levels of GPX4 and SLC7A11 （all P<0.05）. Compared with the model group， the treatment group had significant reductions in liver index， spleen index， ALT， AST， IFN-γ， TNF-α， iron ion， ROS and MDA （all P<0.05） and significant increases in the content of GSH and ATP and the protein expression levels of GPX4 and SLC7A11 （all P<0.05）. HE staining showed that compared with the normal group， the model group showed massive hepatocyte degeneration and necrosis and inflammatory cell aggregation at the portal area， and compared with the model group， the treatment group had alleviation of liver necrosis and inflammatory infiltration. ConclusionLiver injury induced by Con A may be associated with ferroptosis. Yinchenhao Decoction can increase the protein expression levels of SLC7A11 and GPX4 protein and thus inhibit ferroptosis of hepatocytes induced by Con A.

Evaluation of early binocular visual function after implantable collamer lens V4c implantation in patients with high myopia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the binocular visual function in high myopia patients after the implantation of implantable collamer lens(ICL)V4c.METHODS: A total of 35 cases(70 eyes)that received binocular ICL implantation at our hospital from May 2019 to May 2021 were enrolled in this prospective study. Binocular full-range visual acuity, contrast sensitivity, stereopsis, mesopic vision and glare sensitivity, and monocular wavefront and the quality of vision questionnaire were assessed before the surgery and at 1 mo postoperatively.RESULTS: At 1 mo postoperatively, 35 cases(100%)had binocular uncorrected distance visual acuity(UDVA)≤0.00(LogMAR), 16 cases(46%)had binocular UDVA≥preoperative corrected distance visual acuity(CDVA). Binocular UDVA and uncorrected intermediate visual acuity(UIVA,80 cm)were improved compared to preoperative CDVA and distance-corrected intermediate visual acuity(DCIVA,80 cm)(all P&#x003C;0.05).While there were no differences in the binocular postoperative UIVA(60 cm)and preoperative DCIVA(60 cm),and uncorrected near visual acuity(UNVA,40 cm)and preoperative distance-corrected near visual acuity(DCNVA,40 cm)(all P&#x003E;0.05). The binocular contrast sensitivity was significantly improved postoperatively(P=0.001), and the postoperative binocular mesopic vision, glare sensitivity(no glare/glare)and binocular stereopsis(5 m/40 cm)had no differences(all P&#x003E;0.05). The postoperative total higher-order aberration, trefoil aberration, coma and spherical aberration were increased, besides the median of total coma in the right eye with a pupil diameter of 3.0 mm was decreased after surgery. The mean total score of quality of vision questionnaire was significantly increased from 54.87 preoperatively to 80.92 after implantation(P&#x003C;0.05), with high satisfaction and no obvious visual disturbance in patients.CONCLUSION: Although the monocular high-order aberrations increased in the early stage after ICL V4c binocular implantation in patients with high myopia, the binocular visual function was improved.

Total Saponins of Dioscorea Mitigate Nonalcoholic Steatohepatitis in Mice by Regulating AMPK/SREBP-1c/ACC Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the role and mechanism of total saponins of Dioscorea （TSD） in mitigating nonalcoholic steatohepatitis （NASH） in mice. MethodForty-eight C57BL/6J mice were randomized into a normal group and a modeling group. The mice for modeling were fed with a high-fat and high-cholesterol diet + 20% fructose solution for 16 weeks and randomized into model， atorvastatin （4 mg·kg-1·d-1）， and high-， medium-， and low-dose （200， 60， and 20 mg·kg-1·d-1） TSD groups. The mice were administrated with corresponding doses of drugs by gavage for 8 weeks. The mouse activity， liver index， levels of total cholesterol （TC）， triglycerides （TG）， and free fatty acids （FFAs） in the liver， and levels of TC， TG， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， γ-glutamyl transferase （GGT）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the serum were measured. Hematoxylin-eosin staining， Masson staining， oil red O staining， and transmission electron microscopy were employed to observe the pathological changes， lipid accumulation， and morphological changes of liver ultrastructure. Western blot was employed to determine the protein levels of AMP-activated protein kinase （AMPK）， sterol regulatory element-binding protein-1c （SREBP-1c）， acetyl-CoA carboxylase （ACC）， and phosphorylated ACC （p-ACC） in the liver tissue. ResultCompared with the normal group, the activity of mice in the model group decreased(P<0.05， P<0.01), the levels of TC, TG, FFA and serum TC, TG, ALT, AST, GGT, IL-1β and TNF-α, liver coefficient and liver pathology scores were significantly increased, the expression of p-AMPK/AMPK and p-ACC proteins in liver tissues was significantly reduced, and the expressions of SREBP-1c and ACC proteins were significantly increased (P<0.01). Compared with the model group， atorvastatin increased the mouse activity （P<0.05）， while each dose of TSD caused no significant changed in the mouse activity. The levels of TC, TG, FFA in liver and serum TC, TG, ALT, AST, GGT, IL-1β, TNF-α, liver coefficient and liver pathological score in TSD and atorvastatin groups were significantly decreased, and the expressions of p-AMPK/AMPK and p-ACC in liver tissue were significantly increased. The expressions of SREBP-1c and ACC were significantly decreased (P<0.05,P<0.01). ConclusionTSD may alleviate NASH in mice by regulating the AMPK/SREBP-1c/ACC signaling pathway to reduce lipid synthesis.

Early outcomes of anterior segment parameters in patients with high myopia after implantable collamer lens V4c implantation / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To study the early outcomes of anterior segment parameters after implantation of an implantable collamer lens with a central hole(ICL V4c)in patients with high myopia.METHODS:A total of 82 cases(160 eyes)with high myopia, including 42 males(82 eyes)and 40 females(78 eyes), aged 26.0±4.6(21 to 37)years, who underwent ICL V4c implantation at our institution from February 2019 to September 2022 and were followed up for 1 a, were included. The general characteristics of the anterior segment of the eye were measured preoperatively: spherical equivalent, mean horizontal corneal curvature, white-to-white(WTW), and axial length(AL); intraocular pressure(IOP), endothelial cell density(ECD), central anterior chamber depth(CACD), anterior chamber volume(ACV)and anterior chamber angle(ACA)were measured preoperatively and at 1 d, 1 wk, 1, 3 and 6 mo postoperatively. Furthermore, the distance from the centre of the posterior surface of the ICL V4c optical zone to the anterior surface of the lens(vault)was measured at 1 d, 1 wk, 1, 6 mo, and 1 a after surgery.RESULTS: The mean preoperative spherical equivalent of the patients was -7.56±2.55 D, mean horizontal corneal curvature was 42.89±1.47 D, WTW was 11.64±0.37 mm, and AL was 26.64±0.93 mm. The baseline IOP was 15.97±2.13 mmHg, and the differences in IOP at each time point after ICL V4c implantation compared to preoperative were not statistically significant(F=0.875, P=0.504); ECD was 2 989.30±140.78 cells/mm2 at baseline, and ECD at 6 mo after ICL V4c implantation was not statistically significant compared with preoperative ECD(t=1.475, P=0.142); CACD was 3.19±0.21 mm at baseline, and ACV was 210.30±27.7 mm3, and CACD and ACV were significantly lower than preoperative at all postoperative time points(F=111.10, 288.38, all P&#x003C;0.001). The baseline ACA was 35.44°±11.27°, and the ACA at each time point after ICL V4c implantation was significantly lower than preoperatively(F=21.23, P&#x003C;0.001). The vault was 665.32±184.03 μm at 1 d postoperatively, and continued to be significantly reduced at 1 wk, 1, 6 mo, and 1 a postoperatively compared with 1 d(F=52.10, P&#x003C;0.001). However, it remained stable at 6 mo and 1 a postoperatively, and the difference was not statistically significant compared with vault at 1 mo postoperatively(P&#x003E;0.05).CONCLUSION: ICL V4c has certain safety and efficiency in 1 a postoperative follow-up, and the parameters of the anterior segment of the eye stabilized in the early period.

Effect of Direct-acting Antivirals Treatment on Renal Function Among HCV-infected Patients / 中山大学学报(医学科学版)

； ObjectiveTo explore the effect of direct-acting antiviral treatment on renal function in patients with chronic hepatitis C. MethodsA total of 123 HCV-infected patients receiving DAAs treatment at the Third Affiliated Hospital of Sun Yat-sen University from January 2017 to December 2021 were included in this study. To explore the renal function in patients with chronic hepatitis C treated with direct-acting antivirals， serum creatinine values were collected before， during and after the treatment， which were used to estimate the eGFR by the MDRD equation to assess the changes in renal function. ResultsOf the 123 patients enrolled， 67.5%（n=83）were male， and the mean age of participants was （50±11） years old. The mean follow-up period was 24 weeks . Comorbidities included cirrhosis in 26.8%， and diabetes in 10.6%. Meanwhile， 11.4% of the cohort had eGFR < 60 mL/（min ·1.73 m2）， 33.3% of the cohort had eGFR 60 to 90 mL/（min ·1.73 m2）， and 55.3% had eGFR≥90 mL/（min ·1.73 m2）. No decrease in renal function was seen among all the HCV-infected patients at the end of treatment or the follow-up period after treatment. However， compared with the eGFR at the baseline， eGFR in CKD2 patients in the follow-up period was improved 【（88.65±15.52） mL/（min ·1.73 m2）vs （78.12 ±7.60） mL/（min ·1.73 m2）， P< 0.001】. And 14.6% （n=18） of patients experienced progressive deterioration of renal function. Logistic regression analysis showed that diabetes could predict the deterioration of renal function （OR=4.663， P=0.016）. ConclusionsOur study shows renal function is not impair among HCV-infected patients following DAAs treatment， and renal function in CKD2 patients have improvements. However， HCV-infected patients with diabetes mellitus are at a high risk of renal impairment and closely monitoring of renal function is still needed.