ObjectiveTo investigate the effects of modified Ditan tang on genes related to the transcription-translation feedback loop （TTFL） of biorhythm in the rat model of non-alcoholic fatty liver disease （NAFLD） and its mechanism for prevention and treatment of NAFLD. MethodsSixty-five healthy SPF male SD rats were randomly assigned into blank （n=20）， model （n=15）， and low-， medium-， and high-dose （2.68， 5.36， and 10.72 g·kg^-1·d^-1， respectively） modified Ditan tang （n=10） groups. Other groups except the blank group were fed a high-fat diet for 12 weeks. The modified Ditan tang groups were treated with the decoction at corresponding doses by gavage， and the blank and model groups were treated with an equal volume of normal saline from the 9th week for 4 weeks. The levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in the serum were measured by an automatic biochemical analyzer. TG and non-esterified fatty acid （NEFA） assay kits were used to measure the levels of TG and NEFA in the liver. The pathological changes in the hypothalamus and liver were observed by hematoxylin-eosin staining， and the lipid deposition in the liver was observed by oil red O staining. The levels of brain-muscle ARNT-like protein 1 （BMAL1/ARNTL） in the hypothalamus and liver were determined by immunohistochemical staining. The mRNA and protein levels of BMAL1， circadian locomotor output cycles kaput （CLOCK）， period circadian clock 2 （PER2）， and cryptochrome1 （Cry1） in the hypothalamus and liver were determined by Real-time PCR and Western blot， respectively. ResultsCompared with the blank group， the model group showed elevated levels of TG， TC， LDL-C， AST， and ALT （P<0.01） and a lowered level of HDL-C （P<0.05） in the serum， elevated levels of TG and NEFA in the liver （P<0.01）， pyknosis and deep staining of hypothalamic neuron cells， and a large number of vacuoles in the brain area. In addition， the model group showed lipid deposition in the liver， up-regulated mRNA and protein levels of CLOCK and BMAL1 （P<0.01）， and down-regulated mRNA and protein levels of Cry1 and PER2 （P<0.01） in the hypothalamus and liver. Compared with the model group， all the three modified Ditan tang groups showed lowered levels of TG， TC， LDL-C， ALT， and AST （P<0.05， P<0.01） and an elevated level of HDL-C （P<0.05） in the serum， and lowered levels of TG and NEFA （P<0.05， P<0.01） in the liver. Furthermore， the three groups showed alleviated pyknosis and deep staining of hypothalamic neuron cells， reduced lipid deposition in the liver， down-regulated mRNA and protein levels of CLOCK and BMAL1 （P<0.05， P<0.01）， and up-regulated mRNA and protein levels of Cry1 and PER2 （P<0.05， P<0.01） in the hypothalamus and liver. ConclusionModified Ditan tang can reduce lipid deposition in the liver and regulate the expression of CLOCK， BMAL1， Cry1， and PER2 in the TTFL of NAFLD rats.

Objective To investigate the infection status and changing trend of hepatitis C virus(HCV)infection in hospitalized patients in medical institutions,and provide reference for formulating HCV infection prevention and control strategies.Methods HCV infection surveillance results from cross-sectional survey data reported to China Healthcare-associated Infection(HAI)Surveillance System in 2020 were summarized and analyzed,HCV positive was serum anti-HCV positive or HCV RNA positive,survey result was compared with the survey results from 2003.Results In 2020,1 071 368 inpatients in 1 573 hospitals were surveyed,738 535 of whom underwent HCV test,4 014 patients were infected with HCV,with a detection rate of 68.93％and a HCV positive rate of 0.54％.The positive rate of HCV in male and female patients were 0.60％and 0.48％,respectively,with a statistically sig-nificant difference(x2=47.18,P＜0.001).The HCV positive rate in the 50-＜60 age group was the highest(0.76％),followed by the 40-＜50 age group(0.71％).Difference among all age groups was statistically signifi-cant(x2=696.74,P＜0.001).In 2003,91 113 inpatients were surveyed.35 145 of whom underwent HCV test,resulting in a detection rate of 38.57％;775 patients were infected with HCV,with a positive rate of 2.21％.In 2020,HCV positive rates in hospitals of different scales were 0.46％-0.63％,with the highest in hospital with bed numbers ranging 600-899.Patients'HCV positive rates in hospitals of different scales was statistically signifi-cant(X2=35.34,P＜0.001).In 2020,12 provinces/municipalities had over 10 000 patients underwent HCV-rela-ted test,and HCV positive rates ranged 0.19％-0.81％,with the highest rate from Hainan Province.HCV posi-tive rates in different departments were 0.06％-0.82％,with the lowest positive rate in the department of pedia-trics and the highest in the department of internal medicine.In 2003 and 2020,HCV positive rates in the depart-ment of infectious diseases were the highest,being 7.95％and 3.48％,respectively.Followed by departments of orthopedics(7.72％),gastroenterology(3.77％),nephrology(3.57％)and general intensive care unit(ICU,3.10％)in 2003,as well as departments of gastroenterology(1.35％),nephrology(1.18％),endocrinology(0.91％),and general intensive care unit(ICU,0.79％)in 2020.Conclusion Compared with 2003,HCV positive rate decreased significantly in 2020.HCV infected patients were mainly from the department of infectious diseases,followed by departments of gastroenterology,nephrology and general ICU.HCV infection positive rate varies with gender,age,and region.

AIM: To predict the core targets and related signaling pathways of Yi-xin-yin oral liquid for the treatment of arrhythmia, heart failure and myocarditis based on UHPLC-Q-TOF/MS, network pharmacology, molecular docking methods, cell experiments, according to the“homotherapy for heteropathy”theory in traditional Chinese medicine. METHODS: UHPLC-Q-TOF / MS was used to analyze and identify the chemical composition of Yi-xin-yin oral liquid Extract and the blood-absorbing components of rats oral administrated with Yi-xin-yin oral liquid extract, which compounds were applied in the databases searching for the potential targets (TCMSP, SwissTargetPrediction) and disease targets (OMIM, Genecard). Venn diagram was used for target intersection, and the subsequent protein-protein interaction network obtained core targets by STRING11.5 database, and then construct a "disease-component-target" network by cytoscape3.9.0. Finally, DAVID database was used to analysis GO function and KEGG enrichment analysis of core targets, and molecular docking validation was performed using Autodock vina software. And, validated with H9c2 cells for potential active ingredients and targets. RESULTS: A total of 156 compounds were identified from Yi - xin-yin Oral Liquid extract; 34 compounds were identified from rat serum, including 6-gin-gerol, isoliquiritigenin, glycyrrhizic acid and other compounds, and 139 intersecting targets were obtained. The KEGG pathway enrichment analysis mainly involved the TNF signaling pathway, IL-17 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway and so on. The TNF and IL-6 targets were selected for molecular docking with the main compounds, and the docking results were good (less than -5 kcal/mol). In vitro cellular experiments have shown that Yi-xin-yin oral liquid can exert therapeutic effects by regulating TNF and IL-6. CONCLUSION: The main potential active ingredients of Yi-xin-yin oral liquid may be isoliquiritigenin, glycyrrhetinic acid, calycosin-7-glucoside, salvianolic acid B, and 6-gingerol, which mainly act on TNF, IL-6 and other targets to regulate specific signaling pathways and exert therapeutic effects.

Objectives:To analyze the clinical prognosis stratification of fetal heart disease(FHD)and the mid-term follow-up results following integrated prenatal and postnatal management. Methods:Present retrospective analysis was performed on 817 fetuses diagnosed with FHD by fetal echocardiography in Fuwai Hospital,Chinese Academy of Medical Sciences(Fuwai Hospital)from the 8th February 2018 to 30th April 2022.According to the Chinese expert consensus on fetal prognosis score of congenital heart disease(CHD)and Fuwai Hospital Pediatric Center score,FHD was divided into grade Ⅰ(0 point),grade Ⅱ(1-3 points),grade Ⅲ(4-6 points)and grade Ⅳ(7-9 points).For FHD fetuses that need to be treated in the neonatal period,the whole closed-loop management and treatment were completed,including pregnancy,birth,neonatal monitoring,surgery,and follow-up.The clinical data and mid-term follow-up results of FHD fetuses were analyzed. Results:A total of 752 fetuses completed the mid-term follow-up.The mean follow-up time was(18.5±2.3)months.There were 111 cases(14.8%)of FHD grade Ⅰ,251 cases(33.4%)of FHD grade Ⅱ,275 cases(33.6%)of FHD grade Ⅲ and 115 cases(15.3%)of FHD grade Ⅳ.There were 393 cases(52.2%)of fetal preservation,1 case(0.2%)of intrauterine death,and 358 cases(47.6%)of induced abortion.Compared with the induced fetus,the pregnant women in the reserved fetus group were older,the gestational age was longer,the rate of receiving noninvasive DNA and amniocentesis was lower,the proportion of chromosomal abnormalities or genetic abnormalities was smaller,and the FHD prognostic score was lower(all P<0.05).One case(0.9%)of FHD grade Ⅰ fetus experienced intrauterine fetal death,and 110 cases(99.1%)were born and recovered.164 cases(65.3%)of grade Ⅱ fetuses were born,and all of them were cured by surgery or spontaneously.118 cases(42.9%)of grade Ⅲ fetuses were born,117 cases completed biventricular radical operation,and 1 case completed two-stage operation waiting for the second stage biventricular radical operation.One case(0.9%)of grade Ⅳ was born and completed the two-stage bidirectional Glenn procedure.Among the induced FHD grade Ⅱ fetuses,8(9.2%)had abnormal chromosomal or genetic testing results,and 8(9.2%)had other organ abnormalities.Among the induced FHD grade Ⅲ fetuses,5 cases(3.2%)had chromosomal abnormalities,5 cases(3.2%)had genetic abnormalities,and 9 cases(5.7%)had other organ abnormalities.There was only one case(0.9%)of FHD Ⅳ with hypoplastic left heart syndrome,which was retained as one of the twins and was born successfully.Norwood one-stage procedure was performed in the neonatal period,and two-stage bidirectional Greene procedure was performed at 6 months after birth.Other fetuses were induced following the choice of maternity and their family members. Conclusions:Hierarchical management based on clinical prognosis is helpful to scientifically guide the integrated treatment of FHD fetuses and improve the success rate of treatment of FHD fetuses with good prognosis.

Objectives:To summarize the experience of echocardiographic diagnosis and the short-term post-operative outcome of children with cardiac tumors. Methods:A total of 27 infants and children,who underwent echocardiography examination and were preliminarily diagnosed with cardiac tumors in Fuwai Hospital from January 2018 to June 2023,were retrospectively included in this study.Clinical symptoms,echocardiographic results,surgical and perioperative results and early outcomes were analyzed. Results:Among the 27 patients,16 were males.The age ranged from 1 month to 11 years(mean age:[3.2±2.5]years)and the body weight ranged from 5.7 to 40.0 kg(mean body weight:[17.2±11.2]kg).Cardiac tumors were pathologically confirmed in 25 cases,including 14 cases of fibroma,5 cases of rhabdomyoma,3 cases of myxoma,2 cases of lipoma,1 case of hemangioma.Preoperative echocardiographic diagnosis was consistent with postoperative pathologic diagnosis in 14 cases.Nontumor lesions were misdiagnosed as tumors by echocardiography in 2 cases.All the patients underwent surgery,complications occurred in 2 cases early post surgery and underwent reoperations and recovered well.There were no deaths during a median follow-up of 29.8(6.5,72.0)months,recurrence occurred in one child with myxoma. Conclusions:Pediatric patients with cardiac tumors have specific echocardiographic manifestations.It is necessary to sum up related experience constantly to improve the diagnostic accuracy.Short-term outcome post-surgery is satisfactory for the treatment of benign pediatric cardiac tumors.

Objective:To compare the efficacy of unilateral percutaneous kyphoplasty (PKP) and unilateral PKP combined with posterior medial branch block of the contralateral spinal nerve in the treatment of lumbar osteoporotic vertebral compression fracture (OVCF) in the elderly.Methods:A retrospective cohort study was conducted to analyze the clinical data of 161 aged patients with newly developed lumbar OVCF, admitted to Xi′an Central Hospital Affiliated to Xi′an Jiaotong University School of Medicine from January 2019 to January 2023, including 58 males and 103 females, aged 61-88 [(72.9±6.3)years]. All the patients were diagnosed with type II compression fracture based on acute symptomatic osteoporotic thoracolumbar fracture classification (ASOTLF). Seventy-eight patients underwent unilateral PKP (PKP group), while the other 83 patients underwent unilateral PKP combined with posterior medial branch block of the contralateral spinal nerve (PKP+contralateral block group). The operation time, intraoperative blood loss, and length of hospital stay were recorded. Beck index of the injured vertebra, Cobb angle of lumbar lordosis, Roland-Morris disability (RMD) score, visual analogue scale (VAS), and Oswestry disability index (ODI) were evaluated before operation, at 1 day, 1 week, 1 month, 3 months after operation, and at the last follow-up. The incidence of complications such as cement leakage was recorded as well.Results:All the patients were followed up for 6-8 months [(6.7±0.6)months]. There were no significant differences between the two groups in the operation time, intraoperative blood loss, or length of hospital stay ( P>0.05). The Beck index of the injured vertebra and Cobb angle of lumbar lordosis were not significantly different between the two groups before operation, at 1 day, 1 week, 1 month, 3 months after operation, and at the last follow-up ( P>0.05). The RMD score of the injured vertebra, VAS score, and ODI were not significantly different between the two groups before operation ( P>0.05). At 1 day, 1 week, 1 month, 3 months after operation, and at the last follow-up, the RMD scores in the PKP+contralateral block group were (11.23±1.05)points, (10.90±1.11)points, (10.10±1.06)points, (9.94±1.06)points, and (9.60±0.83)points respectively, which were all lower than (17.55±0.71)points, (15.78±0.86)points, (13.42±0.92)points, (10.67±0.78)points, and (9.78±0.72)points in the PKP group ( P<0.05 or 0.01); the VAS scores in the PKP+contralateral block group were (3.02±0.60)points, (2.96±0.55)points, (2.92±0.57)points, (2.88±0.61)points, and (2.70±0.51)points respectively, which were all lower than (3.60±0.57)points, (3.47±0.55)points, (3.32±0.46)points, (2.99±0.47)points, and (2.77±0.42)points in the PKP group ( P<0.05 or 0.01); the ODI values in the PKP+contralateral block group were 14.43±1.29, 14.54±1.24, 14.63±1.32, 14.37±1.31, and 13.42±1.45 respectively, which were all lower than 16.72±1.64, 16.09±1.49, 14.82±1.53, 14.74±1.46, and 13.69±1.75 in the PKP group ( P<0.05 or 0.01). The bone cement leakage rate was 12.0% (10/83) in the PKP+contralateral block group, similar to 11.5% (9/78) in the PKP group ( P>0.05). No other complications such as neurovascular injury, pulmonary embolism or adjacent vertebral fracture were found in either groups. Conclusion:In the treatment of lumbar OVCF in the elderly, unilateral PKP combined with posterior medial branch block of the contralateral spinal nerve is similar to unilateral PKP in terms of the operation time, intraoperative blood loss, length of hospital stay, effectiveness of reduction, and incidence of complications, but it can achieve better pain relief and more satisfactory functional recovery.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective: To investigate the clinical manifestations, pathological features, and treatment of oral and maxillofacial pyogenic granulomas induced by camrelizumab. Methods: A case of pyogenic granuloma of the gums and lips caused by camrelizumab was reported along with a literature review. Results: After 4 months of treatment with camrelizumab for liver cancer, the patient developed systemic reactive capillary hyperplasia (RCH), followed by multiple masses on the lower lip and gingiva. After periodontal therapy, the masses on the lower lip and the gingiva were removed, and camrelizumab administration was stopped. The pathological result was gingival pyogenic granuloma/granulomatous hemangioma. No new masses were found in the oral cavity during postoperative follow-up. A review of the literature showed that RCH is the most common adverse drug reaction to camrelizumab but it occurs infrequently in the oral cavity. At present, the etiology of RCH has not been clarified, but the research has shown that camrelizumab may trigger tissue proliferation into hemangiomas by activating vascular endothelial cells, and the combined use of camrelizumab is safer than single use. RCH is self-limiting and most cases resolve spontaneously after discontinuation of the drug. If the mass causes dysfunction, surgical excision is feasible. Conclusion Camrelizumab can cause oral and maxillofacial reactive capillary hyperplasia complicated by pyogenic granuloma.

OBJECTIVE: This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance (HIVDR) in patients with ART failure from 2014 to 2020 in Hainan, China. METHODS: A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan. We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences. Drug resistance mutations (DRMs) were analyzed using the Stanford University HIV Drug Resistance Database. RESULTS: A total of 307 HIV-infected patients with ART failure were included, and 241 available pol sequences were obtained. Among 241 patients, CRF01_AE accounted for 68.88%, followed by CRF07_BC (17.00%) and eight other subtypes (14.12%). The overall prevalence of HIVDR was 61.41%, and the HIVDR against non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 59.75%, 45.64%, and 2.49%, respectively. Unemployed patients, hypoimmunity or opportunistic infections in individuals, and samples from 2017 to 2020 increased the odd ratios of HIVDR. Also, HIVDR was less likely to affect female patients. The common DRMs to NNRTIs were K103N (21.99%) and Y181C (20.33%), and M184V (28.21%) and K65R (19.09%) were the main DRMs against NRTIs. CONCLUSION The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.
Humans ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV-1/genetics* ; Cross-Sectional Studies ; Phylogeny ; Anti-HIV Agents/therapeutic use* ; Drug Resistance, Viral/genetics* ; HIV Infections/epidemiology* ; Mutation ; China/epidemiology* ; Prevalence ; Genotype

OBJECTIVE: To investigate the expression and clinical significance of T helper cell 9 (Th9) and its cytokine interleukin 9(IL-9) in peripheral blood of patients with chronic lymphocytic leukemia(CLL). METHODS: A total of 43 newly diagnosed patients with chronic lymphocytic leukemia in the First Affiliated Hospital of Xinjiang Medical University from June 2021 to June 2022 were selected as the case group. The patients were divided into Binet A group (13 cases), Binet B group (20 cases) and Binet C group (10 cases) by Binet staging system, and 20 healthy volunteers who underwent physical examinationin in our hospital in the same period served as control group. The proportion of Th9 cells in peripheral blood was detected by flow cytometry, the expression level of Th9 specific transcription factors PU.1 and IRF4 was detected by Western blot, and the expression level of serum cytokine IL-9 was detected by ELISA. The proportion of Th9, the expression of PU.1, IRF4 and IL-9 in each group were compared, and the correlation between the proportion of Th9, IL-9 and clinicopathological indexes of CLL patients was analyzed. RESULTS: The proportion of Th9, the expression of PU.1, IRF4 and IL-9 in CLL group were significantly higher than those in control group (P<0.05), the proportion of Th9 and the expression of IL-9 in Binet B and C group were higher than those in Binet A group (P<0.05), but there was no significant difference in the proportion of Th9 cells between Binet B group and C group (P>0.05). The expression of IL-9 in Binet C group was significantly higher than that in Binet B group (P<0.05) . The proportion of Th9 cells and IL-9 were highly expression in patients with β2 microglobulin abnormality, IGHV unmutation, P53 abnormality and hepatosplenic lymph node enlargement(P<0.05), but not related to age and sex (P>0.05). The results of Spearman correlation analysis showed that the proportion of Th9 in patients with CLL was negatively correlated with the lymphocytic account and lymphocyte proportion(r_s=-0.32，r_s=-0.34). The proportion of Th9 and IL-9 were positively correlated with Binet stage, Rai stage and CLL-IPI Scoring (r_s=0.79，r_s=0.54，r_s=0.58； r_s=0.72，r_s=0.63，r_s=0.45), but not with WBC, CD4⁺ T cells and CD8⁺T cells (P>0.05). The proportion of Th9 was positively correlated with IL-9 (r_s=0.53). CONCLUSION Th9 cells and IL-9 are abnormally highly expressed in CLL, which is related to the poor prognosis of CLL.
Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics* ; Interleukin-9 ; Clinical Relevance ; T-Lymphocytes, Helper-Inducer/pathology* ; Cytokines