OBJECTIVE To predict and validate the mechanisms of Chaiqi yigan granules （CQYG） improving hepatocellular carcinoma （HCC）. METHODS The signaling pathways of CQYG intervention in HCC were predicted using network pharmacology. A mice model of transplanted hepatocellular carcinoma was established by injecting H22 hepatoma cells into the axilla. Successfully modeled mice were randomly divided into model group （normal saline）， sorafenib group （positive control， 50 mg/kg）， and CQYG low-， medium- and high-dose groups （24.83， 49.66， 99.32 g/kg）， with 10 mice in each group. Mice in each group were administered the corresponding drug solution or normal saline intragastrically， once a day， for 14 consecutive days. After last administration， pathological morphological changes in the tumor tissues of mice were observed in each group. Immunohistochemical staining was performed to detect the expression of the nuclear proliferation antigen Ki-67 in tumor tissues of mice. Western blot assay was used to measure the expression of proteins related to epithelial-mesenchymal transition （EMT） [N-cadherin， E-cadherin， Vimentin， matrix metalloproteinase 7 （MMP7）] and the mitogen-activated protein kinase （MAPK） signaling pathway [p38 MAPK， phosphorylated p38 MAPK， c-Jun N-terminal kinase （JNK）， phosphorylated JNK， extracellular regulated protein kinase 1/2 （ERK1/2）， phosphorylated ERK1/2] in tumor tissue of mice. RESULTS Network pharmacology analysis revealed that metabolic pathways， pathways in cancer， and the MAPK signaling pathway were key signaling pathways through which CQYG exert their anti-hepatocellular carcinoma effects. In animal experiments， the tumor tissues of mice in the model group exhibited dense tumor cells and vigorous growth. Compared with model group， CQYG high-dose group showed a decreased density of tumor cells in the tumor tissues of mice. Moreover， the expression levels of Ki-67， N-cadherin， MMP7 and Vimentin proteins， along with the phosphorylation levels of ERK1/2 and JNK proteins， were all significantly reduced （ P ＜0.05）. The expression level of E-cadherin protein was significantly increased （ P ＜0.05）， the phosphorylation level of p38 MAPK protein was increased， the difference was not statistically significant （ P ＞0.05）. CONCLUSIONS CQYG can inhibit EMT by regulating the MAPK signaling pathway， thereby suppressing tumor cell invasion and metastasis and ultimately exerting a therapeutic effect in improving HCC.

OBJECTIVE To systematically evaluate the efficacy and safety of probiotics in the treatment of nonalcoholic fatty liver disease （NAFLD）. METHODS Retrieved from CNKI， Wanfang data， VIP， SinoMed， PubMed， Embase， Web of Science， Cochrane library databases， the published randomized controlled trials （RCTs） about probiotics（treatment group） versus placebo or healthy lifestyle（control group） in the treatment of NAFLD were collected from the inception to Oct. 10th， 2023. The quality of the included literature was evaluated and rated by Cochrane system evaluator manual 5.1.0 and GRADE tools. Meta-analysis and Egger’s test were carried out by using RevMan 5.4 and Stata 17.0 software. RESULTS Overall 24 RCTs were included in this study， involving 1 391 patients with NAFLD. Meta-analysis showed that compared with control group， the levels of alanine aminotransferase [MD＝－6.29， 95%CI （－9.35， －3.22）， P＜0.000 1]， aspartate aminotransferase [MD＝－4.89， 95%CI （－7.55， －2.23）， P＝0.000 3] and γ-glutamyl transferase [MD＝－4.87， 95%CI （－6.54， －3.20）， P＜0.000 01]， the liver stiffness measurement [MD＝－0.36， 95%CI （－0.48， －0.24）， P＜0.000 01]， the levels of triglycerides [MD＝－0.22， 95%CI （－0.27， －0.16）， P＜0.000 01]， total cholesterol [MD＝－0.34， 95%CI （－0.44， －0.25）， P＜0.000 01] and insulin resistance assessed by homeostasis model [MD＝－0.38， 95%CI （－0.63， －0.13）， P＝0.003] were all significantly decreased in the treatment group. However， there was no statistically significant difference of probiotics therapy in the levels of tumor necrosis factor-α [MD＝－0.41， 95%CI （－1.29， 0.48）， P＝0.37]， interleukin-6 [MD＝0.39， 95%CI （ －0.10， 0.88）， P＝0.12]， high- sensitivity C-reactive protein [MD＝－0.30， 95%CI （－0.85，0.25）， P＝0.28]， high-density lipoprotein cholesterol [MD＝0.03， 95%CI （ －0.01， 0.06）， P＝0.10] and low-density lipoprotein cholesterol [MD＝－0.10， 95%CI （－0.27， 0.07）， P＝0.23] and body mass index [MD＝0.07， 95%CI （－0.26， 0.40）， P＝0.68]. Subgroup analysis based on different intervention measures showed that the levels of γ-glutamyl transferase， liver stiffness measurement， and homeostatic model assessment of insulin resistance in the synbiotic group were not significantly improved compared to the control group， with consistent results for the remaining outcomes. Egger’s test results showed no publication bias. CONCLUSIONS The probiotic therapy can regulate liver function indexes， liver stiffness measurement and insulin resistance levels in patients with NAFLD well.

OBJECTIVE To systematically evaluate the efficacy and safety of transcatheter arterial chemoembolization （TACE） combined with anti-angiogenic drugs for the treatment of unresectable primary liver cancer （PLC）. METHODS Retrieved from Chinese and English databases such as CNKI， the Cochrane Library， Google， and Baidu Academic， randomized controlled trial （RCT） about TACE combined with anti-angiogenic drugs for the treatment of unresectable PLC were collected from the inception to May 27， 2024. After screening the literature， extracting data， and evaluating the quality of the literature， network meta-analysis was performed using R 4.2.2 and Stata 17.0. RESULTS A total of 44 RCT were included， involving 5 607 patients and 8 interventions. The network meta-analysis results showed that for prolonging median overall survival （mOS） and median progression- free survival （mPFS）， TACE+apatinib had the best efficacy， with TACE+apatinib and TACE+sorafenib ranking as the top two. For improving objective response rate （ORR） and disease control rate （DCR）， TACE+donafenib had the best efficacy， with TACE+ donafenib and TACE+ lenvatinib ranking as the top two. In terms of safety， TACE+donafenib was the best， with TACE+donafenib and TACE+apatinib ranking as the top two. CONCLUSIONS TACE+apatinib and TACE+donafenib have good efficacy for patients with unresectable PLC， and TACE+donafenib has the best safety profile.

Objective To explore the photodynamic treatment method and therapeutic effect of oral verrucous carci-noma and to provide a reference for the clinic.Methods This study follows the requirements of medical ethics.This paper summarized the photodynamic treatment of an oral verrucous carcinoma with a diameter of approximately 2.5 cm in the right buccal mucosa and retrospectively analyzed the characteristics and treatment of oral verrucous carcinoma and the photodynamic treatment of potential malignant lesions of the oral mucosa through a review of the literature.Results After four rounds of photodynamic therapy,the size of the right buccal lesion was significantly reduced.After 6 months of follow-up,the white verrucous hyperplasia of the right buccal mucosa had completely subsided,and there was no obvious scar formation.Three years after treatment,there was no recurrence of the lesion in the right buccal mu-cosa and no obvious scar formation in the treated area.The degree of mouth opening was 3 fingers,and there was no lymph node enlargement in the bilateral submandibular,submental or neck.The literature review shows that oral verru-cous carcinoma is a rare subtype of squamous cell carcinoma with the characteristics and biological behaviors of slow growth,low malignancy,and rare metastasis.Surgery is the preferred treatment,but there are some limitations.Photody-namic therapy is a minimally invasive,repeatable treatment with mild adverse reactions.In recent years,photodynamic therapy has been gradually applied for the treatment of potential malignant disorders of the oral mucosa and early oral squamous cell carcinoma and has achieved positive results,but it has not been reported for the treatment of oral verru-cous cancer.Conclusion Photodynamic therapy is a new option for nonsurgical resection of oral verrucous carcinoma.

Objective To study mechanical properties of polyethylene terephthalate (PET)-based textile valves woven with nickel-titanium (NiTi) wires by finite element method, and combined with in vitro hemodynamic testing, to analyze the effect of wire quantity and woven position on hemodynamic performance of PET textile valve. Methods The three-dimensional (3D) geometric models of PET valves without wires and models of PET valves with wires by different numbers and distributions in radial direction were constructed using modeling software. Material properties of PET valves and wires were given based on the literature and experimental data. The transvalvular pressure difference curves of PET valves obtained from in vitro pulsatile flow experiments were used as boundary conditions. Stress distributions of the valve during peak systole and diastole were studied by finite element analysis software. Hydrodynamic performance of the valve with wires was evaluated by in vitro pulsatile flow experiments. ResultsThe finite element analysis results showed that the radially woven NiTi wires could enhance support for the PET textile valve, and support force and area of the valve in belly region of the valve leaflet with evenly distributed metal wires increased with the number of metal wires. The situation of support force was similar for silk distributions on both sides of the belly. The weaving of wires reduced stress concentration on the PET textile valve to a certain extent. The pulsatile flow experiment results showed that the stability of opening and closing shapes, effective opening area (EOA), regurgitation fraction (RF) and transvalvular pressure differences for two kinds of the PET valves with woven wires were better than those of the PET valves without wires. Conclusions Weaving metal wires in radial direction of the PET textile valve can effectively reduce stress concentrations on the PET textile valve during the cardiac cycle, and reduce tearing possibility of the valve leaflet. The woven metal wires can improve opening and closing stability of PET textile valve in in vitro hydrodynamic test, increase EOA and reduce RF and transvalvular pressure difference of the PET valve.

Objective: The etiology of schizophrenia is unknown and is associated with abnormal spontaneous brain activity. There are no consistent results regarding the change in spontaneous brain activity of people with schizophrenia. In this study, we determined the specific changes in the amplitude of low-frequency fluctuation/fractional amplitude of low-frequency fluctuation (ALFF/fALFF) and regional homogeneity (ReHo) in patients with drug-naïve first-episode schizophrenia (Dn-FES). Methods: A comprehensive search of databases such as PubMed, Web of Science, and Embase was conducted to find articles on resting-state functional magnetic resonance imaging using ALFF/fALFF and ReHo in schizophrenia patients compared to healthy controls (HCs) and then, anatomical/activation likelihood estimation was performed. Results: Eighteen eligible studies were included in this meta-analysis. Compared to the spontaneous brain activity of HCs, we found changes in spontaneous brain activity in Dn-FES based on these two methods, mainly including the frontal lobe, putamen, lateral globus pallidus, insula, cerebellum, and posterior cingulate cortex. Conclusion We found that widespread abnormalities of spontaneous brain activity occur in the early stages of the onset of schizophrenia and may provide a reference for the early intervention of schizophrenia.

Objective:To explore the reliability of preoperative diagnosis of low-grade infectious nonunion using haematological testing and radioisotope scanning (bone 3-phase image).Methods:A retrospective study was conducted of the 265 patients with bone nonunion who had been treated at Department of Orthopaedics, The Sixth People’s Hospital Affiliated to Shanghai Jiaotong University and at Department of Orthopaedics, The Eighth People’s Hospital Affiliated to Shanghai Jiaotong University from June 2010 to June 2018.They were 151 males and 114 females, aged from 19 to 64 years (average, 39.7 years).The nonunions occurred mainly at the tibia (113 cases) and the femur (72 cases).The preoperative results of their white blood cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and radioisotope scanning were recorded.Taking the intraoperative pathological observations as the gold standards, the sensitivity, specificity, area under curve (AUC) of receiver operator characteristic (ROC) and Youden index were statistically analyzed respectively for every preoperative haematological tests and radioisotope scanning as well as for different combinations of the radioisotope scanning and one or more haematological tests.Results:Compared with the pathological observations, the radioisotope scanning showed a sensitivity of 80.7%, a specificity of 73.3%, an AUC of 0.770 and a Youden index of 0.540.In the combinations of radioisotope scanning and one haematological test, that of radioisotope scanning and CRP produced the largest AUC of 0.683, a sensitivity of 98.0%, a specificity of 70.3%, and a Youden index of 0.848.In the combinations of radioisotope scanning and 2 haematological tests, that of radioisotope scanning and WBC and ESR produced the largest AUC of 0.895, a sensitivity of 94.3%, a specificity of 67.3%, and a Youden index of 0.616 and all the 3 ones yielded an AUC of more than 0.880.The combination of radioisotope scanning and all the 3 haematological tests produced a sensitivity of 96.5%, a specificity of 79.7%, an AUC of 0.925 and a Youden index of 0.762.Conclusion:Combination of haematological testing and radioisotope scanning can be a reliable preoperative diagnosis of low-grade infection nonunion.

OBJECTIVE: To explore the clinical signification of screening 16 target deafness mutations in GJB2, GJB3, SLC26A4, WFS1 and mitochondrial DNA 12S rRNA in 135 children patients with non-syndromic sensorineural hearing loss (NSHL) in Zibo City, Shandong province. METHOD: Peripheral blood samples of 135 subjects in the study diagnosed as NSHL were collected; Polymerase chain reaction (PCR) and direct sequencing were used to analyze the 16 mutation spots. RESULT: Sixty-two cases of 135 patients (45.9%, 62/135) were found out to be carries of at least one pathogenic gene mutation. Among them, 24 cases (17.8%, 24/135) had two mutated alleles (homozygote and compound heterozygote), and 38 cases (28.1%, 38/135) were single mutant carriers. Among all the children patients, 30 cases (22. 2%, 30/135) had SLC26A4 mutations, and 19 cases (14.1%, 19/135) had GJB2 mutations. In the study 86 Mutant alleles were detected, and the allele frequency of SLC26A4 c. 766_2A > G and GJB2 c. 235delC was 11.11% (30/270) and 8.5% (23/270) respectively. The allele frequency of SLC26A4 c. 2168A > G and WFS1 c. 2158A > G is 2.6% (7/270). CONCLUSION SLC26A4 mutation is the primary cause of the patients with NSHL in this study, and GJB2 mutation is the secondary. The most common mutant form is c. 766_2A of SLC26A4, and the second is c. 235delC of GJB2. GJB3 and WFS1 mutations were detected, whereas mtDNA mutations were not found out in this study.
Alleles ; Child ; Connexins ; DNA Mutational Analysis ; DNA, Mitochondrial ; Deafness ; Gene Frequency ; Hearing Loss ; Hearing Loss, Sensorineural ; genetics ; Heterozygote ; Homozygote ; Humans ; Mitochondria ; Mutation ; Polymerase Chain Reaction ; RNA, Ribosomal

Objective To identify Anaplasma species circulating among livestock and rodents from Xitianmu Mountain area in Zhejiang province , Southeastern China and to analyze variations regarding to their 16S rRNA gene.Methods Samples of spleen, liver and blood were collected to extract DNAs .The 16S rRNA gene fragments of Anaplasma species were amplified by using a nested PCR and then sequenced .Ho-mology analysis was conducted by using BLAST program .The multiple sequence alignment and phylogenetic analyses comparing with the sequences of other Anaplasma species in GenBank were conducted by using MEGA 5.0 software.Results The 16S rRNA gene fragments of Anaplasma were detected in 1 cattle, 8 goats, 5 Rattus confucianus, 1 Apodemus agrarius, 1 Berylmys bowersi and 1 squirrel out of 129 animals. The natural infection rate of Anaplasma was 13.2% in animals from Xitianmu Mountain area in Zhejiang . The alignment and phylogenetic analyses indicated that there were at least four Anaplasma species prevalent in livestock and rodents from Xitianmu Mountain area , including Anaplasma phagocytophilum, Anaplasma marginale, Anaplasma centrale and Anaplasma bovis.Moreover, there was a variant that obviously differed from Anaplasmma bovis and other Anaplasma sp.in GenBank.Conclusion The Anaplasma infection was detected among livestock and rodents from Xitianmu Mountain area in Zhejiang province .A newly discovered variant in rodents was likely to be a novel species .More close attention should be paid to Anaplasma infec-tion among human in Xitianmu Mountain area .

Atropa belladonna L. is the officially medicinal plant species and the main commercial source of scopolamine and hyoscyamine in China. In this study, we reported the simultaneous overexpression of two functional genes involved in biosynthesis of scopolamine, which respectively encoded the upstream key enzyme putrescine N-methyltransferase (PMT; EC 2.1.1.53) and the downstream key enzyme hyoscyamine 6beta-hydroxylase (H6H; EC 1.14.11.11) in transgenic hair root cultures of Atropa belladonna L. HPLC results suggested that four transgenic hair root lines produced higher content of scopolamine at different levels compared with nontransgenic hair root cultures. And scopolamine content increased to 8.2 fold in transgenic line PH2 compared with that of control line; and the other four transgenic lines showed an increase of scopolamine compared with the control. Two of the transgenic hair root lines produced higher levels of tropane alkaloids, and the content increased to 2.7 fold in transgenic line PH2 compared with the control. The gene expression profile indicated that both PMT and H6H expressed at a different levels in different transgenic hair root lines, which would be helpful for biosynthesis of scopolamine. Our studies suggested that overexpression of A. belladonna endogenous genes PMT and H6H could enhance tropane alkaloid biosynthesis.