Aim To investigate whether protein inhibitor of activated STAT3(PIAS3)deficiency exacerbates the occurrence and development of atherosclerosis(As)in female ApoE knockout mice.Methods PIAS3 gene knockout mice with ApoE-/-background(PIAS3-/-/ApoE-/-)and their littermate PIAS3+/+/ApoE-/-mice were bred and fed with a high-fat/high-cholesterol diet for 12 weeks to induce As.Body weight(every week)and plasma lipid levels including to-tal cholesterol,triglyceride,high density lipoprotein cholesterol and non-high density lipoprotein cholesterol(every 4 weeks)of the mice were measured.Oil red O staining,HE staining,immunohistochemistry staining and immunofluores-cence staining were performed on mouse aortic tree and frozen sections of aortic root to evaluate the area,cellular composi-tion and stability of As plaques.Moreover,the expression of estrogen receptor α(ERα)and its co-localization with vas-cular smooth muscle cells(VSMC)in plaques were determined by immunofluorescence staining.Results Compared with PIAS3+/+/ApoE-/-mice,PIAS3-/-/ApoE-/-mice showed no significant differences in body weight,major organ weight(heart,liver,spleen,kidney and epididymal fat)and plasma lipid levels;however,PIAS3 deficiency promoted the forma-tion of As in female PIAS3-/-/ApoE-/-mice.Compared with PIAS3+/+/ApoE-/-mice,PIAS3-/-/ApoE-/-mice showed an increased lipid accumulation and a decreased VSMC content in As plaques(P＜0.05),leading to a decrease in plaque stability.In addition,the expression of ERα in the As plaques of PIAS3-/-/ApoE-/-mice was significantly downregulated(P＜0.05),and there was a obvious co-localization between ERα and VSMC.The reduction of VSMC content in PIAS3-/-/ApoE-/-mouse plaques might lead to a decrease of ERα expression,thereby weakening the anti-As effect of es-trogen.Conclusion PIAS3 deficiency exacerbates the formation of As plaques in female PIAS3-/-/ApoE-/-mice,which might be due to the regulatory effect of PIAS3 on ERα expression in plaques.

Aim To investigate whether protein inhibitor of activated STAT3(PIAS3)deficiency exacerbates the occurrence and development of atherosclerosis(As)in female ApoE knockout mice.Methods PIAS3 gene knockout mice with ApoE-/-background(PIAS3-/-/ApoE-/-)and their littermate PIAS3+/+/ApoE-/-mice were bred and fed with a high-fat/high-cholesterol diet for 12 weeks to induce As.Body weight(every week)and plasma lipid levels including to-tal cholesterol,triglyceride,high density lipoprotein cholesterol and non-high density lipoprotein cholesterol(every 4 weeks)of the mice were measured.Oil red O staining,HE staining,immunohistochemistry staining and immunofluores-cence staining were performed on mouse aortic tree and frozen sections of aortic root to evaluate the area,cellular composi-tion and stability of As plaques.Moreover,the expression of estrogen receptor α(ERα)and its co-localization with vas-cular smooth muscle cells(VSMC)in plaques were determined by immunofluorescence staining.Results Compared with PIAS3+/+/ApoE-/-mice,PIAS3-/-/ApoE-/-mice showed no significant differences in body weight,major organ weight(heart,liver,spleen,kidney and epididymal fat)and plasma lipid levels;however,PIAS3 deficiency promoted the forma-tion of As in female PIAS3-/-/ApoE-/-mice.Compared with PIAS3+/+/ApoE-/-mice,PIAS3-/-/ApoE-/-mice showed an increased lipid accumulation and a decreased VSMC content in As plaques(P＜0.05),leading to a decrease in plaque stability.In addition,the expression of ERα in the As plaques of PIAS3-/-/ApoE-/-mice was significantly downregulated(P＜0.05),and there was a obvious co-localization between ERα and VSMC.The reduction of VSMC content in PIAS3-/-/ApoE-/-mouse plaques might lead to a decrease of ERα expression,thereby weakening the anti-As effect of es-trogen.Conclusion PIAS3 deficiency exacerbates the formation of As plaques in female PIAS3-/-/ApoE-/-mice,which might be due to the regulatory effect of PIAS3 on ERα expression in plaques.

Combining domestic and international studies, an overview of the development of human papilloma virus (HPV) vaccine in the world and China is presented. The current situation of HPV vaccination for adolescents in China is analysed in the light of the latest policies in China, and rationalized recommendations are made to improve the HPV vaccination rate for adolescents in China.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Objective:To analyze the patterns of dynamic functional connectivity(dFC) at rest in different obsessive-compulsive disorder(OCD) subtypes based on gray matter volume, and explore the relationship between abnormal gray matter volume and dFC patterns and clinical symptoms in different OCD subtypes.Methods:Clinical data were prospectively collected from a total of 48 patients with OCD from inpatient and outpatient departments of the Fourth Affiliated Hospital of Qiqihar Medical College(20 cases) and Qiqihar Mental Health Center(28 cases) from September 2013 to March 2020. There were 33 males and 15 females, aged 18 to 42(27.1±6.7) years. During the same period, 39 age-matched healthy controls were also recruited, including 31 males and 8 females, aged 18 to 43(28.5±8.6) years. Structural and resting-state functional magnetic resonance imaging scans were performed on 48 OCD patients(OCD group) who met the ICD-10 diagnostic criteria and 39 healthy controls(control group). Using voxel-based morphometry(VBM) and semi-supervised machine learning methods, the patient group was characterized by gray matter volume to perform subtype analysis, and brain regions with abnormal gray matter volume were selected as regions of interest for whole-brain voxel-wise dFC analysis. Correlations between abnormal gray matter volume and dFC and clinical symptoms in OCD patients were analyzed.Results:Based on gray matter volume, OCD patients were computed into two subtypes, of which subtype 1 increased gray matter volume in the right central posterior gyrus(809 voxels; t=4.31; GRF corrected voxel P<0.001, cluster P<0.05 two-tailed), and subtype 2 showed reduced gray matter volume in the left superior temporal gyrus(1 118 voxels; t=-4.37; GRF corrected voxel P<0.001, cluster P<0.05 two-tailed). In subtype 1, the dFC between the right central posterior gyrus and left medial superior frontal gyrus was significantly reduced(187 voxels; t=-4.42; GRF corrected voxel P<0.001, cluster P<0.05 two-tailed); in subtype 2, dFC between the left superior temporal gyrus and left hippocampus, and left central opercular cortex was significantly reduced(272 voxels、99 voxels; t=-4.69, -5.01; GRF corrected voxel P<0.001, cluster P<0.05 two-tailed). In subtype 1, dFC between the right central posterior gyrus and left medial superior frontal gyrus was negatively correlated with illness duration( r=-0.579; P=0.002, uncorrected). In subtype 2, dFC between the left superior temporal gyrus and left hippocampus was positively correlated with illness duration( r=0.578; P=0.003, uncorrected). Conclusions:In the resting state, patients with different subtypes of OCD may have different patterns of dFC abnormalities based on gray matter volume.

Objective:To analyze the patterns of dynamic functional connectivity(dFC) at rest in different obsessive-compulsive disorder(OCD) subtypes based on gray matter volume, and explore the relationship between abnormal gray matter volume and dFC patterns and clinical symptoms in different OCD subtypes.Methods:Clinical data were prospectively collected from a total of 48 patients with OCD from inpatient and outpatient departments of the Fourth Affiliated Hospital of Qiqihar Medical College(20 cases) and Qiqihar Mental Health Center(28 cases) from September 2013 to March 2020. There were 33 males and 15 females, aged 18 to 42(27.1±6.7) years. During the same period, 39 age-matched healthy controls were also recruited, including 31 males and 8 females, aged 18 to 43(28.5±8.6) years. Structural and resting-state functional magnetic resonance imaging scans were performed on 48 OCD patients(OCD group) who met the ICD-10 diagnostic criteria and 39 healthy controls(control group). Using voxel-based morphometry(VBM) and semi-supervised machine learning methods, the patient group was characterized by gray matter volume to perform subtype analysis, and brain regions with abnormal gray matter volume were selected as regions of interest for whole-brain voxel-wise dFC analysis. Correlations between abnormal gray matter volume and dFC and clinical symptoms in OCD patients were analyzed.Results:Based on gray matter volume, OCD patients were computed into two subtypes, of which subtype 1 increased gray matter volume in the right central posterior gyrus(809 voxels; t=4.31; GRF corrected voxel P<0.001, cluster P<0.05 two-tailed), and subtype 2 showed reduced gray matter volume in the left superior temporal gyrus(1 118 voxels; t=-4.37; GRF corrected voxel P<0.001, cluster P<0.05 two-tailed). In subtype 1, the dFC between the right central posterior gyrus and left medial superior frontal gyrus was significantly reduced(187 voxels; t=-4.42; GRF corrected voxel P<0.001, cluster P<0.05 two-tailed); in subtype 2, dFC between the left superior temporal gyrus and left hippocampus, and left central opercular cortex was significantly reduced(272 voxels、99 voxels; t=-4.69, -5.01; GRF corrected voxel P<0.001, cluster P<0.05 two-tailed). In subtype 1, dFC between the right central posterior gyrus and left medial superior frontal gyrus was negatively correlated with illness duration( r=-0.579; P=0.002, uncorrected). In subtype 2, dFC between the left superior temporal gyrus and left hippocampus was positively correlated with illness duration( r=0.578; P=0.003, uncorrected). Conclusions:In the resting state, patients with different subtypes of OCD may have different patterns of dFC abnormalities based on gray matter volume.

OBJECTIVE: To isolate the phenolic amides from the dried bulbs of Allium chinense and investigate their myocardium protective activities. METHODS: The chemical constituents were isolated and purified by combining with silica gel column, Sephadex LH-20 column, HPLC and other chromatography techniques. Their structures were elucidated by NMR techniques and mass spectrometry. The isolated compounds were evaluated to determine their protective effect for myocardium cells in vitro. RESULTS: Two new phenolic amides, namely, alichinemide I ( 1) and alichinemide II ( 2), and six konwn amides were isolated from the dried bulbs of A. chinense. The structures of compounds 3- 8 were identified as 3-indolcarbaldehyde ( 3), 1-(2-aminophenyl)urea ( 4), 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid ( 5), N-trans-feruloyltyramine ( 6), N-trans-p-coumaroyltyramine ( 7), and N-(3,4-dimethoxyphenethyl) acetamide ( 8). Compound 3 (50 μmol/L) showed significant inhibitory effect on the damage of H9c2 myocardial cells induced by H₂O₂in vitro. CONCLUSION Compounds 1 and 2 were new phenolic amides. Compound 3 could be one of the potential myocardium protective constituents of A. chinense.

ObjectiveTo investigate the mechanism of Gegen Qinliantang（GQT） on the intestinal flora of antibiotic-associated diarrhea（AAD） by 16S rRNA sequencing and network pharmacology. MethodSixty SD rats were randomly divided into six groups（n=10）， including blank group， model group， GQT high-， medium- and low-dose groups（10.08， 5.04， 2.52 g·kg^-1） as well as Lizhu Changle group（0.15 g·kg^-1）， except for the blank group， each group was given clindamycin（250 mg·kg^-1） by gavage once a day for 7 consecutive days. After successful modeling， the blank group and the model group were given equal volumes of normal saline by gavage. The other groups were given corresponding doses of drugs by gavage for 14 days. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） was used to screen the active components and targets of GQT， GeneCards， Online Mendelian Inheritance in Man（OMIM） database， Pharmacogenetics and Pharmacogenomics Knowledge Base（PharmGKB）， DrugBank and DisGeNET were used to search for AAD disease targets. The drug-disease common targets were obtained by R software. STRING was applied to analyze the target protein-protein interaction， and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis was performed. Then hematoxylin-eosin（HE） staining was used to observe the pathological changes of the colon， and 16S rRNA sequencing of AAD colon content flora structure further verified the results of network pharmacology. ResultThrough network pharmacology， it was found that 238 active components were screened from GQT and acted on 276 component targets， among which quercetin， puerarin， wogonin and apigenin were the main core components of GQT， 1 097 AAD disease targets and 127 drug-disease intersection targets. The protein-protein interaction network mainly included core targets such as protein kinase B1（Akt1）， interleukin（IL）-6 and IL-1β， which were mainly enriched in the IL-17 signaling pathway. It was verified through animal experiments that compared with the blank group， the colon structure of the model group was seriously abnormal， the intestinal epithelial columnar cells were damaged， the goblet cells were reduced， and a large number of inflammatory cells were infiltrated. Compared with the model group， the colon structure of the GQT high-dose group improved， but there were still abnormalities， the colon structure of GQT medium- and low- dose groups and Lizhu Changle group improved significantly and reached the normal level. GQT could improve the structural diversity of AAD intestinal flora. At the phylum level， the abundance of Firmicutes was increased and the abundance of Bacteroidetes was decreased. At the genus level， the abundance of Lactobacillus was increased， and the abundances of Prevotella and Bacteroides were decreased. Among them， Lactococcus could be used as a biomarker for AAD treatment with GQT， and the prediction of functional metabolism of intestinal flora revealed that GQT could promote acetate and lactate metabolic pathways in the intestine. ConclusionGQT may activate IL-17 signaling pathway by acting on the targets of Akt1 and IL-6 through key components such as quercetin and wogonin， and improve the abundance of Lactococcus in the intestinal tract as well as acetate and lactate metabolic pathways， so as to play a role in repairing the intestinal barrier for the treatment of AAD.

Objective To study the chemical constituents from ethyl acetate extracts of the strips of Semiliquidambar cathayensis.Methods The strips of S.cathayensis were extracted by 80%ethanol and the extracts were evaporated.Fourteen compounds in ethyl acetate extracts were isolated and purified by various chromatographic techniques,such as silica gel,Sephadex LH-20 column and pre-HPLC,etc.Their structures were identified on the basis of physicochemical properties and spectroscopic analysis.Antioxidant activity test was used to evaluate total extraction,each extraction part and the isolates.Results Fourteen compounds were isolated from the strips of S.cathayensis and identified by NMR as tetradecanoic acid(1),stearic acid(2),sesamin(3),9-octadecenoic acid(4),linoleic acid(5),dibutylphthalate(6),stigmasterol(7),β-sitosterol(8),lupeol(9),oleanolic acid(10),lup-20(29)-ene-3-[3-keto-hexadecanoate](11),peujaponisin(12),C-veratroylglycol(13),and 2,3-dihydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone(14).Conclusion Compounds 1,3,4,5,6,7,9,11,12,13 and 14 were isolated from this plant for the first time.The EA part,compounds 13(C-veratroylglycol)and 14(2,3-dihydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone)showed significant antioxidative effects.