ObjectiveTo investigate the effects of jujuboside A （JuA） on the learning and memory abilities and histopathological changes in the rat model of vascular cognitive impairment （VCI） and explore the potential mechanisms by which JuA treats VCI. MethodsA total of 50 male SPF-grade SD rats were randomized into a sham operation group （n=10）， a blank control group （n=10）， and a modeling group （n=30）. The rats in the modeling group underwent bilateral carotid artery ligation （2-VO） for the modeling of VCI. After stabilization， the VCI rats were randomized into model， JuA （20 mg·kg^-¹）， and donepezil （0.45 mg·kg^-¹） groups. After 4 weeks of gavage， the novel object recognition and Morris water maze tests were conducted to evaluate the learning and memory abilities of rats. Nissl staining was employed to evaluate the morphology and number of hippocampal neurons. Real-time PCR was employed to measure the mRNA levels of glycogen synthase kinase-3β （GSK-3β）， cAMP response element-binding protein （CREB）， B cell lymphoma-2 （Bcl-2）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） in the hippocampal tissue. Western blot was employed to quantify the protein levels of GSK-3β， p-GSK-3β， p-CREB， Bcl-2， PI3K， p-PI3K， Akt， and p-Akt in the hippocampal tissue. ResultCompared with the sham operation group， the model group exhibited declines in the learning and memory abilities （P<0.01）， neuronal damage and decreased neurons in the hippocampal CA1 region （P<0.01）， up-regulation in the mRNA level of GSK-3β （P<0.01）， and down-regulation in the mRNA levels of PI3K， Akt， CREB， and Bcl-2， as well as the protein levels of p-PI3K， p-Akt， p-GSK-3β， p-CREB， and Bcl-2 （P<0.01）. In comparison to the model group， both the JuA and donepezil groups demonstrated improvements in the learning and memory abilities （P<0.05， P<0.01）， with reduced neuronal damage and increased neurons （P<0.05， P<0.01）. In addition， the two groups showed down-regulation in the mRNA level of GSK-3β （P<0.01） and up-regulation in the mRNA levels of PI3K， Akt， CREB， and Bcl-2 and the protein levels of p-PI3K， p-Akt， p-GSK-3β， p-CREB， and Bcl-2 （P<0.05， P<0.01）. There were no statistically significant differences between the blank control and sham operation groups in terms of the learning and memory abilities， neuron count， and mRNA and protein levels of PI3K/Akt/GSK-3β pathway-related factors. ConclusionJuA can ameliorate the cognitive impairment in the rat model of VCI by activating the PI3K/Akt signaling pathway， reducing the apoptosis of hippocampal neurons， and alleviating the hippocampal neuronal damage.

Schistosomiasis is prevalent in 78 countries and territories worldwide, while the eastern and western parts of sub-Sahara Africa bear the highest disease burden due to schistosomiasis. Recently, climate change, international trade and travel, urbanization and war have increased the risk of cross-boundary importation and transmission of schistosomiasis, and schistosomiasis has increasingly become a public health concern in non-endemic countries and territories. Biomphalaria straminea, the intermediate host of Schistosoma mansoni, has colonized in southern China and its habitats continue to move northward. In addition, cross-boundary imported cases of schistosomiasis have been reported occasionally in China. However, the real number of cases may be underestimated greatly due to insufficient diagnostic capacity and weak awareness of case reporting for overseas imported schistosomiasis in healthcare facilities. It is necessary to establish a multi-party collaborative mechanism, improve corresponding systems and technical specifications, reinforce surveillance and early warning, and border management, enhance technical reserves and capability building, and improve the awareness of schistosomiasis prevention and healthcare-seeking among entry-exit personnel, in order to effectively address the threat of cross-boundary imported schistosomiasis.

ObjectiveTo observe the effect of Youguiwan on the leptin/Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway in the lung tissue of the rat model of chronic obstructive pulmonary disease （COPD） due to kidney-Yang deficiency. MethodForty rats were modeled for COPD with the syndrome of kidney-Yang deficiency by intratracheal instillation of lipopolysaccharide on day 1 and day 14 and continuous fumigation for 6 weeks， during which hydrocortisone was injected intramuscularly at an interval of 3 days. The modeled rats were randomized into model， high- （11.7 g·kg^-1）， medium- （5.85 g·kg^-1）， and low-dose （2.93 g·kg^-1） Youguiwan， and aminophylline （0.054 g·kg^-1） group. In addition， 8 SD rats were set as the blank group. After the completion of modeling， the rats in each group were administrated with the corresponding drug by gavage for 28 consecutive days. After the last administration， samples were collected. A lung function analyzer was used to evaluate the lung function of rats. Enzyme-linked immunosorbent assay was employed to measure the levels of interleukin-17A （IL-17A）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the bronchoalveolar lavage fluid （BALF）. Hematoxylin-eosin staining was employed to observe the pathological changes in the lung tissue， and Masson staining was employed to observe the deposition of blue collagen fibers around bronchi in the lung tissue and calculate the inflammation score. The immunofluorescence assay was employed to measure the protein content of collagen type Ⅰ （ColⅠ） and α-smooth muscle actin （α-SMA） in the bronchi. The protein and mRNA levels of leptin， IL-17A， JAK2， and STAT3 in the lung tissue were determined by Western blot and real-time fluorescence quantitative polymerase chain reaction， respectively. ResultCompared with the blank group， the model group showed decreased lung function （P<0.01）， elevated levels of IL-6， IL-17A， and TNF-α in the BALF （P<0.01）， and increased lung inflammation score， deposition of subcutaneous collagen fibers in the airway， and ColⅠ and α-SMA proteins （P<0.01）. Furthermore， the modeling up-regulated the proteins and mRNA levels of leptin， IL-17A， JAK2， and STAT3 in the lung tissue （P<0.01） and enhanced the phosphorylation of JAK2 and STAT3 （P<0.01）. Compared with the model group， high- and medium-dose Youguiwan improved the lung function， decreased the inflammation score， reduced collagen fiber deposition and ColⅠ and α-SMA proteins， lowered the levels of IL-6， IL-17A， and TNF-α in the BALF， down-regulated the mRNA and protein levels of leptin， JAK2， STAT3， and IL-17A， and weakened the phosphorylation of JAK2 and STAT3 （P<0.05， P<0.01）. The aminophylline group had higher IL-17A and TNF-α levels than the high-dose Youguiwan group， lower IL-17A level than the medium and low-dose Youguiwan groups， and lower TNF-α level than the low-dose Youguiwan group. Compared with the aminophylline group， the high- and medium-dose Youguiwan groups showed reduced deposition of collagen fibers and protein levels of ColⅠ and α-SMA around the bronchi in the lung tissue （P<0.05， P<0.01）， decreased inflammation score， and down-regulated protein and mRNA levels of leptin， JAK2， STAT3， and IL-17A in the lung tissue. ConclusionYouguiwan can prevent airway remodeling by inhibiting IL-17A to reduce inflammation and collagen deposition in COPD rats， which may be related to the inhibition of the leptin/JAK2/STAT3 signaling pathway.

italic>Artemisia argyi is a traditional Chinese medicine in China, which is used as medicine with its leaves. The leaves of A. argyi mainly contain flavonoids, phenolic acids, volatile oils and other compounds, and have a variety of pharmacological activities. AP2/ERF transcription factors are abundant in plants and are mainly involved in plant growth and development, abiotic stress response and secondary metabolite biosynthesis regulation. However, there are few reports on the AP2/ERF gene family and its functions in A. argyi. In this study, we systematically identified the AP2/ERF gene family in A. argyi genome, and analyzed its phylogenetic tree, protein physicochemical properties, subcellular localization, conserved motifs, promoter elements, and expression patterns. The results showed that a total of 204 AP2/ERF transcription factors were identified in A. argyi genome, encoding proteins consisting of 88-483 amino acids with a relative molecular mass of 10-52.94 kDa and a theoretical isoelectric point of 4.62-9.88. Subcellular prediction showed that the majority of AP2/ERFs were located in the nucleus, cytoplasm, and the minority of them is located in the membrane and chloroplasts. According to the Arabidopsis AP2/ERF family classification, A. argyi AP2/ERF proteins were divided into four subfamilies: Soloist, AP2, ERF (B3, B4, B5, B6), and DREB (A1, A2, A4, A5, A6), among which DREB family accounted for the largest proportion, and the same subfamily had similar conserved motifs. cis-Acting element analysis showed that AP2/ERF promoters have a large number of elements responding to light and abiotic stress. Expression pattern analysis showed that most of the genes of the AP2/ERF family were dominantly expressed mainly in roots and stems, of which 19 were dominantly expressed in leaves, 77 would be induced to be expressed by methyl jasmonate, of which 16 genes were both dominantly expressed in leaves and induced to be expressed by methyl jasmonate, and these AP2/ERF genes may be the key regulatory genes for the synthesis of active ingredients in A. argyi leaves.This study lays the foundation for the functional study of AP2/ERF family genes and their regulating roles in the active components biosynthesis in A. argyi leaves.

Objective To investigate the expression level of tetratricopeptide repeat protein 9A in tumors and its association with the patients'prognosis and immune infiltration.Methods TTC9A expression in different tumor tissues and its association with prognosis,DNA methylation,tumor mutation burden(TMB),and microsatellite instability(MSI)were analyzed based on data from TCGA and GTEx.TIMER and xCell were used to analyze the relationship between TTC9A expression and immune infiltration.Western blotting and RT-qPCR were used to detect the expression of TTC9A in 4 types of cancer cell lines.Results TTC9A expressions were significantly increased in many tumors and down-regulated in a few cancer types(P<0.05).Western blotting and RT-qPCR showed that TTC9A expressions were elevated in lung,colon and liver cancer cells but decreased in bladder cancer cells.In head and neck squamous cell carcinoma,renal clear cell carcinoma,renal papillary cell carcinoma,low-grade glioma,malignant mesothelioma,and endometrial carcinoma tumors,a high expression of TTC9A was strongly correlated with better overall survival(OS),disease-specific survival(DSS),and progression-free interval(PFI)(P<0.05),but was correlated with worse OS,DSS,and PFI in lung adenocarcinoma,pancreatic adenocarcinoma,adrenal carcinoma,and rectal adenocarcinoma(P<0.05).TTC9A hypermethylation was associated with a more favorable prognosis of glioblastoma multiforme,low-grade glioma,uveal melanoma,and ovarian plasmacytoid cystadenocarcinoma(P<0.05)but with poor prognosis of squamous cell carcinoma of the uterine cervix and intracervical adenocarcinoma,squamous cell carcinoma of head and neck,squamous cell carcinoma of the lungs,adrenal carcinoma,and endometrial carcinoma(P<0.05).In most of the cancer types,TTC9A was significantly correlated with the level of immune cell infiltration(P<0.05).Conclusion TTC9A can be used as a prognostic marker for a variety of cancers and is strongly associated with TBM,MSI and immune cell infiltration.

Objective To investigate the expression level of tetratricopeptide repeat protein 9A in tumors and its association with the patients'prognosis and immune infiltration.Methods TTC9A expression in different tumor tissues and its association with prognosis,DNA methylation,tumor mutation burden(TMB),and microsatellite instability(MSI)were analyzed based on data from TCGA and GTEx.TIMER and xCell were used to analyze the relationship between TTC9A expression and immune infiltration.Western blotting and RT-qPCR were used to detect the expression of TTC9A in 4 types of cancer cell lines.Results TTC9A expressions were significantly increased in many tumors and down-regulated in a few cancer types(P<0.05).Western blotting and RT-qPCR showed that TTC9A expressions were elevated in lung,colon and liver cancer cells but decreased in bladder cancer cells.In head and neck squamous cell carcinoma,renal clear cell carcinoma,renal papillary cell carcinoma,low-grade glioma,malignant mesothelioma,and endometrial carcinoma tumors,a high expression of TTC9A was strongly correlated with better overall survival(OS),disease-specific survival(DSS),and progression-free interval(PFI)(P<0.05),but was correlated with worse OS,DSS,and PFI in lung adenocarcinoma,pancreatic adenocarcinoma,adrenal carcinoma,and rectal adenocarcinoma(P<0.05).TTC9A hypermethylation was associated with a more favorable prognosis of glioblastoma multiforme,low-grade glioma,uveal melanoma,and ovarian plasmacytoid cystadenocarcinoma(P<0.05)but with poor prognosis of squamous cell carcinoma of the uterine cervix and intracervical adenocarcinoma,squamous cell carcinoma of head and neck,squamous cell carcinoma of the lungs,adrenal carcinoma,and endometrial carcinoma(P<0.05).In most of the cancer types,TTC9A was significantly correlated with the level of immune cell infiltration(P<0.05).Conclusion TTC9A can be used as a prognostic marker for a variety of cancers and is strongly associated with TBM,MSI and immune cell infiltration.

This report presented the endemic status of schistosomiasis and analyzed the data collected from the national schistosomiasis prevention and control system and national schistosomiasis surveillance program in the People’s Republic of China in 2022. Among the 12 provinces (municipality and autonomous region) endemic for schistosomiasis, Shanghai Municipality, Zhejiang Province, Fujian Province, Guangdong Province and Guangxi Zhuang Autonomous Region continued to maintain the achievements of schistosomiasis elimination, and Sichuan and Jiangsu provinces maintained the criteria of transmission interruption, while Yunnan, Hubei, Anhui, Jiangxi and Hunan provinces maintained the criteria of transmission control by the end of 2022. A total of 452 counties (cites, districts) were found to be endemic for schistosomiasis in China in 2022, with 27 434 endemic villages covering 73 424 400 people at risk of infections. Among the 452 endemic counties (cities, districts), 75.89% (343/452), 23.45% (106/452) and 0.66% (3/452) achieved the criteria of elimination, transmission interruption and transmission control of schistosomiasis, respectively. In 2022, 4 317 356 individuals received serological tests for schistosomiasis, and 62 228 were sero-positive. A total of 208 646 individuals received stool examinations for schistosomiasis, with one positive and another two cases positive for urine microscopy, and these three 3 cases were imported schistosomiasis patients from Africa. There were 28 565 cases with advanced schistosomiasis documented in China by the end of 2022. Oncomelania hupensis snail survey was performed in 18 891 endemic villages in China in 2022 and O. hupensis snails were found in 6 917 villages (36.62% of all surveyed villages), with 8 villages identified with emerging snail habitats. Snail survey was performed at an area of 655 703.01 hm² and 183 888.60 hm² snail habitats were found, including 110.58 hm² emerging snail habitats and 844.35 hm² re-emerging snail habitats. There were 477 200 bovines raised in the schistosomiasis endemic areas of China in 2022, and 113 946 bovines received serological examinations for schistosomiasis, with 204 sero-positives detected. Among the 131 715 bovines received stool examinations, no positives were identified. In 2022, there were 19 726 schistosomiasis patients receiving praziquantel chemotherapy, and expanded chemotherapy was performed in 714 465 person-time for humans and 234 737 herd-time for bovines in China. In 2022, snail control with chemical treatment was performed at an area of 119 134.07 hm², and the actual area of chemical treatment was 65 825.27 hm², while environmental improvements were performed at an area of 1 163.96 hm². Data from the national schistosomiasis surveillance program of China showed that the mean prevalence of Schistosoma japonicum infections was both zero in humans and bovines in 2022, and no S. japonicum infection was detected in O. hupensis snails. These data demonstrated that the endemic status of schistosomiasis continued to decline in China in 2022, with 3 confirmed schistosomiasis patients that had a foreign nationality and all imported from Africa, and the areas of snail habitats remained high. Further improvements in the construction of the schistosomaisis surveillance and forecast system, and reinforcement of O. hupensis survey and control are required to prevent the re-emerging schistosomiasis.

Objective:To report pediatric endoscopic retrograde cholangiopancreatography (ERCP) intubation techniques and to analyze the influencing factors of pediatric ERCP in China.Methods:Retrospective analysis was performed on 90 cases of pediatric and adult ERCP operations respectively at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2016 to June 2020. The anatomic data, intubation time, and endoscopic intubation measures were reviewed. The anatomic differences in duodenal papilla between the children and adults were analyzed to find the factors affecting ERCP intubation time in children.Results:There were 88 cases of successful infantile intubation with the success rate of 97.8%, and 90 cases of successful adult intubation with the success rate of 100.0%. The intubation time in the pediatric group was 187±67 s, and that in the adult group was 247±86 s with significant difference ( t=5.220, P<0.001). The duodenal diameter of pediatric patients was 3.38±1.57 cm, and that of adult patients was 5.94±1.87 cm with significant difference ( t=9.832, P<0.001). The horizontal distance from the duodenal bulb to the papilla in pediatric patients was 2.44±1.15 cm, which was significantly shorter than 4.22±1.43 cm in adult patients ( t=9.077, P<0.001). Most duodenal papillae in children were hemispherical [flat 26.1% (23/88), hemispherical 51.1% (45/88), cylindrical 22.7% (20/88)], while most of those in the adult patients were cylindrical [flat 9.1% (8/88), hemispherical 23.9% (21/88), cylindrical 67.0% (59/88)]. The factors influencing the intubation time of ERCP in children by univariate analysis included the shape of duodenal papilla, duodenal papilla hardness, visual region, distance from junction of duodenal bulb and descending part to duodenal papilla, distance from duodenal papilla to endoscope, and degree of incising. Conclusion:Shorter and stiffer duodenal papillae in children with normal papilla orientation are associated with shorter intubation time. These indicators are favorable factors for intubation.

Orthodontic tooth movement elicits alveolar bone remodeling and orofacial pain that is manifested by tooth mechanical hyperalgesia. Nerve growth factor (NGF) is upregulated in periodontium and may modulate tooth mechanical hyperalgesia. The objectives were to examine the role of NGF in tooth mechanical hyperalgesia and to elucidate the underlying mechanisms. Tooth mechanical hyperalgesia was induced by ligating closed coil springs between incisors and molars in Sprague-Dawley rats. Retrograde labeling was performed by periodontal administration of fluor-conjugated NGF and the detection of fluorescence in trigeminal ganglia (TG). Lentivirus vectors carrying NGF shRNA were employed to knockdown the expression of NGF in TG. The administration of agonists, antagonists, and virus vectors into TG and periodontium was conducted. Tooth mechanical hyperalgesia was examined through the threshold of biting withdrawal. Our results revealed that tooth movement elicited tooth mechanical hyperalgesia that could be alleviated by NGF neutralizing antibody and that NGF was upregulated in periodontium (mainly in periodontal fibroblasts) and TG. Retrograde labeling revealed that periodontal NGF was retrogradely transported to TG after day 1. Acid-sensing ion channel 3 (ASIC3) and NGF were co-expressed in trigeminal neurons and the percentage of co-expression was significantly higher following tooth movement. The administration of NGF and NGF neutralizing antibody into TG could upregulate and downregulate the expression of ASIC3 in TG, respectively. NGF aggravated tooth mechanical hyperalgesia that could be alleviated by ASIC3 antagonist (APETx2). Moreover, NGF neutralizing antibody mitigated tooth mechanical hyperalgesia that could be recapitulated by ASIC3 agonist (GMQ). NGF-based gene therapy abolished tooth mechanical hyperalgesia and downregulated ASIC3 expression. Taken together, in response to force stimuli, periodontal fibroblasts upregulated the expressions of NGF that was retrogradely transported to TG, where NGF elicited tooth mechanical hyperalgesia through upregulating ASIC3. NGF-based gene therapy is a viable method in alleviating tooth-movement-induced mechanical hyperalgesia.

OBJECTIVE：To inv estigate the effects of 4-hydroxy-2（3H）-benzoxazolone on inflammatory and apoptosis signaling pathways in non-alcoholic fatty liver disease （NAFLD）model rats. METHODS ：SD rats were divided into normal control group（10 rats）and modeling group （50 rats）. Normal control group was given basic diet ，and modeling group were given high-fat diet to induce NAFLD model. After modeling ，the rats were divided into normal control group ，model group ，silibinin group （26.25 mg/kg），and 4-hydroxy-2（3H）-benzoxazolone high-dose ，medium-dose and low-dose groups （100，50，25 mg/kg），with 8 rats in each group. Normal control group and modeling group were given 0.6％ CMC-Na intragastrically ，and other groups were given relevant medicine 10 mL/kg intragastrically ，once a day ，for consecutive 4 weeks. After last medication ，the serum levels of albumin（ALB），total protein （TP），globulin（GLB），ALB/GLB and free fatty acid （FFA）were detected ；TUNEL staining was used to observe the apoptosis of rat hepatocytes. Western blot assay was used to detect the protein expression and phosphorylation level of inflammatory signaling pathway related proteins [Toll-like receptor 4（TLR4），myeloid differentiation factor 88（MyD88）， nuclear factor-κB p65（NF-κB p65），NF-κB inhibitor protein（IκBα）] in liver tissue as well as the expression of apoptosis signaling pathway related proteins [B cell lymphoma 2（Bcl-2），Bax，caspase-3]. RESULTS ：Compared with model group ，serum levels of TP （except for low-dose group ），GLB and FFA ，the protein expression of TLR 4（except for low-dose group ），MyD88 （except for medium-dose group ）and caspase- 3，the phosphorylation levels of NF-κB p65 and IκBα protein were decreased significantly（P＜0.05 or P＜0.01）. The ratio of A LB/GLB in serum and the ratio of Bcl- 2/Bax in liver tissue were significantly increased（P＜0.05 or P＜0.01），and the phenomenon of hepatocyte apoptosis was improved. CONCLUSIONS ：4-hydroxy-2 （3H）-benzoxazolone can ameliorate NAFLD in rats ，and the mechanism may be associated with inhibiting the expression TLR 4/ MyD88/NF-κB signaling pathway-related proteins and apoptosis-related proteins in liver tissues.