ObjectiveThe purpose of this study was to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) on cognitive function of vascular dementia (VD) rats and its mechanism. MethodsVD rat model was established by modified two-vessel occlusion (2-VO). After modeling, TEAS and electroacupuncture (EA) were used to stimulate Baihui and Zusanli points of rats respectively for 14 d. After treatment, novel object recognition test, Morris water maze test, and Y maze test were used to evaluate the spatial memory and learning ability of rats. Hematoxylin and eosin staining was used to observe the morphology of hippocampal neurons. Transmission electron microscopy was used to observe the ultrastructure of hippocampal mitochondria. Enzyme-linked immunosorbent assay kits were used to detected the levels of SOD, CAT, GSH-Px, MDA and ROS in serum of rats. Western blot was used to detect the expression of PGC-1α, TFAM, HO-1, NQO1 proteins in the hippocampus, Keap1 protein in the cytoplasm and Nrf2, NRF1 proteins in the nucleus. ResultsAfter treatment for 14 d, compared to the model group, the escape latency of VD rats decreased, while the discrimination index, the times of rats crossing the original platform area, the residence time in the original platform quadrant, and the percentage of alternation increased. TEAS can improve the structure of hippocampal neurons and mitochondria of VD rats, showing that neurons were arranged more regularly and distributed more evenly, nuclear membrane and nucleoli were clearer, and mitochondrial swelling were reduced, mitochondrial matrix density were increased, and mitochondrial cristae were more obvious. The levels of SOD, GSH-Px and CAT in serum increased significantly, while the concentration of MDA and ROS decreased. TEAS also up-regulated the expression levels of PGC-1α TFAM, NQO1 and HO-1 proteins in the hippocampus and Nrf2, NRF1 proteins in the nucleus, but down-regulated the Keap1 protein in the cytoplasm. ConclusionTEAS can improve cognition, hippocampal neurons and mitochondrial structure of VD rats, and the effect is better than EA. The mechanism may be the activation of PGC-1α mediated mitochondrial biogenesis and antioxidant stress, which also provides a potential therapeutic technology and experimental basis for the treatment of VD.

PI3Kγ and PI3Kδ have important regulatory roles in the immune system, and targeting these two subtypes helps to reshape the tumor microenvironment. PI3Kγ and PI3Kδ are potential targets for tumor immunotherapy. In this study, a series of new pyrazolopyrimidine derivatives were designed and synthesized on the basis of our previously reported PI3K inhibitors, resulting in the discovery of compound 16l as a potent and selective PI3Kγ/δ dual inhibitor. Compound 16l demonstrated strong biochemical potencies against PI3Kγ and PI3Kδ with IC₅₀ values of 0.11 and 0.79 nmol·L^-1. In cell-based assays, it potently inhibited the PI3Kγ and PI3Kδ mediated Akt S473 phosphorylation with EC₅₀ values of 3 and 7 nmol·L^-1. In vivo, compound 16l exhibited acceptable pharmacokinetic properties in Sprague-Dawley (SD) rats and suppressed the tumor growth in a MC38 syngeneic mouse model. The animal experiments were approved by the Animal Ethics Committee of Hefei Institutes of Physical Science, Chinese Academy of Sciences (approval number: DWLL-2000-06). In addition, no appreciable human ether-a-go-go-related gene (hERG) inhibition was observed for compound 16l even at 30 μmol·L^-1. These results suggested that compound 16l might be a potential research tool for studying the PI3Kγ/δ mediated signaling pathways.

Applying Chinese medicine (CM) is an important strategy for malignant tumor treatment in China. One of the significant characteristics of CM is to treat diseases based on syndrome differentiation. For Western medicine, it is of important clinical significance to formulate guidelines for the diagnosis and treatment of cancer patients based on the characteristics of disease differentiation. In Chinese clinical practice, the combination of disease differentiation and syndrome differentiation is an important feature for cancer treatment in the past. Currently, molecular profiling and genomic analysis-based precision medicine optimizes the anticancer drug design and holds the greatest success in treating cancer patients. Therefore, we want to know which populations of cancer patients can benefit more from CM treatment if the theory of precision medicine is applied to CM clinical practice. So, we developed a novel diagnostic and therapeutic strategy "disease-syndrome differentiation-genomic profiling-prescriptions" for cancer patients by CM syndrome differentiation and precision medicine. As a result, this strategy has greatly enhanced the anti-tumor efficacy of CM and improved clinical outcomes for cancer patients with some gene mutations. Our idea will hopefully establish a novel approach for the inheritance and innovation of CM.
Antineoplastic Agents ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Neoplasms/therapy* ; Precision Medicine ; Syndrome

Objective: To estimate the incidence of HIV-1 infection in men who have sex with men (MSM) in key areas of China through HIV-1 limiting antigen avidity enzyme immunoassay (LAg-Avidity EIA), analyze the deviation from the actual results and identify influencing factors, and provided reference for improving the accuracy of estimation results. Methods: Based on the principle of the cohort randomized study design, 20 cities were selected in China based on population size and the number of HIV-positive MSM. The sample size was estimated to be 700 according to the HIV-1 infection rate in MSM. MSM mobile phone app. was used to establish a detection appointment and questionnaire system, and the baseline cross-sectional survey was conducted from April to November 2019. LAg-Avidity EIA was used to identify the recent infected samples. The incidence of HIV-1 infection was calculated and then adjusted based on the estimation formula designed by WHO. The influencing factors were identified by analyzing the sample collection and detection processes. Results: Among the 10 650 blood samples from the participants, 799 were HIV-positive in initial screening, in which 198 samples (24.78%) missed during confirmation test. Only 621 samples were received by the laboratory. After excluding misreported samples, 520 samples were qualified for testing. A total of 155 samples were eventually determined as recent infection through LAg-Avidity EIA; Based on the estimation formula , the incidence of HIV-1 infection in MSM in 20 cities was 4.06% (95%CI:3.27%-4.85%), it increased to 5.53% (95%CI: 4.45%-6.60%)after the adjusting for sample missing rate. When the sample missing rate and misreporting rate were both adjusted, the incidence of HIV-1 infection in the MSM increased to 5.66% (95%CI:4.67%-6.65%). The actual incidence of HIV-1 infection in MSM in the 20 cities might be between 4.06% and 5.66%. Conclusions: Sample missing and misreporting might cause the deviation of the estimation of HIV-1 infection incidence. It is important to ensure the sample source and the quality of sample collection and detection to reduce the deviation in the estimation of HIV-1 infection incidence.
Cross-Sectional Studies ; HIV Infections/epidemiology* ; HIV-1 ; Homosexuality, Male ; Humans ; Immunoenzyme Techniques ; Incidence ; Male ; Sexual and Gender Minorities

Accurate methods for identifying pelvic lymph node metastasis (LNM) of prostate cancer (PCa) prior to surgery are still lacking. We aimed to investigate the predictive value of peripheral monocyte count (PMC) for LNM of PCa in this study. Two hundred and ninety-eight patients from three centers were divided into a training set (n = 125) and a validation set (n = 173). In the training set, the independent predictors of LNM were analyzed using univariate and multivariate logistic regression analyses, and the optimal cutoff value was calculated by the receiver operating characteristic (ROC) curve. The sensitivity and specificity of the optimal cutoff were authenticated in the validation cohort. Finally, a nomogram based on the PMC was constructed for predicting LNM. Multivariate analyses of the training cohort demonstrated that clinical T stage, preoperative Gleason score, and PMC were independent risk factors for LNM. The subsequent ROC analysis showed that the optimal cutoff value of PMC for diagnosing LNM was 0.405 × 109 l

OBJECTIVE: The clinical symptoms of diarrhea-predominant irritable bowel syndrome (IBS-D) can be effectively improved by traditional Chinese medicine (TCM) treatment, based on the usage of specific therapies for different TCM syndromes. However, in the stage of diagnosis, the standard criteria for the classification of TCM syndrome were still deficient. Through serum metabolic profiling, this study aimed to explore potential biomarkers in IBS-D patients with different TCM syndromes, which can assist in diagnosis of the disease. METHODS: Serum samples were collected from healthy controls (30 cases), IBS-D patients with Liver-Stagnation and Spleen-Deficiency syndrome (LSSD, 30 cases), Yang Deficiency of Spleen and Kidney syndrome (YDSK, 11 cases) and Damp Abundance due to Spleen-Deficiency syndrome (DASD, 22 cases). Serum metabolic profiling was conducted by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The potential biomarkers were screened by orthogonal partial least square-discriminate analysis, while metabolic pathways undergoing alterations were identified by pathway enrichment analysis in MetaboAnalyst 4.0. RESULTS: Overall, 34 potential biomarkers were identified in LSSD group, 36 in YDSK group and 31 in DASD group. And the 13 metabolites shared by three groups were determined as the potential biomarkers of IBS-D. Glycerophospholipid metabolism was disturbed significantly in IBS-D patients, which may play a role in IBS-D through inflammation. What's more, three TCM syndromes have the specific potential biomarkers in glycerophospholipid metabolism. CONCLUSION The serum metabolomics revealed that different TCM syndrome types in IBS-D may have different metabolic patterns during disease progression and glycerophospholipid metabolism was one of the pathways, whose metabolism was disturbed differently among three TCM syndromes in IBS-D. Therefore, the specific potential biomarkers in glycerophospholipid metabolism of three TCM syndromes in IBS-D can serve as the objective indicators, which can facilitate the TCM-syndrome objective classification of IBS-D.

Objective To understand the current distribution of Oncomelania snails in Sichuan Province, so as to provide scientific evidence for formulating the schistosomiasis elimination strategy and implementing the precision schistosomiasis control measures in the province. Methods According to the National Scheme on Oncomelania hupensis Snails in China and the Scheme on Oncomelania hupensis Snails in Sichuan Province, snail surveys were performed in current snail habitats, historical snail habitats and suspected snail habitats using systematic sampling in Sichuan Province from 2016 to 2017, and the survey results were analyzed. Results From 2016 to 2017, a total of 88 346 settings were surveyed in schistosomiasis-endemic areas of Sichuan Province, and 19 314 settings were detected with snails, covering an area of 4 829.25 hm², with no Schistosoma japonicum infection identified in snails. A total of 3 017 915 frames were investigated in Sichuan Province, and 1 041 417 frames were found to have living snails, with totally 1 791 115 living snails captured. The mean density of living snails was 0.59 snails/0.1 m², and the mean percentage of frames with living snails was 34.51% in Sichuan Province. The current snail habitats were mainly distributed in 1 704 villages, 377 townships, 54 counties (districts) of 9 cities (prefectures) across the schistosomiasis-endemic areas of Sichuan Province. Snail habitats were mainly found in ditches (70.22%), and weeds were the predominant vegetation in snail habitats (66.45%). Snails were firstly discovered in Sichuan Province in 1913, and S. japonicum-infected snails were firstly identified in 1956, with the latest identification of S. japonicum-infected snails in 2008. Conclusion There are many settings suitable for snail breeding in Sichuan Province, and snail monitoring and control should be intensified in the future.

Objective To investigate the epidemic factors of schistosomiasis in wetlands in Sichuan Province, so as to provide scientific evidence for the prevention and control of schistosomiasis in wetlands. Methods The artificial and natural wetlands were selected from Sichuan Province, and the relevant data regarding wetlands were collected. Routine snail survey, investigation on human morbidity due to schistosomiasis, snail diffusion experiments, questionnaire survey, determination of water infectivity and retrospective survey were conducted. Results In Sichuan Province, the mean densities of living snails were 0.003 snails/0.1 m² and 2.033 snails/0.1 m² in the upper and lower reaches of the Meiwan Reservoir wetlands, 0.08 snails/0.1 m² in the Jinyan Lake of Guanghan City, 0.21 snails/0.1 m² in Muhe River of Guanghan City, and 0.02 snails/0.1 m² prior to the construction of Qiong-hai wetland park in Xichang City in 2015. Artificial simulation experiments showed that the largest distance of snail diffusion in water was 2 000 m. There were 8.80% (41/466) of subjects that lived neighboring wetlands, worked in wetlands and visited wet-lands having infested water contact behaviors. A total of 690 sentinel mice were assigned, and no Schistosoma japonicum infection was detected in the 677 mice dissected. Retrospective survey showed that the construction of the Meiwan Reservoir caused the spread of schistosomiasis in Dailing County, and snails were found in the ditches entering the Jinyan Lake and in Jinyan Lake areas 5 years following the construction of the Jinyan Lake in Guanghan City, with S. japonicum -infected snails detected in the ditches entering the Jinyan Lake. Conclusions O. hupensis snails are found in some wetlands in Sichuan Province. Protection of wetlands and snail control with environmental improvements are recommended for the prevention of snail importation in natural wetlands, while in artificial wetlands, thorough snail control is recommended during the construction of the wetlands because of the likelihood of snail importation via water systems. In addition, both natural and artificial wetlands require long-term systematic surveillance of schistosomiasis.

·AIM: To evaluate a deep learning - assisted diagnostic system with an artificial intelligence for the detection of diabetic retinopathy (DR). ·METHODS:A total of 186 patients (372 eyes) with diabetes were recruited from January to July 2017. Discrepancies between manual grades and artificial intelligence results were sent to a reading center for arbitration. The sensitivity and specificity in the detection of DR were determined by comparison with artificial intelligence diagnostic system and experts human grading. ·RESULTS:Based on manual grades, the results as follows:non DR (NDR) in 42 eyes (11.3%), 330 eyes (88.7%) in different stages of DR. Among 330 DR eyes, there were mild non proliferative DR (NPDR) in 62 eyes (16.7%), moderate NPDR in 55 eyes (14.8%), severe NPDR in 155 eyes (41.7%), and proliferative DR (PDR) in 58 eyes (15. 6%). Based on artificial intelligence diagnostic system, the results were as follows: NDR in 38 eyes (10.2%),PDR in 44 eyes (11.8%), others were NPDR. The sensitivity and specificity of artificial intelligence diagnostic system, compared with human expert grading, for the detection of any DR were 0.82 and 0.91, and the kappa value was 0.77 (x2=20.39, P<0.05). ·CONCLUSION:This study shows that a deep learning-assisted diagnostic system with an artificial intelligence for grading diabetic retinopathy is a reliable alternative to diabetic retinopathy assessment, thus the use of this system may be a valuable tool in evaluating the DR.

Objective To investigate the clinical efficacy of intraoperative methylprednisolone used in combination with perioperative enteral nutrition support in improving liver synthetic function after hepatectomy and postoperative recovery.Methods In this prospective controlled trial,79 patients treated with hepatectomy at Departement of Hepatobiliary Pancreatic Surgery in Drum Tower Hospital between June 2013 and May 2014 were included and divided into control group (n =39) and steroid group (n =40) according to the order of surgery.The control group underwent hepatectomy only,while the steroid group received intraoperative methylprednisolone (500 mg) at the start of liver excision.Both of the two groups were given the same perioperative enteral nutrition support.Liver function,prealbumin (PA),and C-reactive protein (CRP) levels were measured before and on days 1,3,and 5 after the operation.Human blood albumin infusion volume,postoperative gas passing,postoperative hospital stay,and incidence of complications were recorded.Results The serum level of PA on day 3 after hepatectomy was significantly higher in the steroid group than in the control group [(101.26 ±61.17) mg/L vs.(81.84 ±43.58) mg/L,t =-1.607,P =0.049].The serum level of cholinesterase on day 1 after hepatectomy was significantly higher in the steroid group than in the control group [(5.60±1.54) kU/Lvs.(4.68±1.01) kU/L,t=-3.136,P=0.004].On day1 and day 3 after hepatectomy,the serum levels of CRP were significantly lower in the steroid group than in the control group [(41.79 ±20.86) mg/L vs.(62.08 ±38.33) mg/L,t =2.933,P=0.027;(64.14 ±32.38) mg/L vs.(102.64 ± 49.05) mg/L,t =4.127,P =0.006].The postoperative hospital stay was significantly shorter in the steroid group than in the control group [(12.62 ±5.74) d vs.(15.41 ± 10.00)d,t =1.514,P =0.002].Conclusion Intraoperative use of methylprednisolone combined with perioperative enteral nutrition support may inhibit postoperative inflammatory response,promote early recovery of liver synthetic function,and help to promote rehabilitation after hepatectomy.