scHybridBERT: integrating gene regulation and cell graph for spatiotemporal dynamics in single-cell clustering.

Graph learning models have received increasing attention in the computational analysis of single-cell RNA sequencing (scRNA-seq) data. Compared with conventional deep neural networks, graph neural networks and language models have exhibited superior performance by extracting graph-structured data from raw gene count matrices. Established deep neural network-based clustering approaches generally focus on temporal expression patterns while ignoring inherent interactions at gene-level as well as cell-level, which could be regarded as spatial dynamics in single-cell data. Both gene-gene and cell-cell interactions are able to boost the performance of cell type detection, under the framework of multi-view modeling. In this study, spatiotemporal embedding and cell graphs are extracted to capture spatial dynamics at the molecular level. In order to enhance the accuracy of cell type detection, this study proposes the scHybridBERT architecture to conduct multi-view modeling of scRNA-seq data using extracted spatiotemporal patterns. In this scHybridBERT method, graph learning models are employed to deal with cell graphs and the Performer model employs spatiotemporal embeddings. Experimental outcomes about benchmark scRNA-seq datasets indicate that the proposed scHybridBERT method is able to enhance the accuracy of single-cell clustering tasks by integrating spatiotemporal embeddings and cell graphs.

Leptin promotes proliferation of human undifferentiated spermatogonia by activating the PI3K/AKT/mTOR pathway.

BACKGROUND: Male infertility is a common disease affecting male reproductive health. Leptin is an important hormone that regulates various physiological processes, including reproductive function. However, few experimental studies have been carried out to elucidate the mechanism of leptin's effects on male reproductive function. OBJECTIVE: The purpose of this study was to investigate the effects of leptin on testicular spermatogenesis and its mechanism, so as to provide potential targets for the treatment of patients with spermatogenic dysfunction. METHODS: Testicular tissues were collected from eight prostate cancer patients undergoing surgical castration. GPR125-positive spermatogonia were isolated by two consecutive magnetic activated cell sorting (MACS), followed by incubation with conditioned medium. To identify the signaling pathway(s) involved in the effects of leptin, undifferentiated spermatogonia were treated with different concentrations of leptin and antagonists of leptin-related pathways. The proliferative effect of leptin was evaluated by cell counting using a hemocytometer. Expressions of p-AKT, p-ERK, p-STAT, and p-S6K were determined by western blotting analysis. RESULTS: Leptin promoted the growth of human GPR125-positive spermatogonia in a concentration-dependent manner. The most significant proliferative effect was observed using 100 ng/mL leptin after 6 days of culture. Leptin significantly increased the phosphorylation of STAT3, AKT, and ERK in undifferentiated spermatogonia. Phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 inhibited the leptin-induced activation of AKT, ERK, and downstream S6K. Treatment with the mammalian target of rapamycin (mTOR) inhibitor rapamycin also inhibited S6K phosphorylation. Moreover, both LY294002 and rapamycin were found to inhibit the leptin-induced proliferation of undifferentiated spermatogonia. These results suggested that the leptin-induced proliferation of GPR125-positive spermatogonia was dependent on the PI3K/AKT/mTOR pathway. Further exploration of proliferation and apoptotic markers suggested that leptin may alleviate cell apoptosis by regulating the expression of Bax and FasL. CONCLUSIONS: A certain concentration of leptin (25∼100 ng/mL) could promote proliferation of undifferentiated spermatogonia, which was mediated by PI3K/AKT/mTOR pathway.

Hazards of game addiction to health in adolescents / 上海预防医学

Gaming addiction， as a main manifestation of internet addiction， is characterized by a pattern of persistent or recurrent gaming behaviors. Gaming behaviors are common among adolescents and can result in marked distress or significant impairment in personal， family， social or other important areas of functioning. Recent research on health hazards of gaming addiction is relatively scattered. This article reviews the harm of adolescent game addiction to physical and mental health.

Up-regulated miR-452-5p suppressed the expression of RORα and promoted the proliferation and migration of HCC cells / 中国药科大学学报

@#To study the prognosis-related regulation mechanism of miR-452-5p and its influence on the proliferation and migration of hepatocellular carcinoma (HCC) cells, liver hepatocellular carcinoma (LIHC) dataset in The Cancer Genome Atlas (TCGA) was used to validate the differential expression of miR-452-5p and perform the Kaplan-Meier analysis of overall survival (OS).Target genes of miR-452-5p from TargetscanHuman and miRDB databases were predictived; and differentially expressed genes(DEGs) and weighted gene co-expression network analysis (WCGNA) were completed with GSE14520.Lipofectmine-2000 was used to transfect miR-452-5p mimics, mimics negative control, miR-452-5p inhibitor and inhibitor negative control into Huh7 cells,respectively.The mRNA and protein expression level of RORα in 4 groups were determined by RT-qPCR and Western blot.CCK-8 assay and Transwell assay were conducted to testify the capabilities of proliferation and migration.The regulation between miR-452-5p and RORα was confirmed by the dual luciferase reporter assay.After analysis in the TCGA-LIHC dataset, miR-452-5p had higher expression in HCC tissue than that in normal tissue, which was also associated with a shorter OS.RORα and LAMC1 were discriminated by intersecting of DEGs, WGCNA module genes, and predictive target genes.Survival analysis exhibited that dysregulation of RORα was significantly related to the OS.Overexpression of miR-452-5p in HCC cells suppressed the expression of RORα both in mRNA and protein, and also enhanced the viability and migration of HCC cells.The results of the dual luciferase reporter assay showed that miR-452-5p targeted 3′UTR of RORα.Up-regulated miR-452-5p inhibited the expression of RORα, facilitated the proliferation and migration of HCC cells, and promoted the progression and poor prognosis of HCC.

Progress in Research on Exosomes in Diagnosis of Pancreatic Cancer / 胃肠病学

Pancreatic cancer is a highly malignant tumor of digestive system, with poor prognosis because of the difficulties in early diagnosis. Recent studies have shown that exosomal proteins and nucleic acids have extremely high sensitivity and specificity as the diagnostic markers for pancreatic cancer, giving a minimally invasive approach to obtain tumor molecular information, thereby providing a new clue for the early diagnosis of pancreatic cancer. This article reviewed the progress in research on exosomes in diagnosis of pancreatic cancer.

Comorbidity of amyotrophic lateral sclerosis and progressive supranuclear palsy: a case report and literature review / 中华神经科杂志

The co-existence of different neurodegenerative diseases in the same case has received increasing attention and reports. A rare comorbidity of amyotrophic lateral sclerosis (ALS) and progressive supranuclear palsy (PSP) in a sporadic patient was reported. The patient presented with pseudobulbar palsy, freezing gait, and developed muscle weakness and fasciculation. Brain magnetic resonance imaging, positron emission computed tomography and whole exomesequencing showed no evident abnormality. The patient had no response towards the treatment of levodopa, and received supportive treatment and gastrostomy. He is in stable condition by now. Totally 23 cases of ALS with PSP were reviewed, and found that the clinical manifestations were related to the main distribution of pathological inclusion bodies and the location of neuron loss, and the deposition of the same pathological protein in multiple systems may lead to the coexistence of different neurodegenerative diseases. Traditional treatment is generally ineffective, thus support treatment is pivotal. The genetic background and pathogenesis of this comorbidity should be studied in the future.

Analysis of the clinical characteristics and related background diseases of 134 type 1 gastric neuroendocrine tumor / 中华消化杂志

Objective To explore the clinical characteristics and related background diseases of type 1 gastric neuroendocrine tumor (g-NET) and to provide reference information for clinical diagnosis and treatment.Methods From Januayy 2011 to February 2019,at the First Affiliated Hospital of Sun Yat-sen University and China-Japan Friendship Hospital,the clinical features and related background diseases of type 1 g-NET patients (41 cases and 93 cases respectively)were retrospectively analyzed.The clinical symptoms,serological indicators,gastroscopic and pathological features,tumor location,metastasis and treatment,and concomitant diseases were statistically described.Results Among 134 patients with type 1 g-NET,there were 53 males (39.6％) and 81 females (60.4 ％);and the mean diagnosed age was (51 ± 11) years (21 to 76 years).Main clinical manifestations were non-specific gastrointestinal symptoms.The mean level of serum chromogranin A was (237.7 ± 176.8) μg/L.The endoscopic findings of 97.8％ (131/134) of the patients were polypoid or protuberant lesions at gastric fundus or gastric body.And 75.0％ (96/128) of the patients had multiple tumors.65.7％ (88/134) of the patients had the tumors with the maximum diameter less than 1 cm (77.2％,88/114) and the lesions mainly located in mucosa (59.8％,52/87) and submucosa (40.2％,35/87).The pathological classification of 79.3％ (96/121) of the tumors was G1 grade and 20.7％ (25/121) were G2 grade.The rate of local lymph node metastasis was 1.4％ (1/73) and no distant metastasis was found.About 70.9％ (95/134) of the patients received endoscopic treatment.Among the patients,93.6％ (103/110) of the patients had chronic atrophic gastritis confirmed by endoscopy or pathology,45.6％ (47/103) were confirmed by both endoscopy and pathology.Among the patients with chronic atrophy gastritis,serum gastrin levels of 93.2％ (96/103) patients were twice higher than the upper limit of the normal value.The positive rates of antiparietal cells antibody (PCA) and intrinsic factor (IFA) were 78.5％ (73/93) and 51.9％ (14/27),respectively.The incidence of Helicobacter pylori (H.pylori) infection was 28.1％ (16/57).The incidence of autoimmune atrophy gastritis was 80.6％ (75/93).The percentage of patients with deficiency of serum vitamin B12 and ferritin was 70.8％ (63/89) and 30.7％ (27/88),respectively.Patients with anemia accounted for 27.8％ (25/90).The patients with microcytic anemia,normocyticanemia and macrocytic anemia were 28.0％ (7/25),56.0％ (14/25) and 16.0％ (4/25),respectively.46.9％ (45/96) of the patients had increased thyroid autoantibodies and 17.9％ (17/95) patients had changes of thyroid hormone level.Conclusions Type 1 g-NET is more common in women and mainly caused by autoimmune atrophic gastritis.The level of serum PCA and IFA increase in more than half of the patients.And it is often accompanied by vitamin B12 deficiency and autoimmune thyroid disease.

Induced pluripotent stem cells: advances in research and application in dermatology / 中华皮肤科杂志

Induced pluripotent stem cells (iPSCs) are a kind of stem cells induced from somatic cells by reprogramming with some specific pluripotent transcription factors.Compared with traditional stem cells,iPSCs have many advantages,including a wide range of sources,the ability of totipotent differentiation,and less ethical and sourcing issues associated with embryonic stem cells which have been debated for a long time.In dermatology,iPSCs can be used to make regenerative skin,establish models of skin diseases,provide a new platform for studying the pathogenesis of skin diseases,and perform cell treatment or gene modification treatment for specific skin diseases.At present,the application value of iPSCs has been verified among animal models,and clinical trials are also under way.

Color Doppler ultrasonography of renal vein embolism and its diagnostic value / 中华医学超声杂志（电子版）

Objective Explore the diagnostic value of color Doppler ultrasonography in renal vein embolism compared with contrast-enhanced CT.Analyze and summarize the sonographic features and reasons of misdiagnosis of renal vein embolism.Methods Reports of color Doppler ultrasonography and contrast-enhanced CT in 15 patients with 20 renal vein thrombosis and 25 patients with 25 renal vein tumor thrombosis were retrospectively analyzed.We summarized the sonographic features including the location of emboli,the lumen and wall of the involved veins,the information of collateral circulation and the color Doppler sonographic features.Results The diagnostic accuracy of renal vein thrombosis and tumor thrombosis were 85%and 84%for ultrasound,100%and 96%for contrast-enhanced CT,the difference was not statistically significant(all P＞0.05).The typical sonographic features include(1)Expansion of the renal vein and full of solid echogenicity;(2)No flow signals or flow filling defect in renal veins;(3)No or sparse venous flow signal in the involved kidney.Conclusions Color Doppler ultrasonography and contrast-enhanced CT have a good consistency in the diagnosis of renal vein embolism.Color Doppler ultrasonography can be used as an important imaging method to evaluate the renal vein embolism,which can combine medical history and provide a more reliable basis for the diagnosis of renal vein embolism.

Efficacy of bronchial blocker outside endotracheal tube for one-lung ventilation in pediatric patients / 中华麻醉学杂志

Objective To evaluate the efficacy of bronchial blocker outside the endotracheal tube for one-lung ventilation (OLV) in pediatric patients. Methods Thirty-eight American Society of Anesthe-siologists physical status ⅠorⅡ patients of both sexes, aged 4-8 yr, weighing 14. 0-28. 6 kg, scheduled for elective thoracic surgery under general anesthesia, were enrolled in this study. The size of tracheal tube was selected according to the endotracheal diameter at the level of clavicle and sternum on chest X-ray. Af-ter anesthesia induction, the distal end of the bronchial blocker was bent toward the target bronchus with a videolaryngoscope and then inserted until resistance was felt, and the preselected tracheal tube was inserted with a videolaryngoscope at a depth of (age∕2+12) cm. The position of the bronchial blocker was adjusted using a bronchofiberscope so that the upper edge of the blue cuff was 0. 5-1. 0 cm below the carina. The heart rate, mean arterial pressure, SpO2and airway pressure were recorded, arterial blood gas analysis was performed, and PaCO2and PaO2were recorded immediately before OLV (T1), at 30 min after OLV (T2) and at the end of OLV (T3). The intubation time, success rate of intubation at first attempt, displacement of bronchial blocker and occurrence of postoperative laryngeal pain and hoarseness were recorded. The pul-monary collapse was evaluated according to the standard described by Campos.Results Compared with the baseline at T1, PaO2was significantly decreased and airway pressure was increased at T2,3(P＜0. 05), and no significant change was found in heart rate, mean arterial pressure, PaCO2or SpO2at T2,3( P＞0. 05). The average intubation time was (185±38) s. The success rate of intubation at first attempt, rate of bronchial blocker displacement, excellent and good rates of pulmonary collapse and incidence of laryngeal pain and hoarseness were 95%, 16%, 100% and 11%, respectively. Conclusion Bronchial blocker outside the endotracheal tube can be effectively used for OLV in pediatric patients.

Efficacy of WeChat platform combined with problem-based learning teaching method when applied to the standardized training for residents in a department of anesthesiology / 中华麻醉学杂志

Objective To evaluate the efficacy of WeChat platform conbined with problem-based learning (PBL) teaching method when applied to the standardized training for residents in a department of anesthesiology.Methods Ninety-six residents who were undergoing the standardized training in the Department of Anesthesiology of our hospital were divided into 3 groups (n =32 each) using a random number table:lecture-based learning teaching method group,PBL teaching method group and WeChat platform plus PBL teaching method group.The examination scores after the end of teaching,satisfaction with teaching and scores of interest in anesthesiology were recorded.Results The total scores of examination,scores of comprehension memory problems,clinical application problems and comprehensive analysis problems,rate of satisfactory teaching and scores of interest in anesthesiology were significantly higher in WeChat platform plus PBL teaching method group than in the other two groups (P＜0.05).Conclusion WeChat platform combined with PBL teaching method can improve the teaching quality of the standardized training for residents in a department of anesthesiology and win praise from residents,and it is worth promoting the application.

Pregnancy outcome of frozen-thawed embryo transfers in different endometrial progesterone preparation time / 中华妇产科杂志

Objective To investigate the pregnancy outcome of frozen-thawed embryos transfer in different endometrial progesterone preparation time.Methods From January to December 2012,pregnant outcome of 1 103 frozen-thawed embryo transfer cycles using artificial periodic endometrial preparation were studied retrospectively in Reproductive Medical Center of Henan Provincial People's Hospital.It was divided into 4 groups:group 3-3 (n =543,3 days after endometrial progesterone preparation and transfer D3 embryo),group 4-3(n =330,4 days after endometrial progesterone preparation and transfer D3 embryo),group 5-5 (n =150,5 days after endometrial progesterone preparation and transfer D5 blastula),group 6-5 (n =80,6 days after endometrial progesterone preparation and transfer D5 blastula).The rate of implantation,pregnancy,ectopic pregnancy,multiple pregnancy,and first trimester abortion were compared among those groups.Results (1) With the different endometrial progesterone preparation methods and transfer D3 embryos,implantation rate [group 3-3:39.9％ (429/1 074) ; group 4-3:44.1％ (286/648)],pregnancy rate [group 3-3:56.0％ (304/543) ; group 4-3:59.4％ (196/330)],ectopic pregnancy rate [group 3-3:3.3％ (10/304) ; group 4-3:2.6％ (5/196)],multiple pregnancy rate [group 3-3:38.5％ (117/304) ; group 4-3:43.4％ (85/196)]and early abortion rate[group 3-3:13.5％ (41/304); group 4-3:13.3％ (26/196)] had no significant differences between group 3-3 and group 4-3 (all P ＞ 0.05).(2) With the different endometrial progesterone preparation methods and transfer D5 blastocysts,implantation rate [group 5-5:64.7％ (191/295) ; group 6-5:69.4％ (100/144)],pregnancy rate [group 5-5:80.7％ (121/150) ; group 6-5:78.8％ (63/80)],ectopic pregnancy rate [group 5-5:2.5％ (3/121) ; group 6-5:0],multiple pregnancy rate[group 5-5:55.4％ (67/121) ; group 6-5:46.3％ (37/80)] and early abortion rate[group 5-5:5.8％ (7/121); group 6-5:7.9％ (5/63)].However,there were no significantly differences between group 5-5 and group 6-5 (all P ＞ 0.05).Conclusions The two different progesterone transformed endometrial methods can obtain satisfactory clinical outcome with D3 embryo or D5 blastocysts transfor.It is convenient to clinical and laboratory work arrangements.

Expression, purification and renaturation of Pol P51 antigen of HIV-1 strain CN54 and its application in antibody detection / 生物工程学报

To obtain the pure and soluble P51 antigen of HIV-1 strain CN54, we transformed the Escherichia. coli strain BL21 codonplus-RIL with recombinant plasmid pTHioHisA51 which carries a gene encoding the Polymerase (Pol) P51 antigen of HIV-1 CN54 formerly, and induced protein expression by IPTG. We purified the recombinant protein with Chelating Sepharose FF-Ni and DEAE-Sepharose FF column chromatography, then renatured the recombinant protein by dialyzation. Purified protein was identified by Western blotting. We labeled and coated antigen P51 in a dual-antigen sandwich system, and tested it with serum samples from HIV-infected individuals. The results showed that P51 was expressed as inclusion body, and represented about 50% of total cellular protein. After purification and renaturation, the purity of P51 was up to 95%. Western blotting and sandwich ELISA demonstrated that recombinant P51 had good anti-HIV antibody specificity and sensitivity. The results suggested that recombinant HIV-1 P51 can be prepared as diagnostic reagent, and provides valuable support for HIV-1 detection and vaccine research.

Determination of chlorogenic acid and mangiferin in Folium Pyrrosiae from different habitats and species by HPLC / 中国中药杂志

An HPLC method for simultaneous determination of chlorogenic acid and mangiferin in original medicinal materials and decoction pieces of Pyrrosiae Folium was developed. The assay was performed on a Diamonsil C18 (4.6 mm x 250 mm, 5 microm) column eluted with a mobile phase consisted of acetonitrile and 0.5% phosphoric acid solution in gradient elution at a flow rate of 1.0 mL x min(-1). The column temperature was set at 25 degrees C. The detection wavelength was 320 nm. The results showed that The linear ranges of chlorogenic acid and mangiferin were 5.2-130 mg x L(-1) (r = 0.9999) and 1.2-18 microg x mL(-1) (r = 0.9999), and the average recoveries (n=6) were 97.9% (RSD 1.9%) and 99.6% (RSD 2.9%), respectively. The method was simple, reproducible and valid. It can be used for quality evaluation and control of original medicinal materials and decoction pieces of Pyrrosiae Folium.

Construction, purification and substrate specificity identification of recombinant human platelet-activating factor acetylhydrolase isoformⅠ / 上海交通大学学报（医学版）

Objective To construct and purify the recombinant protein of platelet-activating factor acetylhydrolase (PAF-AH) isoform I , and study the enzyme activity by different substrates. Methods The (3 subunit of PAF-AH isoform I was cloned and expressed in E. coli. Exogenously expressed recombinant protein was purified to SDS-PAGE homogeneity, and its activity was identified by arylesterase detection. Phenylacetate, 1-O-hexadecyl-2-deoxy-2-thioacetyl-sn-glycero-3-phosphocholine ( 2-Thio PAF) and l-myristoy1-2-( 4-nitrophenylsuccinyl) phosphatidylcholine (the latter two were commercial plasma PAF-AH substrates) were used for the substrate identification. The plasma type PAF-AH was served as positive control. Results Recombinant protein of β subunit of PAF-AH isoform I was successfully constructed and expressed in E. coli after purification. Compared with positive control, the recombinant protein could hydrolyze phenylacetate and 2-Thio PAF, but could not hydrolyze l-myristoyl-2-( 4-nitrophenylsuccinyl) phosphatidylcholine. Conclusion Recombinant protein of β subunit of PAF-AH isoform I can be successfully constructed. There are differences in the substrate specification to the two commercial PAF substrates for PAF-AH isoform I and plasma type PAF-AH, which provides a quick method to differentiate PAF-AH isoform I from plasma type PAF-AH.

[Fungal biotransformation of ginsenoside Rg3].

OBJECTIVE: Ginsenosides are important bioactive compounds in Ginseng. Sugar chains of ginsenosides are closely related to the bioactivity. Rare ginsenosides can be achieved by modifying sugar chains through biotransformation. Samples of Ginseng root soils, collected from Changbai Mountain, were used to screen active microorganism which can transform total ginsenosides and single ginsenoside, so as to obtain anti-tumor components. METHODS: The strains were isolated and screened on solid transfer medium and yield transfer process for active strains. Then the active strains were tested for their biotransformation properties by using different purified ginsenosides, including ginsenoside Rg3. The biotransformation products were separated and purified through column chromatography on silica gel (300mesh), and identified by spectral analysis and physical constants. Simultaneously, the active strain was identified based on morphological characteristics of colonies, conidium and conidiophore, as well as ITS-5.8S rDNA sequences. RESULTS: Total 68 fungal strains were isolated and 12 active strains showed positive activity on total ginsenosides. One strain, SYP2353, was found to have the strong activity on Rg3. CONCLUSION: The active strain SYP2353 was identified as Myrothecium verrucaria, and the biotransformation products of Rg3 were identified to be rare ginsenoside Rh2 and aglycon PPD.

Content Determination of Astragaloside Ⅳ in Qizhi Jiangtang Granules by HPLC-ELSD / 中国药房

OBJECTIVE:To establish HPLC-ELSD method for content determination of astragaloside Ⅳ in Qizhi jiangtang granules. METHODS:The separation was performed on Hypersil ODS2(250 mm?4.6 mm,5 ?m)column with acetonitrile-water(32 ∶ 68)as mobile phase. The flow rate was 1.0 mL?min-1. Injection volume was 10 ?L. The column temperature was 25 ℃. The temperature of drift tube for measurement was 110 ℃ and flow rate of N2 was 3.12 SLPM. RESULTS:Regression equation was A=1.699 C+6.181. The linear range of astragaloside Ⅳ was 0.259～1.295 mg?mL-1(r=0.999 6,n=5) with lowest detectable limit of 5.18 ?g?mL-1. An average recovery rate were 97.75%(RSD=2.17%). CONCLUSION:The method is simple,rapid and reliable for quality control of Qizhi jiangtang granules.