Sodium-glucose co-transporter protein 2 inhibitor(SGLT2i)has steadily demonstrated benefits in the treatment of type 2 diabetes complicated with cardiovascular diseases based on evidence-based medicine,but its precise mechanism is yet unknown.We identified type 2 diabetes patients with HFpEF by searching PubMed,Web of Science,China knowledge network(CNKI),and other databases.We then summarized the pathological mechanism of HFpEF caused by type 2 diabetes.At the same time,to link to evidence-based medical,we explored the future of SGLT2i in clinical application.

OBJECTIVE: To compare the safety of low-dose cyclophosphamide and high-dose cyclophosphamide in the treatment of systemic lupus erythematosus (SLE). METHODS: A total of 1 022 patients with systemic lupus erythematosus from 24 hospitals in China between March 2017 to July 2018 were enrolled. Their clinical manifestations, laboratory tests, adverse events, reasons for stopping receiving intravenous cyclophosphamide and comorbidities were collected. Among them, 506 SLE patients received short-interval low-dose intravenous cyclophosphamide therapy (SILD IV-CYC, 400 mg every two weeks), and 256 patients underwent high-dose cyclophosphamide therapy (HD IV-CYC, 500 mg/m² of body surface area every month), the side effects between the two groups were compared, the remaining 260 SLE patients were treated with IV-CYC irregularly. Moreover, a total of 377 patients in SILD IV-CYC group and 214 patients in HD IV-CYC group had medical records of the reasons for stopping recei-ving IV-CYC. The reasons for stopping receiving IV-CYC in these two groups were analyzed. RESULTS: In this study, only 40.27%(238/591)of the SLE patients stopped receiving intravenous cyclophosphamide for the causes of disease improvement, however, up to 33.67% (199/591) of the patients for the reason of drug-related side effects. There were 83 patients out of 214 (38.79%) with high-dose intravenous cyclophosphamide treatment who stopped receiving IV-CYC for the drug-related side effects, which was significantly higher than that in the low-dose cyclophosphamide group (30.77%, 116/337, P=0.048). Of theses 506 patients in SILD IV-CYC group, 88 (17.39%) patients experienced gastrointestinal reactions, 66 (13.04%) suffered from infections, 49 (9.68%) had myelosuppression and 68 (13.44%) had alopecia, respectively. Among the 256 patients in the HD IV-CYC group, 80 (31.25%) experienced gastrointestinal reactions, 57 (22.27%) suffered from infections, 51 (19.92%) had myelosuppression and 49 (19.14%) had alopecia. Moreover, 71 (25.18%) of 282 female patients with age between 16 to 45 years in SILD IV-CYC group had abnormal menstruation, while menstrual disorder occurred in 39.72% (56/141) patients of HD IV-CYC group. There was no difference of drug-induced hepatic injury, hemorrhagic cystitis and fatigue between the two groups. CONCLUSION Low-dose cyclophosphamide showed a lower prevalence of adverse events than high-dose cyclophosphamide in systemic lupus erythematosus patients.
Humans ; Female ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Immunosuppressive Agents/adverse effects* ; Cyclophosphamide/therapeutic use* ; Lupus Erythematosus, Systemic/drug therapy* ; Administration, Intravenous ; Alopecia/drug therapy*

OBJECTIVE: To evaluate the incidence and clinical characteristics of metabolic syndrome (MS) within one year after hematopoietic stem cell transplantation (HSCT) in order to screen the risk factors for HSCT-MS, provide early intervention and improve the long-term quality of survival of patients. METHODS: The clinical follow-up data of 64 HSCT patients (survival time > 1 year) who received HSCT in our center from January 2007 to August 2018 were collected. Among them, 50 cases were allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 14 cases were autologous hematopoietic stem cell transplantation (auto-HSCT). The changes of MS-related indexes and clinical characteristics before and 1, 3, 6 and 12 months after HSCT were analyzed retrospectively. RESULTS: In allo-HSCT group, 14 cases were diagnosed as MS before operation, including high-density lipoprotein cholesterol (hypo-HDL-C)> hyper triglycerides（hyper-TG）> hyper fasting glucose（hyper-FBG）> abdominal obesity (AO) > hypertension. The preoperative diagnosis of MS in the auto-HSCT group was 5 cases, in the order of hyper-FBG> hyper-TG> AO> hypo-HDL-C> hypertension. Incidence of MS at 1, 3, 6 and 12 months after transplantation: 19, 26, 24 and 20 cases in the allo-HSCT group, respectively; auto-HSCT group were 7, 7, 6 and 6 cases, respectively. Hyper-TG and hypo-HDL-C were prominent in both groups. CONCLUSION The incidence of HSCT-MS is significantly higher within 1 year after HSCT. Regardless of allo-HSCT and auto-HSCT, the prevention and control of HSCT-MS is emphasized as an important guarantee to improve the long-term survival quality of HSCT patients.
Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Metabolic Syndrome ; Retrospective Studies ; Transplantation, Homologous

【Objective】 To analyze the metagenomics and microbiology of voluntary blood donors in China, so as to assess the potential threats of emerging infectious diseases to the safety of blood transfusion. 【Methods】 12 300 plasma samples (10 mL each) collected by central blood stations in Chongqing, Liuzhou, Urumqi, Mianyang, Wuhan, Nanjing, Mudanjiang, and Dehong Prefecture area from 2012 to 2018 were subjected to total DNA extraction after ultracentrifugation (32 000 rpm/min, centrifugal radius 91.9 mm) in minipools of 160 donations. The metagenomic library was constructed, and deep sequencing was conducted by Illumina Hiseq 4 500. By comparing with reference sequences of bacteria, fungi, parasites and viruses, metagenomic data were analyzed, classification of microbes were identified, and potentially harmful pathogens were evaluated. 【Results】 A total of 632 GB clean data were obtained by deep sequencing, and the top three pathogens were Pseudomonas(0.561 1%), Burkholderia(0.468 7%) and Serratia(4.242 0%). Pathogens with potential threat which could be transmitted by blood transfusion or blood products were found, such as human parvovirus B19(0.126 6%), Leishmania spp(1.348 5%) and Toxoplasma gondii(0.615 8%). 【Conclusion】 Our study analyzed metagenomics of voluntary blood donors in parts of China and revealed pathogens that may cause potential harm to blood safety, which were helpful for targeted prevention and control of emerging infectious diseases.

The mammalian epididymis not only plays a fundamental role in the maturation of spermatozoa, but also provides protection against various stressors. The foremost among these is the threat posed by oxidative stress, which arises from an imbalance in reactive oxygen species and can elicit damage to cellular lipids, proteins, and nucleic acids. In mice, the risk of oxidative damage to spermatozoa is mitigated through the expression and secretion of glutathione peroxidase 5 (GPX5) as a major luminal scavenger in the proximal caput epididymidal segment. Accordingly, the loss of GPX5-mediated protection leads to impaired DNA integrity in the spermatozoa of aged Gpx5

Transcription factors (TFs) as key regulators play crucial roles in biological processes. The identification of TF–target regulatory relationships is a key step for revealing functions of TFs and their regulations on gene expression. The accumulated data of chromatin immunoprecip-itation sequencing (ChIP-seq) provide great opportunities to discover the TF–target regulations across different conditions. In this study, we constructed a database named hTFtarget, which inte-grated huge human TF target resources (7190 ChIP-seq samples of 659 TFs and high-confidence binding sites of 699 TFs) and epigenetic modification information to predict accurate TF–target regulations. hTFtarget offers the following functions for users to explore TF–target regulations:(1) browse or search general targets of a query TF across datasets;(2) browse TF–target regulations for a query TF in a specific dataset or tissue;(3) search potential TFs for a given target gene or non-coding RNA; (4) investigate co-association between TFs in cell lines; (5) explore potential co-regulations for given target genes or TFs; (6) predict candidate TF binding sites on given DNA sequences; (7) visualize ChIP-seq peaks for different TFs and conditions in a genome browser. hTFtarget provides a comprehensive, reliable and user-friendly resource for exploringhuman TF–target regulations, which will be very useful for a wide range of users in the TF and gene expression regulation community. hTFtarget is available at http://bioinfo.life.hust.edu.cn/hTFtar-get.

Background: Automated peritoneal dialysis (APD) can cater to individual needs, provide treatment while asleep, take into account the adequacy of dialysis, and improve the quality of life. Currently, independent research and development of APD machines made in China are more conducive to patients. A randomized, multicenter, crossover study was conducted by comparing an APD machine made in China with an imported machine. The safety, effectiveness, and manipulability of the two machines were compared. Methods: Two hundred and sixty patients who underwent peritoneal dialysis (PD) on a regular basis in 18 centers between August 2015 and February 2016 were included. The inclusion criteria include age ≥18 years and PD ≥30 days. The exclusion criteria were as follows: hemodialysis; exit site or tunnel infection; and peritonitis ≤30 days. The patients were randomly divided into Group A, who were first treated with a FM machine made in China, then changed to an imported machine; and Group B, who were treated using the reverse sequence. APD treatment was performed with 10 L/10 h and 5 cycles of exchange. After 72 h, the daily peritoneal Kt/V, the accuracy of the injection rate, accuracy of the injection temperature, safety, and manipulability of the machine were assessed. Noninferiority test was conducted between the two groups. Results: The daily peritoneal Kt/V in the APD machine made in China and the imported APD machine were 0.17 (0.14, 0.25) and 0.16 (0.13, 0.23), respectively. There was no significant difference between the groups (Z = 0.15, P = 0.703). The lower limit of the daily Kt/V difference between the two groups was 0.0069, which was greater than the noninferiority value of -0.07 in this study. The accuracy of the injection rate and injection temperature was 89.7% and 91.5%, respectively, in the domestic APD machine, which were both slightly better than the accuracy rates of 84.0% and 86.8% in the imported APD machine (89.7% vs. 84.0%, P = 0.2466; 91.5% vs. 86.8%, P = 0.0954). Therefore, the APD machine made in China was not inferior to the imported APD machine. The fuselage of the imported APD machine was space-saving, while the APD machine made in China was superior with respect to body mobility, man-machine dialog operation, alarm control, and patient information recognition. Conclusions: The FM machine made in China was not inferior to the imported APD machine. In addition, the FM machine made in China had better operability. Trial Registration Clinicaltrials.gov, NCT02525497; https://clinicaltrials.gov/ct2/results?cond=&term=NCT02525497&cntry=& state=&city=&dist=.
Adult ; China ; Cross-Over Studies ; Female ; Humans ; Male ; Middle Aged ; Multicenter Studies as Topic ; Peritoneal Dialysis ; adverse effects ; instrumentation ; methods ; Quality of Life ; Temperature

Increasing evidence suggests that cytokines and chemokines play crucial roles in chronic itch. In the present study, we evaluated the roles of tumor necrosis factor-alpha (TNF-α) and its receptors TNF receptor subtype-1 (TNFR1) and TNFR2 in acute and chronic itch in mice. Compared to wild-type (WT) mice, TNFR1-knockout (TNFR1-KO) and TNFR1/R2 double-KO (DKO), but not TNFR2-KO mice, exhibited reduced acute itch induced by compound 48/80 and chloroquine (CQ). Application of the TNF-synthesis inhibitor thalidomide and the TNF-α antagonist etanercept dose-dependently suppressed acute itch. Intradermal injection of TNF-α was not sufficient to evoke scratching, but potentiated itch induced by compound 48/80, but not CQ. In addition, compound 48/80 induced TNF-α mRNA expression in the skin, while CQ induced its expression in the dorsal root ganglia (DRG) and spinal cord. Furthermore, chronic itch induced by dry skin was reduced by administration of thalidomide and etanercept and in TNFR1/R2 DKO mice. Dry skin induced TNF-α expression in the skin, DRG, and spinal cord and TNFR1 expression only in the spinal cord. Thus, our findings suggest that TNF-α/TNFR1 signaling is required for the full expression of acute and chronic itch via peripheral and central mechanisms, and targeting TNFR1 may be beneficial for chronic itch treatment.
Animals ; Chloroquine ; toxicity ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Etanercept ; therapeutic use ; Ganglia, Spinal ; drug effects ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Pruritus ; chemically induced ; drug therapy ; metabolism ; pathology ; RNA, Messenger ; metabolism ; Receptors, Tumor Necrosis Factor, Type I ; deficiency ; genetics ; Receptors, Tumor Necrosis Factor, Type II ; deficiency ; genetics ; Signal Transduction ; drug effects ; Skin ; drug effects ; metabolism ; Spinal Cord ; drug effects ; metabolism ; Thalidomide ; therapeutic use ; Time Factors ; Tumor Necrosis Factor-alpha ; adverse effects ; genetics ; metabolism ; p-Methoxy-N-methylphenethylamine ; toxicity

Adult ; Aged ; Aneurysm ; diagnosis ; pathology ; Computed Tomography Angiography ; methods ; Female ; Humans ; Male ; Middle Aged ; Splenic Artery ; pathology

BACKGROUNDA multi-center large scale study is needed to confirm the efficacy and safety of domestic peritoneal dialysis (PD) solutions. Some researchers believe that 6 L/d is enough for adequate dialysis, but there is no multi-center prospective study on Chinese population to confirm this. In this study, we evaluated the efficacy and safety of domestic PD solution (Changfu) and its difference between 6 L and 8 L dosage.

METHODSAdult PD patients who had taken PD therapy for at least one month were selected and divided into four groups according to two dialysis solution brands and two dialysis dosages, i.e., 6 L dose with Changfu dialysis solution, 6 L dose with Baxter dialysis solution, 8 L dose with Changfu dialysis solution, and 8 L dose with Baxter dialysis solution. After 48 weeks, the changes of primary and secondary efficacy indices were compared between different types and different dosages. We also analyzed the changes of safety indices.

RESULTSChanges of Kt/V from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of creatinine clearance rate (Ccr). Normalized protein catabolic rate (nPCR) from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of net ultrafiltration volume (nUF) and estimated glomerular filtration rate (eGFR). Changes of nPCR from baseline to 48 weeks between 6 L and 8 L showed no statistical differences; so did those of nUF and eGFR. The decline of Kt/V from baseline to 48 weeks in 6 L group was more than that in 8 L group. Change of Ccr was similar. During the 48-week period, the mean Kt/V was above 1.7/w, and mean Ccr was above 50 L×1.73 m(-2)×w(-1). More adverse events were found in Changfu group before Changfu Corporation commenced technology optimization, and the statistical differences disappeared after that.

CONCLUSIONSThe domestic PD solution (Changfu) was proven to be as effective as Baxter dialysis solution. During 48-week period, a dosage of 6 L/d was enough for these patients to reach adequate PD. Clinical study promotes technological optimization, further helps to improve the safety indices of the medical products.

Adolescent ; Adult ; Aged ; Dialysis Solutions ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Peritoneal Dialysis ; methods ; Young Adult