OBJECTIVESTo study the change of telomerase activity in rat spermatogonia when the telomerase RNA was enclosed, and reactivity of the change to cytokine(SCF, TGF-beta 1).

METHODSThe antisense oligonucleotides(PS-ASON) of telomerase was transfected into proliferating spermatogonia in vitro with the liposomes as the vector. Then the cytokine, stem cell factor (SCF) or transforming growth factor-beta 1(TGF-beta 1), was added. The proliferative activity of the spermatogonia was determined before and after the inhibition by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]assay. The change of telomerase activity was detected by telomeric repeat amplification protocol (TRAP).

RESULTS1 mumol/L PS-ASON obviously downregulated the telomerase activity and inhibited spermatogonia proliferation. When the inhibition was over, the activity recovered to some extent(P < 0.01). Growth factors can regulate the spermatogonia after inhibition, SCF may improve the activity of telomerase and the proliferation of spermatogonia. Adversely, TGF-beta 1 may inhibit the recovery of telomerase activity.

CONCLUSIONSTo inhibit spermatogonia telomerase activity antisensely can limit the proliferation of spermatogonia efficiently, which was regulated by cytokine. This method might be a new and efficient way in male birth control.

Animals ; Bacterial Proteins ; analysis ; Cell Division ; drug effects ; Contraceptive Agents, Male ; pharmacology ; Cytokines ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Male ; Oligonucleotides, Antisense ; pharmacology ; RNA-Binding Proteins ; analysis ; Rats ; Rats, Sprague-Dawley ; Spermatogonia ; cytology ; drug effects ; enzymology ; Stem Cell Factor ; metabolism ; Telomerase ; antagonists & inhibitors ; genetics ; metabolism ; Transcription Factors ; analysis ; Transfection

OBJECTIVE: To compare accuracy of anterior cervical pedicle screws between assist of rapid prototyping 3D guide plate and free-hand insertion, and evaluate the safety of two methods. METHODS: Eight adult cervical cadaver specimens after formaldehyde immersion, including 4 males and 4 females, aged 32 to 65(40.3±5.6) years old. After X-ray examination to exclude bone damage and deformity, 4 of them (3D guide plate group) randomly selected were for CT scan to obtain DICOM format data, and the data was imported into Mimics software for model, designed the ideal entry point and nail path for anterior cervicaltranspedicular screw (ATPS). After obtaining the personalized guide plate of the nail channel, it was exported as STL data, and the individual guide plate was printed by rapid prototyping and 3D printing technology. In turn, with the assistance of 3D guide plates, one-to-one personalized ATPS screws were placed on the four lower cervical cadaver specimens. Another 4 (free-hand group) lower cervical cadaver specimens were implanted with ATPS screws using free-hand technique. All specimens were performed CT thin-layer scanning and three-dimensional reconstruction after operation. The Tomasino method was used to evaluate the safety of the screws on the CT cross-sectional and sagittal images, to determine whether there was a cortical puncture of the lower and inner edges of the pedicle. According to the CT rating results, gradeⅠandⅡwere safe, and grade Ⅲ- Ⅴ were dangerous.And the accuracy of screws was recorded and analyzed between two groups. RESULTS: Two screws were inserted in each segment from C CONCLUSION The 3D printing rapid prototyping guide plate assisted insertion of the anterior cervical pedicle screw can significantly improve the accuracy and safety, and provide a theoretical basis for further clinical application.
Adult ; Aged ; Bone Plates ; Cervical Vertebrae/surgery* ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Pedicle Screws ; Printing, Three-Dimensional

OBJECTIVETo isolate and chondro-inductive culture of human adipose tissue-derived stromal cells and to study their heterotopic chondrogenesis by loading them on alginate gel.

METHODSLiposuction human adipose tissues were minced and digested with collagenase type I. The obtained stromal cells were primarily cultured in BGJb medium for ten days. Secondary harvested cells were cultured in DMEM-F12 medium supplemented with 10%FBS, 6.25 mg/L insulin, 10 mg/L TGF-beta1, 50 mg/L of freshly prepared L-ascorbate for 14 days. After in vitro assay of chondrogenic phenotypes, the cells at density of 10(10)/L were mixed with 1.2% alginate sodium and 102 mmol/L CaCl(2). The cross-linking cell-alginate gel were injected into four BALB/C athymic mice subcutaneously (1 ml for each mouse). Meanwhile, the auto-controls were set by injecting equal dose of simple alginate gel and pure cells in two opposite buttocks of the same mouse subcutaneously. Two mice were sacrificed at fourth and eighth week postoperatively and all samples were removed, fixed, embedded in paraffin and cut into sections of 5 micro m thick. HE staining, Alcian blue and modified Masson's trichrome staining were employed to observe chondrogenesis histologically.

RESULTSAlcian blue and immunocytochemical staining revealed chondroitin sulfate and collagen II in cell matrix after having been chondro-inductive cultured for 14 days. At intervals of fourth and eighth week, heterotopic chondrogenesis is (cartilage formed) within cell-alginate injected sites were found in all mice but negatively in auto-controls. Histologically the hypertrophic chondrocytes were among cartilage matrix in different staining. All alginate gel and solitory cells absorbed within two to three weeks postoperatively in auto-controls.

CONCLUSIONIt seems that stromal cells derived from human adipose tissue presents a potential for chondrogenic differentiation.

Adipose Tissue ; cytology ; Alginates ; pharmacology ; Animals ; Cell Differentiation ; Cells, Cultured ; Chondrocytes ; cytology ; metabolism ; Chondrogenesis ; Female ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Stem Cell Transplantation ; Stromal Cells ; cytology ; metabolism ; transplantation ; Tissue Engineering

Chronic graft-versus-host disease (cGVHD) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which is also one of the major causes of patients' death following transplantation. Recently, extracorporeal photochemotherapy (ECP) has shown a considerable efficacy in cGVHD treatment, which is based on the infusion of autologous peripheral blood mononuclear cells collected by aphesis, incubated with the photoactivable drug 8-methoxypsoralen (8-MOP) and UV-A irradiation. The therapeutic effect of ECP is mainly achieved by the induction of cell apoptosis, influencing the function of dendritic cells and the induction of immune tolerance. ECP has many advantages in the treatment of cGVHD, such as no increasing the risk of infection in patients, unaffecting the graft-versus-leukemia effect, nearly no side effect and so on. Many medical centers have done a lot of research on the treatment of cGVHD in both children and adults by using ECP and achieved good results. CD19(+) CD21(-) B lymphocytes, serum BAFF and serum TNFα can be used to measure and early evaluate the efficacy of ECP treatment. The effect of ECP is associated with many factors, and certain complications may occur during the treatment. At present, the application of ECP treatment is limited by the unclear mechanisms, varying treatment cycles in different studies, and small number of patients in clinical research. In the near future, with deeper basic research, increasing the case number and standard clinical treatment, ECP will have a more extensive application prospects. This review focuses mainly on the clinical advances of ECP in the treatment of cGVHD.
Apoptosis ; Graft vs Host Disease ; Humans ; Leukocytes, Mononuclear ; Photochemotherapy ; Photopheresis ; Ultraviolet Rays

OBJECTIVE: Mental disorders of the elderly population in China deserve attention. Social health is significantly associated with depression. This study aimed to evaluate the rate of depressive symptoms and to test the relationships between social health and depressive symptoms among a large sample of community-dwelling elderly adults. METHODS: We conducted a cross-sectional study among community-dwelling adults aged 60 years or above in Zhejiang Province, China. Face-to-face interviews were used to complete a structured questionnaire for all participants. We used the Social Health Scale for the Elderly (SHSE) to evaluate social health status and used the short form of the Geriatric Depression Scale to evaluate depressive symptoms. Multivariate logistic regression was used to evaluate the association between social health status and depressive symptoms. RESULTS: Of the total of 3757 participants included, 1887 (50.23%) were female, and the mean±standard deviation (SD) age was (70.0±8.3) years. The rate of depressive symptoms was 25.92%. The social health score was higher in non-depressed participants than in depressed participants (raw score 50.7 vs. 48.3, P<0.001). Participants with "moderate" or "good" social health had a significantly lower risk of depressive symptoms than those with "poor" social health (odds ratio (OR)=0.55, 95% confidence interval (CI): 0.46-0.66 for moderate social health; OR=0.45, 95% CI: 0.35-0.60 for good social health). The association between social health and depressive symptoms was consistent across several subgroups. CONCLUSIONS Social health is significantly inversely associated with depressive symptoms. The SHSE may serve as an efficient screener to identify those elderly adults with social health deficits, but systematic assessment to guide intervention merits further investigation.
Aged ; Aged, 80 and over ; Cross-Sectional Studies ; Depression/epidemiology* ; Female ; Health Status ; Humans ; Independent Living ; Logistic Models ; Male ; Middle Aged

The efficacy of Chinese herbal formulas in treating Alzheimer has been proved in many studies. In this study, six different Kaixin San formulas were compared to investigate their effects on learning and memory decline, brain-derived neurotrophic factor (BDNF) in the hippocampus, tau protein, acetylcholinesterase (AChE) and N-terminal pro-brain natriuretic peptide (NT-proBNP). Kunming mice were selected and established a mouse model of Alzheimer's by intraperitoneal injection of D-galactose and sodium nitrite, continued intragastric 4 weeks, using the ability of learning and memory in Morris water maze test to evaluate the animals in each group; the content of BDNF in the hippocampus of mice with Western blotting detected; ELISA method for the detection of each group of mice hippocampal tau protein,p-Tau protein, Aβ,Ach,AchE and serum NT-proBNP levels. The results showed that, Kaixin San of Qianjin Yaofang three dose recorded significantly improved learning and memory ability of mice; increased the content of BDNF and Ach in the hippocampus; decreased the content of Aβ, Tau protein, p-Tau protein in the hippocampus; high, middle dose significantly decreased the serum NT-proBNP and AchE in hippocampus, the effect is most significant. Part dose of Kaixin San of Yixin Fang, Kaixin Wan of Yimen Fang, Dingzhi Xiaowan of Beji Qianjin Yaofang and Dingzhi Wan of Guji Luyan could improve the learning and memory ability evaluation indicators, significantly increased BDNF and Ach in the hippocampus of AD model mice, reduced the Aβ, Tau protein, p-Tau protein in hippocampus of AD model mice, decreased the NT-proBNP and AchE in serum of AD mice, the effect is more significant. Three does of Buxin Tang of Qianjin Yi had no effects of treatment in Alzheimer's disease. The results showed the treatment in AD of Kaixin San of Qianjin Yaofang is the most significant.

OBJECTIVE: To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS: In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS: Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.

Nagilactone E (NLE), a natural product with anticancer activities, is isolated from Podocarpus nagi. In this study, we reported that NLE increased programmed death ligand 1 (PD-L1) expressions at both protein and mRNA levels in human lung cancer cells, and enhanced its localization on the cell membrane. Mechanistically, NLE increased the phosphorylation and expression of c-Jun, and promoted the localization of c-Jun in the nucleus, while silencing of c-Jun by small interfering RNA (siRNA) reduced NLE-induced PD-L1. Further study showed that NLE activated the c-Jun N-terminal kinases (JNK), the upstream of c-Jun, and its inhibitor SP600125 reversed the NLE-increased PD-L1. Moreover, NLE-induced PD-L1 increased the binding intensity of PD-1 on the cell surface. In summary, NLE upregulates the expression of PD-L1 in lung cancer cells through the activation of JNK-c-Jun axis, which has the potential to combine with the PD-1/PD-L1 antibody therapies in lung cancer.