Objective:To determine the differential expressions of long non-coding RNA(lncRNA)and messenger RNA(mRNA)in normal and asthenospermia(AS)men and analyze their biological significance in AS.Methods:We isolated and ex-tracted total RNAs from 9 normal and 9 AS sperm samples,determined the expressions of RNAs in the sperm using the DNBSEQ se-quencing platform,and analyzed their relevant functions by gene ontology enrichment(GO)and Kyoto encyclopedia of genes and ge-nomes pathway(KEGG)analyses.Results:An average of 10.64G data was generated per group,with 282 185 RNAs detected,in-cluding 107 009 lncRNAs.Among the total number of lncRNAs,15 157 were differentially expressed,2 190 upregulated and 12 967 downregulated;and among the 19 514 mRNAs,13 736 were differentially expressed,4 995 upregulated and 8 741 downregulated.Differentially expressed genes were enriched mainly in the sperm cell membrane and the pathways related to the ion channel functions,sperm development and fertilization.Conclusion:Differentially expressed lncRNAs and mRNAs can be identified by sequencing a-nalysis of AS and normal sperm.Regulation of sperm function through membrane ion channels may contribute to the development of AS,which provides a molecular basis for further research on AS.

Humans ; Blast Crisis/genetics* ; Leukemia, Promyelocytic, Acute/genetics* ; Oncogene Proteins, Fusion/genetics* ; Tretinoin

The mammalian target of rapamycin (mTOR) pathway is abnormally activated in lung cancer. However, the anti-lung cancer effect of mTOR inhibitors as monotherapy is modest. Here, we identified that ginsenoside Rh2, an active component of Panax ginseng C. A. Mey., enhanced the anti-cancer effect of the mTOR inhibitor everolimus both in vitro and in vivo. Moreover, ginsenoside Rh2 alleviated the hepatic fat accumulation caused by everolimus in xenograft nude mice models. The combination of everolimus and ginsenoside Rh2 (labeled Eve-Rh2) induced caspase-independent cell death and cytoplasmic vacuolation in lung cancer cells, indicating that Eve-Rh2 prevented tumor progression by triggering paraptosis. Eve-Rh2 up-regulated the expression of c-MYC in cancer cells as well as tumor tissues. The increased c-MYC mediated the accumulation of tribbles homolog 3 (TRIB3)/P62⁺ aggresomes and consequently triggered paraptosis, bypassing the classical c-MYC/MAX pathway. Our study offers a potential effective and safe strategy for the treatment of lung cancer. Moreover, we have identified a new mechanism of TRIB3/P62⁺ aggresomes-triggered paraptosis and revealed a unique function of c-MYC.

Objective:Cushing′s disease(CD) is caused by the pituitary adrenocorticotroph hormone(ACTH) secreting adenomas, leading to increased serum cortisol levels and various abnormal metabolic processes. Untreated CD is linked to high mortality, thus it is critical to elucidate its pathogenesis. This study aims to explore the pathogenesis of pituitary ACTH adenomas using whole-genome sequencing analysis.Methods:Fresh tumor tissues and peripheral blood samples were collected in 9 confirmed cases of pituitary ACTH adenomas who underwent surgery. Whole genome sequencing was then performed, followed by analysis and verification of single nucleotide mutations, copy number variation(CNV) and chromosome structure variations.Results:Somatic USP8 mutations(p.Ser718del, p. Ser718Pro, p. Pro720Arg, p. Pro720Gln) were found in 5 patients, with a rate of 55.6%; CNV of USP8 was detected in 1 patient; TP53(p.Cys135Tyr), NF1(p.Val1049Glufs*11) and KMT2C(c.3323+ 1G>A) mutations were identified in 1 patient harboring wild-type USP8. CNV analysis showed a loss of heterozygosity in multiple chromosomes in a wild-type USP8 patient. Structural variations were found in 2 with unknown significance. No germline gene mutations were detected in this study.Conclusion:Somatic USP8 mutations, increased copy number of USP8, variations of tumor-related genes such as TP53 and extensive somatic CNV all contribute to pathogenesis of CD. Chromosomal structure variations may suggest high-risk pituitary ACTH adenomas, and call for frequent follow-up and aggressive treatment.

Aim To investigate the effectiveness and safety of alfentanil in general anesthesia.Methods In this study, a multicenter randomized double-blind con¬trolled study was conducted.A total of 352 subjects were selected and randomly assigned to fentanyl group (group A, n =176) and alfentanil group (group 15, n = 176).Anesthesia induction: intravenous midazolam 0.03 mg • kg-1 + fentanyl 25 p.g • kg"'(group A) or alfentanil 4 p,g • kg-1 ( group 15) + propofol 2 mg • kg"1 + rocuronium 0.8 mg • kg"1.Sevoflurane + fent¬anyl ( group A ) or alfentanil ( group B ) + rocuronium were used for anesthesia.The vital signs of patients re¬covery time and extuhation time, anesthesia-related complications and the use of related remedial drugs during anesthesia induction and maintenance were compared between the two groups.Results During the induction and maintenance period of anesthesia, alfentanil and fentanyl could equally effectively inhibit the stress response induced by endotracheal intubation and surgical stimulation.Alfentanil also showed more effective inhibition on stress response induced by endo¬tracheal intubation and surgical stimulation than that of fentanyl ( P < 0.05 ) .However, there was no signifi¬cant difference in the incidence of intraoperative hypo¬tension and hypertension and the time of anesthesia re¬covery and extubation between the two groups.Conclu¬sions Both alfentanil and fentanyl can effectively in¬hibit the stress response induced by surgical stimulation and could be safely used in general anesthesia in sur¬gery.Alfentanil has more advantages in maintaining the stability of blood pressure and heart rate during an¬esthesia induction and maintenance.

OBJECTIVE: This study aimed to characterize the diagnostic and vaccine potential of a novel Mycobacterium tuberculosis antigen Rv0674. METHODS: To evaluate the diagnostic potential and antigenicity of Rv0674, IgG was evaluated using ELISA and interferon (IFN)-γ was done by using ELISpot assay among TB patients and healthy donors. For immunogenicity evaluation, BALB/c mice were immunized with Rv0674. Cytokine production was determined by cytokine release assay using an ELISA kit, and the antibodies were tested using ELISA. RESULTS: The results of serum Elisa tests showed that Rv0674 specific immunoglobulin G (IgG) response was higher in TB patients than negative controls. And Rv0674 had good performance in serological test with sensitivity and specificity of 77.1% and 81.1%, respectively. While it shows poor sensitivity and specificity of 26.23% and 79.69% for IFN-γ tests. In BALB/c mice, Rv0674 adjuvant by DDA/Poly I:C could also induce a high level of IFN-γ, interleukin-2 and interleukin-6 as well as a high IgG titer in both high- and low-dose groups indicating that Rv0674 is essential in humoral and cellular immunity. Moreover, the cytokine profile and IgG isotype characterized Rv0674 as a Th1/Th2-mixed-type protective immunity with the predominance of Th1 cytokines. CONCLUSION Rv0674 may be a good potential candidate for the development of TB serological diagnosis and a new TB vaccine.
Adult ; Aged ; Animals ; Antigens, Bacterial ; immunology ; Female ; Humans ; Immunity, Cellular ; Immunity, Humoral ; Male ; Mice ; Mice, Inbred BALB C ; Middle Aged ; Tuberculosis ; diagnosis ; immunology ; Young Adult

OBJECTIVE: To systematic evaluate the outcome of open-wedge high tibial osteotomy(OWHTO) and unicomartmental knee arthroplasty (UKA) in treating medial compartment osteoarthritis of the knee. METHODS: According to the retrieval strategy made by the Cochrane collaboration, a computer-base research of Medline, Pubmed, EMbase, Cochrane Library, CBM, CNKI, and Wanfang databases was performed and search deadline was March 2018. Related Chinese and English orthopedic journals and conference papers were manually searched. Controlled studies of OWHTO and UKA in the treatment of medial knee osteoarthritis were included. The quality of included researches was evaluated, and the data of postoperative knee function, complications, total knee arthroplasty(TKA) revision rates, and postoperative pain were extracted. Meta analysis was performed using the RevMan 5.0 software. RESULTS: A total of 8 articles that met the criteria were included containing a total of 675 patients. Meta-analysis showed that there was no significant difference in postoperative HSS score, knee score, functional score, and Lysholm score between the OWHTO and UKA groups(=0.32, =0.87, =0.22, =0.53). The range of joint motion in the OWHTO group was better than that in the UKA group, and the difference was statistically significant(=0.009). There was no significant difference in postoperative complications and the rates of revision to TKA between the two groups(=0.81, =0.23). There was no difference in postoperative knee pain between the two groups. CONCLUSIONS In the treatment of medial compartmental osteoarthritis of the knee that meets the surgical indications, OWHTO had better postoperative joint mobility. The results were similar in postoperative knee score, postoperative complications, and postoperative TKA revision rates between OWHTO and UKA groups.
Arthroplasty, Replacement, Knee ; Humans ; Knee Joint ; Osteoarthritis, Knee ; Osteotomy ; Tibia ; Treatment Outcome

Objective:To investigate the effect of Lycium Barbarum polysaccharides on immune function of erythrocytes in doxorubicin-treated mice.Methods:BALB/c mice were treated with doxorubicin and used as immunosuppression model.The mice were treated with Lycium Barbarum polysaccharides(62.5,125,250 mg/kg) for 7 days,the normal control mice and model control mice were also used in this study.Expression level of CD59 molecule in erythrocytes was analyzed with flow cytometry.The Band-3 level was analyzed by Coomassie Brilliant Blue method.The NKEF-A and NKEF-B expression level in erythrocytes was analyzed by Western blot.The killing activity of NK cells was analyzed with flow cytometry.Results: The level of Band-3,NKEF-A and NKEF-B was decrease in erythrocytes of doxorubicin-treated mice.The killing activity of NK cells was also decrease in the mice when the expression level of CD59 molecule was not change obviously.Lycium Barbarum polysaccharides treatment could promote the recovery of Band-3, NKEF-A and NKEF-B in erythrocytes of the mice.Conclusion:Lycium Barbarum polysaccharides can promote the recovery of immune function of erythrocytes in doxorubicin-treated mice.

Objective To improve clinically the recognition of fungal infection associated with hemophagocytic lymphohistiocytosis (HLH) in children. Methods Clinical data of 3 children with fungal infection complicated with HLH in our hospital was retrospectively analyzed. Results All the 3 cases complained of recurrent fever, 2 cases with cough and one case with vomiting. Hepatosplenomagaly and lymphadenectasis were found in the medical examination. The time of diagnosis of fungal infection through etiological examination was 5 days after admission. It was further diagnosed as hemophagocytic lymphohistiocytosis after failure of effective antifungal therapy. Routine blood test showed the counts of leukocytes were increased in early stage, while the number of platelets and hemoglobin decreased in different degrees. The recovery is not satisfactory using antifungal therapy alone, and 2 of them are gradually aggravated and treated with mechanical ventilation. On the basis of antifungal therapy, 2 cases were treated under HLH-2004 regimen, 1 received dexamethasone treatment. All the 3 cases received intravenous immune globulin, and showed improvement. Conclusions Fungal infection complicated with HLH in childhood is rare. The effect of simple antifungal therapy on the progression is limited. However, increasing immunosuppressive therapy based on effective antifungal therapy can improve the prognosis.

Once-daily tadalafil administration has been well established; however, studies about tadalafil once-daily treatment in the Chinese population are lacking. In this phase 4, postmarketing study, we ascertained the long-term safety and effectiveness of tadalafil 2.5 mg and 5.0 mg once daily in Chinese men with erectile dysfunction (n = 635). The primary endpoint of the study was safety at 12 months as assessed by the proportion of patients experiencing at least one treatment-emergent adverse event (serious or nonserious). The secondary endpoints included safety and effectiveness, measured by the International Index of Erectile Function-Erectile Function (IIEF-EF) domain scores. Similar adverse events to the known safety profile of tadalafil, such as nasopharyngitis, upper respiratory tract infection, headache, and dizziness, were detected. No new cardiovascular safety concerns were observed. After 3 months of treatment, significant increases in IIEF-EF domain scores were detected for both 2.5-mg (least squares [LS] mean change: 6.3; 95% confidence interval [CI]: 5.4-7.1; P < 0.001) and 5.0-mg (LS mean change: 7.4; 95% CI: 6.8-7.9; P < 0.001) tadalafil doses, and significance was maintained up to 12 months. In addition, approximately 40% of patients regained normal erectile function (IIEF-EF ≥26) following 1 year of tadalafil once-daily treatment. The findings in this study provide evidence for the extended effectiveness and tolerability of tadalafil, demonstrating no new safety concerns, in a Chinese population and make once-daily tadalafil administration a viable option for improving sexual performance and satisfaction in Chinese men with erectile dysfunction.
Adult ; Aged ; Asian People ; Double-Blind Method ; Erectile Dysfunction/drug therapy* ; Female ; Humans ; Male ; Middle Aged ; Patient Safety ; Phosphodiesterase 5 Inhibitors/therapeutic use* ; Product Surveillance, Postmarketing ; Prospective Studies ; Tadalafil/therapeutic use* ; Treatment Outcome ; Young Adult