Male infertility has become a global concern, accounting for 20-70% of infertility. Dysfunctional spermatogenesis is the most common cause of male infertility; thus, treating abnormal spermatogenesis may improve male infertility and has attracted the attention of the medical community. Mitochondria are essential organelles that maintain cell homeostasis and normal physiological functions in various ways, such as mitochondrial oxidative phosphorylation (OXPHOS). Mitochondrial OXPHOS transmits electrons through the respiratory chain, synthesizes adenosine triphosphate (ATP), and produces reactive oxygen species (ROS). These mechanisms are vital for spermatogenesis, especially to maintain the normal function of testicular Sertoli cells and germ cells. The disruption of mitochondrial OXPHOS caused by external factors can result in inadequate cellular energy supply, oxidative stress, apoptosis, or ferroptosis, all inhibiting spermatogenesis and damaging the male reproductive system, leading to male infertility. This article summarizes the latest pathological mechanism of mitochondrial OXPHOS disorder in testicular Sertoli cells and germ cells, which disrupts spermatogenesis and results in male infertility. In addition, we also briefly outline the current treatment of spermatogenic malfunction caused by mitochondrial OXPHOS disorders. However, relevant treatments have not been fully elucidated. Therefore, targeting mitochondrial OXPHOS disorders in Sertoli cells and germ cells is a research direction worthy of attention. We believe this review will provide new and more accurate ideas for treating male infertility.
Male ; Humans ; Infertility, Male/metabolism* ; Oxidative Phosphorylation ; Mitochondria/metabolism* ; Spermatogenesis/physiology* ; Sertoli Cells/metabolism* ; Oxidative Stress/physiology* ; Animals ; Reactive Oxygen Species/metabolism*

Objective:To evaluate the efficacy and safety of bendamustine monotherapy in Chinese patients with relapsed/refractory (R/R) B cell non-Hodgkin lymphoma (B-NHL) .Methods:This prospective, multicenter, open label, single-arm, phase Ⅱ study investigated bendamustine’s efficacy and safety in Chinese patients with R/R B-NHL. A total of 78 patients with B-NHL in 11 hospitals in China from March 2012 to December 2016 were included, and their clinical characteristics, efficacy, and survival were analyzed.Results:The median age of all patients was 58 (range, 24-76) years old, and 69 (88.4% ) patients had stage Ⅲ/Ⅳ disease. 61 (78.2% ) patients were refractory to previous treatments. Patients received a median of 4 (range, 1-10) cycles of bendamustine treatment. The overall response rate was 61.5 (95% CI 49.8-72.3) % , the median response duration was 8.3 (95% CI 5.5-14.0) months, and the complete remission (CR) rate was 5.1 (95% CI 1.4-12.6) % . In the full analysis set, median progression-free survival (PFS) and median OS were 8.7 (95% CI 6.7-13.2) months and 25.5 months (95% CI 14.2 months to not reached) , respectively, after a median follow-up of 33.6 (95% CI 17.4-38.8) months. Lymphopenia (74.4% ) , neutropenia (52.6% ) , and leukopenia (39.7% ) , thrombocytopenia (29.5% ) and anemia (15.4% ) were the most common grade 3-4 hematologic adverse events (AE) . The most frequent non-hematologic AEs included nausea (43.6% ) , vomiting (33.3% ) , and anorexia (29.5% ) . Univariate and multivariate analysis showed that <4 cycles of bendamustine treatment was a poor prognostic factor for PFS ( P=0.003) , and failure to accept fludarabine containing regimen was a poor prognostic factor for OS ( P=0.009) . Conclusion:Bendamustine monotherapy has good efficacy and safety in the treatment of patient with R/R B-NHL.

Many sensitizers have not only photodynamic effects, but also sonodynamic effects. Therefore, the combination of sonodynamic therapy (SDT) and photodynamic therapy (PDT) using sensitizers for sono-photodynamic therapy (SPDT) provides alternative opportunities for clinical cancer therapy. Although significant advances have been made in synthesizing new sensitizers for SPDT, few of them are successfully applied in clinical settings. The anti-tumor effects of the sensitizers are restricted by the lack of tumor-targeting specificity, incapability in deep intratumoral delivery, and the deteriorating tumor microenvironment. The application of nanotechnology-based drug delivery systems (NDDSs) can solve the above shortcomings, thereby improving the SPDT efficacy. This review summarizes various sensitizers as sono/photosensitizers that can be further used in SPDT, and describes different strategies for enhancing tumor treatment by NDDSs, such as overcoming biological barriers, improving tumor-targeted delivery and intratumoral delivery, providing stimuli-responsive controlled-release characteristics, stimulating anti-tumor immunity, increasing oxygen supply, employing different therapeutic modalities, and combining diagnosis and treatment. The challenges and prospects for further development of intelligent sensitizers and translational NDDSs for SPDT are also discussed.

Preeclampsia is the main cause of poor maternal-fetal outcomes. A series of cell and animal experiments, and a small number of clinical studies have shown that pravastatin can prevent and treat preeclampsia by regulating angiogenesis, increasing the expression of heme oxygenase, and stimulating the production of nitric oxide without any reported adverse effects during pregnancy. We review the latest progress on the mechanism, effect, and safety of pravastatin in the prevention and treatment of preeclampsia.

OBJECTIVE：To stud y the correlatio n between the contents of active ingredients and the color of Morus alba ，to establish fingerprint and conduct cluster analysis of samples from different producing areas ，so as to provide reference for its quality control and evaluation. METHODS ：HPLC and HCl-Mg reaction colorimetry were used to determine the contents of morusin and total flavonoids in M. alba . The color of M. alba was observed by naked eye ，and chromaticity values （L＊，a＊，b＊） were measured by color difference meter and color aberration （E＊ab）were calculated. Pearson correlation of the contents of morusin and total flavonoids with color indicators （L＊，a＊，b＊，E＊ab）were analyzed by SPSS 21.0 software. HPLC method was used to establish the fingerprint of 20 batches of M. alba from 3 different producing areas ，and the similarity analysis was carried out. K-means cluster analysis （based on the contents of morusin and total flavonoids and corlor index ）and hierarchical cluster analysis （based on relative peak area of common peaks in fingerprint ）were performed for 20 batches of samples by SPSS 21.0 software. RESULTS：The average contents of morusin and total flavonoids in M. alba were 0.096 0-0.618 6 mg/g，0.48％-1.51％，which were significantly correlated with each color index （P＜0.01）. The smaller L＊，b＊，E＊ab and the larger a＊were，the higher the content of morusin was ；the higher the value of L＊，b＊，E＊ab and the smaller the value of a＊were，the higher the content of total flavonoids was. The similarity between the fingerprints of 20 batches of samples and the control ranged from 0.883 to 0.983；13 common peaks were demarcated ，and No. 1 peak was identified as chlorogenic acid. K-means cluster analysis showed that 20 batches of samples could be divided into 2 categories. Category Ⅰ were mainly from Anhui province with higher content of morusin，lower content of total flavonoids ，darker and yellowish brown color ；category Ⅱ were mainly from Sichuan province and Guizhou province ，with lower content of morusin ，higher content of total flavonoids ，lighter and yellowish white color. The results of hierarchical cluster analysis were consistent with the results. CONCLUS IONS：The color of M. alba is closely related to the contents of morusin and total flavonoids. The content of morusin in yellow-brown M. albais is higher ，while the content of total flavonoids in yellow-white M. albais is higher.

OBJECTIVES: To investigate glucocorticoid receptor (GR) and histone deacetylase 2 (HDAC2) gene expression and protein levels in peripheral blood mononuclear cells (PBMCs) of patients with severe or profound sudden sensorineural hearing loss (SSNHL) and to explore the roles of GRs and HDAC2 in glucocorticoid (GC) insensitivity. METHODS: Fifty-five severe or profound SSNHL patients were enrolled in the study. According to hearing improvement after GC treatment, patients were assigned into two groups: GC-sensitive and GC-resistant. A normal reference group included 20 healthy volunteers without hearing loss. Quantitative real-time polymerase chain reaction and Western blot analyses were used to detect the relative expression of GRα, GRβ, and HDAC2 in PBMCs at the mRNA and protein levels. RESULTS: The protein levels of GRs and HDAC2 in PBMCs of SSNHL patients were lower than the normal reference values before GC treatment. Compared with the GC-resistant group, both the mRNA and protein levels of GRα and HDAC2 were significantly increased in the GC-sensitive group after GC treatment. CONCLUSION: A lack of GRα and HDAC2 induction following steroid treatment in GC-resistant SSNHL patients may play a fundamental mechanistic role in GC insensitivity. Response of GRα and HDAC2 to steroid treatment may, thus, predict the prognosis of hearing improvement in SSNHL patients.
Blotting, Western ; Gene Expression ; Healthy Volunteers ; Hearing ; Hearing Loss ; Hearing Loss, Sensorineural ; Histone Deacetylase 2 ; Histone Deacetylases ; Histones ; Humans ; Prognosis ; Real-Time Polymerase Chain Reaction ; Receptors, Glucocorticoid ; Reference Values ; RNA, Messenger

Objective To investigate the protective effects of astragalosides Ⅳ (ASI) on high glucose-induced renal proximal tubular epithelial cells (NRK-52E).Methods NRK-52E were cultured and divided randomly into three groups:control group,high glucose group (HG in short),ASI groups (with various doses).Cells were treated with increasing concentrations of ASI (20,40,80 and 100 μg/ml) for 24 h in high glucose and we also stimulated cells in ASI 100 μg/ml with high glucose for various lengths of time.The apoptosis rate was detected by flow cytometric analysis.The mRNA and protein expression of transforming growth factor-β1 (TGF-β1),a-smooth muscle actin (α-SMA),Smad2,Smad3 and their phosphorylated forms were detected by real-time polymerase chain reaction (PCR) and Western blot,respectively.Results Compared with the control group,apoptosis was increased in the high glucose group (P ＜ 0.01).However,ASI inhibited high glucose-induced cell apoptosis in a dose-dependent manner,with a maximal inhibitory effect achieved at 100 μg/ml (P ＜ 0.05).The significant inhibition caused by ASI was observed at 8h after the start of pretreatment (P ＜ 0.05) and increased in a time-dependent manner.ASI can inhibit the expression of TGF-β1,α-SMA,Smad2,Smad3 both at mRNA and protein level.Conclusions ASI inhibited NRK-52E cells apoptosis induced by high glucose and reduced expression of TGF-β1,α-SMA,Smad2,Smad3 both at the mRNA and protein level in NRK-52E cells,thus delayed epithelial-to-mesenchymal transition progress.

Objective To study the effect of astragaloside on TGF-β1,SMAD2/3,and α-SMA expression in the kidney tissue of diabetic KKAy mice,and evaluate its potential role in renal interstitial fibrosis.Methods 20 type 2 diabetic KKAy mice were randomly divided into model group and astragaloside group,while 10 male C57BL/6J mice were selected as the control.Astragaloside at 40 mg · kg-1 · d-1 was given when the KKAy mice fed with high-fat diet to 14 weeks old.The mice in the control and model group received normal saline at 40 mg · kg-1 · d-1.Blood glucose meter was used to detect the blood glucose value of each mice at 16th,20th and 24th week.The mice were killed at 24 weeks old and the kidney tissue samples were collected.Pathology morphological changes were observed.Results (1) blood glucose value:cmpared with the control group,the blood glucose value of KKAy mice at 14 week increased significantly,and that of model group also increased significantly at 16th,20th and 24th week (P＜0.05);the blood glucose value of astragaloside group decreased compared with control group (P＜0.05).(2) Morphology of kidney:in the control group,the glomerular and tubular had clear structure,there was no renal interstitial fibrosis;in the model group,the renal glomerular mesangial matrix had broaden,mesangial cell had increased,renal tubular epithelial cell cytoplasm showed vacuole degeneration,renal interstitial inflammatory cell had increaised.In astragaloside group,there were few renal tubular epithelial cell cytoplasm,and there was no obvious fibrosis.(3)TGF-β1,SMAD2/3,and α-SMA expression levels of the kidney issuse:compared with control group,mice in model group up-regulated TGF-β1,SMAD2/3 and α-SMA expression (P＜ 0.05).TGF-β1,SMAD2/3,and α-SMA expression levels in astragaloside group were significantly lower than those in the model group (P＜0.05).There was few phosphorylated SMAD2/3 expression in renal tubular and glomerular nuclei,while that of model group increased (P＜0.01),and compared with model group,that of the astragaloside group decreased (P＜0.05).Conclusion Astragaloside can delay the renal fibrosis process in diabetic mice by influencing the TGF-β/SMADS signaling pathway and down-regulating TGF-β1 and α-SMA expression,thus to relieve renal fibrosis in diabetic mice.

OBJECTIVETo evaluate the efficacy and safety of anagrelide in essential thrombocythemia (ET).

METHODSPatients who diagnosed as ET according to the World Health Organization classification were enrolled. Each patient was assigned to take anagrelide hydrochloride capsule or hydroxyurea tablet by random 1∶1 ratio. Dose of anagrelide started at 2 mg/d, then increased gradually and the maximum dose was 10 mg/d until the platelet counts dropped to (100-400) × 10⁹/L, one month later gradually reduced to maintain dose. The dose of hydroxyurea was 1000 mg/d at beginning, then increased gradually, when platelet counts dropped to (100-400)×10⁹/L and kept for one month, reduced to maintain dose as 10 mg·kg⁻¹·d⁻¹. The observation period was 12 weeks.

RESULTSA total of 222 patients were enrolled in seventeen centers (including 113 patients treated with anagrelide and 109 with hydroxyurea). Therapy efficacy can be evaluated in 198 patients (including 97 patients administered with anagrelide and 101 with hydroxyurea). At 12th weeks of therapy, the hematologic remission rate was 87.63% (85/97) in anagrelide group and 88.12% (89/107) in hydroxyurea group, the differences between the two groups were not significant (P=0.173). Treatment with anagrelide lowered the platelet counts by a median of 393 (362-1 339) × 10⁹/L from a median of 827 (562-1657) × 109/L at the beginning of the observation to 400(127-1130)×10⁹/L after 12 weeks (P<0.001), which were similar to the treatment result of hydroxyurea by a median drop of 398 (597-1846)× 10⁹/L (P=0.982). The median time to achieving response of anagrelide group was 7 (3-14) days, superior to that of hydroxyurea for 21 (14-28) significantly (P=0.003). Frequency of anagrelide related adverse events was 65.49 % (74/113), including cardiopalmus (36.28% ), headache (21.24% ), fatigue (14.16% ) and dizzy (11.50% ).

CONCLUSIONAnagrelide was effective in patients with ET which had similar hematologic remission rate to hydroxyurea and could take effect more quickly than hydroxyurea. Incidence of adverse events was undifferentiated between anagrelide and hydroxyurea, but anagrelide treatment had tolerable adverse effects and no hematologic toxicity.

Humans ; Hydroxyurea ; administration & dosage ; therapeutic use ; Platelet Aggregation Inhibitors ; administration & dosage ; therapeutic use ; Platelet Count ; Quinazolines ; administration & dosage ; therapeutic use ; Thrombocythemia, Essential ; drug therapy ; Treatment Outcome

BACKGROUNDNovel influenza A viruses of avian-origin may be the precursors of pandemic strains. This descriptive study aims to introduce a novel avian-origin influenza A (H10N8) virus which can infect humans and cause severe diseases.

METHODSCollecting clinical data of three cases of human infection with a novel reassortment avian influenza A (H10N8) virus in Nanchang, Jiangxi Province, China.

RESULTSThree cases of human infection with a new reassortment avian influenza A(H10N8) virus were described, of which two were fatal cases, and one was severe case. These cases presented with severe pneumonia that progressed to acute respiratory distress syndrome (ARDS) and intractable respiratory failure.

CONCLUSIONThis novel reassortment avian influenza A (H10N8) virus in China resulted in fatal human infections, and should be added to concerns in clinical practice.

Aged ; Antiviral Agents ; therapeutic use ; Female ; Fluoroquinolones ; therapeutic use ; Humans ; Imipenem ; therapeutic use ; Influenza A Virus, H10N8 Subtype ; drug effects ; pathogenicity ; Influenza, Human ; complications ; diagnosis ; drug therapy ; Male ; Middle Aged ; Oseltamivir ; therapeutic use