Effects of Systolic Blood Pressure Elevation on Internal Sperm Artery Identification During Microsurgical Subinguinal Varicocelectomy.

Microsurgical subinguinal varicocelectomy (MSV) is the gold standard for treating varicoceles. Preservation of the internal spermatic arteries (ISAs) during MSV is important for sperm production. This study aimed to evaluate the safety and efficacy of elevating systolic blood pressure (SBP) using MSV. Data from 252 consecutive adult male patients were retrospectively reviewed. The patients were divided into two groups: a traditional group that underwent conventional MSV (n = 134) and a modified group that underwent MSV with a transiently elevated SBP of 140-160 mm Hg (n = 118). Arterial identification time, unilateral operative time, number of ISAs, arterial injury rate, and other postoperative indicators, including postoperative complications and sperm parameters, were compared between the groups. All the procedures were successful. The arterial identification and unilateral operative times were significantly shorter in the modified group (31.34 ± 10.44 vs. 42.94 ± 12.39 min and 61.48 ± 8.78 vs. 76.35 ± 12.33 min, p < .01, respectively). Intraoperatively, the number of preserved ISAs was significantly higher in the modified group (1.92 ± 0.53 vs. 1.45 ± 0.32, p < .01). The arterial injury rate did not differ significantly between the groups (2.74% vs. 0%, respectively). Compared with preoperative values, sperm parameters improved significantly 6 months postoperatively. Significant differences in semen parameters or postoperative complications were not observed between the groups. Elevated intraoperative SBP can be used to rapidly, safely, and effectively identify ISAs, increase the number of retained spermatic arteries, and markedly reduce the operative time for MSV.

Clinical observation of acupotomology combined with Bushenzhuanggu prescription in the treatment of residual lumbar pain after PKP for osteoporotic vertebral compression fracture / 中国现代医生

@#Objective To investigate the clinical effect of acupotomology combined with Bushenzhuanggu prescription in the treatment of residual lumbar pain after percutaneous kyphoplasty(PKP)for osteoporotic vertebral compression fractures.Methods A total of 77 patients with PKP postoperative residual lumbar pain admitted to the Department of Orthopedics,Ningbo Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University from January 2018 to December 2021 were randomly divided into control group and observation group.Patients in control group were treated with calcitriol soft capsules and calcium carbonate D3 tablets,and patients in observation group were treated with acupotomy combined with Bushenzhuanggu prescription.The pain degree,lumbar function and self-care ability of the two groups were compared.Results After treatment,the pain level,lumbar function,and self-care abilityof the two groups of patients improved compared to before treatment.Compared with control group,the visual analogue score(VAS)score and Oswestry disability index(ODI)index of observation group decreased more significantly,and the difference was statistically significant(P<0.05);The Barthel index of observation group increased more significantly in the early stage(3 days and 1 month after treatment),with a statistically significant difference(P<0.05).However,there was no statistically significant difference in Barthel index between the two groups at 3 months after treatment(P>0.05).Conclusion Acupotomy combined with Bushenzhuanggu prescription has satisfactory clinical efficacy in the treatment of residual lumbar pain after PKP operation of osteoporotic vertebral compression fracture.It can significantly reduce pain,improve lumbar function,shorten the improvement time of patients'self-care ability,improve patients'quality of life,and effectively promote patients'rapid recovery.

[Intrauterine Device Totally Embedded in the Bladder Wall:Report of One Case].

Intrauterine device(IUD)migrating to the bladder is rare,especially the migration far away from the uterus into the bladder wall.Due to no obvious clinical symptom in the early stage and being far away from the uterus,the IUD totally embedded in the bladder wall is prone to misdiagnosis and delay in treatment.We reported one case of such migration,aiming to improve the clinical management of the IUD totally embedded in the bladder wall.

The prevalence of osteoporosis in China, a community based cohort study of osteoporosis.

Background: Osteoporosis has already been a growing health concern worldwide. The influence of living area, lifestyle, socioeconomic, and medical conditions on the occurrence of osteoporosis in the middle-aged and elderly people in China has not been fully addressed. Methods: The study was a multicenter cross-sectional study on the middle-aged and elderly permanent residents, which gathered information of 22,081 residents from June 2015 to August 2021 in seven representative regions of China. The bone mineral density of lumbar vertebrae and hip were determined using the dual-energy X-ray absorptiometry densitometer instruments. Serum levels of bone metabolism markers were also measured. Information about education, smoking, and chronic diseases were also collected through face-to-face interviews. Age-standardized prevalence and 95% confidence intervals (CIs) of osteopenia and osteoporosis by various criteria were estimated by subgroups and overall based on the data of China 2010 census. The relationships between the osteoporosis or osteopenia and sociodemographic variables or other factors were examined using univariate linear models and multivariable multinomial logit analyses. Results: After screening, 19,848 participants (90%) were enrolled for the final analysis. The age-standardized prevalence of osteoporosis was estimated to be 33.49%(95%CI, 32.80-34.18%) in the middle-aged and elderly Chinese permanent residents, for men and women was 20.73% (95% CI, 19.58-21.87%) and 38.05% (95% CI, 37.22-38.89%), respectively. The serum concentrations of bone metabolic markers, and calcium and phosphorus metabolism were influenced by age, body mass index (BMI), gender, education level, regions, and bone mass status. Women, aged 60 or above, BMI lower than 18.5 kg/m2, low education level including middle school, primary school and no formal education as well as current regular smoking, a history of fracture were all significantly associated with a higher risk of osteoporosis and osteopenia in the middle-aged and elderly people. Conclusions: This study revealed dramatic regional differences in osteoporosis prevalence in China, and female, aged 60 or older, low BMI, low education level, current regular smoking, and a history of fracture were associated with a high risk of osteoporosis. More prevention and treatment resources should be invested into particular population exposed to these risk factors.

Help-seeking efficacy and the intention of social assistance among medical care personnel during the major public health events / 中华劳动卫生职业病杂志

Objective: To explore the help seeking efficacy and social assistance willingness of medical staff during major public health events, so as to provide basis for improving the psychological resources and service quality of medical staff and further optimizing the prevention and treatment policies. Methods: In February 2020, a convenient sampling method was used to conduct an online questionnaire survey on medical staff in Henan Province, and a total of 2136 questionnaires were collected. Among them, there were 1940 valid questionnaires, and the effective recovery rate was 90.82%. The questionnaire of help seeking efficacy and willingness to social assistance under epidemic situation was used to investigate the help seeking efficacy and willingness of medical staff. The frequency and rate (%) were used to analyze the overall situation of medical staff's help seeking efficacy and social assistance willingness. The differences among different demographic variables were tested by χ(2) test. Results: Among the 1940 medical and nursing staff, 18.81% (365/1940) did not know how to obtain appropriate psychological assistance. Compared with the low age group, the medical staff in the high age group had the ability of information query, the ability to occupy knowledge resources, the ability to distinguish rumors and facts and the sense of efficacy of obtaining appropriate medical help, and the difference was statistically significant (P<0.05) . The willingness of medical and nursing staff to actively cooperate with the government, maintain social stability and volunteer work were 99.43% (1929/1940) , 98.81% (1917/1940) and 97.11% (1884/1940) . Conclusion: The medical staff had a higher sense of help seeking efficacy and willingness to social assistance. It is necessary to further strengthen the resource support of psychological, social and humanistic care for medical staff.

Is mild erectile dysfunction associated with severe psychological symptoms in Chinese patients with moderate-to-severe chronic prostatitis/chronic pelvic pain syndrome?

This study aimed to assess the association between psychological disorders and erectile dysfunction (ED) in patients with different degrees of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). This was a retrospective study conducted from June 2017 to October 2019 and included 182 outpatients. Patients were interviewed using the Structured Interview on Erectile Dysfunction (SIEDY) for pathogenic quantification. The National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) and the International Index of Erectile Function-5 (IIEF-5) were used for the evaluation of CP/CPPS and ED. The Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were used to assess anxiety symptoms and depressive symptoms. The number of patients with mild CP/CPPS and mild ED, mild CP/CPPS and moderate-to-severe ED, moderate-to-severe CP/CPPS and mild ED, and moderate-to-severe CP/CPPS and moderate-to-severe ED was 69 (37.9%), 36 (19.8%), 35 (19.2%), and 42 (23.1%), respectively. The corresponding PHQ-9 scores of the four groups were 6.22, 7.19, 10.69, and 7.71, respectively. The corresponding GAD-7 scores of the four groups were 5.26, 6.31, 8.77, and 6.36, respectively. Among patients with moderate-to-severe CP/CPPS, the PHQ-9 and GAD-7 scores of the moderate-to-severe ED group were significantly lower than those of the mild ED group (P = 0.007 and P = 0.010, respectively). The prevalence of ED and premature ejaculation (PE) in patients with moderate-to-severe CP/CPPS was significantly higher than that in patients with mild CP/CPPS (P = 0.001 and P = 0.024, respectively). Our findings proved that the severity of ED was negatively associated with psychological symptoms in outpatients with moderate-to-severe CP/CPPS.

Clinical Characteristics and Prognosis Analysis of Pediatric Severe Aplastic Anemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical characteristics and factors affecting prognosis in children with severe aplastic anemia (SAA).@*METHODS@#Two hundred and five children with SAA treated in our department from January 2008 to April 2018 were selected, and the clinical characteristics and factors affecting prognosis were retrospectively analyzed.@*RESULTS@#Among 205 SAA children, the effective rate (CR+PR) at 3, 6 and 12 months after immunosuppressive therapy (IST) treatment was 50.9%, 59.0% and 73.9%, respectively, and 5-year overall survival rate was 93.1%±2.0%. Univariate analysis showed that 5-year overall survival rate of SAA children of spontaneous delivery was higher than that of cesarean section (P=0.039), while multivariate analysis showed that birth way had no significant influence on 5-year overall survival rate (P>0.05). The response rate at 3 months after IST of children with a recent history of decoration before SAA onset was higher than those without history of decoration (P<0.05).@*CONCLUSION@#Most of the SAA children can achieve high response rate and overall survival rate. Patients with recent history of home/school decoration may be the factor affecting hematological response after 3 months of IST, but have no influence on long-term overall survival.

Is milder psychological stress responsible for more severe erectile dysfunction?

China is a sexually conservative country compared with Western countries. To evaluate the psychological characteristics of Chinese erectile dysfunction (ED) patients, we conducted a cross-sectional study of 153 ED outpatients. Patients were interviewed with the Structured Interview on Erectile Dysfunction (SIEDY) for pathogenic quantification. ED was measured by International Index of Erectile Function (IIEF). Depression and anxiety were evaluated with 9-item Patient Health Questionnaire (PHQ-9) and 7-item Generalised Anxiety Disorder Scale (GAD-7) respectively. Most patients (74.5%) were <40 years old. IIEF-5 were significantly correlated with SIEDY scale 3 (r = .16, p = .040) and GAD-7 (p = .15, p = .033). The SIEDY scale 1 increased with age, but the IIEF-5, SIEDY scale 3, PHQ-9 and GAD-7 decreased with age. A negative correlation was observed between ED and psychological stress, which conflicts with many Western-country studies. Younger patients were characterised by milder ED but more psychological stress, while older patients were characterised by worse ED but less psychological stress. Which may be responsible for the conflicting result. Meanwhile, the much younger age distribution among Chinese ED outpatients may indicate that quite a few older ED patients (≥40 years) in China do not seek outpatient service which should merit more attention.

Metformin protects paraquat-poisoned rats against acute lung injury / 医学研究生学报

Objective Metformin (MET) can reduce blood glucose, act against inflammation, lessen oxidative stress and prevent fibrosis. This study was to investigate the protective effect of MET against acute lung injury (ALI) induced by paraquat poisoning (PQP) in rats. Methods Totally 78 healthy adult SPF male SD rats were randomly divided into five groups, normal control, PQP model control, and low-, medium- and high-dose MET. The PQP model was established in the latter four groups of rats by intraperitoneal injection of paraquat solution at 30 mg/kg and, at 2 hours after modeling, the rats in the three MET intervention groups were treated intragastrically with MET at 100, 400 and 800 mg/kg/d respectively, while those in the normal and PQP model control groups with the same amount of normal saline, all for 7 successive days. Six of the animals from each group were sacrificed at 1, 3 and 7 days and their lung tissues harvested for measurement of the wet/dry weight ratio of the pulmonary tissue and contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in the plasma, determination of the levels of serum interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) by ELISA, and observation of the pathological changes in the pulmonary tissue by HE staining. Results In the normal control, PQP model control and low-, medium- and high-dose MET groups, the contents of MDA were (2.53±0.36), (3.68±0.26), (3.57±0.52), (3.56±0.83) and (3.68±0.60) nmol/mL respectively on the 1st day of intervention and (2.53±0.36), (5.18±0.56), (5.09±0.88), (3.80±0.91) and (3.96±0.78) nmol/mL at 7 days; those of SOD were (256.18±18.18), (229.24±18.26), (224.65±19.27), (223.20±19.37) and (226.45±11.62) U/mL on the 1st day and (256.18±18.18), (152.06±17.03), (150.76±18.18), (205.95±13.16) and (208.37±12.23) U/mL at 7 days; those of IL-1β were (10.57±2.24), (21.97±5.03), (22.33±4.88), (21.78±5.21) and (22.11±4.19) pg/mL on the 1st day and (10.57±2.24), (91.86±8.40), (91.36±10.65), (63.52±7.06) and (60.35±6.70) pg/mL at 7 days; those of IL-6 were (21.35±2.62), (45.61±3.71), (44.83±5.97), (46.17±7.33) and (45.78±6.55) pg/mL on the 1st day and (21.35±2.62), (84.38±10.21), (85.88±6.70), (49.08±7.70) and (50.26±7.65) pg/mL at 7 days; and those of TNF-α were (32.37±3.74), (71.89±6.98), (72.52±8.23), (71.13±4.50) and (70.15±6.47) pg/mL on the 1st day and (32.37±3.74), (197.04±14.80), (201.59±13.61), (140.17±14.84) and (139.86±11.12) pg/mL at 7 days. Compared with the normal controls, the rats in the PQP model control and the MET intervention groups showed significant increases in the wet/dry weight ratio of the pulmonary tissue and contents of MDA, IL-1β, IL-6 and TNF-α (all P < 0.05), but a decrease in the SOD level in the plasma at 1, 3 and 7 days (P < 0.05). In comparison with the PQP model controls, the animals in the medium- and high-dose MET groups exhibited remarkable decreases in the wet/dry weight ratio of the lungs and contents of MDA, IL-1β, IL-6 and TNF-α (all P < 0.05), but an increase in the SOD level at 7 days (P < 0.05). Massive inflammatory cell infiltration, diffuse pulmonary hemorrhage, alveolar collapse and extensive alveolar septal thickening were observed in the PQP model control and low-dose MET groups but significantly alleviated in the medium- and high-dose MET groups at 7 days. Conclusion Metformin can protect paraquat-poisoned rats against acute lung injury by reducing pulmonary edema and the expressions of inflammation- and oxidation-related factors in the pulmonary tissue.

Advances in the treatment of juvenile myelomonocytic leukemia / 中国当代儿科杂志

Juvenile myelomonocytic leukemia (JMML) is a rare chronic myeloid leukemia in children and has the features of both myelodysplastic syndrome and myeloproliferative neoplasm. It is highly malignant and has a poor treatment outcome. Children with JMML have a poor response to conventional chemotherapy. At present, hematopoietic stem cell transplantation is the only possible cure for this disease. In recent years, significant progress has been made in targeted therapy for mutant genes in the Ras signaling pathway and demethylation treatment of aberrant methylation of polygenic CpG islands. This article reviews the treatment and efficacy evaluation of JMML.

Value of multiparameter flow cytometry in the diagnosis and prognostic evaluation of childhood myelodysplastic syndrome / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the value of multiparameter flow cytometry (MFC) and flow cytometric scoring system (FCSS) in the diagnosis and prognostic evaluation of childhood myelodysplastic syndrome (MDS).</p><p><b>METHODS</b>A retrospective analysis was performed for the clinical data of 42 children who were diagnosed with MDS. MFC was performed to investigate the phenotype and proportion of each lineage of bone marrow cells. The correlations of FCSS score with MDS type, International Prognostic Scoring System (IPSS) score, and revised IPSS (IPSS-R) score were analyzed.</p><p><b>RESULTS</b>Of all the 42 children, 20 (48%) had an increase in abnormal marrow blasts, 19 (45%) had a lymphoid/myeloid ratio of >1, 14 (33%) had abnormal cross-lineage expression of lymphoid antigens in myeloid cells, 8 (19%) had abnormal CD13/CD16 differentiation antigens, 5 (12%) had abnormal expression of CD56, 3 (7%) had reduced or increased side scatter of granulocytes, 3 (7%) had reduced expression of CD36 in nucleated red blood cells, 2 (5%) had reduced expression of CD71 in nucleated red blood cells, 1 (2%) had absent expression of CD33 in myeloid cells, 1 (2%) had reduced or absent expression of CD11b in granulocytes, and 1 (2%) had absent expression of CD56 and CD14 in monocytes. There were significant differences in the median overall survival time and event-free survival time among the low-, medium-, and high-risk FCSS groups (P<0.05). Among the low-, medium-, and high-risk FCSS groups, the low-risk FCSS group had the highest 2-year overall survival rate, while there was no significant difference between the medium- and high-risk FCSS groups (P>0.05). The three groups had a 2-year event-free survival rate of 95%, 60%, and 46% respectively (P<0.05). FCSS score was positively correlated with MDS type, IPSS score, and IPSS-R score (P<0.05).</p><p><b>CONCLUSIONS</b>MFC and FCSS help with the diagnosis and prognostic evaluation of childhood MDS.</p>

Sasanquasaponin induces increase of Cl­/HCO3­ exchange of anion exchanger 3 and promotes intracellular Cl­ efflux in hypoxia/reoxygenation cardiomyocytes.

Anion exchanger 3 (AE3) is known to serve crucial roles in maintaining intracellular chloride homeostasis by facilitating the reversible electroneutral exchange of Cl­ for HCO3­ across the plasma membrane. Our previous studies reported that sasanquasaponin (SQS) can inhibit hypoxia/reoxygenation (H/R)­induced elevation of intracellular Cl­ concentration ([Cl­]i) and elicit cardioprotection by favoring Cl­/HCO3­ exchange of AE3. However, the molecular basis for SQS­induced increase of Cl­/HCO3­ exchange of AE3 remains unclear. The present study demonstrated that SQS activates protein kinase Cε (PKCε) and stimulates the phosphorylation of AE3 in H9c2 cells. Notably, SQS­induced AE3 phosphorylation was blocked by the PKCε selective inhibitor εV1­2, and a S67A mutation of AE3, indicating that SQS could promote phosphorylation of Ser67 of AE3 via a PKCε­dependent regulatory signaling pathway. Additionally, both inhibition of PKCε by εV1­2 and S67A mutation of AE3 eradicated the SQS­induced increase of AE3 activity, reversed the inhibitory effect of SQS on H/R­induced elevation of [Cl­]i, Ca2+ overload and generation of reactive oxygen species, and eliminated SQS­induced cardioprotection. In conclusion, PKCε­dependent phosphorylation of serine 67 on AE3 may be responsible for the increase of Cl­/HCO3­ exchange of AE3 and intracellular chloride efflux by SQS, and contributes to the cardioprotection of SQS against H/R in H9c2 cells.

Sasanquasaponin-induced cardioprotection involves inhibition of mPTP opening via attenuating intracellular chloride accumulation.

Sasanquasaponin (SQS) has been reported to elicit cardioprotection by suppressing hypoxia/reoxygenation (H/R)-induced elevation of intracellular chloride ion concentration ([Cl-]i). Given that the increased [Cl-]i is involved to modulate the mitochondrial permeability transition pore (mPTP), we herein sought to further investigate the role of mPTP in the cardioprotective effect of SQS on H/R injury. H9c2 cells were incubated for 24h with or without 10µM SQS followed by H/R. The involvement of mPTP was determined with a specific mPTP agonist atractyloside (ATR). The results showed that SQS attenuated H/R-induced the elevation of [Cl-]i, accompanied by reduction of lactate dehydrogenase release and increase of cell viability. Moreover, SQS suppressed mPTP opening, and protected mitochondria, as indicated by preserved mitochondrial membrane potential and respiratory chain complex activities, decreased mitochondrial reactive oxygen species generation, and increased ATP content. Interestingly, extracellular Cl--free condition created by replacing Cl- with equimolar gluconate resulted in a decrease in [Cl-]i and induced protective effects similar to SQS preconditioning, whereas pharmacologically opening of the mPTP with ATR abolished all the protective effects induced by SQS or Cl--free, including suppression of mPTP opening, maintenance of mitochondrial membrane potential, and subsequent improvement of mitochondrial function. The above results allow us to conclude that SQS-induced cardioprotection may be mediated by preserving the mitochondrial function through preventing mPTP opening via inhibition of H/R-induced elevation of [Cl-]i.

Involvement of DJ­1 in ischemic preconditioning­induced delayed cardioprotection in vivo.

DJ­1 protein, as a multifunctional intracellular protein, has been demonstrated to serve a critical role in regulating cell survival and oxidative stress. To provide in vivo evidence that DJ­1 is involved in the delayed cardioprotection induced by ischemic preconditioning (IPC) against oxidative stress caused by ischemia/reperfusion (I/R), the present study subjected male Sprague­Dawley rats to IPC (3 cycles of 5­min coronary occlusion/5­min reperfusion) 24 h prior to I/R (30­min coronary occlusion/120­min reperfusion). A lentiviral vector containing short hairpin RNA was injected into the left ventricle three weeks prior to IPC, to knockdown DJ­1 in situ. Lactate dehydrogenase (LDH) and creatine kinase­MB (CK­MB) release, infarct size, cardiac function, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities, malondialdehyde (MDA), intracellular reactive oxygen species (ROS), and DJ­1 protein expression levels were assessed. IPC caused a significant increase in the expression levels of DJ­1 protein. In addition, IPC reduced LDH and CK­MB release, attenuated myocardial infarct size, improved cardiac function following I/R, and inhibited the elevation of ROS and MDA and the decrease in activities of the antioxidant enzymes SOD, CAT and GPx. However, in situ knockdown of DJ­1 attenuated the IPC­induced delayed cardioprotection, and reversed the inhibitory effect of IPC on I/R­induced oxidative stress. The present study therefore provided novel evidence that DJ­1 is involved in the delayed cardioprotection of IPC against I/R injury in vivo. Notably, DJ­1 is required for IPC to inhibit I/R­induced oxidative stress.

Clinical characteristics of clonal evolution after immunosuppressive therapy in children with severe/very severe aplastic anemia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To evaluate the clinical characteristics and risk factors of clonal evolution after immunosuppressive therapy (IST) in children with severe/very severe aplastic anemia (SAA/VSAA).</p><p><b>METHODS</b>The clinical data of 231 children with newly-diagnosed SAA/VSAA who received IST were retrospectively studied. The incidence and risk factors of clonal evolution after IST were analyzed.</p><p><b>RESULTS</b>The 5-year overall survival rate of the 231 patients was 82.7%. Except for 18 cases of early deaths, 213 patients were evaluated for IST efficacy. Among the 231 patients, cytogenetic abnormalities for at least two chromosome metaphase were detectable in 14 (7.4%) patients, and PNH clones were detectable in either peripheral red blood cells or neutrophils for 95 patients. Among the 213 patients evaluated for IST efficacy, 15 patients experienced clonal evolution after IST. Five patients had PNH and trisomy 8 which were defined as favorable progressions, and ten patients experienced monosomy 7 and MDS/AML as unfavorable progressions. The 5-year accumulative incidence of favorable and unfavorable progression were (2.2±2.2)% and (4.8±3.3)%, respectively. Until the last follow-up, 100% (5/5) of patients with favorable progressions and 50% (5/10) of patients with unfavorable progressions survived. WBC>3.5×10/L, CD3T cell percentage>80%, dosage of antithymocyte globulin >3.0 mg/(kg·d) and no response to IST were related to unfavorable progressions by univariate analysis. Cox multivariate analysis revealed that an increased CD3T cell percentage (>80%) and no response to IST were independent risk factors for unfavorable progressions.</p><p><b>CONCLUSIONS</b>The children with SAA/VSAA who have an increased CD3T cell percentage at diagnosis or have no response to IST are in high risks of unfavorable progressions.</p>

Diagnostic Value of Serum GP73 Combined with Dickkopf-1 and AFP in Hepatocellular Carcinoma / 现代生物医学进展

Objective:To investigate the diagnostic value of serum GP73 combined with Dickkopf-1 and AFP in hepatocellular carcinoma.Methods:117 cases of hepatocellular carcinoma in our hospital were collected as hepatocellular carcinoma group,80 patients with hepatitis B virus as the hepatitis group,and randomly selected 80 healthy subjects as the control group from September 2014 to September 2016.The serums GP73,Dickkopf-1,AFP level of every group were detected by the enzyme-linked immunosorbent assay (ELISA),and the relationship between the GP73,Dickkopf-1,AFP between clinicopathological features were analyzed,the diagnostic value of GP73,Dickkopf-1 and AFP in hepatocellular carcinoma were analyzed.Results:The serums GP73,Dickkopf-1,AFP level of hepatocellular carcinoma group were higher than those of hepatitis group,control group,and the serum AFP level of hepatitis group was higher than that of control group,the difference was statistically significant (P＜0.05).The GP73,Dickkopf-1,AFP in patients with classification B～C were higher than those in classification A among the Child Pugh classification,the difference was statistically significant (P＜0.05).No statistical significance on difference of GP73,Dickkopf-1,AFP between different differentiation,tumor size,number of tumors was found (P＞0.05).The sensitivity,specificity,positice predictive value,negative predictive value,and accuracy of GP73+Dickkopf-1+AFP in the diagnosis of hepatocellular carcinoma were higher than those of GP73,Dickkopf-1,AFP respectively,the difference was statistically significant (P＜0.05).Conclusion:Serums GP73,Dickkopf-1,AFP in patients with hepatocellular carcinoma have high expression levels,combined with the three indicators can obviously improve the diagnostic value of hepatocellular carcinoma,which has clinically important reference value.

Sasanquasaponin promotes cellular chloride efflux and elicits cardioprotection via the PKCε pathway.

Sasanquasaponin (SQS) is an active component of Camellia oleifera Abel. A recent study by our group demonstrated that SQS was able to inhibit ischemia/reperfusion­induced elevation of the intracellular chloride ion concentration ([Cl­]i) and exerted cardioprotective effects; however, the underlying intracellular signal transduction mechanisms have yet to be elucidated. As protein kinase C ε (PKCε) is able to mediate Cl­ homeostasis, the present study investigated its possible involvement in the effects of SQS on cardiomyocytes subjected to ischemia/reperfusion injury. Cardiomyocytes were pre­treated with or without SQS or SQS plus εV1­2, a selective PKCε inhibitor, followed by simulated ischemia/reperfusion (sI/R). The effects on cell viability, PKCε phosphorylation levels, [Cl­]i, mitochondrial membrane potential and reactive oxygen species (ROS) production were assessed using an MTS assay, western blot analysis, colorimetric assays and flow cytometry. The results revealed that treatment with SQS prior to sI/R increased the viability of cardiomyocytes, and efficiently attenuated lactate dehydrogenase and creatine phosphokinase release induced by sI/R. In addition, SQS promoted PKCε phosphorylation and inhibited sI/R­induced elevation of [Cl­]i, paralleled by the attenuation of mitochondrial membrane potential loss and ROS generation. However, when the cardiomyocytes were treated with εV1­2 prior to SQS pre­conditioning, the cardioprotection induced by SQS was reduced and the inhibitory effects of SQS on sI/R­induced elevation of [Cl­]i, production of ROS and loss of mitochondrial membrane potential were also attenuated. These findings indicated that SQS may inhibit sI/R­induced elevation of [Cl­]i through the PKCε signaling pathway to elicit cardioprotection in cultured cardiomyocytes.

DJ-1 upregulates anti-oxidant enzymes and attenuates hypoxia/re-oxygenation-induced oxidative stress by activation of the nuclear factor erythroid 2-like 2 signaling pathway.

DJ-1 protein, as a multifunctional intracellular protein, has an important role in transcriptional regulation and anti-oxidant stress. A recent study by our group showed that DJ-1 can regulate the expression of certain anti­oxidant enzymes and attenuate hypoxia/re­oxygenation (H/R)­induced oxidative stress in the cardiomyocyte cell line H9c2; however, the detailed molecular mechanisms have remained to be elucidated. Nuclear factor erythroid 2­like 2 (Nrf2) is an essential transcription factor that regulates the expression of several anti­oxidant genes via binding to the anti­oxidant response element (ARE). The present study investigated whether activation of the Nrf2 pathway is responsible for the induction of anti­oxidative enzymes by DJ­1 and contributes to the protective functions of DJ­1 against H/R­induced oxidative stress in H9c2 cells. The results demonstrated that DJ­1­overexpressing H9c2 cells exhibited anti­oxidant enzymes, including manganese superoxide dismutase, catalase and glutathione peroxidase, to a greater extent and were more resistant to H/R­induced oxidative stress compared with native cells, whereas DJ­1 knockdown suppressed the induction of these enzymes and further augmented the oxidative stress injury. Determination of the importance of Nrf2 in DJ­1­mediated anti­oxidant enzymes induction and cytoprotection against oxidative stress induced by H/R showed that overexpression of DJ­1 promoted the dissociation of Nrf2 from its cytoplasmic inhibitor Keap1, resulting in enhanced levels of nuclear translocation, ARE­binding and transcriptional activity of Nrf2. Of note, Nrf2 knockdown abolished the DJ­1­mediated induction of anti­oxidant enzymes and cytoprotection against oxidative stress induced by H/R. In conclusion, these findings indicated that activation of the Nrf2 pathway is a critical mechanism by which DJ-1 upregulates anti-oxidative enzymes and attenuates H/R-induced oxidative stress in H9c2 cells.

DJ-1 Mediates the Delayed Cardioprotection of Hypoxic Preconditioning Through Activation of Nrf2 and Subsequent Upregulation of Antioxidative Enzymes.

We have recently shown that DJ-1 is implicated in the delayed cardioprotective effect of hypoxic preconditioning (HPC) against hypoxia/reoxygenation (H/R) injury as an endogenous protective protein. This study aims to further investigate the underlying mechanism by which DJ-1 mediates the delayed cardioprotection of HPC against H/R-induced oxidative stress. Using a well-characterized cellular model of HPC from rat heart-derived H9c2 cells, we found that HPC promoted nuclear factor erythroid 2-related factor 2 (Nrf2) and its cytoplasmic inhibitor Kelch-like ECH-associated protein-1 (Keap1) dissociation and resulted in increased nuclear translocation, antioxidant response element-binding, and transcriptional activity of Nrf2 24 hours after HPC, with subsequent upregulation of manganese superoxide dismutase (MnSOD) and heme oxygenase-1 (HO-1), which provided delayed protection against H/R-induced oxidative stress in normal H9c2 cells. However, the aforementioned effects of HPC were abolished in DJ-1-knockdown H9c2 cells, which were restored by restoration of DJ-1 expression. Importantly, we showed that inhibition of the Nrf2 pathway in H9c2 cells mimicked the effects of DJ-1 knockdown and abolished HPC-derived induction of antioxidative enzymes (MnSOD and HO-1) and the delayed cardioprotection. In addition, inhibition of Nrf2 also reversed the effects of restored DJ-1 expression on induction of antioxidative enzymes and delayed cardioprotection by HPC in DJ-1-knockdown H9c2 cells. Taken together, this work revealed that activation of Nrf2 pathway and subsequent upregulation of antioxidative enzymes could be a critical mechanism by which DJ-1 mediates the delayed cardioprotection of HPC against H/R-induced oxidative stress in H9c2 cells.