ObjectiveTo reveal the molecular mechanism by which the traditional Chinese medicine compound prescription Qiangjing tablets regulate the aging of the testicular tissue and Leydig cells in rats through the cyclin-dependent kinase 4 （CDK4）-early 2 factor （E2F） signaling pathway. MethodsFor the cell experiment， 2-month-old SPF-grade SD male rats were selected and randomly assigned into a blank control group （administrated with an equal volume of 0.9% sodium chloride injection） and a Qiangjing tablets group （20 rats in each group） according to body weight. The Leydig cell model of aging was established by treatment of TM3 cells with 100 μmol·L^-1 H₂O₂， and the modeling performance was evaluated based on the levels of p16 and p21 determined by Western blot. The antioxidant NAC （1 mmol·L^-1） was used as the positive control for eliminating reactive oxygen species （ROS）. Cells were intervened with Qiangjing tablets-containing serum at low （2.5%）， medium （5%）， and high （10%） concentrations. The testosterone level in the cell supernatant was determined by enzyme-linked immunosorbent assay （ELISA）， and the protein levels of CDK4， E2F1， and E2F2 were analyzed by Western blot. In the animal experiment， 19-month-old naturally aging rats were used as the model group， and 2-month-old rats as the young control group. The positive control group was subcutaneously injected with 5.21 mg·kg^-1·d^-1 testosterone propionate. Qiangjing tablets were administered by gavage at low， medium， and high doses of 0.72， 1.44， 2.88 g·kg^-1·d^-1， respectively. The general conditions of rats were observed， and the protein levels of CDK4， E2F1， and E2F2 in the testicular tissue were determined by Western blot. ResultsIn the cell experiment， compared with the blank control group， the model group showed upregulated expression of CDK4 and E2F1 （P<0.05） and slightly downregulated expression of E2F2. Compared with that in the model group， the expression of CDK4 was upregulated in the NAC group and the low-dose Qiangjing tablets group （P<0.05）， slightly upregulated in the medium-dose Qiangjing tablets group， and downregulated in the high-dose Qiangjing tablets group （P<0.05）. The NAC group showed downregulated expression of E2F1 （P<0.05） and E2F2， and the low-， medium-， and high-dose Qiangjing tablets groups showed downregulated expression of both E2F1 and E2F2 （P<0.05）. Compared with that in the NAC group， the expression of CDK4 was upregulated in the low-dose Qiangjing tablets group and downregulated in the medium-dose and high dose （P<0.05） groups. The expression of E2F1 was down-regulated in all the three dose groups， with statistically significance in the high dose group （P<0.05）， and that of E2F2 were downregulated in all the three dose groups （P<0.05）. In the animal experiment， compared with the young control group， the model group exhibited downregulated expression of CDK4 （P<0.05） and slightly upregulated expression of E2F1 and E2F2. Compared with that in the model group， the expression of CDK4 decreased in the testosterone propionate group and the low-dose Qiangjing tablets group （P<0.05） but increased in the medium-dose （P<0.05） and high-dose groups. In addition， the expression of E2F1 decreased （P<0.05）， and that of E2F2 was slightly elevated. Compared with that in the NAC group， CDK4 expression was elevated in the Qiangjing tablets groups， with statistical significance in the medium- and high-dose groups （P<0.05）. Similarly， the E2F1 expression was also upregulated in the Qiangjing tablets groups， with statistical significance in the medium-dose group （P<0.05）. The expression of E2F2 was downregulated in all the Qiangjing tablets groups. ConclusionQiangjing tablets delay the aging process of Leydig cells and testicular tissue by up-regulating the expression of CDK4 and lowering the levels of E2F1 and E2F2.

ObjectiveBased on the multidimensional correlation analysis framework of "disease， syndrome， formula， and medicine"， this study aims to systematically elucidate the regulatory effects of effective components in Qiangjing tablet on testosterone synthesis pathways in testicular Leydig cells under oxidative stress， providing a theoretical basis for the treatment of male infertility with traditional Chinese medicine and modern research on compounds. MethodsDisease targets for male infertility were obtained from The Human Gene Database （GeneCards， score ≥20）， the Comparative Toxicogenomics Database （CTD， score ≥150）， DrugBank （score ≥0.2）， and DisGeNET （score ≥0.2）. Targets related to the syndrome of kidney deficiency and blood stasis were acquired from the traditional Chinese medicine syndrome association database SymMap. Components of Qiangjing tablet were retrieved based on The Encyclopedia of Traditional Chinese Medicine （ETCM） database and the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP）， and they were screened according to a quantitative estimate of drug-likeness （QED ≥ 0.49） and a target confidence index>0.8. Intersecting targets were taken to construct a protein-protein interaction （PPI） network using the STRING database. The network was visualized with Cytoscape software and subjected to the functional annotation of gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment analysis. Quality markers （Q-markers） were predicted via the ADMETlab 2.0 platform based on Lipinski's rule， Pfizer's rule， GSK's rule， and the Golden Triangle. For experimental validation， rats' testicular Leydig cells were used. Exosomes were extracted and loaded with active components via the ultrasonic method. Exosome concentration was determined using a BCA protein quantification kit. Morphology was observed using a transmission electron microscope. The particle size was analyzed with a particle size analyzer. The surface marker proteins such as cluster of differentiation 9 （CD9）， cluster of differentiation 63 （CD63）， and cluster of differentiation 81 （CD81） were identified by Western blot， and drug loading capacity was measured by high-performance liquid chromatography （HPLC）. An oxidative stress model was induced by alpha， alpha'-azodiisobutyramidine dihydrochloride （AAPH）， and Leydig cells were divided into the following groups： A control group， an AAPH group， a quercetin group （Que group）， an exosome group （Exo group）， and a QUE-loaded Exo group （Que-Exo group）. The cell viability was detected using the 3-（4，5-dimethylthiazol-2-yl）-2，5-diphenyltetrazolium bromide （MTT） thiazolyl blue assay. The reactive oxygen species （ROS） levels and mitochondrial membrane potential were measured by flow cytometry. The levels of oxidative indicators， including malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， catalase （CAT）， and testosterone （T）， were detected by enzyme-linked immunosorbent assay （ELISA）. The expressions of steroidogenic enzymes such as cytochrome p450 family 11 subfamily a member 1 （CYP11A1）， hydroxy-delta-5-steroid dehydrogenase， 3 beta- and steroid delta-isomerase 1 （HSD3B1）， and hydroxysteroid 17-beta dehydrogenase 3 （HSD17B3）， regulatory factors such as steroidogenic factor 1 （SF-1） and steroidogenic acute regulatory protein （StAR）， and miR-145-5p content， were detected by Western blot and real-time polymerse chain reaction （Real-time PCR）. ResultsNetwork pharmacology analysis reveals that the main active components of Qiangjing tablet for intervening in male infertility with kidney deficiency and blood stasis syndrome were Que， luteolin， etc.， with the core mechanism involving pathways such as steroid hormone biosynthesis. Experimental results show that compared with the control group， the AAPH group exhibits significantly reduced cell viability （P<0.01）， decreased mitochondrial membrane potential （P<0.01）， significantly elevated levels of ROS， MDA， and miR-145-5p （P<0.01）， significantly reduced activities of SOD， GSH-Px， and CAT， as well as reduced testosterone content （P<0.01）， and significantly downregulated protein and mRNA expressions of steroidogenic enzymes， SF-1， and StAR （P<0.01）. The above indicators were reversed in the Que and Que-Exo groups （P<0.05）. Compared with the Que group， the Que-Exo group showed more significant effects in enhancing cell viability， mitochondrial membrane potential， testosterone level， antioxidant enzyme activities， and expressions of key molecules in the steroidogenic pathway （P<0.05）. ConclusionThis study demonstrates that Que， an active component of Qiangjing tablet， inhibits oxidative stress reaction， improves mitochondrial function in Leydig cells， upregulates steroidogenic enzyme expression， and restores testosterone production. As a carrier for Que， Exo enhance its stability， delivery efficiency， and biological effect. Additionally， miR-145-5p may be closely associated with testosterone synthesis， though its precise molecular mechanism requires further exploration. By integrating traditional Chinese medicine compounds with modern scientific technology， this research expands the paths for the modernized research of traditional Chinese medicine and opens a novel therapeutic direction with translational potential for clinical intervention of male infertility.

Objective To assess and compare the incidence,clinical characteristics,treatment,and prognosis of acute heart failure patients from different grades hospitals in Beijing.Methods In this prospective internet prognosis registered study (Beijing AHF Registry),a total of 3 335 consecutive patients admitted to 14 emergency departments in Beijing from January 1st 2011 to September 23rd 2012 were enrolled.According to hospital grade,these patients were divided into two groups,349 patients were from secondary hospitals,and 2 956 patients were from tertiary hospitals.Results Among the 3 335 patients,the medium age was 71 (58,79) years,and male accounted for 53.16％.The most common underlying disease were coronary disease (43.27％),hypertension (17.73％),cardiomyopathy (16.07％) etc.The average treatment time in Emergency Department was 66.82 h.The emergency department mortality rate was 3.81％ (127 cases).The 30-day and 1-year cumulative all-cause mortality were 15.3％ and 32.27％,respectively.The 30-day and 1-year cumulative all-cause readmission were 15.64％ and 46.89％,respectively.Compared with patients in tertiary hospitals,patients in secondary hospitals had more onset acute heart failure patients (63.64％ vs.49.93％),shorter emergency department treatment time (12 h vs.41 h),lower discharge rate (3.43％ vs.37.45％) and emergency department mortality(1.58％ vs.4.09％).Compared with those in tertiary hospitals,1-year cumulative all-cause mortality (25.6％ vs.33.2％),cardiovascular disease mortality (20.2％ vs.26.0％),aggravated heart failure mortality (22.4％ vs.28.8％) were lower in secondary hospitals.Following propensity score matching,compared to tertiary hospitals,patients in secondary hospitals showed lower utilization rate of beta-blockers and ACEFARB (4.51％ vs.28.17％,1.41％ vs.9.58％),except the pironolactone.Conclusion Acute heart failure in emergency department is associated with a high mortality rate and readmission rate.There is still a big gap between guidelines recommend medication current treatments for acute heart failure.

advocates painless acupuncture,arrival to strength the body and eliminate pathogenic factors,as well as enhancing the immune function. Also,he stresses the application of both the Chinese and western medicine theories. The academic thought and clinical experience of professorregulating the immune function are explored through three aspects,namely the application of 12-source points and loweracupoints,implementing moxibustion at health care points,the usage of acupoints related to immune organs.

OBJECTIVETo explore the effects of hydrogen-rich saline (HS) on liver of severely scalded rats with delayed resuscitation.

METHODSTwenty-four SD rats were inflicted with 40% TBSA full-thickness scald using a temperature-controlled scalding apparatus. The injured rats were divided into lactated Ringer's solution (RS) and HS groups according to the random number table, with 12 rats in each group. Rats in groups RS and HS were respectively resuscitated with an intraperitoneal injection of 4 mL × kg⁻¹ × %TBSA⁻¹ of RS or HS (self-prepared, with concentration of hydrogen 0.6 mmol/L) 6 hours after injury up to 48 hours after scald. The infusion volume of the second 24 hours after injury was a half of that of the first 24 hours. At post scald hour (PSH) 6 (before resuscitation), 12, 24, and 48, blood was collected from the heart of 3 rats in each group, and then the rats were sacrificed for harvesting liver tissue. The pathological change in liver tissue was observed with HE staining. The number of hepatic neutrophils was counted with a hematocytometer. Serum levels of AST and ALT were determined with full-automatic biochemical analyzer. Contents of TNF-α, IL-1β, IL-6, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in liver tissue were determined with ELISA. Absorbance value of malondialdehyde (MDA) in liver tissue was detected and quantified with spectrophotometer. Data were processed with analysis of variance of repeated measurement and LSD-t test.

RESULTSAt PSH 48, moderate infiltration of inflammatory cells and hepatic hyperemia were observed in rats of group HS as compared with group RS. At PSH 12, 24, and 48, the number of neutrophils in group HS was respectively (25.3 ± 1.8) × 10⁵, (19.6 ± 0.6) × 10⁵, and (14.1 ± 3.2) × 10⁵ cells per mililitre, and they were significantly lower than those in group RS \[(31.9 ± 2.0) × 10⁵, (30.9 ± 2.2) × 10⁵, and (23.8 ± 3.0) × 10⁵ cells per mililitre, with t values respectively 5.6, 7.6, and 8.7, P values below 0.05\]. At PSH 6 and 12, the serum levels of AST and ALT and the levels of TNF-α, IL-1β, and IL-6 in liver tissue were close between the two groups (with t values respectively 0.3-3.9 and 0.9-3.8, P values above 0.05). At PSH 24 and 48, the serum levels of AST and ALT in group HS were respectively (308 ± 24) and (210 ± 15) U/L and (93 ± 7) and (70 ± 5) U/L, which were significantly lower than those in group RS \[(541 ± 39) and (505 ± 18) U/L, with t values respectively 17.5 and 16.7, P values below 0.05; (156 ± 9) and (166 ± 21) U/L, with t values respectively 30.3 and 6.9, P values below 0.05\]. At PSH 24 and 48, the levels of TNF-α, IL-1β, and IL-6 in liver tissue in group HS were respectively (20.7 ± 1.6) and (13.7 ± 1.5) pg/mg, (7.7 ± 1.5) and (6.3 ± 1.2) pg/mg, and (8.7 ± 1.2) and (6.0 ± 2.0) pg/mg, which were significantly lower than those in group RS \[(32.7 ± 5.0) and (25.7 ± 4.0) pg/mg, with t values respectively 5.2 and 5.7, P values below 0.05; (16.3 ± 2.5) and (12.0 ± 2.7) pg/mg, with t values both as 4.7, P values below 0.05; (14.7 ± 2.1) and (13.3 ± 1.5) pg/mg, with t values respectively 10.4 and 4.4, P values below 0.05\]. The level of MDA at PSH 6 and levels of 8-OHdG at PSH 6 and 12 in liver tissue were close between the two groups (with t values respectively 0.1, 0.7, and 4.3, P values above 0.05). In group HS, the levels of MDA in liver tissue at PSH 12, 24, and 48 were respectively (15.3 ± 1.5), (8.7 ± 1.2), and (6.7 ± 1.5) mmol/mg, and the levels of hepatic 8-OHdG at PSH 24 and 48 were respectively (124 ± 12) and (79 ± 10) pg/mg, which were significantly lower than those in group RS \[(27.3 ± 4.7), (20.3 ± 1.5), and (14.0 ± 1.0) mmol/mg, with t values respectively 5.2, 5.7, and 5.1, P values below 0.05; (191 ± 10) and (136 ± 15) pg/mg, with t values respectively 8.0 and 8.1, P values below 0.05\].

CONCLUSIONSResuscitation with HS could protect liver of severely scalded rats with delayed resuscitation possibly by reducing infiltration of neutrophils, thus lowering the content of inflammatory cytokines, and effectively alleviating oxidative stress.

Animals ; Burns ; metabolism ; physiopathology ; Deoxyguanosine ; analogs & derivatives ; blood ; Hydrogen ; pharmacology ; Interleukin-6 ; Liver ; drug effects ; metabolism ; physiopathology ; Male ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Resuscitation ; Sodium Chloride ; pharmacology ; Soft Tissue Injuries ; Time Factors ; Tumor Necrosis Factor-alpha ; blood

Objective To investigate the inhibitory effects of trichostatin A(TSA)on bladder cancer cell lines and its synergetic effect with anticancer drugs in treating bladder cancer in vitro and in vivo.Methods The inhibitory effects of TSA on human bladder cancer cell lines in vitro were detected by MTT assay.Hoechst staining was used to observe morphology for apoptotic cells after TSA treatment.Western blot was used to detect expression of acetyl-histone H3 and survivin.In vivo synergetic effects of TSA with anticancer drugs were detected in bladder cancer model rats.Results TSA significantly inhibited growth of bladder cancer cell lines in concentration and time dependent manner.Better results of tumor inhibition have been achieved when it was combined with DDP,MMC and ADM than used alone.After TSA treatment,the survivin expression in bladder cancer cells decreased and acetyl-histone H3 expression increased.Intravesical application of TSA combined with MMC can significantly inhibited tumor growth and progression.Conclusion TSA has direct anti-cancer effect and can enhance the action of several chemotherapy agents markedly.TSA may be an excellent candidate agent for intravesical application to treat bladder cancer.

Objective To explore the value of ~(18)F 2-deoxy-2-fluoro-d-glucose(~(18)F-FDG)positron e-mission tomography (PET)/computed tomographic (CT) imaging and CT perfusion in evaluating metabolic and blood flow characteristics in breast cancer.Methods 32 women with untreated breast masses were both ex-amined with ~(18)F-FDG PET/CT and CT perfusion at the same day.All the lesions were confirmed histopothologi-cally by surgery or biopsy.The PET/CT images were analyzed semi-quantitatively.CT perfusion images were analyzed using the GE perfusion 3 soft package.The findings of two modalities above were commed with patho-logical diagnosis.Results There were significant differences between standardized uptake values (SUVs) of ~(18)F-FDG of benign tumors and breast cancer (Wilcoxon test:P=0.000 3,T=15.000,u=3.433,C=1).Differ-ences of SUVs between the center and periphery of breast Inasses were also significant.In addition.the SUVs were related to the pathological type and the grading of tumors.In the CT perfnsion,the differences of perfusion including bloodflow (BF),blood volume(BV)and permeability surface area product (PS) values between tumor and normal breast tissue were statistically significant(t=8.065,P<0.000 1;t=2.769 1,P=0.011 5;T~+=253.000 0,T~- =0.000 0,P<0.000 1)respectively.The differences of BF,BV and PS values between pe-ripheral zone and central portions of tumor were also statistically significant (t=8.015 8,P<0.000 1;t=2.243 4,P=O.017 9;t=3.485 7,P=0.002 2),respectively.Conclusion ~(18)F-FDG PET/CT imaging and CT peffusion reveal the metabolic and blood flow characteristics,and reflect biological behavior of breast tumor indirectly and have important value for the diagnosis and prognosis of breast cancer.

Objective To evaluate the significance of MRI before surgery to remove polyaeryl-amide hydrogel (PAMHG) which has been used for augmentation mammaplasty. MethodsTwenty female patients with 40 breasts, having been injected PAMHG as augmentation mammaplasty, under-went bilateral breast axial T1WI, T2WI-fat saturation (FS) and sagittal T2WI-FS by 4-channal phased-assay breast coil at 3.0T (Philips) before removal surgery, in which 8 patients underwent axial multiphase contrast-enhanced MRI with THRIVE after Gd-DTPA (2.0 ml/s, 0.1 mmol/kg) adminis- tration. The results of MRI were compared with that of operation and pathology. ResultsPAMHG showed iso-intensity compared with breast gland on T1WI and hyperintensity on T2WI-FS. Low signal septa were noted within PAMHG in 40 breasts (20 patients), 90% (36/40) PAMHG without capsule, 10 % (4/40) with smooth capsule which showing homogenous low signal on T1WI and T2WI-FS. Subcutaneous lump of PAMHG was 70 % (28/40), lump of that in breast gland was 20% (8/40). Diffuse gel along spatium intermusculare of pectoralis major was 100 % (40/40), that along spatium intermusculare of intercostal muscle was 10 % (4/40). All PAMHG in breast of the 8 patients showed no enhancement, an irregular enhanced mass was found in gland of 1 patient. All distributions of PAMHG and appearances of its complications on T2WI-FS were consistent with the results of operation. ConclusionsT2WI-FS can accurately display the distribution of PAMHG and its complication before removal surgery. MRI plane scan combined with muhiphase contrast-enhanced MRI can differentiate PAMHG from the lesions in the gland and find the breast carcinoma, so that it can guide clinicians before surgery to remove PAMHG used for augmentation mammaplasty.

目的观察分期综合疗法治疗颈椎间盘突出症的疗效。方法将100例颈椎间盘突出症住院患者随机分为治疗组(采用分期综合疗法)与对照组(采用传统综合疗法)各50例,评定两组患者的疗效。结果治疗组总有效率88%,对照组总有效率78%,两组间有显著性差异(P<0.05)。结论分期综合疗法治疗颈椎间盘突出症的疗效优于传统综合疗法。

OBJECTIVETo observe the effects of Chinese herbal composition Zengjing Granule (ZJG) on the quality of sperm in the epididymis of infertile rats, and to study its therapeutic mechanisms of improving sperm quality.

METHODSA total of 40 GTW infertile rats were divided into 4 groups of 10 rats each, including an infertility group[GTW 2 mg/(ml.100 g)], a high-dosage group[ZJG 0.67 g/(ml.100 g) + GTW 2 mg/(ml.100 g)], a medium-dosage group[ZJG 0.33 g/(ml.100 g) + GTW 2 mg/(ml.100 g)], a low-dosage group[ZJG 0.17 g/(ml.100 g) + GTW 2 mg/(ml.100 g)], and a normal control group(1% CMC). This study consisted of a 3-week modeling period and a 3-week ZJG period. The changes of sperm quality, the thickness of the epididymal gland canal wall and sexual organ coefficient were detected after 3-week ZJG period.

RESULTSOf the 3 ZJG groups, the sperm density was (59.6 +/- 3.72), (63.3 +/- 5.70) and (69.7 +/- 6.91) x 10(6)/ml, the sperm motility rates were (65.4 +/- 6.33)%, (69.3 +/- 10.96)% and (72.6 +/- 9.61)%, the sperm deformity rates were (52.3 +/- 7.47)%, (46.2 +/- 7.73)% and (33.2 +/- 7.97)% respectively. The ZJG groups showed significant difference from the infertility group (P < 0.05), whose sperm density, motility and deformity were (13.1 +/- 6.81) x 10(6)/ml, (7.6 +/- 5.87)%, and (77.2 +/- 8.75)% respectively. But there was no significant difference between ZJG groups and the normal control group (P > 0.05), whose sperm density, motility and deformity were (75.6 +/- 10.82) x 10(6)/ml, (83.00 +/- 8.02)%, and (8.80 +/- 3.49)% respectively. The thickness of the epididymal gland canal wall was (37.07 +/- 3.38), (37.16 +/- 6.69) and (43.42 +/- 10.23) nm in the three ZJG groups respectively, different from the infertility group[(28.65 +/- 6.96) nm] (P < 0.05) significantly, but not from the normal control group [(45.79 +/- 11.13) nm] (P > 0.05). The ZJG groups showed an increase in the organ coefficient of the epididymal gland canal wall. And these was obvious statistical difference compared with the infertility group (P < 0.05), but no statistical significance compared with the normal control group (P > 0.05).

CONCLUSIONSZJG can obviously improve the sperm quality of infertile rats. Its therapeutic mechanisms can be summed up as follows: restoring the thickness of epididymal gland wall, increasing the organ coefficient of testes and epididymis, and hence improving the spermatozoa maturing function of epididymis of infertile rats.

Animals ; Dose-Response Relationship, Drug ; Epididymis ; drug effects ; pathology ; Male ; Medicine, Chinese Traditional ; Rats ; Rats, Sprague-Dawley ; Spermatozoa ; drug effects