Apoptosis of small cell lung cancer cells H1688 and H446 induced by nitidine chloride through PI3K/Akt/Bcl-2/caspase-3/PARP pathway / 中国药理学通报

Aim To explore the apoptosis of small eell lung eancer ( SCLC ) eells HI688 and H446 induced by nitidine chloride and its possible mechanism.Methods The effect of nitidine chloride or cisplatin ( DDP ) on the activity of SCLC cells was detected by j J MTT method; the morphological changes of cells trea¬ted with nitidine chloride or DDP were observed by in- verted fluorescence microscope and HE staining; the effect of nitidine chloride or DDP on apoptosis was de¬tected by flow cytometry; the effect of apoptosis inhibi¬tor Z-VAD-FMK on apoptosis induced by nitidine chlo¬ride or DDP was detected by MTT method.The expres¬sions of Bax , Bcl-2, caspase-3 , PARP, p-PI3K and p- Akt in the cells treated with nitidine chloride or DDP were detected by Western blot.Results MTT results showed that the viability of SCLC cells was significantly reduced after 48 hours of treatment with nitidine chlo¬ ride; compared with DDP, nitidine chloride could in¬hibit SCLC cells with less IC50; inverted fluorescence microscope and HE staining showed that nitidine chlo¬ride could induce apoptosis in SCLC cells, similar to DDP; flow cytometry showed that nitidine chloride J J could induce apoptosis in SCLC cells.The results of MTT assay showed that the inhibitory effect of nitidine chloride on apoptosis of SCLC cells could be partially antagonized by apoptosis inhibitor Z-VAD-FMK.West¬ern blot results showed that, similar to DDP, nitidine chloride could inhibit the expression of PI3K and Akt, increase Bax, inhibit Be 1-2, and promote the cleavage of caspase-3 and PAH P.Conclusion Nitidine chlo¬ride can induce apoptosis of SCLC cells by inhibiting the activation of P13K and Akt.

Research progresses on correlation between connexin subcellular distribution and tumorigenesis and development / 中国药理学通报

Connexin (Cx), a multigene-encoded transmembrane protein family, forms either gap junctions ( GJ) or hemichannels (HC) to mediate intercellular communication in plasma mem¬brane between adjacent cells or interacts with proteins by its car- boxyl terminal in the cytoplasm to participate in the process of tumor cell proliferation, apoptosis, necrosis, invasion, metasta¬sis, drug resistance and stem cell characteristics.However, mi- slocalization of Cx in cytoplasm or nucleus often occurs in many tumors, and involved in the occurrence and development of tumors.Subcellular localization of Cx is affected by post-transla- tional modifications, including phosphorylation, ubiquitination, and acetylation.In this paper the classification and function of Cx, the relationship between subcellular localization of Cx and tumorigenesis and the regulation of post-translational modifica¬tion on Cx are reviewed in order to provide new ideas for the study of Cx as a potential target for cancer therapy.

Clinical and socioeconomic factors associated with delayed orchidopexy in cryptorchid boys in China: a retrospective study of 2423 cases / 亚洲男科学杂志(英文版)

We investigated the associations of clinical and socioeconomic factors with delayed orchidopexy for cryptorchidism in China. A retrospective study was conducted on cryptorchid boys who underwent orchidopexy at Children's Hospital at Chongqing Medical University in China from January 2012 to December 2017. Of 2423 patients, 410 (16.9%) received timely repair by 18 months of age, beyond which surgery was considered delayed. Univariate analysis suggested that the laterality of cryptorchidism (P = 0.001), comorbidities including inguinal hernia/scrotal hydrocele (P < 0.001) or urinary tract disease (P = 0.016), and whether patients lived in a poverty county (P < 0.001) could influence whether orchidopexy was timely or delayed. Logistic regression analysis suggested that the following factors were associated with delayed repair: unilateral rather than bilateral cryptorchidism (odds ratio [OR] = 1.752, P < 0.001), absence of inguinal hernia or hydrocele (OR = 2.027, P = 0.019), absence of urinary tract disease (OR = 3.712, P < 0.001), and living in a poverty county (OR = 2.005, P < 0.001). The duration of postoperative hospital stay and hospital costs increased with the patient's age at the time of surgery.

DEHP exposure destroys blood-testis barrier (BTB) integrity of immature testes through excessive ROS-mediated autophagy.

Di-(2-ethylhexyl) phthalate (DEHP), is known to impair testicular functions and reproduction. However, its effects on immature testis Blood-testis barrier (BTB) and the underlying mechanisms remain obscure. We constructed a rat model to investigate the roles of autophagy in BTB toxicity induced by DEHP. Sprague-Dawley rats were developmentally exposed to 0, 250 and 500 mg/kg DEHP via intragastric administration from postnatal day (PND) 1 to PND 35. Testicular morphology, expressions of BTB junction proteins and autophagy related proteins were detected. In addition, expressions of oxidative stress markers were also analyzed. Our results demonstrated that developmental DEHP exposure induced decreasing organ coefficients of immature testes and severe testicular damage in histomorphology. The expressions of junctional proteins were down-regulated significantly after DEHP treatment. Intriguingly, DEHP simultaneously increased the number of autophagosomes and the levels of autophagy marker LC3-II and p62, suggesting that the accumulated autophagosomes resulted from impaired autophagy degradation. Moreover, the expressions of HO-1 and SOD levels remarkably decreased after DEHP exposure. Vitamins E and C could alleviate the DEHP-induced oxidative stress, reverse the autophagy defect and restore the BTB impairment. Taken together, DEHP exposure destroys immature testis blood-testis barrier (BTB) integrity through excessive ROS-mediated autophagy.

Circulating tumor cell levels and carcinoembryonic antigen: An improved diagnostic method for lung adenocarcinoma.

BACKGROUND: The aim of this study was to determine a correlation between benign and malignant lung solitary pulmonary nodules (SPN), and analyze the association between circulating tumor cell (CTC) levels and different subtypes of lung adenocarcinoma. METHODS: A total of 200 patients (80 with SPNs and 120 diagnosed with lung cancer) were included in the study. The CTC levels were quantified by identifying the folate receptor on the surface of tumor cells; clinical tumor specific markers were detected by biochemical immunization. The content of peripheral blood CTCs in benign and malignant lung SPN patients was detected and the differences in preoperative CTC levels in different pathological subtypes were analyzed. Based on the collected data, receiver operating characteristic curves were calculated and the rate of lung cancer was predicted. RESULTS: The peripheral blood CTC levels in patients with malignant lung SPNs were higher than in patients with benign SPNs. The maximum nodule diameter, carcinoembryonic antigen, and CTC levels were independent risk factors for malignant lung SPNs. The peripheral blood CTC levels in patients with stage III-IV lung adenocarcinoma were higher than in stage I-II patients. The peripheral blood CTC levels in patients with microinvasive and invasive adenocarcinoma were higher than in adenocarcinoma in situ patients. The CTC levels in the peripheral blood of patients with maximum tumor diameter > 2 cm were higher than in patients with tumors < 2 cm. CONCLUSION: The detection of CTCs can be used as a biomarker for screening SPNs and diagnosing early-stage lung cancer. Using the combination of CTC levels and CEA significantly improves the efficacy of lung adenocarcinoma diagnosis.

Management of undescended testis may be improved with educational updates and new transferring model.

BACKGROUND: To investigate whether management of undescended testis (UDT) may be improved with educational updates and new transferring model among referring providers (RPs). METHODS: The age of orchidopexies performed in Children's Hospital of Chongqing Medical University were reviewed. We then proposed educational updates and new transferring model among RPs. The age of orchidopexies performed after our intervention were collected. Data were represented graphically and statistical analysis Chi-square for trend were used. RESULTS: A total of 1543 orchidopexies were performed. The median age of orchidopexy did not matched the target age of 6-12 months in any subsequent year. Survey of the RPs showed that 48.85% of their recommended age was below 12 months. However, only 25.50% of them would directly make a surgical referral to pediatric surgery specifically at this point. After we proposed educational updates, tracking the age of orchidopexy revealed a statistically significant trend downward. CONCLUSIONS: The management of undescended testis may be improved with educational updates and new transferring model among primary healthcare practitioners.

Effect of Di-(2-ethylhcxyl) phthalate exposure on blood-testis barrier integrity in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate mechanism of di-(2-ethylhcxyl)phthalate (DEHP) exposure in causing blood-testis barrier (BTB) impairment in rats.</p><p><b>METHODS</b>Two-months-old male SD rats were randomly divided into corn oil control group and DEHP (750 mg/kg) exposure group for daily intragastic treatment for 30 consecutive days. After the treatments the rats were examined for histomorphological changes of the testicle using HE staining and the expressions of the junction proteins N-cadherin β-catenin, occludin and connexin43 of the BTB using Western blot. In the in vitro study, the vitality and ROS generation level in Sertoli cells exposed to different concentrations of DEHP were examined with MTT and ROS assay kits, respectively, and Nrf2 and p-p38 expressions were detected with Western blot.</p><p><b>RESULTS</b>Compared with the control group, the rats with DEHP exposure showed structural damage of the seminiferous tubule and polarity loss of the spermatids. DEHP exposure caused significantly decreased expressions of occludin and connexin43 but increased expressions of N-cadherin and β-catenin in the testicle tissues of the rats (P<0.05). The vitality of Sertoli cells was obviously decreased and ROS level increased significantly after exposure of the cells to increasing concentrations of DEHP, which also resulted in significantly up-regulated Nrf2 and p-p38 expressions (P<0.05).</p><p><b>CONCLUSIONS</b>DEHP exposure causes increased oxidative stress in the Sertoli cells of the testis, activates p38 MAPK signaling pathway, and results eventually in impaired spermatogenesis in rats.</p>

Long-term exposure to PM2.5 from automobile exhaust results in reproductive dysfunction in male rats / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore the effects of long-term exposure to particulate matter 2.5 (PM2.5) from automobile exhaust on the reproductive function of Sprague Dawley (SD) rats.</p><p><b>METHODS</b>Forty-five male SD rats, weighing 80 - 94 g and aged 28 days, were randomly assigned to receive intra-tracheal administration of 0.9% normal saline (control group, n = 15), PM2. 5 at 2 μg per 100 g body weight per day (low-dose PM2.5 group, n = 15), and PM2.5 at 16 μg per 100 g body weight per day (high-dose PM2.5 group, n = 15), qd, for 60 successive days. After the last 24-hour exposure, 10 rats were taken from each group for copulation with normal female ones, while the others were sacrificed, their testes removed for sperm count and deformity, pathological examination, and determination of the Connexin43 expression.</p><p><b>RESULTS</b>The conception rate was significantly decreased in the low- and high-dose PM2.5 groups as compared with that of the control (70% and 50% vs 100%), and so were the sperm count and quality. The rats in the PM2.5-exposed groups showed significantly disordered histological structure of the seminiferous tubules, reduced sperm count in the testicular lumen, some exfoliated secondary spermatocytes, downregulated Connexin43 expression in the testis, and damaged blood-testis barrier.</p><p><b>CONCLUSION</b>Long-term exposure to PM2.5 from automobile exhaust damages the reproductive function of male SD rats.</p>

Effect of propofol on apoptosis of PC12 cells under hypoxic condition and the mechanism / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the mechanism by which propofol exposure causes PC12 cell apoptosis under hypoxic conditions.</p><p><b>METHODS</b>PC12 cells were exposed to room air, 35% oxygen, or 5% oxygen (hypoxia) for 24 h in the presence of either 10 µmol/L lipid emulsion or 10 µmol/L propofol. After the treatments, the cell apoptosis was measured by flow ceytometry, and the level of reactive oxygen species (ROS) and the activity of superoxide dismutase (SOD) were evaluated.</p><p><b>RESULTS</b>In room air, PC12 cells treated with propofol showed increased apoptosis rate and ROS production as compared with the cells treated with the lipid emulsion; propofol treatment of the cells exposed to 35% oxygen showed obvious enhancement of the apoptosis rate, ROS production and SOD activity. Under the hypoxic condition, propofol treatment even further increased the apoptosis rate, ROS production and SOD activity. Lipid emulsion caused no such changes in cells exposed to room air, 35% oxygen or 5% oxygen.</p><p><b>CONCLUSION</b>Under hypoxic conditions, propofol can cause apoptosis in PC12 cells by inducing oxidative stress injury.</p>

6-Bromo-pyridine-2-carboxamide.

In the the title compound, C(6)H(5)BrN(2)O, an intra-molecular N-H⋯N hydrogen bond generates an S(5) ring. In the crystal structure, inter-molecular bifurcated N-H⋯(O,O) hydrogen bonds link the mol-ecules, leading to sheets propagating in (100).

Thoughts on the authorized operation with state-owned assets in public hospitals / 中华医院管理杂志

In view of the current conditions and reasons about the reform of medical and health system in China,the paper expounds the feasibility of authorized operation with state-owned assets of public hospital and the concrete operational pattern from the angle of hospital operational mechanism, which proposes a new idea about how to effectively solve the contradiction between the limited investment on state-owned health resources and the growing demands on medical health.

Computer simulation of the adsorption of thiophene in all-silica Y and Na-Y.

A grand canonical ensemble Monte Carlo simulation is performed to investigate the adsorption, heat of adsorption, and distributions of thiophene in all-silica Y and Na-Y zeolites. Biased particle insertions and deletions were implemented to allow the computation of equilibrium adsorption isotherms of such molecules. The calculated number of absorbed thiophene molecules in these zeolites is in good agreement with the experimental data. The calculated results show that the number absorbed of thiophene molecules in Na-Y is much greater than that in all-silica Y over the range of pressure. The calculated heat of adsorption is in good agreement with experimental results. The Na-Y zeolite, rather than all-silica Y, preferentially adsorbs the thiophene. A distribution analysis of the adsorbed phase structure reveals a different adsorption site in the zeolites.

Effect of diameter of adriamycin polybutylcyanoacrylate nanoparticles on liver targeting / 中南大学学报(医学版)

OBJECTIVE@#To observe the different tissue distributions of the adriamycin polybutylcyanoacrylate nanoparticle (ADM-PBCA-NP) in the mice body after the injection via lateral tail vein, and to study the liver targeting effects of ADM-PBCA-NP in different diameters on normal mice livers.@*METHODS@#One hundred and eighty mice were randomly divided into 6 groups with 30 mice in each group: non-conjugated free ADM (Group 1); (22.3+/-6.2) nm in diameter ADM-PBCA-NP group (Group 2); (48.6+/-9.2) nm ADM-PBCA-NP group (Group 3); (101.9+/-20.3) nm ADM-PBCA-NP group (Group 4); (143.5+/-23.5) nm ADM-PBCA-NP group (Group 5), and (194.2+/-28.4) nm ADM-PBCA-NP group (Group 6). A single dose of either conjugated or free adriamycin equaled 2 mg/kg of body weight was delivered via the tail vein. Five mice in each trail were sacrificed at 5, 15, 30 minutes, 1, 5 and 12 hours after the injection, respectively. The adriamycin concentrations in the collected livers, kidneys, spleens, hearts, lungs and plasma were demonstrated using a high performance liquid chromatography with fluorescence detector.@*RESULTS@#Compared with that of the control group, adriamycin was hardly detected in the heart muscles of the treatment groups (P<0.05). The nanoparticle-conjugated adriamycin was cleaned up quickly from the kidney tissues. The adriamycin concentrations of the mice liver and spleen in the experimental groups was significantly higher than those in the control group, except for the group with the nanoparticles diameters of (22.3+/-6.2) nm (P<0.05). The ADM-PBCA-NP in (101.9+/-20.3) nm diameter had the highest liver distribution, and the second highest adriamycin distribution in the liver was the group of (143.5+/-23.5) nm diameter (P<0.05). Adriamycin was released slowly in the liver during the detection period in the experimental groups. ADM-PBCA-NP in (22.3+/-6.2) nm diameter was not distributed in the tissues of the livers, kidneys, hearts, spleens, and lungs.@*CONCLUSION@#ADM-PBCA-NP with a 100 - 150 nm diameter range has the best liver targeting with slow medicine release. It also decreases the medicine distribution in the heart and other organs. In the treatment of liver cancer, the polybutylcyanoacrylate nanoparticle system has a good liver targeting ability, which increases the anticancer activity and markedly decreases the toxicity of adriamycin.

Liver targeting and the delayed drug release of the nanoparticles of adriamycin polybutylcyanoacrylate in mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Liver targeting drug delivery systems can improve the curative effects and relieve the cytotoxicity of the chemotherapy drugs in the treatment of liver diseases. Nanoparticles carrying therapeutic drugs are currently under hot investigation with great clinical significance. This study was aimed to investigate the different tissue distribution of the adriamycin polybutylcyanoacrylate nanoparticle (ADM-PBCA-NP) in the mice body after an injection via lateral tail vein, and to study the liver targeting effects of ADM-PBCA-NP in different diameters on normal mice liver.</p><p><b>METHODS</b>One hundred and eighty Kunming mice were randomly divided into 6 groups with 30 mice in each group (5 treatment groups of ADM-PBCA-NP in the different diameter ranges, non-conjugated free adriamycin injection was employed as the control group). A single dose of either conjugated or free adriamycin equaled 2 mg/kg of body weight was delivered via the tail vein. Five mice in each trail were sacrificed at 5, 15, 30 minutes, 1, 5 and 12 hours postinjection, respectively. The adriamycin concentrations in the respectively collected liver, kidney, spleen, heart, lung and plasma were demonstrated using a high performance liquid chromatography with fluorescence detector.</p><p><b>RESULTS</b>Compared with the control group, adriamycin was hardly detected in the heart muscle of the treatment groups (P < 0.05). The nanoparticle-conjugated adriamycin was cleaned up quickly from the kidney tissue. The adriamycin concentrations of the mice liver and spleen in the experimental groups were significantly higher than that in the control group, except for the group with the nanoparticles diameters of (22.3 +/- 6.2) nm (P < 0.05). The ADM-PBCA-NP in (101.0 +/- 20.3) nm diameter had the highest liver distribution, and the second highest adriamycin distribution in liver was the group of (143.0 +/- 23.5) nm diameter (P < 0.05). Moreover, adriamycin was released slowly in the liver during the detection period in the experimental groups. ADM-PBCA-NP in (22.3 +/- 6.2) nm diameter was not distributed in the tissue of the liver, kidney, heart, spleen, and lung.</p><p><b>CONCLUSIONS</b>ADM-PBCA-NP in 100 - 150 nm diameter range has the best liver targeting with a characteristic of slow medicine release. It also decreases the medicine distribution in the heart, kidney and lung. In the treatment of liver cancer, the polybutylcyanoacrylate nanoparticles system has a good liver targeting ability, which increases the anticancer activity and markedly decreases the toxicity of adriamycin.</p>

Determnination of betaine in Fufang Guilu granule by HPLC / 中国中药杂志

<p><b>OBJECTIVE</b>To describe a HPLC method for assessing betaine in Fufang Guilu granule.</p><p><b>METHOD</b>The content of betainephenaxcyl bromide in Fufang Guilu granule was determined by HPLC. The analytical column was a shim-pack CLC-ODS (6.0 mm x 150 mm) filling a 5 microm stationary phase; The mobile phase consisted of acetonitrile-water(35:65) with 0.1 mol x L(-1) NaClO4; The flow-rate was 1 mL x min (-1); The detector was set at 254 nm.</p><p><b>RESULT</b>The calibration curve was linear over the range of 0.09-0.585 microg (r = 0.9997). The average recovery of the method was 98.4%, RSD 2.5% (n = 5).</p><p><b>CONCLUSION</b>The results showed that this method was reliable and accurate, and can be used for quality control of Fufang Guilu granule.</p>

Computer simulation of the adsorption of ethanethiol in silicalite of MFI and MOR.

The method of configurational-bias Monte Carlo simulation is used for investigating the adsorption and distributions of ethanethiol in MFI and MOR type zeolites. The calculated adsorption quantity of ethanethiol in MFI is close agreement with the experimental data by means of IR spectroscopy and thermogravimetry. The calculated results show the adsorption quantity of ethanethiol in MFI is much more than that in MOR under coequal conditions. The observation of distribution of MFI is attributed to preferential adsorption of the ethanethiol molecules in the straight and zig-zag channels. In the intersection of straight channels and zig-zag channels, it accommodates the ethanethiol molecules like a reservoir. The straight channels for MOR accommodate all ethanethiol molecules almost, however, in the other channels, the ethanethiol molecules cannot be found.

Retrospective analyses of 1 310 cases of lung cancer diagnosed with fibrobronchoscopy / 第三军医大学学报

Objective　To explore the relationship of pathological types of lung cancer with sex, age, site, and clinical diagnosis. Methods　The data of 1 310 patients with lung cancer diagnosed with fibrobronchoscopy, was retrospectively analyzed. Results　①The preliminary clinical diagnosed lung cancers which were comfirmed by fibrobronchoscopic biopsy later were mainly small cell lung cancer. ②The percentage of squamous carcinoma was significantly greater in male (78.0%) than in female (49.7%), but the percentage of adenocarcinoma was significantly higher in female (38.1%) than in male (13.1%)(P<0.0001). ③Among the patients with lung cancer, 53.7% was from 40 to 59 years old and 40.2% over 60. The average age of male patients (56.9 years old) was significantly greater than that of female (51.1 years old) (P<0.0001). ④ The average age of patients with squamous carcinoma and adenocarcinoma was greater in male than in female, but that with small cell carcinoma and squamous carcinoma was greater in female than in male. ⑤The percentage of male with lung cancer in the left lung (37.3%) was greater than that of female (26.0%), but the female had lung cancer in the right lung (59.7%) while male had (49.3%). The left and right upper lobe was more (45.4%) in male, but the right upper and lower lobe was more(43.3%) in female. Conclusion　①The fibrobronchoscopic examination is very important in the diagnosis of lung cancer. ②The pathological types and sites of lung cancer is different in different sex and age, which provide the exact bases for medical and surgical treatment for lung cancer.

Retrospective analyses of 1 310 cases of lung cancer diagnosed with fibrobronchoscopy / 第三军医大学学报

Objective　To explore the relationship of pathological types of lung cancer with sex, age, site, and clinical diagnosis. Methods　The data of 1 310 patients with lung cancer diagnosed with fibrobronchoscopy, was retrospectively analyzed. Results　①The preliminary clinical diagnosed lung cancers which were comfirmed by fibrobronchoscopic biopsy later were mainly small cell lung cancer. ②The percentage of squamous carcinoma was significantly greater in male (78.0%) than in female (49.7%), but the percentage of adenocarcinoma was significantly higher in female (38.1%) than in male (13.1%)(P<0.0001). ③Among the patients with lung cancer, 53.7% was from 40 to 59 years old and 40.2% over 60. The average age of male patients (56.9 years old) was significantly greater than that of female (51.1 years old) (P<0.0001). ④ The average age of patients with squamous carcinoma and adenocarcinoma was greater in male than in female, but that with small cell carcinoma and squamous carcinoma was greater in female than in male. ⑤The percentage of male with lung cancer in the left lung (37.3%) was greater than that of female (26.0%), but the female had lung cancer in the right lung (59.7%) while male had (49.3%). The left and right upper lobe was more (45.4%) in male, but the right upper and lower lobe was more(43.3%) in female. Conclusion　①The fibrobronchoscopic examination is very important in the diagnosis of lung cancer. ②The pathological types and sites of lung cancer is different in different sex and age, which provide the exact bases for medical and surgical treatment for lung cancer.