c-MYC-mediated TRIB3/P62+ aggresomes accumulation triggers paraptosis upon the combination of everolimus and ginsenoside Rh2

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

Preliminary research of / 中国针灸

OBJECTIVE@#To explore the impacts on weight reduction effect treated with acupoint thread embedding therapy at different tissue levels under ultrasonic guidance.@*METHODS@#A total of 70 patients with overweight or obesity were randomized into a shallow-tissue thread embedding group (35 cases, 5 cases dropped off) and a deep-tissue thread embedding group (35 cases, 4 cases dropped off). Under ultrasonic guidance, the thread was embedded in the shallow tissue level and the deep tissue level respectively. The acupoints were Zhongwan (CV 12), Xiawan (CV 10), Shuifen (CV 9), Zhongji (CV 3), etc. The thread embedding therapy was exerted once every 2 weeks, totally for 3 times. Before and 2 weeks after treatment, body mass, body mass index (BMI), waist circumference and hip circumference were recorded in the patients of the two groups separately. After each treatment, the number and the property of blood vessels under each acupoint were detected by ultrasound. Besides, the needling sensation and the intensity were scored and the adverse events were observed after thread embedding therapy.@*RESULTS@#After treatment, the reduction range of body mass, BMI and waist circumference in the deep-tissue thread embedding group were larger than those in the shallow-tissue thread embedding group successively (@*CONCLUSION@#The deep-tissue thread embedding therapy achieves the stronger

Therapeutic effect of long-snake moxibustion combined with western medication on diarrhea type irritable bowel syndrome of spleen and kidney / 中国针灸

OBJECTIVE@#To compare the therapeutic effect between long-snake moxibustion combined with western medication and simple medication on diarrhea type irritable bowel syndrome (IBS-D) of spleen and kidney @*METHODS@#A total of 60 patients with IBS-D of spleen and kidney @*RESULTS@#Compared before treatment, the symptom scores of abdominal pain, defecation frequency, mucous stool and appetite reduction were decreased (@*CONCLUSION@#Long-snake moxibustion combined with western medication can effectively treat the IBS-D of spleen and kidney

Nagilactone E increases PD-L1 expression through activation of c-Jun in lung cancer cells / 中国天然药物

Nagilactone E (NLE), a natural product with anticancer activities, is isolated from Podocarpus nagi. In this study, we reported that NLE increased programmed death ligand 1 (PD-L1) expressions at both protein and mRNA levels in human lung cancer cells, and enhanced its localization on the cell membrane. Mechanistically, NLE increased the phosphorylation and expression of c-Jun, and promoted the localization of c-Jun in the nucleus, while silencing of c-Jun by small interfering RNA (siRNA) reduced NLE-induced PD-L1. Further study showed that NLE activated the c-Jun N-terminal kinases (JNK), the upstream of c-Jun, and its inhibitor SP600125 reversed the NLE-increased PD-L1. Moreover, NLE-induced PD-L1 increased the binding intensity of PD-1 on the cell surface. In summary, NLE upregulates the expression of PD-L1 in lung cancer cells through the activation of JNK-c-Jun axis, which has the potential to combine with the PD-1/PD-L1 antibody therapies in lung cancer.

Effect of long-snake moxibustion on nonspecific low back pain with symptom of cold and dampness / 中国针灸

OBJECTIVE@#To compare the clinical therapeutic effect of long-snake moxibustion and ginger-partitioned moxibustion at point on nonspecific low back pain (NLBP) with symptom of cold and dampness.@*METHODS@#A total of 120 patients were randomized into a long-snake moxibustion group, an ashi point group and a waiting for treatment group, 40 cases in each one. Ginger-partitioned moxibustion was applied from Dazhui (GV 14) to Yaoshu (GV 2) of governor vessel in the long-snake moxibustion group, and was applied at point of affected area in the ashi point group, 40 min each time, once every other day and totally 8 times were required. No intervention was adopted in the waiting for treatment group, and after the trial, long-snake moxibustion was applied. Before and after treatment, the visual analogue scale (VAS) scores of rest and activity, the Oswestry disability index (ODI) score and the score of cold and dampness symptom were observed in the 3 groups.@*RESULTS@#Compared before treatment, the VAS scores of rest and activity, the ODI scores and the scores of cold and dampness symptom after treatment were decreased in the long-snake moxibustion group and the ashi point group (<0.05). After treatment, the variations of the above indexes in the long-snake moxibustion group and the ashi point group were larger than those in the waiting for treatment group (<0.05), and the variations of the above indexes in the long-snake moxibustion group were larger than those in the ashi point group (<0.05).@*CONCLUSION@#Long-snake moxibustion can effectively improve the pain, dysfunction and the symptom of cold and dampness in patients with nonspecific low back pain, and the improvement is superior to the ginger-partitioned moxibustion at point.

Establishment and application of a cell model for LRRC8A physiological characteristic study / 生理学报

The aim of the present study was to establish a cell model of volume-regulated anion channel subunit LRRC8A and investigate the physiological characteristics of LRRC8A. The eukaryotic expression vectors of LRRC8A and YFP-H148Q/I152L were constructed and transfected into Fischer rat thyroid (FRT) cells by Lipofectamine 2000. The FRT cell lines co-expressing LRRC8A and YFP-H148Q/I152L were obtained by antibiotic screening. The expression of LRRC8A and YFP-H148Q/I152L in FRT cells was detected by the inverted fluorescence microscope. The fluorescence quenching kinetic experiment was done to verify the function and effectiveness of the cell model. Then the cell model was utilized to study the physiological characteristics of LRRC8A, such as the characteristics of anion transport, the opening of LRRC8A by osmotic pressure, the effect of anion transport velocity, and the effect of chloride channel inhibitors on LRRC8A anion channel. The results of the inverted fluorescence microscope showed that LRRC8A was expressed on the cell membrane and YFP-H148Q/I152L was expressed in the cytoplasm. The results of fluorescence quenching kinetic test showed that under the condition of low osmotic state, LRRC8A could transport some kinds of anions, such as iodine and chloride ions. Osmotic pressure played a key role in the regulation of LRRC8A volume-regulated anion channel opening. Chloride channel inhibitors inhibited ion transport of LRRC8A channel in a dose-dependent manner. It is suggested that LRRC8A has the characteristics of classic volume-regulated anion channels by using the cell model of FRT cells co-expressing LRRC8A and YFP-H148Q/I152L.

Clinical comparative study of laparoscopy versus open surgery for appendicitis / 复旦学报（医学版）

Objective To compare and evaluate the effect of laparoscopic and traditional open surgery in the treatment of appendicitis.Methods From Jan.2013 to Oct.2016,the clinical data of 862 cases with acute appendicitis from Jinshan Hospital,Fudan University were analyzed retrospectively.Among them,335 cases were treated with laparoscopic appendectomy (LA) and 527 cases with open appendectomy (OA).The time of operation,bleeding volume,the postoperative hospital stay,hospitalization costs,incision infection,intestinal obstruction and intra-abdominal abscess were compared between the two groups.Results In LA group,325 cases had successful LA,and 10 cases turned to OA (3.0％).Compared with OA,LA was associated with reduced risk of surgical-site infection (0.9 ％ vs.4.9 ％,P＜ 0.001),less bleeding volume [(16.6 ± 13.2) mL vs.(24.7 ± 18.3) mL,P＜0.001],shorter hospital stay [(4.4 ± 1.9) d vs.(5.1 ± 2.5) d,P＜0.001],less postoperative pain (4.5％ vs.11.6％,P＜0.001).The time of operation and hospitalization costs in the LA group [(41.4 ± 8.1) min,(7 806 ± 1 406) yuan] were longer and higher than that in the OA group [(38.8 ± 11.7) min,(4 871 ± 1 308) yuan],respectively (P all＜0.001).There was no significant difference in intra-abdominal abscesses,intestinal obstruction and reoperation rate between the two groups.The total incidence of complications in LA group [9.55 ％ (32/335)] was lower than that in OA group [14.42 ％(76/527),P =0.035].LA had the advantages of minimal invasion,shorten operation time[(45.2 ±7.7) min vs.(49.0 ± 7.6) min,P =0.004],without increasing the cost [(7 951 ± 1 485) yuan vs.(7 717 ± 1 705) yuan,P =0.396],which was a more popular choice for overweight or obesity (BMI≥24) patients.Conclusions LA is a safe and reliable operational way compared with OA.It has obvious advantages in reducing the complications such as incision infection,postoperative pain and so on.While it is not completely accepted because of its higher costs and longer time of operation for the hospital.LA seems to be favored especially in patients with BMI≥24.

HIV-1 molecular epidemiological survey of drug users in Jiangxi province / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate HIV-1 molecular epidemiology of drug users in Jiangxi Province to analyze epidemic situation, subtype, origin of strain, and variation, and to provide information for prevention and control of AIDS.</p><p><b>METHODS</b>Combining principles of traditional epidemiology and molecular epidemiology, the authors analyzed the epidemiologically related factors, the gene sequences and systematic mutation of HIV-1 gene in nine drug users in Jiangxi province.</p><p><b>RESULTS</b>The HIV spread through the drug users in Jiangxi not only by injection but also by sexual contacts. The main epidemic strain found by sequence analysis was HIV-1 CRF01-AE that was closely related to the strain among drug users in Vietnam and Guangxi Zhuang Autonomous Region, with the average gene distance of 9.00 +/- 2.27 from the Vietnam strain. The origin of strain among drug users in the province was entirely the same.</p><p><b>CONCLUSION</b>At present, HIV-1 CRF01-AE strain has spread in the whole province among the drug users. Vigorous behavioral interventions should be developed in drug users and un-safe sexual behavior population to prevent the epidemic.</p>