Interleukin-6(IL-6)is associated with cancer staging, survival, apoptosis and the sensitivity to chemotherapeutic drugs, and it is overexpressed in the cancer tissue and serum of cancer patient.IL-6 Can regulate proliferation and differentiation of cancer cells through IL-6/STAT3 signaling pathway. Therefore, blocking IL-6/STAT3 signaling pathway has potential therapeutic implications for cancer.

Objective To study the effects of siltuximab on the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (Stat3) signaling pathway in ovarian epithelial carcinoma.Methods (1) Expressions of IL-6 in ovarian cancer patient specimens were assessed by immunohistochemistry.(2) Expression of phosphorylation Stat3 (pStat3) protein in siltuximab and IL-6 treated SKOV3 cell lines was determined by western blot, and expression levels of Stat3-induced bcl-XL,MCL-1, survivin, in siltuximab treated SKOV3/TR and CAOV3/TR cells lines were also determined by western blot.(3) Real-time image analysis was used to study the nuclear translocation of pEGFP-Stat3 fusion protein in ovarian cancer cell line SKOV3-pEGFP-Stat3 treated with siltuximab and IL-6.(4)Paclitaxel sensitivity in siltuximab treated SKOV3/TR and CAOV3/TR cell lines were assessed using the methyl thiazolyl tetrazolium (MTT).The 50% inhibiting concentration ( IC50 ) was defined as the paclitaxel concentration required to decrease the A490 value to 50%.Results ( 1 ) There were significantly difference in IL-6 staining density and the positive rate of IL-6 protein stained among the metastatic, and drug-resistant recurrent tumors,and matched primary tumors [69%(18/26)] vs.77% (20/26)vs.23% (6/26), P＜0.05].(2)A clear increase in Stat3 phosphorylation levels was observed in the IL-6-treated SKOV3 cell lines as compared to the SKOV3 cell lines.When the IL-6-treated SKOV3 cells were incubated with siltuximab with a range of concentrations of 0.001,0.01,0.1, 1.0 and 10 μg/ml, there were trends toward reduced pStat3 expression in the treated cell lines.Compared without treatment with siltuximab, the expression of the anti-apoptotic proteins MCL-1, bcl-XL and survivin in SKOV3/TR and CAOV3/TR cell lines were significantly decreased after treated with siltuximab.(3) In resting cells, the majority of pEGFPStat3 was cytoplasmic until the addition of human IL-6, which promptly induced the translocation of fluorescent Stat3 molecules to the nucleus.Exposure of cells to siltuximab with a range of concentrations of 0.001, 0.01,0.1, 1.0 and 10 μg/ml, followed by an incubation in IL-6 significantly reduced pEGFP-Stat3 nucleocytoplasmic translocation.(4) MTT cytotoxicity assay demonstrated that siltuximab increased paclitaxel-induced cell death and partially overcame paclitaxel resistance.Treated with siltuximab ( 1 and 10 μg/ml) ,the paclitaxel IC50 value of siltuximab in SKOV3/TR (0.49, 0.19 μg/ml) and CAOV3/TR (0.0010, 0.0008 μg/ml) cells were significantly lower than those in untreated cells (0.71,0.0021 μg/ml;all P ＜ 0.05).Conclusions These results demonstrated that siltuximab effectively block the IL-6 signaling pathways, which .Blockage of IL-6 signaling may provide benefits for the treatment of ovarian cancer.

OBJECTIVETo investigate the effect of Qianlie Huichun on the expression of vascular endothelial growth factor(VEGF) in prostate tissues and expound its anti-prostatomegaly action in model rats with prostatic hypertrophy induced by injected testosterone.

METHODSA total of 60 male rats were eventy randomized into six groups. All were gelded except the normal control group. After a week, the gelded rats were injected with testosterone(4 mg/kg/d), meanwhile the first group were fed with a small dosage of Qianlie Huichun(0.4 g/kg/d), the second group with a medium dosage(0.8 g/kg/d), the third group with a large dosage(1.6 g/kg/d), and the fourth group injected with estriol(2.5 mg/kg/d), all for a month. The fifth group were model controls, and the sixth the normal controls, both fed with the same amount of pure water for a month. Then all the six groups of rats were killed and their prostate glands were resected for the examination of the expression rate of VEGF by immunohistochemical method.

RESULTSThe difference of VEGF expression between Qianlie Huichun groups and the model group was significant(P < 0.01), and so was it between the medium and large dosage middle, large amount of Qianlie Huichun groups and the estriol group(P < 0.01).

CONCLUSIONQianlie Huichun depressed the VEGF expression of the prostate gland in model rats, and the expression rate decreased with the increased amount of the drug, which shows that Qianlie Huichun has a definite therapeutic effect on prostatic hypertrophy by depressed the vascular growth of the vessel in the prostate gland.

Animals ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; pharmacology ; Male ; Prostate ; chemistry ; drug effects ; Rats ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor A ; analysis

Objective:To evaluate the effect of intravenous infusion of lidocaine on the efficacy of conventional treatment for rheumatoid arthritis.Methods:Forty-four patients with rheumatoid arthritis of either sex, aged 32-85 yr, weighing 40-76 kg, who were admitted to the Department of Pain and Nephrology in our hospital from September 2019 to September 2020, were divided into 2 groups ( n=22 each) according to the random number table method: control group (C group) and lidocaine group (L group). Both groups received conventional treatment.When visual analogue scale (VAS) score ≥5, glucocorticoid (GC) and non-steroidal anti-inflammatory drugs (NSAIDs) were taken orally to maintain the VAS score ≤4.In group L, 0.2% lidocaine hydrochloride injection 3 mg/kg (diluted with 0.9% sodium chloride injection 500 ml) was intravenously infused at a rate of 25 ml/h for 2 h, once a day, for 5 consecutive days, based on the conventional treatment.The VAS score, 28-joint Disease Activity Score (DAS28 score), simplified disease activity index score (SDAI score), consumption of GC and NSAIDs and adverse reactions were recorded before treatment (T 1) and at 1, 4 and 8 weeks after treatment (T 2-4). The temperature of the pain area of the affected joint was evaluated through infrared thermal imaging at T 1 and T 2. Results:Compared with the baseline at T 1, VAS score, DAS28 score and SDAI score were significantly decreased at each time point, and the temperature of the pain area of the affected joint at T 2 was decreased in the two groups ( P<0.05). There were no significant differences in VAS score, DAS28 score and SDAI score at each time point between two groups ( P>0.05). Compared with group C, the consumption of GC and NSAIDs was significantly decreased, and the temperature of the pain area of the dorsum of both hands and the dorsum of right foot at T 2 and incidence of adverse reactions were decreased in group L ( P<0.05). Conclusions:Intravenous infusion of lidocaine can optimize the efficacy of conventional treatment for rheumatoid arthritis.

Objective To evaluate the effect of hydromorphone postconditioning on the electrophysiological stability during ischemia-reperfusion (I/R) in isolated rat hearts.Methods Healthy adult male Sprague-Dawley rats,aged 2-3 months,weighing 280-360 g,were heparinized and anesthetized with pentobarbital sodium.Their hearts were excised and perfused in a Langendorff apparatus with K-H solution saturated with 95％ O2-5％ CO2 at 37 ℃.Twenty-four Langendorff-perfused hearts were divided into 3 groups (n =8 each) using a random number table:control group (group C),I/R group and hydromorphone postconditioning group (group HM).The isolated hearts were subjected to 60 min ischemia followed by 60 min reperfusion to establish the model of isolated heart I/R injury.The isolated hearts were perfused with K-H solution containing 4.1 ng/ml hydromorphone for 10 min starting from onset of reperfusion in group HM.Heart rate,electrocardiogram,coronary flow,and monophasic action potential amplitude,in the left ventricular endocardium,mid-myocardium and epicardium the maximal increase rate (Vmax) at the 0 phase,and monophasic action potential duration at 50％ and 90％ repolarization (MAPD50 and MAPD90,respectively) were recorded at 20 min of stabilization (T0) and 10,25,40 and 60 min of reperfusion (T1-4).The transmural dispersion of repolarization (TDR) was calculated,and the time for restoratiou of spontaneous heart beat was recorded.Results There was no significant difference in the heart rate,coronary flow or monophasic action potential amplitude between the three groups (P＞0.05).Compared with group C,V in the epieardium was significantly decreased,MAPD50 and MAPD90 in the three transmural layers were prolonged,and TDR was prolonged in group I/R (P＜0.05).Compared with group I/R,the time for restoration of spontaneous heart beat,MAPD50 in the endoeardium and mid-myocardium,and MAPD90 and TDR in the endocardium were significantly shortened (P＜0.05),and no significant change was found in V in group HM (P＞0.05).Conclusion Hydromorphone postconditioning is helpful in maintaining the electrophysiological stability during I/R in isolated rat hearts.

Objective To evaluate the role of δ-opioid receptors in hydromorphone postcondition-ing-induced maintenance of electrophysiological stability during ischemia-reperfusion(I∕R)in isolated rat hearts. Methods Healthy male Sprague-Dawley rats, aged 2-3 months, weighing 280-360 g, were used in this study. The animals were anesthetized with intraperitoneal pentobarbital 60 mg∕kg. Their hearts were immediately removed and perfused in a Langendorff apparatus. Thirty-two isolated hearts were divided into 4 groups after successful preparation of Langendorff perfusion model(n=8 each)using a random number ta-ble: control group(group C), group I∕R, hydromorphone postconditioning group(group HP)and hydro-morphone plus δ-opioid receptor antagonist naltridole postconditioning group(group HNP). In HP and HNP groups, the hearts were perfused for 10 min with K-H solution containing 41 ng∕ml hydromorphone and 41 ng∕ml hydromorphone plus 5 μmol∕L naltridole, respectively, and then with K-H solution for 50 min. At 20 min of stabilization(T0)and 10, 25 and 60 min of reperfusion(T1-2), heart rate(HR), monophasic action potential(MAP)duration at 90% repolarization(MAPD90)of the two layers(endocar-dium, epicardium)of the anterior left ventricular wall were recorded. Transmural dispersion of repolariza-tion(TDR)was calculated. The development of arrhythmia, time for restoration of spontaneous heart beat and duration of arrhythmia were recorded during the period of reperfusion. Results Compared with group C, MAPD90of endocardium at T1-2and MAPD90of epicardium at T1were significantly prolonged in I∕R and HP groups, HR was significantly decreased at T2-3, MAPD90of endocardium and epicardium was prolonged at T1-3in group HNP, TDR was significantly enlarged at T1in group I∕R and at T2in group HNP, and TDR was decreased at T3in group HP(P<005). Compared with group I∕R, no significant change was found in arrhythmia score(P>005), the time for restoration of spontaneous heart beat was significantly shortened, and TDR was decreased at T1in HP and HNP groups, duration of arrhythmia was significantly shortened, and MAPD90of endocardium was shortened at T1in group HP, and HR was significantly decreased at T2-3, MAPD90of endocardium and epicardium was prolonged at T1-3, and TDR was decreased at T2-3in group HNP(P<005). Compared with group HP, no significant change was found in time for restoration of spon-taneous heart beat, duration of arrhythmia or arrhythmia score(P>005), HR was significantly decreased at T2-3, MAPD90of endocardium and epicardium was prolonged at T1-3, and TDR was increased at T3in group HNP(P<005). Conclusion The mechanism underlying hydromorphone postconditioning-induced maintenance of electrophysiological stability during I∕R is related to activating δ-opioid receptors in isolated rat hearts.

Objective: A resilient health system plays a crucial role in pandemic preparedness and response. Although the World Health Organization (WHO) has required all states parties to strengthen core capacities to respond to public health emergencies under the International Health Regulations (2005), the actions of most countries to combating coronavirus disease 2019 (COVID-19) has showed that they are not well-prepared. This cross-sectional study aimed to examine the health system resilience of selected countries and analyze their strategies and measures in response to the COVID-19 pandemic.Methods: This study selected five countries including the Iran, Japan, Republic of Korea (South Korea), the U.K., and the U.S., based on the severity of the national epidemic, the geographical location, and the development level. Cumulative number of death cases derived from WHO COVID-19 dashboard was used to measure the severity of the impact of the pandemic in each country; WHO State Parties Self-Assessment Annual Reporting (SPAR) Scores and Global Health Security (GHS) Index were applied to measure the national health system resilience; and research articles and press materials were summarized to identify the strategies and measures adopted by countries during response to COVID-19. This study applied the resilient health systems framework to analyze health system resilience in the selected countries from five dimensions, including awareness, diversity, self-regulation, integration and adaptation. Results: The SPAR Scores and GHS Index of the four developed countries, Japan, South Korea, the U.K. and the U.S. were above the global and regional averages; the SPAR Scores of Iran were above the global average while the GHI Index lain below the global average. In terms of response strategies, Japan, the U.K. and the U.S. invested more health resources in the treatment of severe patients, while South Korea and Iran had adopted a strategy of extensive testing and identification of suspected patients. In terms of specific measures, all the five countries adopted measures such as restrictions on entry and international travel, closure of schools and industries, lockdown and quarantine. Nevertheless, the effectiveness of implementing these measures varied across countries, based on the response strategies. Conclusion: Although SPAR Scores and GHS Index have evaluated the national core capacities for preparedness and response, the actions to cope with the COVID-19 pandemic has revealed the fact that most countries still do not build resilient health systems in response to public health emergencies. Health system strengthening and health security efforts should be pursued in tandem, as part of the same mutually reinforcing approach to developing resilient health systems.

Background: Global spread and impact of the coronavirus disease 2019 (COVID-19) pandemic are determined to a large extent,by resistance to the pandemic and public response of all countries in the world;while a country's resistance and response are in turn determined by its political and socio economic conditions.To inform future disease prevention and control,we analyzed global data to exam the relationship between state vulnerabilities and COVID-19 incidences and deaths.Methods: Vulnerability was measured using the Fragile States Index (FSI).FSI is created by the Fund for Peace to assess levels of fragility for individual countries.Total FSI score and scores for 12 specific indicators were used as the predictor variables.Outcome variables were national cumulative COVID-19 cases and deaths up to September 16,2020,derived from the World Health Organization.Cumulative incidence rates were computed using 2019 National population derived from the World Bank,and case fatality rates were computed as the ratio of deaths/COVID-19 cases.Countries with incomplete data were excluded,yielding a final sample of 146 countries.Multivariate regression was used to examine the association between the predictor and the outcome measures.Results: There were dramatic cross-country variations in both FSI and COVID-19 epidemiological measurements.FSI total scores were negatively associated with both COVID-19 cumulative incidence rates (β =-0.0135,P ＜ 0.001) and case fatality rates (β =-0.0147,P ＜ 0.05).Of the 12 FSI indicators,three negatively associated with COVID-19 incidences were E1(Economic Decline and Poverty),E3 (Human Flight and Brain Drain),and S2 (Refugees and Internally Displaced Persons);two positively associated were P1 (State Legitimacy) and X1 (External Intervention).With regard to association with case fatality rates,C1 (Security Apparatus) was positive,and P3 (Human Rights and Rule of Law) and X1 was negative.Conclusion: With FSI measures by the Fund of Peace,overall,more fragile countries are less likely to be affected by the COVID-19 pandemic,and even if affected,death rates were lower.However,poor in state legitimacy and lack of external intervention are risk for COVID-19 infection and lack of security apparatus is risky for COVID-19 death.Implications of the study findings are discussed and additional studies are needed to examine the mechanisms underpinning these relationships.

Objective:To observe the short-term efficacy of 3D-printed custom-made hemipelvic prosthesis in the treatment of primary malignant bone tumors of the pubis.Methods:From June 2017 to May 2019, a total of 5 patients with pubic primary malignant tumor received type Ⅲ hemipelvectomy and reconstruction with a 3D-printed custom-made hemipelvic prosthesis at Department of Orthopedics, West China Hospital. They were 3 males and 2 females with an average age of 36.3 years (range, from 26 to 46 years). Of them, 3 underwent resection of the upper pubic ramus and 2 resection of both pubic rami. All their tumors were chondrosarcomas, with one case of Enneking stage Ⅱa and 4 cases of Enneking stage Ⅱb. Preoperative CT/MRI image fusion was used to determine the tumor-free resection margin, design guide templates for osteotomy and prosthesis, and simulate surgical procedures. A total of 5 3D-printed custom-made hemipelvic prostheses were designed, including 3 ones with an intramedullary stem to preserve partial pubis and 2 ones with a non-intramedullary stem not to preserve the pubis. The functional recovery was assessed by Musculoskeletal Tumor Society (MSTS) scores. The prosthetic position and osseointegration were evaluated by imaging examination. Oncological outcomes and complications were recorded.Results:R0 resection and precise reconstruction were accomplished in all patients. Their intraoperative blood loss ranged from 300 to 3, 700 mL (mean, 1, 680 mL), operation time from 180 to 430 min (mean, 294 min), and follow-up time from 13 to 29 months (mean, 20.6 months). All the 5 patients were alive with no evidence of disease or tumor recurrence. The functional MSTS scores at the final follow-up ranged from 29 to 31 (mean, 29.8). One male patient complained of erectile dysfunction. Fretting wear around the prosthetic stem was found in 3 patients while bone wear on the normal pubic side in 2. Osseointegration was observed in all patients with no complications like deep infection, prosthesis dislocation, prosthetic or screw breakage.Conclusion:Since 3D-printed custom-made hemipelvic prostheses can result in fine short-term efficacy for pubic primary malignant bone tumors, they may be a reliable method to reconstruct pelvic malignant tumors.

OBJECTIVE: To investigate the long-term effectiveness of uncemented allograft-prosthesis composite (APC) for reconstruction of bone defects after proximal femur tumor resection. METHODS: Between June 2007 and March 2014, 21 patients who underwent uncemented APC reconstruction of proximal femur after tumor resection were retrospectively evaluated. There were 9 males and 12 females with an average age of 33.2 years (range, 19-54 years). There were 9 cases of giant cell tumor of bone, 5 cases of osteosarcoma, 4 cases of osteoblastic osteosarcoma, 2 cases of chondrosarcoma, and 1 case of undifferentiated pleomorphic sarcoma. Thirteen cases of benign bone tumors were all classified as stage 3 by Enneking staging; and 8 cases of malignant bone tumors were classified as grade ⅡB in 7 cases and grade ⅡA in 1 case according to the American Joint Committee on Cancer (AJCC) staging system. Among them, 7 patients underwent reoperation after recurrence, and the rest were primary operations; 8 patients presented with pathological fractures. The preoperative Harris hip score (HHS) and American Musculoskeletal Tumor Society (MSTS) score was 40 (30, 49) and 9.1±3.5, respectively. The length of osteotomy was 80-154 mm, with an average of 110 mm. At 1 year after operation and last follow-up, HHS and MSTS scores were utilized to evaluate the function of hip joint; the gluteus medius strength score was used to evaluation of the hip abduction function. Image examinations were taken at 1, 3, 6, 9, and 12 months after operation and every year thereafter to assess the union of allograft-host bone interfaces. Intra- and post-operative complications were also recorded. RESULTS: All patients were followed up 84-163 months (mean, 123.5 months). At 1 year after operation and last follow-up, the HHS and MSTS scores significantly improved when compared with the preoperative scores ( P<0.05). However, there was no significant difference in the HHS score, MSTS score, and gluteus medius strength score between the two time points after operation ( P>0.05). Image examination showed that all allograft-host bone interfaces achieved union after 5-10 months (mean, 7.6 months). At last follow-up, all patients had bone resorption, including 11 severe cases, 4 moderate cases, and 6 mild cases; the bone resorption sites included Gruen 1, 2, and 7 regions. Complications included 10 fractures and 1 prosthetic fracture. Local recurrence occurred in 3 patients and pulmonary metastasis in 3 patients. CONCLUSION Uncemented APC is a reliable method for the reconstruction of bone defects after proximal femur tumor resection. It has the good long-term effectiveness and possesses obvious advantages in the union at the bone-bone surface.
Adult ; Female ; Humans ; Male ; Allografts/pathology* ; Bone Neoplasms/surgery* ; Bone Resorption/pathology* ; Bone Transplantation/methods* ; Femur/surgery* ; Osteosarcoma/pathology* ; Prostheses and Implants ; Retrospective Studies ; Treatment Outcome ; Young Adult ; Middle Aged