Research progress and potential medical applications of anaplastic lymphoma kinase in treatment of non-small cell lung cancer / 中国药理学通报

During the treatment of non-small cell lung cancer ( NSCLC) , many patients have developed drug resistance due to the use of targeted EGFR inhibitors. The main reasons for drug resistance are EGFR site mutations and bypass activation. Activation of ALK pathway is one of the major types of bypass activation. A recent authoritative study indicates that ALK is closely related to immunotherapy. This article reviews the treatment of ALK in tumors from three aspects: the structure and physiological function of ALK, the small molecule inhibitor of ALK, the biological function of ALK and its related treatment methods for NSCLC, and prospects future directions for better application of ALK in the treatment of NSCLC.

Social Work Intervention of Stranded Patients from the Ecosystem Perspective: Based on the Clinical Case Record Analysis of Social Work Department in Shanghai D Hospital / 中国医学伦理学

Based on the service of stranded patients in D Hospital, this study aimed to explore the multiple needs of stranded patients and construct an intervention mode from the ecosystem perspective. Using the method of case study, taking the service of stranded patients in hospital D as an example, 49 case records and verbatim interviews with stakeholders were analyzed. The discharge and resettlement of stranded patients faces multiple obstacles from individuals, families, medical and social systems. This study constructed the social work intervention model from the ecosystem perspective: information collection and needs assessment, empowerment of individual system, reconstruction of family support system, coordination of medical system and linking social support system. The intervention process achieved efficient effects. Social work intervention of stranded patients should pay attention to patients’ psychosocial needs and improve awareness of system difficulties; mobilize the multi-system support network and deliver services in combination with case management method; conduct social advocacy for the breakthrough of law and policy.

Efficacy and safety of CM310 in moderate-to-severe atopic dermatitis: A multicenter, randomized, double-blind, placebo-controlled phase 2b trial / 中华医学杂志(英文版)

BACKGROUND@#Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.@*METHODS@#This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.@*RESULTS@#At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs . placebo, 95% CI 31%-69%) and 45% (low vs . placebo, 95% CI 26%-64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator's Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310.@*CONCLUSION@#CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.

Label-free target discovery technology of small molecule drug and its application in traditional Chinese medicines / 药学学报

The discovery of drug targets plays a crucial role in drug research. Accurate information of small molecule drug-protein interaction can be provided by label-free target discovery technology without any structural modification at the small molecule. So, the label-free drug target discovery technology had become the powerful tool to discover the targets of drugs. Due to the “multi-component and multi-target” characteristics of traditional Chinese medicines (TCMs), the research on its targets and mechanism had been restricted. Based on potential of the label-free target discovery technology in the research of TCMs, this paper summarized the label-free target discovery technology and its application in TCMs research. It will provide a reference for the discovery of targets of TCMs and a new view for promoting the modernization of TCMs.

Role of Oxidative Stress in Ulcerative Colitis and Traditional Chinese Medicine Prevention and Treatment： A Review / 中国实验方剂学杂志

Ulcerative colitis （UC） is a commonly seen digestive system disease with unclear pathogenesis. The condition is complex and variable， often chronic， and has a long treatment period with no specific cure. Currently， the treatment of UC often involves the use of corticosteroids， aminosalicylates， and biologics in western medicine， which provide fast-acting and definite efficacy in the short term. However， with prolonged medication， some patients may develop drug resistance and worsening of the disease， leading to the occurrence of colon cancer. Research has found that oxidative stress is one of the important pathogenic factors in UC and influences its onset and development. Oxidative stress is a state of imbalance between oxidative products and the antioxidant system in the body， characterized by overexpression of oxidative products such as malondialdehyde （MDA）， reactive oxygen species （ROS）， nitric oxide （NO）， or deficiency of antioxidant enzymes such as superoxide dismutase （SOD）， catalase （CAT）， and glutathione （GSH）. It is worth noting that traditional Chinese medicine （TCM）， as a unique characteristic medicine of China， has achieved significant efficacy in the treatment of UC. Studies have shown that TCM effectively inhibits the occurrence of UC by suppressing the accumulation of metabolites and antagonizes the development of UC by enhancing the antioxidant system. Therefore， using TCM to regulate the oxidative balance as a diagnostic and therapeutic approach may be a new method and direction for the treatment of UC in the future. Based on the above research， this article summarized the mechanisms of key pathogenic proteins in oxidative stress and the occurrence and development of UC， and compiled the effective ingredients of Chinese medicine， single drugs， prescriptions， and acupuncture and moxibustion in regulating upstream and downstream target proteins of oxidative stress. These interventions can reduce pathological damage to the intestinal mucosa， lower the colon injury index， enrich the intestinal microbiota， increase colon length， and improve clinical symptoms of UC. The article is expected to expand the application of TCM in the treatment of UC and provide a reliable scientific theoretical basis.

Trans fatty acids in food： dietary intake and regulatory policies in China and other countries / 上海预防医学

Numerous studies have highlighted the harmful effect of trans fatty acid （TFAs） on human health. Based on a review of health hazards of TFAs， intake levels among residents in China and other countries， and current regulatory policies， this paper discusses the proposals on strengthening TFAs restriction policies in China. According to the literature review， dietary intake level of TFAs among residents in China was relatively low across the world， which remained a certain distance from the World Health Organization （WHO） recommended limit of 1% of total energy intake. However， consumption of edible oils， baked food and dairy products by Chinese residents is likely to continue to rise in the future， which might lead to an increase in TFAs intake. Therefore， it is suggested that China should strengthen the investigation and assessment of TFAs intake， adopt the WHO best policy of restricting TFAs （a national limit of 2 grams of industrially produced trans fat per 100 grams of total fat in all foods， or a national ban on the production and use of partially hydrogenated oils）， and reduce the use of edible oil.

The indicators of selecting patients with breast cancer undergoing postoperative radiotherapy for deep inspiration breath hold technique / 中华放射肿瘤学杂志

Cardiotoxicity caused by postoperative radiotherapy can increase the risk of cardiovascular adverse events in patients with breast cancer, especially those with left breast cancer, which is proportional to the dose of radiation to the heart. It has been proved that deep inspiration breath-hold (DIBH) technique can significantly reduce the cardiac dose in patients with left breast cancer, but the benefits of this technique vary greatly among different patients, and its implementation requires additional equipment, time, manpower and other resources. Hence, it is necessary to select patients who are suitable for this technique in advance. In addition to comprehensive analysis of general factors before simulation positioning that affect DIBH selection, this review also systematically summarized relevant indicators of CT simulation positioning images. These anatomical indicators included the measurement of the cardiac contact distances in parasagittal (CCD ps) plane, the lateral heart-to-chest distance (HCD), the product of maximum heart width (HW max) and the maximum heart depth (HD max) during CT simulation positioning, and the maximum heart distance, heart volume in the irradiation field (HVIF), the difference of lung volume and heart volume between free breathing (FB) and DIBH measured after CT localization. All of them showed some instructive significance for evaluating whether DIBH should be applied in tangent field based radiotherapy planning. The automatic planning (rapid plan) function in the treatment planning system could quickly predict the benefit of DIBH for breast cancer patients. The purpose of this article is to help clinicians select patients who are suitable for DIBH technique, guaranteeing that DIBH technique resources can be used reasonably.

The study on the repair effect of Dipsacus saponins Ⅵ on tibial fracture model rats based on Wnt/β-catenin pathway / 中国医师杂志

Objective:To observe the repair effect and possible mechanism of Dipsacus saponins Ⅵ on tibial fracture model rats.Methods:Thirty Sprague Dawley (SD) rats were randomly divided into model group, intervention group, and combination group, with 10 rats in each group, to establish a tibial fracture rat model using the sawing method. On the second day after surgery, the intervention group was intraperitoneally injected with 10 mg/kg of Chuanduduan saponin Ⅵ; The combination group received intraperitoneal injection of Dipsacus saponins Ⅵ 10 mg/kg and XAV939 1 mg/animal; The model group was intraperitoneally injected with 0.2 ml of physiological saline solution and 0.2 ml of dimethylsulfoxide (DMSO) solution; Once a day, continuous intervention for 14 days. After 2 to 4 weeks of intervention, Micro CT scan and X-ray scan were used to observe the fracture healing status; After 4 weeks of intervention, the wet weight of the tibia was detected; Hematoxylin eosin (HE) staining was used to observe the pathological changes of callus tissue; The Western blot method was used to detect the expression level of callus tissue β- catenin (β-catenin), p-β-catenin, glycogen synthase kinase 3β (GSK-3 β) and Runt related transcription factor 2 (Runx2) protein.Results:After 2 and 4 weeks of intervention, the bone volume fraction (BV/TV), number of trabeculae (Tb.N), Lane Sandhu score, and callus volume in the intervention group were higher than those in the model group (all P<0.05); After 2 and 4 weeks of intervention, the BV/TV, Tb.N, Lane Sandhu score, and callus volume in the combined group were lower than those in the intervention group (all P<0.05). The wet weight of the tibia in the intervention group was higher than that in the model group at 4 weeks after intervention ( P<0.05); The wet weight of the tibia in the combined group was lower than that in the intervention group ( P<0.05). The HE staining results showed that the model group had fibrous tissue hyperplasia and more bone trabeculae, but the maturity was not high and the thickening was not significant; The intervention group formed more bony callus, with orderly arrangement of bone trabeculae, partially mature, and obvious mineralization, consistent with the direction of stress; The combined group formed more cartilaginous and fibrous callus, with more mineralization at the edge of the cartilaginous callus and the formation of bone trabeculae. Abundant capillaries can be observed in the gaps. The expression level of Runx2 and p-β-catenin/β-catenin protein in callus tissue of the intervention group was higher than that of the model group, the protein expression GSK-3 β level was lower than that of the model group (all P<0.05); The expression level of Runx2 and p-β-catenin/β-catenin protein in the callus tissue of the combined group was lower than that of the intervention group; the protein expression level of GSK-3β was higher than that of the intervention group (all P<0.05). Conclusions:Dipsacus saponins Ⅵ can effectively promote fracture repair in tibial fracture model rats; It is possible to plays a role by activating the Wnt/β-catenin signaling pathway.

Boosting ferroptosis and microtubule inhibition for antitumor therapy via a carrier-free supermolecule nanoreactor / 药物分析学报

Traditional microtubule inhibitors fail to significantly enhance the effect of colorectal cancer;hence,new and efficient strategies are necessary.In this study,a supramolecular nanoreactor(DOC@TA-Fe3+)based on tannic acid(TA),iron ion(Fe3+),and docetaxel(DOC)with microtubule inhibition,reactive oxygen species(ROS)generation,and glutathione peroxidase 4(GPX4)inhibition,is prepared for ferroptosis/apoptosis treatment.After internalization by CT26 cells,the DOC@TA-Fe3+nanoreactor escapes from the lysosomes to release payloads.The subsequent Fe3+/Fe2+conversion mediated by TA reducibility can trigger the Fenton reaction to enhance the ROS concentration.Additionally,Fe3+can consume gluta-thione to repress the activity of GPX4 to induce ferroptosis.Meanwhile,the released DOC controls microtubule dynamics to activate the apoptosis pathway.The superior in vivo antitumor efficacy of DOC@TA-Fe3+nanoreactor in terms of tumor growth inhibition and improved survival is verified in CT26 tumor-bearing mouse model.Therefore,the nanoreactor can act as an effective apoptosis and ferroptosis inducer for application in colorectal cancer therapy.

Regulation of Pyroptosis in Gastric Cancer by Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Pyroptosis， a new type of inflammatory programmed cell death， is different from apoptosis， necrosis， cytosis， ferroptosis， and autophagy. Pyroptosis is dependent on the activation of cysteine aspartate-specific protease （Caspase）， which cleaves key mediator proteins to form pores in the cell membrane and induces the maturation and release of the proinflammatory cytokines interleukin-1β and interleukin-18 into the extracellular environment， resulting in a cascade of inflammatory reactions. Gastric cancer as a malignant tumor of the digestive tract is refractory and has poor prognosis， and the chemoradiotherapy of this disease may lead to a variety of complications. At present， the pathogenesis of gastric cancer remains unclear. Studies have proved that pyroptosis is associated with the occurrence and development of gastric cancer， which has attracted wide attention. Pyroptosis is a double-edged sword for gastric cancer. On the one hand， it can release the contents of proinflammatory cells to amplify or maintain inflammation and induce the "inflammation-cancer" transformation of cells. On the other hand， pyroptosis can enhance the sensitivity of drugs for chemotherapy to improve the therapeutic effect and survival. In recent years， the anti-tumor mechanism of traditional Chinese medicine （TCM） has become a research hotspot as TCM has demonstrated significant effects in clinical application. Therefore， the regulation of pyroptosis by TCM may be a new direction for the treatment of gastric cancer in the future. Based on the available studies， this paper introduces the roles of pyroptosis-associated key proteins in the occurrence and development of gastric cancer. Furthermore， this paper summarizes the effects of TCM prescriptions and active ingredients on alleviating gastric mucosal damage， reducing the incidence of gastric cancer， and preventing tumor metastasis and recurrence by mediating pyroptosis pathways， aiming to provide new ideas for deciphering the mechanism of pyroptosis and exploring the TCM treatment of gastric cancer in the future.

Better timing for HoLEP: a retrospective analysis of patients treated with HoLEP over a 10-year period with a 1-year follow-up / 亚洲男科学杂志(英文版)

The aim of this study was to explore the optimal timing of holmium laser enucleation of the prostate (HoLEP) in patients presenting benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS). A retrospective analysis was conducted based on the perioperative and postoperative outcome data of 1212 patients who underwent HoLEP in Shanghai Ninth People's Hospital (Shanghai, China) between January 2009 and December 2018. According to the preoperative International Prostate Symptom Score (IPSS), all patients whom we analyzed were divided into Group A (IPSS of 8-18) and Group B (IPSS of 19-35). Peri- and postoperative outcome data were obtained during the 1-year follow-up. IPSS changes were the main postoperative outcomes. The postoperative IPSS, quality of life, peak urinary flow rate, postvoid residual, and overactive bladder symptom score (OABSS) improved significantly. The IPSS improved further in the group with severe LUTS symptoms, but the postoperative IPSS was still higher than that in the moderate LUTS group. OABSSs showing moderate and severe cases after follow-up were more frequent in Group B (9.1%) than in Group A (5.2%) (P < 0.05). There were no significant intergroup differences in the intraoperative American Society of Anesthesiologists or hospitalization expense scores, and the medication costs, as well as the total costs, were significantly higher in Group B. In this retrospective study, HoLEP was an effective treatment for symptomatic BPH. For patients with LUTS, earlier surgery in patients with moderate severity may result in a marginally better 12-month IPSS than that in men with severe symptoms.

Treatment Outcomes in COVID-19 Patients with Brucellosis: Case Series in Heilongjiang and Systematic Review of Literature / 生物医学与环境科学（英文）

OBJECTIVE@#Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery.@*METHODS@#We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated.@*RESULTS@#A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery.@*CONCLUSION@#These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.

Acupuncture for lumbar myofascial pain syndrome: systematic review and Meta-analysis / 中国针灸

This study systematically reviewed the clinical efficacy of acupuncture for lumbar myofascial pain syndrome. The randomized controlled trials (RCTs) regarding acupuncture for lumbar myofascial pain syndrome were searched in PubMed, Cochrane Library, Web of Science, EMbase, Scopus, China national knowledge infrastructure (CNKI), Wanfang database, VIP database, and China biomedical literature service system (SinoMed) from database inception until August 1st, 2022. The Cochrane's risk of bias assessment tool was used to assess the risk of bias in all included studies, and Review Manager 5.3 software was used for statistical analysis of the extracted data. As a result, 12 RCTs, involving 1 087 patients with lumbar myofascial pain syndrome, were ultimately included. The Meta-analysis results showed that the visual analog scale (VAS) score of pain in the observation group was lower than those in the oral non-steroidal anti-inflammatory medication control [SMD=-1.67, 95%CI (-2.44, -0.90), Z=4.26, P<0.000 1] and other treatment control [low-frequency electrical stimulation, tuina, electromagnetic wave irradiation combined with piroxicam gel, SMD=-1.98, 95%CI (-2.48, -1.48), Z=7.74, P<0.000 01]. The pain rating index (PRI) score in the observation group was lower than those in the lidocaine injection control [MD=-2.17, 95%CI (-3.41, -0.93), Z=3.44, P=0.000 6] and other treatment control [low-frequency electrical stimulation, tuina, MD=-5.75, 95%CI (-9.97, -1.53), Z=2.67, P=0.008]. The present pain intensity (PPI) score in the observation group was lower than that in other treatment control [low-frequency electrical stimulation, tuina, MD=-1.04, 95%CI (-1.55, -0.53), Z=4.01, P<0.000 1]. In conclusion, compared with oral non-steroidal anti-inflammatory medication, low-frequency electrical stimulation, tuina, and electromagnetic wave irradiation combined with piroxicam gel, acupuncture is more effective in reducing pain in patients with lumbar myofascial pain syndrome; acupuncture also exhibites advantage over lidocaine injection in improving PRI score and showed better outcomes over tuina and low-frequency electrical stimulation in improving PRI and PPI scores.

Advances in the study of the m6A methyltransferase METTL3 promoting bladder cancer progression via AFF4/NF-κB/MYC signaling network / 现代泌尿外科杂志

Bladder cancer (BCa) is one of the most common cancers in urology,whose pathogenesis is still unclear. Methyltransferase-like 3(METTL3) is the most important part of N6-methyladenosine methyltransferase complex (m6A MTC),which mediates the methylation of mRNA to regulate the stability and translation process of mRNA. Researches have shown that METTL3 can promote BCa development via AFF4/NF-κB/MYC signaling network,which involves many kinds of signaling molecules. In addition,METTL3 can affect the expressions of AFF4,NF-κB and MYC,so as to affect their downstream signaling pathways and finally promote the malignant progression of tumor.

Research on the Ethical Dilemmas of Medical Social Workers Involved in the Service Emergency Stranded Patients / 中国医学伦理学

The retention of emergency patients is a common problem faced by hospitals worldwide. In addition to medical problems, social, family, economic and other problems will also cause patients to stay in the emergency department. It not only brings challenges to patients’ own disease treatment and hospital operation and management, but also brings ethical dilemmas. Taking the service cases of medical social workers who involved in stranded patients in Shanghai E Hospital as an example, this paper analyzed 20 service records and interviews with social workers receiving cases, and combed the ethical dilemmas faced by medical social workers in the process of involving in emergency stranded patients. It was found that medical social workers faced many ethical dilemmas in the process of involving in emergency stranded patients, such as interpersonal relations and relevant legal regulations, the right to life and health and the right to informed consent, the self-determination of case owners and the allocation of medical resources. In this regard, it is suggested to solve the problem of patient retention by advocating the improvement of relevant systems and policies, building cooperative teams to smooth referral channels, strengthening education, and promoting family shared decision-making.

Research advances in the minimally invasive treatment of benign prostatic obstruction / 现代泌尿外科杂志

The number of benign prostatic obstruction (BPO) patients in China is increasing, and patients tend to be younger and younger. The former "gold standard" scheme of transurethral resection of the prostate (TURP) is more suitable for patients with prostate volume ranging from 40 mL to 80 mL, which may lead to excessive resection in patients with small prostate volume and low efficiency in patients with large prostate volume. New minimally invasive techniques have been introduced,including prostate artery embolization, laser surgery (such as holmium, green, diode, and thulium), minimally invasive simple prostatectomy, transperineal laser ablation, prostatic urethral lift,and robot-assisted water jet ablation of the prostate. These methods are alternatives to TURP and increasingly used in the treatment of BPO. This article reviewed the advances in minimally invasive treatment of BPO.

Research status of adolescent mental health under the COVID-19 pandemic： a visual quantitative analysis based on Citespace / 四川精神卫生

BackgroundDue to the COVID-19 pandemic， both teenagers' studies and personal life are critically affected， which has resulted in a variety of mental health problems. In this regard， scholars at home and abroad have carried out a large number of research concerning adolescent mental health， of which there still exists a lack of systematic combing and review. ObjectiveTo understand the status and development trend of research on adolescent mental health during the COVID-19 pandemic at home and abroad， and to grasp the current research hotspots and trends in this field， so as to provide references for relevant research and practice in the post-epidemic era. MethodsOn October 30， 2022， we searched through China Knowledge Network Infrastructure （CNKI） and Web of Science database， and the publishing time of articles to be retrieved was limited between December 1， 2019 and October 30， 2022. Excel and CiteSpace were used to perform visual analysis on these articles in terms of number， author， institution， country and keywords of the articles. ResultsA total of 7 608 articles were included. At home and abroad， the number of papers related to adolescent mental health generally increased at first and then decreased under the pandemic situation. Compared with foreign countries， the connection and cooperation among domestic scholars and institutions was not close enough. The top three countries in the number of English literature published were the United States， Britain and China， and those in intermediary center were Tunis， Cameroon and Anguilla. The parent-child relationship and mental health of teenagers during were much concerned by scholars both at home and abroad. With the passage of time， researchers at home and abroad had shifted their focus from only negative factors to positive factors. ConclusionChinese scholars or institutions need to strengthen more domestic and international exchanges and cooperation. Scholars from different countries can carry out cross-cultural study on research topics of common concern， and continue to explore the positive psychological changes of teenagers in the post-epidemic era.［Funded by National Social Science Foundation 2020 Education Youth Project of 13th Five-Year Plan （number， CHA200259）］

The efficacy of radiotherapy based combined therapy for unresectable locally invasive bladder cancer and its associated factors analysis / 中华肿瘤杂志

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.

Association between blood pressure during 12-28 weeks gestation and pre-eclampsia: predictive value of blood pressure trajectories constructed by latent class growth modeling / 中华心血管病杂志

Objective: To explore the associations between blood pressure trajectories during pregnancy and risk of future pre-eclampsia in a large cohort enrolling pregnant women at gestational age of ~12 weeks from community hospitals in Tianjin. Latent class growth modeling (LCGM) was used to model the blood pressure trajectories. Methods: This was a large prospective cohort study. The study enrolled pregnant women of ~12 weeks of gestation in 19 community hospitals in Tianjin from November 1, 2016 to May 30, 2018. We obtained related information during 5 antepartum examinations before gestational week 28, i.e., week 12, week 16, week 20, week 24 and week 28. LCGM was used to model longitudinal systolic (SBP) and diastolic blood pressure (DBP) trajectories. For the association study, the predictors were set as SBP and DBP trajectory membership (built separately), the outcome was defined as the occurrence of preeclampsia after 28 weeks of gestation. Results: A total of 5 809 cases with known pregnant outcomes were documented. After excluding 249 cases per exclusion criteria, 5 560 cases with singleton pregnancy were included for final analysis. There were 128 cases preeclampsia and 106 cases gestational hypertension in this cohort. Univariate logistic regression and multivariate logistic regression showed the higher baseline SBP level and DBP level were related with increased risk of preeclampsia. Four distinctive SBP trajectories and DBP trajectories from 12 weeks to 28 weeks of gestation were identified by LCGM. After controlling for potential confounders (baseline BMI, being primipara or not, white blood cell counts, hemoglobin level, platelet counts and alanine aminotransferase level), the OR for SBP latent classification trajectory_ 4 was 4.023 (95%CI: 2.368 to 6.835, P<0.001), and the OR for SBP latent classification trajectory_3 was 1.854 (95%CI: 1.223 to 2.811, P=0.004). Logistic regression showed that: using the DBP latent classification trajectory_1 as the reference group, the OR for DBP latent classification trajectory_4 was 4.100 (95%CI: 2.571 to 6.538, P<0.001), and 2.632 (95%CI: 1.570 to 4.414, P<0.001) for DBP latent classification trajectory_2. After controlling for potential confounders (baseline BMI, being primipara or not, white blood cell counts, hemoglobin level, platelet counts and alanine aminotransferase level), the OR for DBP_traj_4 was 2.527 (95%CI: 1.534 to 4.162, P<0.001), and the OR for DBP_traj_3 was 1.297 (95%CI: 0.790 to 2.128, P=0.303), and 2.238 (95%CI: 1.328 to 3.772, P=0.002) for DBP_traj_2. Therefore, BP trajectories from 12 weeks to 28 weeks identified by LCGM served as novel risk factors that independently associated with the occurrence of preeclampsia. Receiver operating characteristic (ROC) curve analysis showed incremental diagnostic performance by combing baseline blood pressure levels with blood pressure trajectories. Conclusion: By applying LCGM, we for the first time identified distinctive BP trajectories from gestational week 12 to 28, which can independently predict the development of preeclampsia after 28 weeks of gestation.

Mesenchymal Stem Cells Ameliorate Fibrosis by Enhancing Autophagy via Inhibiting Galectin-3/Akt/mTOR Pathway and by Alleviating the EMT via Inhibiting Galectin-3/Akt/GSK3β/Snail Pathway in NRK-52E Fibrosis

Background and Objectives@#Epithelial-Mesenchymal transition (EMT) is one of the origins of myofibroblasts in renal interstitial fibrosis. Mesenchymal stem cells (MSCs) alleviating EMT has been proved, but the concrete mechanism is unclear. To explore the mechanism, serum-free MSCs conditioned medium (SF-MSCs-CM) was used to treat rat renal tubular epithelial cells (NRK-52E) fibrosis induced by transforming growth factor-β1 (TGF-β1) which ameliorated EMT. @*Methods@#and Results: Galectin-3 knockdown (Gal-3 KD) and overexpression (Gal-3 OE) lentiviral vectors were established and transfected into NRK-52E. NRK-52E fibrosis model was induced by TGF-β1 and treated with the SF-MSCs-CM for 24 h after modelling. Fibrosis and autophagy related indexes were detected by western blot and immunocytochemistry. In model group, the expressions of α-smooth muscle actin (α-SMA), fibronectin (FN), Galectin-3, Snail, Kim-1, and the ratios of P-Akt/Akt, P-GSK3β/GSK3β, P-PI3K/PI3K, P-mTOR/mTOR, TIMP1/MMP9, and LC3B-II/I were obviously increased, and E-Cadherin (E-cad) and P62 decreased significantly compared with control group. SF-MSCs-CM showed an opposite trend after treatment compared with model group. Whether in Gal-3 KD or Gal-3 OE NRK-52E cells, SF-MSCs-CM also showed similar trends. However, the effects of anti-fibrosis and enhanced autophagy in Gal-3 KD cells were more obvious than those in Gal-3 OE cells. @*Conclusions@#SF-MSCs-CM probably alleviated the EMT via inhibiting Galectin-3/Akt/GSK3β/Snail pathway. Meanwhile, Gal-3 KD possibly enhanced autophagy via inhibiting Galectin-3/Akt/mTOR pathway, which synergistically ameliorated renal fibrosis. Targeting galectin-3 may be a potential target for the treatment of renal fibrosis.