Objective: To investigate the trends in mortality and life loss of gastric cancer in Wenzhou City, Zhejiang Province from 2014 to 2023, so as to provide the evidence for formulating the prevention and control strategy for gastric cancer. Methods: The surveillance on causes of death data of permanent residents in Wenzhou City were collected through the Wenzhou Chronic Disease Monitoring and Management Information System from 2014 to 2023. The crude mortality of gastric cancer was calculated, and standardized by the data from the Sixth Chinese National Population Census in 2010. The life loss were measured using potential years of life lost (PYLL) and rate of potential years of life lost (PYLLR). The characteristics of mortality and life loss of gastric cancer in different genders and age groups were described. The trends in mortality and PYLLR of gastric cancer were analyzed using the average annual percent change (AAPC). Results: Totally 17 080 deaths were reported due to gastric cancer in Wenzhou City from 2014 to 2023, accounting for 12.58% and ranking third in the order of malignant tumor deaths. The crude mortality of gastric cancer was 20.73/105, and the standardized mortality was 15.22/105, showing decreasing trends (AAPC=-3.311%, -6.470%, both P<0.05). The crude mortality of gastric cancer was 29.22/105 in men and 11.61/105 in women, with standardized mortality rates of 20.81/105 and 8.74/105 (both P<0.05). The crude mortality of gastric cancer appeared a tendency towards a rise with increasing age (P<0.05), reaching the highest rate of 225.88/105 in the group aged 80 to <85 years. The PYLL and PYLLR of gastric cancer were 107 607.50 person-years and 1.37‰. The PYLLR appeared a tendency towards a decline from 2014 to 2023, with AAPC of -6.667% (P<0.05). Conclusions The mortality and PYLLR of gastric cancer in Wenzhou City appeared a tendency towards a decline from 2014 to 2023. Men and the elderly populations were the key groups for the prevention and treatment of gastric cancer.

Objective: To analyze the trends in mortality of liver cancer in Wenzhou City, Zhejiang Province from 2014 to 2022, so as to provide the evidence for improving liver cancer control measures. Methods: Data of liver cancer mortality in Wenzhou City from 2014 to 2022 were collected from Wenzhou Chronic Disease Monitoring Information System. The crude mortality were estimated and standardized by the national population census data in China in 2010, and the trends in mortality of liver cancer were analyzed with average annual percent change (AAPC). Results: There were 22 033 liver cancer deaths from 2014 to 2022, accounting for 18.08% of malignant tumor deaths and ranking the second in malignant tumor deaths. The crude mortality of liver cancer was 30.00/105 and the standardized mortality was 24.32/105, both showing decreasing trends (AAPC=-2.812% and -5.742%, both P<0.05). The standardized mortality of liver cancer were higher in men than in women (36.66/105 vs. 11.21/105, P<0.05), both showing decreasing trends (AAPC=-5.702% and -5.521%, both P<0.05). The crude mortality of liver cancer appeared a tendency towards a rise with age (P<0.05), with the highest crude mortality in the group aged 80 to 84 years, reaching 145.12/105. The crude mortality of liver cancer showed a tendency towards a decline among residents aged under 15 years, 15 to 44 years, 45 to 64 years and 65 years and above (AAPC=-20.311%, -6.569%, -7.408% and -3.177%, all P<0.05). Conclusions The mortality of liver cancer showed a tendency towards a decline in Wenzhou City from 2014 to 2022. Men and the elderly were high-risk groups for liver cancer deaths, and prevention should be strengthened based on risk factors.

Pain management, listed as the fifth vital sign, has gained increasing attention from clinicians. Conventional analgesics have limited duration, leading to intense monitor and frequent dosing during the early phase in order to prevent the progression of chronic pain. Thus, prolonging the duration of analgesics has become one focus of the pain research. Several strategies, such as adding adjuvants, producing derivatives, and applying extended-release carriers, make it possible for super long-acting analgesics to come into reality. This review briefly introduces the strategies and development of the super long-acting analgesics, including the successful translation and commercialization of the present products of super long-acting analgesics. It also summarizes the application and translation of extended-release drug carriers, providing invaluable reference for the future research on the field of super long-acting analgesics.

Objective: To investigate the mortality and life loss of female breast cancer in Wenzhou City, Zhejiang Province from 2014 to 2022, so as to provide the evidence for prevention and control of breast cancer. Methods: Data of female breast cancer deaths in Wenzhou City were collected through the Wenzhou Chronic Disease Monitoring and Management information System from 2014 to 2012. The mortality of breast cancer was calculated, and standardized by the data from the Sixth Chinese National Population Census in 2010 (Chinese-standardized rate) and the world standard population first introduced by Segi (world-standardized rate). The life loss were measured using potential years of life lost (PYLL), rate of potential years of life lost (PYLLR) and average years of life lost (AYLL). The trends in mortality, PYLLR and AYLL were analyzed using the average annual percent change (AAPC). Results: Totally 2 523 deaths were reported due to breast cancer from 2014 to 2022, ranking fifth in the order of female malignant tumor deaths. The crude mortality of female breast cancer was 7.13/105, showing an increasing trend with AAPC of 2.186% (P<0.05). The Chinese population-standardized mortality and global population-standardized mortality were 5.93/105 and 4.39/105, showing no significant trend with AAPC of -0.617% and -0.602% (both P>0.05), respectively. The crude mortality of female breast cancer appeared a tendency towards a rise with age (P<0.05). The crude mortality of breast cancer in females aged 65 years and older showed an increasing trend (AAPC=3.283%, P<0.05), but there were no significant tendency aged 15 to <45 years and 45 to <65 years (AAPC=-1.011% and -1.850%, both P>0.05). The PYLL, PYLLR and AYLL of breast cancer were 41 227.50 person-years, 1.23‰ and 19.44 years per person, respectively. AYLL showed a decreasing trend (AAPC=-1.969%, P<0.05), and PYLLR showed no significant trend (AAPC=-0.527%, P>0.05). Conclusions The mortality of female breast cancer in Wenzhou City appeared a tendency towards a rise from 2014 to 2022, and AYLL appeared a downward trend. Females aged 65 years and older were the key groups for the prevention and control of breast cancer.

Objective:To investigate whether endoplasmic reticulum transmembrane protein IRE1(encoded by Ern1)can modulate the immunogenicity and tumorigenicity of cancer cells and explore the underlying mechanism.Methods:Correlation between ERN1 expression and the overall survival of cancer patients was explored with public cancer databases.CRISPR-Cas9 technology was used to delete Ern1 in mouse tumor cell lines MCA205 and TC-1.By CCK-8,flow cytometry,ELISA,luciferase reporter systems,subcutaneous tumor models,prime-boost regimens,we analyzed impact of Ern1 on tumor cell proliferation in vitro and tumor growth in vivo,intratumoral immune cell composition,tunicamycin-induced immunogenic cell death and activation of anti-tumor effector T cells.The growth kinetics of Ern1-/-tumors was also monitored in Ifnar-/-mice.Results:ERN1 expression was found to be negatively correlated with the overall survival of cancer patients across multiple cancer types.Although Ern1 deficiency didn't affect tumor cell proliferation in vitro,it largely delayed tumor growth or caused spontaneous tumor regression in immune-competent mice.As compared to wild type counterparts,Ern1-/-tumors harbored much more neutrophils but significantly less CD4+T cells.Upon tunicamycin-induced endoplasmic reticulum stress,Ern1-/-cells were more vulnerable to cell death.Although Ern1-deficiency reduced HMGB1 release and calreticulin exposure,IFN-α/β secretion was increased,and strongly elevated type Ⅰ IFN response in tumor cells and augmented IFN-γ production by anti-tumor effector T cells.Ern1-/-tumor cells restored the tumorigenic capacity in Ifnar-/-mice.Conclusion:Ern1 defi-ciency can enhance the immunogenicity of tumor cells and inhibit tumor outgrowth by boosting endoplasmic reticulum stress-induced type Ⅰ IFN response.

Objective:To summarize the clinical characteristics of patients with unicentric Castleman disease(UCD).Method:The clinical data of 8 abdominal UCD patients who received surgical resection at the Second Hospital of Hebei Medical University from Oct 2019 to Oct 2022 were analyzed, and the imaging characteristics, pathological types and prognosis were summarized.Result:There were 2 males and 6 females. The average age of patients was (33.0±13.7) years old, and their BMI was (23.2±4.5) kg/m 2. The median maximum diameter of the tumor was 4.5 (3.0-4.9) cm. The average postoperative hospital stay was 6.5 (3.3-12.0) days. One was lost during follow up, there was no recurrence or other postoperative complications in the remaining 7 patients. Conclusion:The incidence of unicentric Castleman disease is rare. Complete resection of the tumor is the main treatment for UCD patients, and the prognosis of UCD is good.

Objective:To investigate the prognostic factors of community-acquired pneumonia(CAP)in the elderly.Methods:Clinical and laboratory data of elderly patients(≥65 years old)hospitalized for CAP in the Department of Respiratory and Critical Care Medicine of Beijing Hospital from January to December 2019 were retrospectively analyzed.The patients were followed up after discharge.The patients were divided into a death group and a survival group according to their prognosis, and long-term mortality risk factors were analyzed by Cox regression.Results:A total of 118 elderly patients hospitalized for CAP with a male-to-female ratio of 1∶1 were included.The follow-up period was 20.7-39.0 months, with a median follow-up time of 29.8 months.The all-cause cumulative mortality rates at 1-2, 3, 6, 12, 24, and 36 months after discharge were 3.4%(4/118), 4.2%(5/118), 5.1%(6/118), 9.3%(11/118), 16.1%(19/118), and 21.6%(24/118), respectively.Pneumonia was the leading cause of death.Multifactorial Cox regression indicated that the Charlson comorbidity index score( HR=1.42, 95% CI: 1.11-1.83, P=0.006), the score of activities of daily living at discharge( HR=0.44, 95% CI: 0.23-0.84, P=0.013), body mass index( HR=0.83, 95% CI: 0.72-0.97, P=0.012), and the level of serum albumin( HR=0.84, 95% CI: 0.73-0.98, P=0.031)were independently associated with long-term mortality. Conclusions:The leading cause of long-term death for elderly CAP patients after discharge is pneumonia.High Charlson comorbidity index scores, lower BMI, low serum albumin levels and low scores of activities of daily living at discharge are independent risk factors for long-term mortality in these patients.Therefore, in order to reduce the occurrence of adverse prognosis and improve the quality of life, a multidimensional, comprehensive assessment and timely intervention should be performed during the acute phase of the disease.

Objective:To compare the effects of different anesthetic methods on the prognosis in the patients with stage Ⅲ breast cancer.Methods:Based on a multicenter randomized controlled trial (NCT00418457), 274 patients with untreated stage Ⅲ breast cancer, aged 18-85 yr, of American Society of Anesthesiologists physical statusⅠ-Ⅲ, were enrolled in the study and assigned to thoracic paravertebral block (TPVB) combined with total intravenous anesthesia group (TPVB+ TIVA group, n=141) and general anesthesia group (GA group, n=133) by computer-generated randomization stratified by study site.The primary outcome parameter of this study was postoperative recurrence rate.The secondary outcome parameters were the degree of postoperative acute pain (assessed using visual analogue scale score), the incidence of postoperative nausea and vomiting (PONV), postoperative hospital stay time, and the incidence of persistent pain after breast cancer surgery (PPBCS) at 6 and 12 months after surgery (assessed using the modified Brief Pain Inventory). Results:Compared with group GA, no significant change was found in the postoperative recurrence rate ( HR=0.711, 95% confidence interval (CI) 0.418-1.210, P=0.209), the degree of postoperative acute pain and the incidence of PONV were decreased (mean difference ( MD) of visual analogue scale score -0.890, 95% CI -1.344--0.436, P<0.001; OR=0.236, 95% CI 0.083-0.674, P=0.007), and no significant change was found in postoperative hospital stay time and the incidence of PPBCS ( HR=1.000, 95% CI 0.778-1.286, P=1.000; OR=2.100, 95% CI 0.599-7.362, P=0.246) in group TPVB+ TIVA. Conclusion:Compared with general anesthesia alone, TPVB combined with total intravenous anesthesia can provide lower degree of postoperative acute pain and lower incidence of PONV, and exert no effects on postoperative recurrence, postoperative hospital stay time and PPBCS in patients with stage Ⅲ breast cancer.

Systemic lupus erythematosus (SLE) is a complex autoimmune syndrome characterized by various co-existing autoantibodies (autoAbs) in patients' blood. However, the full spectrum of autoAbs in SLE has not been comprehensively elucidated. In this study, a commercial platform bearing 9400 antigens (ProtoArray) was used to identify autoAbs that were significantly elevated in the sera of SLE patients. By comparing the autoAb profiles of SLE patients with those of healthy controls, we identified 437 IgG and 1213 IgM autoAbs that the expression levels were significantly increased in SLE (P < 0.05). Use of the ProtoArray platform uncovered over 300 novel autoAbs targeting a broad range of nuclear, cytoplasmic, and membrane antigens. Molecular interaction network analysis revealed that the antigens targeted by the autoAbs were most significantly enriched in cell death, cell cycle, and DNA repair pathways. A group of autoAbs associated with cell apoptosis and DNA repair function, including those targeting APEX1, AURKA, POLB, AGO1, HMGB1, IFIT5, MAPKAPK3, PADI4, RGS3, SRP19, UBE2S, and VRK1, were further validated by ELISA and Western blot in a larger cohort. In addition, the levels of autoAbs against APEX1, HMGB1, VRK1, AURKA, PADI4, and SRP19 were positively correlated with the level of anti-dsDNA in SLE patients. Comprehensive autoAb screening has identified novel autoAbs, which may shed light on potential pathogenic pathways leading to lupus.

Objective To investigate the expression and clinical significances of miR-215 and runtrelated protein1 (RUNX1) in retinoblastoma (RB),and to study the regulation effect of miR-215 on RUNX1 in the retinoblastoma cell line PMC-RB.Methods The expressions of miR-215 and RUNX1 in the tumor tissue,non tumor tissues adjacent to cancer,human RB cell line FMC-RB and human normal retinal vascular endothelial cell line ATCC of RB patients were detected by quantitative real-time polymerase chain reaction (qRT-PCR).miR-215 mimics (miR-215-mimic),miR-NC,si-RUNX1 and si-NC were transfected into FMC-RB cell line respectively.Cell proliferation,migration and invasion ability were measured respectively,thus detecting the regulation effect of miR-215 on RUNX1.Results The expression of miR-215 in RB tissues was significantly lower than that in non tumor tissues adjacent to cancer,while the mRNA expression of RUNX1 was higher than that in non tumor tissues adjacent to cancer (P ＜ 0.05).The expression of miR-215 in PMC-RB cells was lower than that in ATCC,while the mRNA expression of RUNX1 was higher than that in ATCC (P ＜0.05).The expression of miR-215 and RUNX1 in RB tumor tissues were closely related to the clinicopathological features of optic nerve infiltration,tumor tissue differentiation and lymph node metastasis (P ＜ 0.05).Cell proliferation,migration and invasion in miR-215-mimic group were significantly lower than those in miR-NC group (P ＜ 0.05).In transfected 3' untranslated region (3 'UTR)-Wt cells,the luciferase activity in miR-215-mimic group was lower than that in miR-NC group (P ＜ 0.05);the expression level of RUNX1 protein in transfected miR-215-mimic cells was lower than that in transfected miR-NC cells (P ＜ 0.05).Cell proliferation,migration and invasion in si-RUNX1 group were all lower than those in si-NC group (P ＜ 0.05).There was a negative correlation between mRNA expression level of miR-215 and RUNX1 in RB tumor tissues.Conclusions During the occurrence and development of RB,the down-regulation of miR-215 expression can promote malignant progression of tumor by targeting RUNX1.miR-215 can be used as a biological markers and therapeutic target for RB diagnosis.