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 investigate the trends in mortality and life loss due to falls among the elderly in Wenzhou City, Zhejiang Province, so as to provide the basis for formulating prevention and control measures for falls among the elderly. Methods: The data on fall-related deaths among the elderly aged 60 and above in Wenzhou City were collected through the Wenzhou Chronic Disease Monitoring and Management Information System from 2015 to 2023. The crude mortality was calculated and standardized using the data from the Sixth National Population Census in 2010. The life loss were measured using potential years of life lost (PYLL), average years of life lost (AYLL), and potential years of life lost rate (PYLLR). The trends in mortality and life loss among the elderly were analyzed using the annual percent change (APC) and average annual percent change (AAPC). Results: There were 11 378 deaths due to falls among the elderly in Wenzhou City from 2015 to 2023, with a crude mortality of 82.67/100 000 and a standardized mortality of 65.32/105, which appeared no significant changing trend (AAPC=3.401%、2.995%,both P>0.05). There was a tendency towards a rise from 2019 to 2023 (APC=12.592%、11.507%, both P<0.05). The majority of falls occurred at home, with 6 312 cases accounting for 55.48%. The primary types of fall-related deaths were slips, trips, and falls on the same level, with 8 541 cases representing 75.07%. The crude mortality and standardized mortality of falls in males were 76.63/105 and 60.86/105, which were lower than that in females at 88.72/100 000 and 70.33/100 000 (both P<0.05), and the trends were consistent with the overall population. The crude mortality of falls among the elderly increased with age (P<0.05). From 2015 to 2023, the crude mortality of falls among the elderly aged 60 to <65 years showed an upward trend (AAPC=4.860%, P<0.05), while no significant trend was observed in other age groups (all P>0.05). The PYLL was 5 123 person-years, the AYLL was 0.45 years per person, and the PYLLR was 0.37‰. From 2015 to 2023, PYLL showed an upward trend (AAPC=5.477%, P<0.05). The PYLL, AYLL, and PYLLR for males were 3.08 times, 3.48 times, and 2.67 times those of females, respectively. Conclusions From 2015 to 2023, the mortality of falls among the elderly in Wenzhou City had remained relatively stable. However, PYLL showed an upward trend. Males and older seniors were key groups for falls prevention. It is recommended to enhance health education and promote age-friendly home modifications to prevent falls among the elderly.

In this study, we constructed a series of recombinant Fc variants of immunoglobulin G4 (IgG4), screened the fragment crystallizable (Fc) variants with significantly prolonged serum half-lives, and analyzed the relationship between mutation site and half-life, aiming to provide a theoretical basis for the development of IgG4 antibodies and Fc fusion protein-based drugs. Nine gene sites were selected for mutation, and different mutation sites were combined. The variant expression plasmids pET24b-Fc were constructed by molecular cloning and point mutation. The plasmids were transformed into Escherichia coli BL21(DE3) for the expression of different recombinant proteins of Fc. Fc2 and Fc3 variants had slightly lower recombinant protein yields, and the expression of other variants was not affected. The toxicity of different Fc variants was determined by cell counting kit-8 (CCK-8) and calcein acetoxymethyl ester/ propidium iodide (calcein AM/PI) in vitro and enzyme-linked immuno sorbent assay (ELISA) in vivo. The results showed that the recombinant Fc variants had good biocompatibility and safety. Finally, the Fc variants were labeled with fluorescent markers, and the effects of different mutations on their serum half-lives were investigated by in vivo experiments. The Fc5 variant with prolonged serum half-life was successfully screened out, which provided a theoretical and practical basis for the optimal design of IgG4 subtype antibody and Fc fusion protein drugs.
Immunoglobulin G/blood* ; Immunoglobulin Fc Fragments/biosynthesis* ; Half-Life ; Animals ; Escherichia coli/metabolism* ; Humans ; Recombinant Fusion Proteins/biosynthesis* ; Recombinant Proteins/biosynthesis* ; Mice

Objective To systematically evaluate the incidence rate of low-level viremia(LLV)in chronic hepatitis B(CHB)patients and related influencing factors,and to provide evidence-based medicine evidence for effective intervention and prevention of LLV in clinical practice.Methods This study was conducted according to the PRISMA guideline,with a PROSPERO registration number of CRD42023455304.CNKI,Wanfang Data,VIP,SinoMed,PubMed,Embase,Web of Science,and the Cochrane library were searched for observational studies on LLV and related influencing factors in CHB patients published up to July 21,2023.Stata 16.0 software was used to perform the meta-analysis.Results A total of 12 articles were included,with a total sample size of 3408 cases,among whom there were 1181 patients with LLV.The meta-analysis showed that the incidence rate of LLV was 32.8%(95%confidence interval[CI]:27.6%—38.3%)in treatment-experienced CHB patients.High HBsAg quantification(odds ratio[OR]=2.107,95%CI:1.782—2.491,P<0.001),positive HBeAg(OR=3.258,95%CI:2.629—4.038,P<0.001),high HBV DNA level at baseline(OR=1.286,95%CI:1.157—1.430,P<0.001),and history of entecavir treatment(OR=3.089,95%CI:1.880—5.074,P<0.001)were risk factors for LLV;duration of antiviral therapy≥3 years(OR=0.175,95%CI:0.093—0.331,P<0.001)and high alanine aminotransferase level at baseline(OR=0.985,95%CI:0.978—0.992,P<0.001)were protective factors against LLV.The sensitivity analysis showed no significant change in effective value,suggesting that the results of the meta-analysis were relatively stable.The funnel plot of the studies included was basically symmetrical,and the results of the Egger's test and the Begg's test suggested that there was no obvious publication bias in the articles included.Conclusion Clinicians should guide decision making based on the influencing factors for LLV and related clinical evidence,so as to reduce long-term clinical risks and avoid adverse outcomes.

As a potential vectored vaccine,Newcastle disease virus(NDV)has been subject to various studies for vaccine development,while relatively little research has outlined the immunomodulatory effect of the virus in antigen presentation.To elucidate the key inhibitory factor in regulating the interaction of infected dendritic cells(DCs)and T cells,DCs were pretreated with the NDV vaccine strain LaSota as an inhibitor and stimulated with lipopolysaccharide(LPS)for further detection by enzyme-linked immunosorbent assay(ELISA),flow cytometry,immunoblotting,and quantitative real-time polymerase chain reaction(qRT-PCR).The results revealed that NDV infection resulted in the inhibition of interleukin(IL)-12p40 in DCs through a p38 mitogen-activated protein kinase(MAPK)-dependent manner,thus inhibiting the synthesis of IL-12p70,leading to the reduction in T cell proliferation and the secretion of interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),and IL-6 induced by DCs.Consequently,downregulated cytokines accelerated the infection and viral transmission from DCs to T cells.Furthermore,several other strains of NDV also exhibited inhibitory activity.The current study reveals that NDV can modulate the intensity of the innate?adaptive immune cell crosstalk critically toward viral invasion improvement,highlighting a novel mechanism of virus-induced immunosuppression and providing new perspectives on the improvement of NDV-vectored vaccine.

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.

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 explore the effect of high intensity interval training (HIIT) on cardiac rehabilitation in patients after heart transplantation.Methods:According to the search terms, the search was conducted on China National Knowledge Infrastructure, VIP, WanFang Data, China Biology Medicine disc, Web of Science, PubMed, Cochrane Library, Embase, and EBSCO. The search time limit was from the establishment of the database to January 31, 2022. After 2 researchers screened the article, extracted information, and evaluated the quality, a Meta-analysis was conducted using RevMan 5.4 software.Results:According to the inclusion and exclusion criteria, 10 English articles were selected, including 191 patients in the intervention group and 212 patients in the control group, with a total of 403 patients. Meta-analysis showed that during cardiac rehabilitation exercise in patients after heart transplantation, HIIT could improve peak oxygen uptake in cardiopulmonary function exercise testing [ MD=1.98, 95% confidence interval ( CI) (0.55, 3.41), P=0.007], peak heart rate in chronotropic responses [ MD=6.93, 95% CI (2.62, 11.24), P=0.002], and muscle exercise ability [ MD=337.18, 95% CI (12.02, 62.35), P=0.04]. There was no statistically significant difference in systolic blood pressure, diastolic blood pressure, peak systolic blood pressure, peak diastolic blood pressure, resting heart rate and respiratory exchange rate between the two groups ( P>0.05). A subgroup analysis of peak oxygen uptake was conducted based on the intervention period and the start time of rehabilitation exercise after heart transplantation. The results showed that there were statistically significant differences in peak oxygen uptake between the intervention group and the control group when the intervention period was ≤ 12 weeks or the start time was > 6 weeks ( P<0.01) . Conclusions:HIIT effectively improves the peak oxygen uptake, peak heart rate, and muscle exercise activity of patients after heart transplantation. HIIT has a significant impact on peak oxygen uptake when the rehabilitation exercise start time after heart transplantation is > 6 weeks or the intervention period is ≤ 12 weeks.

Objective    To investigate the early clinical results of MitraClip system in domestic patients. Methods     We retrospectively analyzed the clinical data of 36 patients who underwent transcatheter edge-to-edge repair procedure using MitraClip system in Beijing Fuwai Hospital, Shenzhen Fuwai Hospital and Fuwai Yunnan Cardiovascular Hospital between January and June 2021. There were 24 males and 12 females, with a median age of 70 (47-86) years. Ten (27.8%) patients had 3+ mitral regurgitation (MR) and 26 (72.2%) patients had 4+ MR preoperatively. Results    All procedures were successfully performed. The reduction in MR was 2+ at least immediately after surgery, and 91.7% of patients had MR≤2+ at 3 days postoperatively. There was no statistical difference in left ventricular ejection fraction change postoperatively. Forward velocity and peak gradient of mitral valve were increased after the procedure. Mean gradient of mitral valve were increased at 3 days postoperatively than immediately after surgery (P<0.001). Two patients had acute pericardial effusion intraoperatively, and received pericardial puncture and drainage immediately. Conclusion    MitraClip system has been applied well in domestic patients and can significantly improve MR. This sutdy has a good consistency with foreign studies, and the early results are satisfactory.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, and its high mortality rate is closely associated with the unsatisfactory diagnostic and monitoring methods for HCC at present. Some microRNAs (miRNAs) play an important role in the development and progression of HCC, and their abnormal expression is a common phenomenon in HCC pathology; in addition, miRNAs can be released into the circulating blood and remain stable in blood. By reviewing the research advances in the role of miRNAs in HCC, it is pointed out that miRNAs are expected to become potential markers for the early diagnosis, monitoring and treatment, and prognostic evaluation of HCC, and this article also analyzes related issues in the clinical verification of such potential markers.