Background: Epimedii Folium, first recorded in the Shennong’s Classic of Materia Medica (Shen Nong Ben Cao Jing), is a traditional Chinese medicine (TCM) known for its effects of “benefiting Qi and strengthening the heart.” Icariside II (ICS II) is one of the main active components of Epimedii Folium, possessing cardiovascular protective and anti-inflammatory properties. However, the potential mechanisms of ICS II on myocardial ischemia (MI) remain unclear. Objective: The aim of the study was to investigate the effects and preliminary molecular mechanisms of ICS II in treating isoproterenolinduced MI in rats. Methods: A rat model of MI was established by subcutaneous injection of isoproterenol. Electrocardiography, echocardiography, myocardial enzymes analysis, heart weight index, triphenyltetrazolium chloride staining, histopathology, TUNEL staining, RT-qPCR, and Western blot were employed to evaluate the effects and preliminary molecular mechanisms of ICS II on MI rats. Results: Pharmacodynamic studies suggested that ICS II inhibited ST-segment elevation in electrocardiograms, improved cardiac function, reduced heart weight index and myocardial enzyme levels, decreased myocardial infarct size, alleviated cardiac histological damage, and inhibited apoptosis, thereby exerting cardioprotective effects in MI rats. Further studies revealed that ICS II may partially inhibit the expression of NLRP3/Caspase-1 axis-related targets at both protein and mRNA levels. Conclusions: Our findings indicate that ICS II exerts anti-MI effects, and its preliminary molecular mechanisms may be related to inhibiting the activation of the NLRP3/Caspase-1 axis to alleviate inflammatory responses.

Background: Epimedii Folium, first recorded in the Shennong’s Classic of Materia Medica (Shen Nong Ben Cao Jing), is a traditional Chinese medicine (TCM) known for its effects of “benefiting Qi and strengthening the heart.” Icariside II (ICS II) is one of the main active components of Epimedii Folium, possessing cardiovascular protective and anti-inflammatory properties. However, the potential mechanisms of ICS II on myocardial ischemia (MI) remain unclear. Objective: The aim of the study was to investigate the effects and preliminary molecular mechanisms of ICS II in treating isoproterenolinduced MI in rats. Methods: A rat model of MI was established by subcutaneous injection of isoproterenol. Electrocardiography, echocardiography, myocardial enzymes analysis, heart weight index, triphenyltetrazolium chloride staining, histopathology, TUNEL staining, RT-qPCR, and Western blot were employed to evaluate the effects and preliminary molecular mechanisms of ICS II on MI rats. Results: Pharmacodynamic studies suggested that ICS II inhibited ST-segment elevation in electrocardiograms, improved cardiac function, reduced heart weight index and myocardial enzyme levels, decreased myocardial infarct size, alleviated cardiac histological damage, and inhibited apoptosis, thereby exerting cardioprotective effects in MI rats. Further studies revealed that ICS II may partially inhibit the expression of NLRP3/Caspase-1 axis-related targets at both protein and mRNA levels. Conclusions: Our findings indicate that ICS II exerts anti-MI effects, and its preliminary molecular mechanisms may be related to inhibiting the activation of the NLRP3/Caspase-1 axis to alleviate inflammatory responses.

Background: Epimedii Folium, first recorded in the Shennong’s Classic of Materia Medica (Shen Nong Ben Cao Jing), is a traditional Chinese medicine (TCM) known for its effects of “benefiting Qi and strengthening the heart.” Icariside II (ICS II) is one of the main active components of Epimedii Folium, possessing cardiovascular protective and anti-inflammatory properties. However, the potential mechanisms of ICS II on myocardial ischemia (MI) remain unclear. Objective: The aim of the study was to investigate the effects and preliminary molecular mechanisms of ICS II in treating isoproterenolinduced MI in rats. Methods: A rat model of MI was established by subcutaneous injection of isoproterenol. Electrocardiography, echocardiography, myocardial enzymes analysis, heart weight index, triphenyltetrazolium chloride staining, histopathology, TUNEL staining, RT-qPCR, and Western blot were employed to evaluate the effects and preliminary molecular mechanisms of ICS II on MI rats. Results: Pharmacodynamic studies suggested that ICS II inhibited ST-segment elevation in electrocardiograms, improved cardiac function, reduced heart weight index and myocardial enzyme levels, decreased myocardial infarct size, alleviated cardiac histological damage, and inhibited apoptosis, thereby exerting cardioprotective effects in MI rats. Further studies revealed that ICS II may partially inhibit the expression of NLRP3/Caspase-1 axis-related targets at both protein and mRNA levels. Conclusions: Our findings indicate that ICS II exerts anti-MI effects, and its preliminary molecular mechanisms may be related to inhibiting the activation of the NLRP3/Caspase-1 axis to alleviate inflammatory responses.

Objective:To investigate the differences in programmed death-ligand 1 (PD-L1) expression and immune cell infiltration characteristics in different molecular subtypes of endometrial cancer.Methods:A retrospective case series study was conducted. Ninety primary treated EC patients who underwent surgery without preoperative neoadjuvant therapy at the Second Hospital of Tianjin Medical University from November 2016 to May 2022 were collected. The surgical paraffin-embedded tissues were selected, and the molecular subtypes of endometrial cancer were classified according to 2020 World Health Organization (WHO) molecular subtypes using POLE gene Sanger sequencing and immunohistochemical staining. The expression of PD-L1, CD3, CD4, CD8, CD68, and CD20 proteins were detected by immunohistochemistry. Stained slides were digitally scanned for quantitative analysis of PD-L1 and immune cell infiltration density. The PD-L1-related scores were evaluated, including tumor cell score (TCS, the percentage of PD-L1 positive tumor cells among total tumor cells ≥1% was TCS positive, <1% was TCS negative), immune cell score (ICS, the percentage of PD-L1 positive tumor-associated lymphocytes and macrophages among total tumor-associated lymphocytes and macrophages ≥1% was ICS positive, <1% was ICS negative) and combined positive score [CPS, PD-L1 positive stained cells (including tumor cells, lymphocytes and macrophages)/total number of viable tumor cells ×100 ≥ 1 was CPS positive, < 1 was CPS negative]. Clinicopathological characteristics, PD-L1 scores and immune cell infiltration densities among different molecular subtypes were analyzed. Kaplan-Meier method was used to plot disease-free survival (DFS) curves for molecular subtypes, PD-L1 scores and immune cell infiltration densities, with subgroup comparisons using log-rank test. Cox proportional hazards models were used for univariate and multivariate analyses of poor DFS in endometrial cancer patients.Results:The median age of 90 patients was 58 years old (range: 33-72 years old); endometrioid carcinoma was present in 78 cases (86.7%), and non-endometrioid carcinoma was present in 12 cases (13.3%). Molecular subtyping identified POLE-mutated subtype in 6 cases (6.7%), mismatch repair deficient (MMRd) subtype in 23 cases (25.6%), p53 abnormal subtype in 14 cases (15.6%), and non-specific molecular profile (NSMP) subtype in 47 cases (52.2%). Significant differences were observed among the 4 molecular subtypes in International Federation of Gynecology and Obstetrics (FIGO) stage, histological grade, morphological subtype, tertiary lymphoid structures, estrogen receptor expression, and progesterone receptor expression (all P < 0.05). Among the 90 cases, 18 cases (20.0%) were positive for TCS, 31 cases (34.4%) were positive for ICS, and 39 cases (43.3%) were positive for CPS. Significant differences were found among the 4 molecular subtypes in PD-L1 + cell density, distribution of patients with ICS positivity, and distribution of patients with CPS positivity (all P < 0.01), but not in distribution of patients with TCS positivity ( P = 0.090); compared to NSMP subtype, the proportions of ICS-positive patients in POLE-mutated and MMRd subtypes were higher, the proportion of CPS-positive patients and PD-L1 + cell density in MMRd and p53 abnormal subtypes were higher, and the differences were statistically significant (all P < 0.05). Significant differences in immune cell densities were observed among the 4 molecular subtypes (all P < 0.01); compared to NSMP subtype, POLE-mutated, MMRd and p53 abnormal subtypes had higher densities of CD3 + and CD8 + cells, MMRd subtype had higher CD4 + cell density, and POLE-mutated and MMRd subtypes had higher CD68 + and CD20 + cell densities (all P < 0.05). The median follow-up was 43 months (range: 7-75 months). Among the molecular subtypes, p53 abnormal patients had the worst DFS, and POLE-mutated patients had the best DFS, and the difference in DFS among the 4 subtypes was statistically significant ( P = 0.046). Grouping according to the median density of immune cells in the entire group, patients with high CD8 + cell density (45 cases) had better DFS than those with low density (45 cases) ( P = 0.010), PD-L1 ICS-positive patients had worse DFS than negative patients ( P = 0.019), and NSMP subtype patients with high CD4 + cell density (24 cases) had better DFS than those with low density (23 cases) ( P < 0.001). There was no statistically significant difference in DFS among patients grouping with other PD-L1 scoring modes and other immune cell infiltration density (all P > 0.05). Cox regression analysis indicated that high CD8 + cell density ( HR = 0.335, 95% CI: 0.113-0.990, P = 0.048) was an independent protective factor for poor DFS in endometrial cancer patients, and high CD4 + cell density was an independent protective factor for poor DFS in NSMP subtype patients ( HR = 0.035, 95% CI: 0.003-0.345, P = 0.004). Conclusions:There are significant differences in PD-L1 expression and immune cell infiltration density among the different molecular subtypes of endometrial cancer, which are correlated with the prognosis of patients, and may provide reference for the selection of immunotherapy strategies and prognosis judgment.

[Purpose]To investigate the trends of incidence and age at onset of uterine corpus can-cer in Jiangsu cancer registration areas from 2009 to 2019.[Methods]The continuous monitoring data of uterine corpus cancer from 2009 to 2019 were collected from 16 cancer registries in Jiang-su Province.The crude incidence rate,the age-standardized incidence rate by Chinese standard population(ASIRC),crude and adjusted mean age,and standardized age-specific incidence composition were calculated.The average annual percentage change(AAPC)were analyzed by the Joinpoint regression model.The linear regression model was used to analyze the relationship be-tween mean age at onset and year.The standardized age-specific incidence composition in 2009 and 2019 were compared.[Results]The ASIRC of uterine corpus cancer in all registration areas and in rural areas of Jiangsu Province showed upward trends with AAPC of 1.78％and 2.38％,re-spectively(P＜0.05),but not showed in the urban areas(AAPC=1.30％,P＞0.05).The crude mean age at onset increased from 56.48 years old in 2009 to 58.26 years old in 2019 with an average annual growth of 0.173 years old(P=0.001).After the population structure standardized,the trends disappeared in all registration areas.[Conclusion]From 2009 to 2019,the standardized incidence rates of uterine corpus cancer were on rise in Jiangsu cancer registration areas,especially in the age group of 50 to 59 years old.

Objective: To investigate the trends in the disease burden of leukemia in Jiangsu Province from 1990 to 2019, so as to provide insights into leukemia control in Jiangsu Province. Methods: The prevalence, incidence, death and disability adjusted life years (DALYs) of leukemia in Jiangsu Province from 1990 to 2019 were retrieved from the 2019 Global Burden of Disease Study (GBD 2019) database, and standardized by the age structure of Chinese populations in 2000. The trends in the disease burden of leukemia in Jiangsu Province from 1990 to 2019 were analyzed using average annual percent change (AAPC). Results : The average annual standardized prevalence, incidence, mortality and DALY rate of leukemia were 63.63/105, 9.76/105, 4.10/105 and 194.83/105 in Jiangsu Province from 1990 to 2019, respectively. The average annual standardized prevalence (AAPC=1.420%, t=5.644, P<0.001) and incidence (AAPC=0.806%, t=3.505, P<0.001) of leukemia appeared a tendency towards a rise, while the average annual standardized mortality (AAPC=-1.589%, t=-14.714, P<0.001) and DALY rate (AAPC=-1.849%, t=-9.046, P<0.001) of leukemia appeared a tendency towards a decline in Jiangsu Province from 1990 to 2019. Higher average annual standardized prevalence (65.27/105 vs. 62.38/105, P<0.001), incidence (10.32/105 vs. 9.29/105, P<0.001), mortality (4.69/105 vs. 3.57/105, P<0.001) and DALY rate of leukemia (216.94/105 vs. 172.80/105, P<0.001) were estimated among men than among women. The crude prevalence of leukemia peaked among patients at ages of 0 to 14 years and 60 to 74 years, and the crude incidence, DALY rate and mortality of leukemia peaked at ages of 0 to 14 years and 75 years and older. Conclusions The mortality and DALY of leukemia appeared a tendency towards a decline and the prevalence and incidence appeared a tendency towards a rise in Jiangsu Province from 1990 to 2019; however, there were high disease burdens of leukemia among men, children and the elderly.

Objective: To investigate the incidence and trends in incidence of stroke among residents in Lianyungang City, Jiangsu Province from 2014 to 2020, so as to provide insights into stroke control. Methods: The stroke morbidity data in Lianyungang City from 2014 to 2020 were captured from Lianyungang Municipal System for Monitoring of Cardiovascular and Cerebrovascular Diseases, and standardized by the sixth national population census data in China in 2010. The trends in stroke incidence were evaluated using average annual percentage change (AAPC), and the gender-, age-, region- and disease type-specific incidence and trends in incidence of stroke were descriptively analyzed. Results: Totally 162 423 new stroke cases were diagnosed in Lianyungang City from 2014 to 2020 new case, and the annual mean crude and standardized incidence rates were 435.32/105 and 357.28/105, which both appeared a tendency towards a rise (AAPC=12.61%, t=39.098, P<0.001; AAPC=9.91%, t=6.123, P<0.001) . The standardized incidence of stroke was significantly higher in men than in women (389.63/105 vs. 327.17/105; χ2=4.056, P=0.044). The crude incidence of stroke appeared a tendency towards a rise with age among residents (χ2trend=258.219, P<0.001), and appeared a tendency towards a rise among residents at ages of <35 (AAPC=22.52%, t=6.723, P<0.001), 35 to 64 (AAPC=9.78%, t=7.867, P<0.001) and 65 years and older (AAPC=10.24%, t=5.156, P<0.001). The crude incidence was higher in rural areas than in urban areas (437.72/105 vs. 425.31/105; χ2=20.709, P<0.001). Ischemic stroke was the predominant type (139 680 cases, 86.00% of all cases), and both the crude and standardized incidence appeared a tendency towards a rise (AAPC=13.79%, t=16.865, P<0.001; AAPC=10.88%, t=5.128, P<0.001). Conclusion The incidence of stroke appeared a tendency towards a rise among residents living in Lianyungang City from 2014 to 2020. Men, middle-age and elderly residents and rural residents are high-risk populations for stroke control.

Objective:To investigate the present situation of unintended pregnancy within two years postpartum and its influencing factors in China.Methods:Participants who delivered a live birth at 60 hospitals in 15 provinces in the eastern, central and western regions of China during July 2015 to June 2016 were interviewed by using structured questionnaire. Information on occurrence of unintended pregnancy within 2 years after delivery, postpartum contraceptive use, sexual resumption, breastfeeding, and women′s socio-demographic characteristics, and so on, were collected. Life-table analysis, cluster log-rank tests and a 2-level Cox regression model were used for data analysis.Results:A total of 18 045 postpartum women were investigated. The cumulative 1- and 2-year unintended pregnancy rates after delivery were 5.3% (95% CI: 4.5%－6.1%) and 13.1% (95% CI: 11.3%－14.8%), respectively. Cox regression model analysis showed that the risk of unintended pregnancy within 2 years postpartum were increased in younger women, ethnic minorities, women with abortion history, and those who had a vaginal delivery with short lactation time and late postpartum contraceptive initiation (all P<0.01). The risk of postpartum unintended pregnancy was not associated with geographic regions and hospitals where women gave a birth (all P>0.05). Conclusions:In China, the risk of unintended pregnancy within 2 years after delivery is relatively high. Service institutions and service providers should improve the quality of postpartum family planning services, promote the use of high effect contraceptive methods, and educate women to use a method at the time of their sexual resumption or even before.

Objective:To study the characteristics of the lens turbidity after long-term exposure to low intensity 635nm laser.Methods:Cluster sampling method was adopted to select 812 employees in a laser leveler workshop in a city of Guangdong Province from January 2014 to December 2018. They were divided into the control group, diffuse reflection (DR) group and direct vision (DV) group for retrospective observation and analysis of lens turbidity. The laser irradiation intensity of each group was investigated, the position and shape of lens opacity were analyzed, and the influencing factors were statistically analyzed with the repeated measurement data of dichotomy.Results:The laser irradiance and radiant exposure of DV group were between 0.72×10 -4 and 9.92×10 -4 mW/cm 2 and between 2.61×10 -2 and 1.53 J/cm 2, respectively. The subjects were mainly diagnosed with lens turbidity lesion, especially for the DV group. Most of lesions occurred in the pole and periphery of the anterior cortex. The lesions exhibited multipoint patterns with greyish white color. The turbidity rates in DV group (before work and work for 1, 2, 3 years) were 0%, 1.99% (8/402) , 4.98% (20/402) and 6.72% (27/402) , respectively, in the order of observation points. The statistical analysis of single factor effect showed that the turbidity rate was higher in DV group and higher in the second year in the DV group ( P<0.01) . Multi-factor analysis of the laser effect on the lens showed that the main effect between groups, between the observation point were statistically significant ( P<0.05) , but no statistical significance in the interaction between group×observation points ( P>0.05) . Conclusion:Lens turbidity lesion can be caused by long-term exposure to low intensity 635 nm laser, so the product safety classification should be strictly strengthened. It is necessary to strengthen the protection of laser photochemical damage in the production process.

Objective:To investigate a cluster epidemic of COVID-19 after a mass gathering activity in Ningbo of Zhejiang province and analyze the transmission chain and status of infection cases of different generations.Methods:The tracking of all the close contacts of the first COVID-19 case and epidemiological investigation were conducted on January 29, 2020 after a cluster epidemic of COVID-19 related with a Buddhism rally on January 19 (the 1.19 rally) in Ningbo occurred. The swabs of nose/throat of the cases and close contacts were collected and tested for nucleic acids by real-time fluorescence quantitative RT-PCR.Results:From January 26 to February 20, 2020, a total of 67 COVID-19 cases and 15 asymptomatic infection cases related with the 1.19 rally were reported in Ningbo. The initial case was the infection source who infected 29 second generation cases and 4 asymptomatic infection cases, in whom 23 second generation cases and 3 asymptomatic infection cases once took bus with the initial case, the attack rate was 33.82% (23/68) and the infection rate was 38.24% (26/68). The risks of suffering from COVID-19 and being infected were 28.91 times and 26.01 times higher in rally participants taking bus with initial case compared with those taking no bus with initial case. In this epidemic, 37 third+generation cases and 11 related asymptomatic infection cases occurred, the attack rate was 2.88% (37/1 283) and the infection rate was 4.76% (48/1 008). The main transmission routes included vehicle sharing and family transmission.Conclusion:It was a cluster epidemic of COVID-19 caused by a super spreader in a massive rally. The epidemic has been under effective control.