Purpose: Dual anti–human epidermal growth factor receptor 2 (HER2) drugs have become the standard regimen for neoadjuvant systemic treatment (NST) to HER2-positive breast cancer patients. However, the efficacy varies greatly among patients with different HER2 protein expression levels. Materials and Methods: A total of 575 HER2-positive breast cancer patients from multiple centers throughout China from 2013 to 2022 were retrospectively analyzed. We compared clinicopathological features in different HER2 immunohistochemistry classes (HER2 2+/in situ hybridization [ISH] + or HER2 3+), and their difference in response to NST and survival with single or dual anti-HER2 drugs. Drug sensitivity assays were used to evaluate different efficacy of anti-HER2 drugs in vitro. Results: Compared to HER2 3+ subgroup, the HER2 2+/ISH+ group had a higher proportion of hormone receptor–positive status (48.7% vs. 76.1%, p < 0.001), more HER2 protein loss after NST, lower pathological complete response (pCR) rate (46.07% vs. 16.24%, p < 0.001), and tended to have worse disease-free survival (DFS). In HER2 2+/ISH+ patients, treated with pertuzumab and trastuzumab in combination had no significant improvement in pCR (19.12% vs. 12.24%, p=0.287) and DFS (p=0.908) than using alone. Drug sensitivity assay showed poor efficacy with dual anti-HER2 drugs in HER2 2+/ISH+ cell lines; however, fam-trastuzumab deruxtecan drugs had a satisfactory effect. Conclusion Owing to the differences in clinicopathological features and treatment efficacy, we considered the HER2 2+/ISH+ group to be a distinct subtype and defined it as the HER2-moderate–positive subgroup. In this subgroup, dual anti-HER2 drugs did not exert significant improvement in pCR and DFS. Therefore, treatment optimization is warranted, with antibody-drug conjugate drugs as potential options.

Background Air pollution has widespread adverse health effects on human health, but research on its impact on reproductive health and related physiological mechanisms remains insufficient. Objective To investigate the associations between short-term exposure to particulate matter and nitrogen dioxide (NO₂) and serum levels of anti-Müllerian hormone (AMH) and testosterone in healthy adults. Methods A total of 152 healthy adults were recruited for a panel study, undergoing four follow-up visits from September 2019 to January 2020. Basic demographic information and serum samples were collected. Reproductive hormone levels were measured by enzyme-linked immunosorbent assay kits. Concurrently, environmental data in the study area were monitored, including fine particulate matter (PM_2.5), black carbon (BC), NO₂, particle number concentrations in the 5-560 nm size fraction (PNC_{5_560}), and meteorological variables. Linear mixed-effects models were constructed to estimate the effects of short-term exposure to these particulate matter on serum reproductive hormone levels. Results The participants had an average age of (23.9±2.4) years, with 102 women. For each interquartile range (IQR) increment in pollutant moving average concentrations, PM_2.5, PNC_{5_25}, PNC_{100_560}, BC, and NO₂ were associated with relative decreases in female serum AMH levels by 10.2%-16.9%, 46.2%-58.0%, 16.9%-21.2%, 14.8%-26.5%, and 11.3%-17.6%, respectively. These negative associations were stronger in females with waist-to-hip ratio > 0.76 and physical activity levels ≤ 1217 metabolic equivalents (MET) min per week. Similarly, in males, an IQR increase in the same pollutants was associated with relative decreases in serum free testosterone by 11.1%-17.2%, 35.2%, 10.5%-18.9%, 18.7%-24.2%, and 10.3%-26.0%, respectively. These effects were more pronounce in male with a waist-to-hip ratios > 0.81 and physical activity levels ≤ 1498 MET-min per week. Conclusion Short-term exposure to particulate matter and NO₂ may reduce serum levels of AMH and testosterone in healthy adults. Furthermore, these adverse effects appears to be stronger in adults with higher waist-to-hip ratios.

Objective To study the root canal morphology of permanent mandibular anterior teeth and explore its correlation with the occurrence of three-rooted mandibular molars using cone beam computed tomographic(CBCT)imaging.Methods CBCT image data of 200 subjects were randomly collected from dental clinics.The root canal morphology of the mandibular anterior teeth was identified and classified by Vertucci's classification,and the root length and labio-lingual dimension at the tooth neck level were measured.The occurrence of three-rooted mandibular first molars was examined as well.The concurrence rates of double-canaled anterior teeth and three-rooted mandibular first molars at each side,and concurrence rates of bilateral double-canaled anterior teeth and three-rooted man-dibular first molars were calculated.Spearman correlation tests were applied to analyze the correlation between the double-canaled ante-rior teeth and three-rooted mandibular first molars,as well as the bilateral antimetric teeth.Results The incidence of double-canaled system was 10.4％,18.6％and 6.5％in mandibular central incisors,lateral incisors and canines,respectively;the bilateral concur-rence rates were 5.7％,11.1％and 3.0％,respectively,and Spearman correlation coefficients(rho)were 0.487,0.505 and 0.440(P＜0.01),respectively;gender difference and side difference were not detected(P＞0.05).The frequency of three-rooted mandibular first molars was 24.6％;gender difference was not detected(P＞0.05),while the incidence was significantly higher at the right side(29.0％)than the left side(20.3％)(P＜0.05).The bilateral concurrence rate was 17.4％,and a moderate correlation was detected(rho=0.666,P＜0.01).The concurrence rates between the double-canaled anterior teeth and three-rooted mandibular first molars at each side were very low(2.6％-7.6％),and Spearman correlation tests demonstrated that no correlation(P＞0.05)could be detected between them.Conclusion The lateral incisors exhibited the highest incidence of two root canals among the mandibular anterior teeth.Ad-ditionally,there was no significant corr-elation between three-rooted mandibular first molars and double-canaled mandibular anterior teeth.

Objective:To analyze application effect of Failure Mode and Effects Analysis(FMEA)in the maintenance and upkeep for equipment in operating room.Methods:The process of FMEA mode was analyzed,and a strategy about maintenance and upkeep for equipment in operating room on the basis of FMEA was formulated from some aspects included preparation stage,analysis for failure mode(FM),construction for the system of prevention,maintenance and upkeep,and improvement and analysis for results.Sixty used equipment in the operating room of Shiyan Taihe Hospital(Affiliated Hospital of Hubei University of Medicine)from January to December 2023 were selected.According to different management methods for equipment,the conventional management mode and the FMEA management mode were respectively selected to conduct maintenance and upkeep for equipment in operating room,with 30 equipment in each management mode.The incidences of adverse events,the satisfaction scores of operators,and the qualities of maintenance and upkeep for equipment of the two kinds of management modes were compared.Results:The number of occurring inadequate preparation of surgical associated facilities,non-standardized operation of surgical equipment,and incidence of faliures in surgical equipment were respectively in 30 equipment in operating room that adopted FMEA management mode,and the total incidence of adverse events was 6.67%(2/30),which was lower than 36.67%(11/30)that adopted conventional management mode,and the difference was statistically significant(x2=7.954,P<0.05).The satisfaction scores of the operators of operating equipment for the operational quality,usage operation,and maintenance and upkeep of the equipment that received the FMEA management mode in operating room were respectively(92.22±3.36),(91.69±2.25)and(93.25±3.69)points,all of which were higher than those that received conventional management mode,and the differences were statistically significant(t=15.418,17.415,16.639,P<0.05).The average increase extents of the response time for fault,repair time for fault,and the cost of operation and maintenance that adopted FMEA management mode were respectively(2.36±0.59)h,(4.25±2.11)h and(1.89±0.14)%for equipment in operating room,all of which were less than those that adopted conventional management mode,and the differences were statistically significant(t=9.943,12.050,11.069,P<0.05).The failure frequency of equipment of adopting FMEA management mode was(1.54±0.21)times per year,which was lower than that of adopting conventional management mode.The average success rate of opening equipment of adopting FMEA management mode was(90.69±3.59)%,which was higher than that of adopting conventional management mode,and the differences of the above two indicators between two modes were statistically significant(t=15.184,18.779,P<0.05).Conclusion:The application of FMEA in the maintenance and upkeep for medical equipment in the operating room can assess the operational quality of the equipment,and carry out preventive operation and maintenance,and reduce the incidence of failures in equipment,and decrease costs for maintenance,and improve the clinical service level for the equipment.

Objective:To analyze the screening results of the Urban Cancer Early Diagnosis and Treatment Project in Qinghai Province from 2019 to 2024.Methods:A summary and statistical analysis were conducted on six years of screening data from the Urban Cancer Early Dia-gnosis and Treatment Program in Qinghai Province,with the high-risk rate,screening rate,and detection rate calculated separately for each type of cancer.Results:From 2019 to 2024,56,882 high-risk individuals were identified.The high-risk rates for lung,colorectal,breast,up-per gastrointestinal,and liver cancer were 22.02%,21.57%,14.23%,13.52%,and 6.10%,respectively.Overall,13,592 individuals com-pleted clinical screening,with detection rates of 0.32%for lung cancer,0.41%for liver cancer,0.08%for precancerous gastric lesions,3.63%for precancerous colorectal lesions,0.08%for esophageal cancer,0.16%for gastric cancer,and 0.14%for colorectal cancer.Conclusions:The implementation of the Urban Cancer Early Diagnosis and Treatment Program in Qinghai Province aids in the early detection of cancer,improves early diagnosis and survival rates,and reduces mortality.Nevertheless,due to low public awareness and limited participation,en-hancements in program management and public outreach are required.

Kupffer cells (KCs), as residents and sentinels of the liver, are involved in the formation of hepatic fibrosis (HF). However, the biological functions of circular RNAs (circRNAs) in KCs to HF have not been determined. In this study, the expression levels of circRNAs, microRNAs, and messenger RNAs (mRNAs) in KCs from a mouse model of HF mice were investigated using microarray and circRNA-Seq analyses. circDcbld2 was identified as a candidate circRNA in HF, as evidenced by its up-regulation in KCs. Silver staining and mass spectrometry showed that Wtap and Igf2bp2 bind to cirDcbld2. The suppression of circDcbld2 expression decreased the KC inflammatory response and oxidative stress and inhibited hepatic stellate cell (HSCs) activation, attenuating mouse liver fibrogenesis. Mechanistically, Wtap mediated the N ⁶-methyladenosine (m6A) methylation of circDcbld2, and Igf2bp2 recognized m6A-modified circDcbld2 and increased its stability. circDcbld2 contributes to the occurrence of HF by binding miR-144-3p/Et-1 to regulate the inflammatory response and oxidative stress. These findings indicate that circDcbld2 functions via the m6A/circDcbld2/miR-144-3p/Et-1 axis and may act as a potential biomarker for HF treatment.

Objective:To explore the effect and application of interventional measures with concept of risk management in adverse events of medical devices,and assess their effectiveness in reducing the incidence of adverse events and in enhancing patients'safety.Methods:The intervention measures with concept of risk management was adopted to carry out risk assessment and hierarchical management for medical devices,and the operating status of medical devices was monitored in real time,and the standard operating procedures of using medical device were formulated for conducting risk management for medical devices.A total of 2,222 conventional medical devices in clinical use at Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University from January 2022 to March 2024 were selected.Among them,1,064 devices(with random values≤0.48)were managed using conventional methods by stratified random sampling without proportional allocation.Another 1,158 devices(random value>0.48)applied the risk intervention management method.A comparative analysis was conducted on the incidence of adverse events of medical devices,the qualified rate of medical device cleaning and the wet package rate of the two management methods,as well as the score of medical device knowledge level of nursing staff.Results:Among the 1,158 medical devices that adopted the risk intervention management method,the incidences of adverse events in non-surgical departments,surgical departments and diagnosis-related departments were 0.69%(8/1,158),1.90%(22/1,158)and 3.11%(36/1,158),respectively.All were lower than 3.85%(41/1,064),4.98%(53/1,064),and 8.93%(95/1,064)of 1,064 medical devices under the conventional management method,respectively.The differences were statistically significant(x2=25.716,16.143,33.852,P<0.05).The incidence of adverse events at different risk levels of medical devices was lower than that of conventional management method,and the difference was statistically significant(x2=7.625,P<0.05).The qualified rate of cleaning medical device was higher than that of the conventional management method,while the rate of wetting package was lower than that of the conventional management method,and the differences were statistically significant(x2=9.091,17.540,P<0.05).The knowledge levels and total scores of nursing staffs for the composition of medical devices,usage norms,cleaning and sterilization,defect examination,maintenance and precautions of management method with risk intervention were all higher than those of conventional management method,and the differences were statistically significant(t=2.158,2.422,2.544,2.391,2.152,4.528,P<0.05).Conclusion:The intervention measure with the concept of risk management can significantly reduce the incidence of adverse events of medical device,and improve the qualified rate of cleaning medical device,and improve the knowledge level of nursing staffs for medical device.

Objective:To explore the relationship between urinary cadmium levels and thyroid hormone levels in people aged 40-89 years old in selected areas of China.Methods:Based on the "Investigation of the Impact of Soil Quality of Agricultural Land on Human Health in Typical Areas" project from October 2019 to August 2020, a multi-stage stratified random sampling method was used to include 6 588 middle-aged and older adults aged 40-89. Demographic characteristics, dietary frequency and disease status were collected through the questionnaire and physical examination. Urinary cadmium and urinary creatinine were detected by random midstream urine. Fasting venous blood was collected for the detection of Triiodothyronine (T3) and Thyroxine (T4). The linear mixed effects model was used to explore the association of urine cadmium levels with thyroid hormone levels. Its dose-response relationship was explored by using the restricted cubic spline.Results:The age of the subjects was (63.48±12.18) years, with males accounting for 51.28%. The M ( Q 1,Q 3) of urinary cadmium level, T3 and T4 was 2.48 (1.36, 4.42) μg/g·creatinine, (1.96±0.51) nmol/L and (113.75±29.11) nmol/L, respectively. The linear mixed effects model showed that the changes of T3 and T4 were 0.027 (0.009, 0.044) nmol/L and 2.019 (1.084, 2.953) nmol/L for each one-unit increase (natural logarithm transformed) of urinary cadmium. The restricted cubic spline showed that there was a positive nonlinear association between urinary cadmium and T3 as well as T4 (all Pnonlinear<0.05). Conclusion:In selected areas of China, the urinary cadmium level of middle-aged and older adults aged 40-89 years is positively associated with T3 and T4.

Objective:To evaluate the levels and source of cadmium exposure by dietary pathway among middle-aged and elderly people ≥40 in cadmium-contaminated areas of China.Methods:A total of 7 193 people aged 40-89 years from four typical cadmium-contaminated areas in China were selected as the study subjects. Food Frequency Questionnaire (FFQ), Total Diet Study (TDS) and a 3-day-24-hour dietary recall survey were conducted. Dietary cadmium intake and food sources through dietary pathways were assessed based on cadmium content in foods, consumption amounts and intake frequencies.Results:The mean age of the participants was 63.39±12.21 years, with 50.05% being males. The average monthly dietary cadmium intake was 7.39 μg/(kg·BW). Staple foods and vegetables were the primary sources of dietary cadmium intake, accounting for 57.51% and 32.48%, respectively. The monthly dietary cadmium intake in all surveyed regions did not exceed the Provisional Tolerable Monthly Intake (PTMI) recommended by the Joint FAO/WHO Expert Committee on Food Additives (JECFA).Conclusion:The monthly dietary cadmium intake among middle-aged and elderly people in cadmium-contaminated areas of China is relatively low, with the risk remaining at an acceptable level. Staple foods and vegetables are the most significant contributors to dietary cadmium intake.

Objective:To describe the body mass index (BMI) level and long-term trends of Chinese older adults aged 65 and above.Methods:Older adults aged 65 and above from six waves (2002-2018) of the China Longitudinal Healthy Longevity Survey were selected as the study population. Multiple cross-sectional design with six survey waves conducted in 2002, 2005, 2008, 2011, 2014, and 2018 was adopted, enrolling 15 647, 15 358, 15 622, 9 166, 6 302, and 12 417 participants, respectively. Additionally, a total of 13, 755 participants were included in the cohort study design. Relevant information was collected through questionnaires and physical examinations. The χ2 trend test was used to compare the changes in the rates of underweight and overweight/obesity over the years, and the linear mixed-e?ects model (LMM) was used to fit trajectory curves of BMI changes with advancing age in older adults. Results:The baseline ages of the participants included in 2002, 2005, 2008, 2011, 2014, and 2018 were (85.16±11.26), (84.23±11.83), (84.99±12.16), (81.10±11.86), (78.89±11.30), and (83.08±12.42) years, respectively, with a relatively high proportion of females and rural residents. In the cohort study, the 13 755 participants had a median ( Q1, Q3) follow-up time of 6.5 (5.2, 10.0) years, with a cumulative follow-up duration of 109 041 person-years. In each wave, males had higher BMI than females, urban residents had higher BMI than rural residents, and BMI gradually decreased with increasing age (all P<0.001). The mean BMI of older adults in China increased from (19.37±3.80) kg/m2 in 2002 to (22.04±4.01) kg/m2 in 2018 ( P<0.001). Across all survey years, the prevalence of underweight was consistently higher in women than in men and in rural areas than in urban areas, with an upward trend as age increased (all P<0.001). In 2018, the underweight rates in the 65-79, 80-89, 90-99, and ≥100-year-old age groups were 8.0%, 16.7%, 26.2%, and 35.5%, respectively. Meanwhile, the prevalence of overweight/obesity was higher in men than in women and in urban areas than in rural areas, showing a declining trend with advancing age (all P<0.001). The prevalence of underweight among the older adults decreased significantly from 45.2% in 2002 to 18.9% in 2018 ( P<0.001), while the prevalence of overweight/obesity increased from 11.0% in 1998 to 29.6% in 2018 ( P<0.001). The trajectory curves fitted by the LMM model showed that individuals born in later decades had higher BMI levels at the same age compared to earlier cohorts. Conclusion:From 2002 to 2018, the BMI level among Chinese older adults showed an increasing trend. The prevalence of underweight showed a declining trend, while the rates of obesity and overweight increased. However, the underweight rate remained notably high among the oldest old.