Recent data suggest that vascular endothelial growth factor receptor inhibitor (VEGFRi) can enhance the anti-tumor activity of the anti-programmed cell death-1 (anti-PD-1) antibody in colorectal cancer (CRC) with microsatellite stability (MSS). However, the comparison between this combination and standard third-line VEGFRi treatment is not performed, and reliable biomarkers are still lacking. We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi (combination group, n=54) or VEGFRi alone (VEGFRi group, n=32), and their efficacy and safety were evaluated. We additionally examined the immune characteristics of the MSS CRC tumor microenvironment (TME) through single-cell and spatial transcriptomic data, and an MSS CRC immune cell-related signature (MCICRS) that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort. Compared with VEGFRi alone, the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit (median progression-free survival: 4.4 vs. 2.0 months, P=0.0024; median overall survival: 10.2 vs. 5.2 months, P=0.0038) and a similar adverse event incidence. Through single-cell and spatial transcriptomic analysis, we determined ten MSS CRC-enriched immune cell types and their spatial distribution, including naive CD4⁺ T, regulatory CD4⁺ T, CD4⁺ Th17, exhausted CD8⁺ T, cytotoxic CD8⁺ T, proliferated CD8⁺ T, natural killer (NK) cells, plasma, and classical and intermediate monocytes. Based on a systemic meta-analysis and ten machine learning algorithms, we obtained MCICRS, an independent risk factor for the prognosis of MSS CRC patients. Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation, and hence a significant relation with the superior efficacy of pan-cancer immunotherapy. More importantly, the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort. Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity. MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.
Humans ; Colorectal Neoplasms/drug therapy* ; Male ; Female ; Immunotherapy ; Middle Aged ; Aged ; Tumor Microenvironment/immunology* ; Retrospective Studies ; Microsatellite Instability ; Transcriptome ; Single-Cell Analysis ; Programmed Cell Death 1 Receptor/immunology* ; Gene Expression Profiling ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors*

Abstract School health education and health promotion have been the focus of China s school health work since the reform and opening up, and have been emphasized at different stages. By reviewing the problems at three different stages, namely, transformation stage of school education into the school health education stage, the institutionalization stage of school health education, and the new concept stage of school health education, the paper traces the development process of school health education in China since the reform and opening up, and summarizes the experience and reflections, so as to provide implications and suggestions for the development of school health education in China.

BACKGROUND:In recent years,a variety of lasers have been widely used in various diseases related to stomatology,including the prevention and treatment of dental caries. OBJECTIVE:To investigate the effect of neodymium-doped:yttrium aluminum perovskite(Nd:YAP)laser combined with two remineralizers on early enamel caries in vitro. METHODS:Early enamel caries models in vitro were artificially established by 60 enamel blocks and randomly divided into 6 groups(n=10).Group A did not undergo any treatment but underwent extracorporeal pH circulation.Group B underwent remineralization of dentin(the main component of casein phosphopeptide-amorphous calcium phosphate composite)and extracorporeal pH circulation.Group C underwent remineralization treatment of Sensodyne toothpaste(the main component of bioactive glass)and then underwent extracorporeal pH circulation.Group D received Nd:YAP laser irradiation and extracorporeal pH circulation.Group E was treated with Nd:YAP laser irradiation,with remineralization of dentin,and then with extracorporeal pH circulation.In group F,Nd:YAP laser irradiation was performed,and then Sensodyne toothpaste was used for remineralization,and the extracorporeal pH circulation was performed;the remineralization treatment was conducted twice a day,and the experimental period was 20 days.Group G was a normal control group,without caries or remineralization,but only underwent extracorporeal pH circulation.After the experiment,the microhardness,morphology and Ca/P ratio of the dental enamel surface were measured in each group. RESULTS AND CONCLUSION:(1)The surface microhardness value of dental enamel in groups B,C and D was higher than that in group A(P<0.000 1);the surface microhardness value of dental enamel in groups E and F was significantly higher than that in groups B,C and D(P<0.000 1),and the surface microhardness value of dental enamel in group F was significantly higher than that in group E(P<0.000 1).(2)Scanning electron microscopy showed that there were a lot of demineralized pores on the enamel surface of group A.There were mineral deposits on the enamel surface of group B,which were uneven and loose.In group C,there were a lot of mineral deposits on the enamel surface,and demineralized pores were found between the calcified masses.The enamel surface of group D was relatively flat;the demineralized pores were significantly smaller than that of group A,and the enamel column interstitium was damaged.In group E,the mineral deposits on the enamel surface were thicker and the demineralized pores were significantly reduced.The mineralized substances deposited on the enamel surface of group F were most dense and uniform and the demineralized pores were small.(3)The Ca/P ratio on the enamel surface of groups B and C was significantly higher than that of group A(P<0.000 1);the Ca/P ratio on the enamel surface of group E was significantly higher than that of groups B,C and D(P<0.000 1),and the Ca/P ratio on the enamel surface of group F was higher than that of group E(P<0.001).(4)These findings indicate that bioactive glass,casein phosphopeptide-amorphous calcium phosphate composite,and Nd:YAP laser after enamel demineralization can promote the remineralization of early enamel caries.Nd:YAP laser combined with bioactive glass or casein phosphopeptide-amorphous calcium phosphate composite can further strengthen the remineralization of dental enamel caries,and the combination of Nd:YAP laser and bioactive glass has the best effect.

Objective:To evaluate the effectiveness of oral-nasal oxygen supply mouth guard in painless gastroscopy for snoring patients.Methods:The snoring patients who underwent painless gastroscopy at two Endoscopy Centers of Shanghai East Hospital, Tongji University in July 2022 were randomly divided into the observation group (using oral-nasal oxygen supply mouth guard) and the control group (using ordinary nasal oxygen tube and mouth guard). Parameters such as the wearing time and the removal time of the mouth guard, lowest pulse oxygen saturation (SpO 2), incidence of hypoxemia, and the satisfaction of medical staff were compared between the two groups. Results:The wearing time of mouth guard was 11.63±0.84 seconds and the removal time was 5.33±0.76 seconds in the observation group ( n=40), which were lower than those in the control group ( n=47) (14.91±1.21 seconds, t=-14.463, P<0.001; 10.38±0.80 seconds, t=-30.095, P<0.001). The wearing satisfaction score was 9.80±0.61, the lowest SpO 2 was (96.70±3.42)%, the removal satisfaction score was 9.75±0.67, and the anesthesiologists' satisfaction score was 9.20±1.42 in the observation group, which were higher than those in the control group [7.70±0.93, t=12.209, P<0.001; (94.06±3.72)%, t=3.417, P=0.001; 7.96±0.98, t=9.803, P<0.001; 8.13±1.35, t=3.615, P=0.001] with significant difference. There was no significant difference in the incidence of hypoxemia [10.00% (4/40) VS 14.89% (7/47), χ2=0.130, P=0.718] and endoscopic physician satisfaction score (9.30±0.97 VS 9.02±1.31, t=1.112, P=0.269) between the two groups. Conclusion:The oral-nasal oxygen supply mouth guard is easy to wear and remove, effectively reducing SpO 2 fluctuations during painless gastroscopy for snoring patients. It can enhance medical staff satisfaction with high clinical value.

ABSTRACT OBJECTIVE To investigate the current situation of pediatric pharmacist-managed clinic in China, and to provide reference for pediatric pharmacist-managed clinic construction and improvement. METHODS Domestic Children's hospitals, Women's & Children's Hospital, and general hospitals with pediatric unit were selected as the survey objects, questionnaires were distributed through the Wenjuanxing Application, and SPSS 26.0 was used to describe the data. The development of pediatric pharmacist-managed clinic, the qualification of visiting pharmacists, the situation of post training and training needs were analyzed. RESULTS A total of 101 valid questionnaires were collected. Pediatric pharmacist-managed clinics had been set up in 55(54.5%) hospitals, of which 35 were independent pharmacists' clinics, and most had well medical document and patient management processes. However, about 70% of hospitals did not charge registration fees, and more than half of hospitals had fewer than 5 patient-visits per day. 85.5% of the hospitals were visited by clinical pharmacists, and about half of them were senior clinical pharmacists with more than 10 years of working experience. But only 3.6% of visiting pharmacists had the right of specific prescription. In 101 hospitals relevant post training for pharmacists had been carried out in 36 hospitals, of which 25 hospitals had set up pharmacist-managed clinic. In addition to pharmaceutical expertise, more than 50% of pharmacists had a strong demand for the improvement of physician-patient communication and problem-solving ability, and 30%-40% of the demand was focused on the collection of medication history, psychological counseling ability, and case-based learning in the pharmacist-managed clinic. CONCLUSION At present, the domestic pediatric pharmacist-managed clinic shows a vigorous development trend, however, there are insufficient registration fees, visits, and post training. Appropriate service methods of pediatric pharmacist-managed clinic should be actively explored, and a pediatric specialized training system for should be well constructed to improve the competency.

Abstract OBJECTIVE To analyze the drug-drug interaction during the use and treatment of nirmatrelvir/ritonavir tablets in children, and to provide reference for rational drug use in clinical practice. METHODS All hospitalized pediatric patients with using nirmatrelvir/ritonavir tablets from December 23, 2022 to February 8, 2023 in Children's Hospital, Zhejiang University School of Medicine were collected. The use of nirmatrelvir/ritonavir was analyzed, and the combination drugs were classified. The potential clinical drug-drug interactions of nirmatrelvir/ritonavir were analyzed through micromedex drug interaction database and the severity was graded. RESULTS A total of 48 patients using nirmatrelvir/ritonavir tablets were collected, with a median age of 6.71 years old(87 d-17.75 years old). The usage departments were mainly in the departments of hematology, ICU, infectious disease, and general internal medicine, and the main underlying disease being tumors. The median fever-reducing time after medication was 3 d. Many drugs were combined during medication period. A total of 15 potential drug-drug interaction drugs of nirmatrelvir/ritonavir tablets were collected, and potential drug interaction with antifungals should be considered. CONCLUSION The department with more usage of nirmatrelvir/ritonavir tablets in children is hematology, and the main underlying disease is tumors. When nirmatrelvir/ritonavir tablets are used in combination with potential drug-drug interaction drugs, attention should be paid to monitoring the efficacy and adverse reactions.

Abstract Chinese school health education began in the late Qing Dynasty. While both local schools and western missionary schools were involved, each had different characteristics. With the goal of strengthening the country, local schools taught both Chinese and western educational content, and gradually embarked on the road of independent research and development. Missionary schools aimed to spread doctrines and western health concepts, and simultaneously introduced the western school health system. By comparing the development of two kinds of school health education in the late Qing government, this study analyzes the differences between them in terms of their educational objectives, approaches and content. The differences between Chinese and western ideas on education, body and health are summarized and regarded as fundamental factors for their differences.

Objective:To analyze the clinical characteristics and prognosis of pregnant women with hemorrhagic fever with renal syndrome (HFRS).Methods:A total of 11 pregnant women with HFRS admitted to The Second Affiliated Hospital of Xi′an Jiaotong University (four cases), The Second Affiliated Hospital of Air Force Medical University (four cases), The First Affiliated Hospital of Xi′an Jiaotong University (one case) and Central Hospital of Xianyang City (two cases) between November 2009 and February 2019 were included as the study group, and 24 age-matched non-pregnant women with HFRS were selected as the control group. The age, complications, clinical classification and laboratory indexes of the two groups were analyzed retrospectively, and the clinical outcomes of pregnant women and their fetuses in the study group were followed up. The data between two groups were compared using Mann-Whitney U test or chi-square test. Results:Patients in the study and control groups were 29 (22, 33) and 32 (24, 37) years old, respectively. Seven of 11 patients in study group were severe and critical cases, which was significantly higher than that in the control group (16.7%(4/24), χ2=7.722, P=0.015). In the study group, 10 patients had hypervolemic syndrome, 10 patients had pulmonary edema and six patients had overlapping hypotension shock phase and oliguria phase, which were all higher than those in the control group ((2/24, 8.3%), (2/24, 8.3%) and (2/24, 8.3%), respectively; χ2=22.828, 22.828 and 9.135, respectively, all P<0.01). Compared with the control group, the pregnant patients in study group had a higher urea nitrogen maximum and serum creatinine maximum, and the differences were both statistically significant ( Z=-2.453 and -2.336, respectively, both P<0.05), while they had a lower serum albumin minimum, hemoglobin maximum and hemoglobin minimum, and the differences were all statistically significant ( Z=-3.742, -3.350 and -4.034, respectively, all P<0.01). All pregnant women with HFRS recovered. Nine pregnant women gave birth to nine healthy infants. All of them received breastfeeding and the feeding duration were more than six months. No abnormal growth and development were found during an average follow-up of three years. Conclusions:Pregnancy can aggravate the severity of HFRS, and pregnant women have higher risk of the multiple stages overlap and the complications such as hypervolemic syndrome and acute pulmonary edema. After recovery from HFRS, mother may carry to full-term pregnancy.

Objective:To explore the effect of intervention strategy based on concept of behavioral goal attainment on medication compliance of patients with hyperthyroidism after discharge.Methods:Using the convenient sampling method, a total of 104 patients with hyperthyroidism who were admitted to Henan Provincial People's Hospital from January to November 2019 were selected as the research objects. They were divided into the control group and the observation group by simple random grouping method, with 52 cases in each group. The control group was given routine follow-up nursing intervention, while the observation group was given follow-up nursing intervention based on the concept of behavioral goal attainment. Before intervention and 12 weeks after intervention, medication compliance, mastery of knowledge, uncertainty, self-efficacy and serological indexes including thyroid stimulating hormone (TSH) , free thyroxine (FT 4) and free triiodothyronine (FT 3) were compared of the two groups. Results:There was no statistically significant difference in scores of compliance, hyperthyroidism-related knowledge questionnaire, uncertainty and self-efficacy and serum TSH, FT 4 and FT 3 levels in the control group before and after intervention ( P>0.05) . After 12 weeks of intervention, scores of compliance, hyperthyroidism-related knowledge questionnaire and self-efficacy score and serum TSH level of the observation group were higher than those before the intervention and the control group, while uncertainty score and serum FT 4 and FT 3 levels were lower than those before intervention and the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Intervention strategies based on concept of behavioral goal attainment can not only improve medication compliance of patients with hyperthyroidism, but also enhance the ability of patients to master disease-related knowledge, which has positive significance for controlling of disease development.

Objective: To identify the characteristics of social network and the association between ego-centric network and HIV status among young MSM Chinese students. Methods: The cross-sectional study was conducted in Chongqing, Tianjin, Harbin and Xi an city from April to December 2017 and from March to May 2018. A mixed recruitment method of snowball sampling and RDS approach was used to recruit participants who reported information on social network and received HIV test. The Multiple Regression Analysis method was used to for the analysis of association between ego-centric social network and HIV status of men who have sex with men (MSM) among young students. Results: The sample included 547 participants who nominated 1 088 social partners in total with average age of 13 to 60 years old. The MSM with different sexual orientation from their social members (aOR=0.38), embedded in a large network (aOR=0.63), with a high individual betweenness centrality (aOR=0.27) were at lower risk of HIV-positive status; while MSM who differed greatly in education level with their social members(aOR=1.60), existed in sexual networks(aOR=1.41), existed in the “risky networks” (aOR=1.88) , with high network density (aOR=1.91) and a high individual degree (aOR=4.10) had higher risk of HIV-positive status(P<0.05). Conclusion MSM with great difference in education level from social members, existed in sexual networks, with a large network density and a high degree were exposed to higher risk of HIV-positive status.