ObjectiveTo explore the molecular mechanism of Buzhong Yiqitang in attenuating cisplatin resistance of non-small cell lung cancer （NSCLC） cells （A549/DDP） by regulating endoplasmic reticulum stress （ERS） via the nuclear factor E₂-related factor 2 （Nrf2）/reactive oxygen species （ROS）/double-stranded RNA-activated protein kinase R （PKR）-like endoplasmic reticulum kinase （PERK）/CCAAT enhancer-binding protein homologous protein （CHOP） signaling pathway. MethodsSprague Dawley （SD） rats were used to prepare blank serum and Buzhong Yiqitang-containing serum samples， and A549/DDP cells were sub-cultured and randomly allocated into 9 groups： Blank （10% blank rat serum medium）， model （10% blank rat serum medium+20 mg·L^-1 cisplatin）， traditional Chinese medicine（TCM） （10% Buzhong Yiqitang-containing rat serum medium+20 mg·L^-1 cisplatin）， TBHQ （10% blank rat serum medium+5 μmol·L^-1 TBHQ+20 mg·L^-1 cisplatin）， TBHQ+TCM （10% Buzhong Yiqitang-containing rat serum medium+5 μmol·L^-1 TBHQ+20 mg·L^-1 cisplatin）， NAC （10% blank rat serum medium+600 μmol·L^-1 NAC+20 mg·L^-1 cisplatin）， NAC+TCM （10% Buzhong Yiqitang-containing rat serum medium+600 μmol·L^-1 NAC+20 mg·L^-1 cisplatin）， Salubrinal （10% blank rat serum medium+20 μmol·L^-1 Salubrinal+20 mg·L^-1 cisplatin）， and Salubrinal+TCM （10% Buzhong Yiqitang-containing rat serum medium+20 μmol·L^-1 Salubrinal+20 mg·L^-1 cisplatin）. The median inhibitory concentration （IC₅₀） of cisplatin in each group was determined by the cell counting kit-8 （CCK-8） method. The ROS level was detected by flow cytometry. The ultrastructure of endoplasmic reticulum （ER） was observed by transmission electron microscopy. Western blot was employed to determine the protein levels of Nrf2， phosphorylated （p）-Nrf2， CHOP， PERK， p-PERK， eukaryotic translation initiation factor 2α （eIF2α）， p-eIF2α， and activated transcription factor 4 （ATF4）. The fluorescence intensity of CHOP and p-PERK was detected by confocal fluorescence localization. ResultsCompared with the model group， the TCM group showed a decrease in IC₅₀ of cisplatin in A549/DDP cells （P<0.01）. TBHQ， NAC， and Salubrinal groups showed increases in IC₅₀ of cisplatin in A549/DDP cells （P<0.01）. TCM combined with TBHQ， NAC， and Salubrinal reduced the IC₅₀ （P<0.01）. Compared with that in the blank group， the ROS level in the model group elevated （P<0.01）. Compared with that in the model group， the ROS level in the TCM group elevated （P<0.01）. The ROS levels in the TBHQ， NAC， and Salubrinal groups were lower than that in the model group （P<0.01）. The combinations of TBHQ， NAC， and Salubrinal with TCM raised the ROS levels of A549/DDP cells （P<0.01）. A flat saclike and neatly arranged ER structure was observed in the blank group， and slight expansion of ER was observed in the model group. Significant expansion of ER was observed in the TCM group. The expansion of ER was not obvious in the TBHQ， NAC， and Salubrinal groups but significant after TBHQ， NAC， and Salubrinal were combined with TCM. CHOP and p-PERK showed higher fluorescence intensity in the model group than in the blank group （P<0.01）， and the fluorescence signal intensity in the TCM group was higher than that in the model group （P<0.01）. The fluorescence intensity in the TBHQ， NAC， and Salubrinal groups was lower than that in the model group （P<0.01）. The fluorescence intensity in the groups of TBHQ， NAC， and Salubrinal combined with TCM was higher than that in corresponding groups without TCM （P<0.01）. Compared with those in the blank group， the expression levels of Nrf2 and p-Nrf2 were up-regulated in the model group （P<0.05）. Compared with the model group， the TCM group showed down-regulated expression levels of Nrf2 and p-Nrf2 （P<0.05）. TBHQ， NAC， and Salubrinal increased the expression levels of Nrf2 and p-Nrf2 （P<0.05）， while their combinations with TCM decreased the expression levels of Nrf2 and p-Nrf2 compared with the corresponding groups without TCM （P<0.01）. There were no significant differences in the expression levels of PERK and eIF2α between groups. The expression levels of CHOP， p-PERK/PERK， p-eIF2α/eIF2α， and ATF4 were up-regulated in the model group compared with those in the blank group （P<0.05）. Compared with the model group， the TCM group showed up-regulated expression levels of CHOP， p-PERK/PERK， p-eIF2α/eIF2α， and ATF4 （P<0.05）， while the TBHQ， NAC， and Salubrinal groups showed down-regulated expression levels （P<0.05）. The groups of TBHQ， NAC， and Salubrinal combined with TCM had higher expression levels than the groups without TCM （P<0.01）. ConclusionBuzhong Yiqitang regulates ERS via the Nrf2/ROS/PERK/CHOP signaling pathway to attenuate cisplatin resistance in NSCLC.

ObjectiveTo explore the molecular mechanism of Buzhong Yiqitang in attenuating cisplatin resistance in non-small cell lung cancer （NSCLC） by inducing ferroptosis via poly（rC）-binding protein 1 （PCBP1）. MethodsThe serum containing Buzhong Yiqitang was prepared and cisplatin-resistant human non-small cell lung cancer （NSCLC） cells （A549/DDP） were cultured and randomly grouped as follows： Blank （10% blank serum）， model （10% blank serum+20 mg·L^-1 cisplatin）， Buzhong Yiqitang （10% serum containing Buzhong Yiqitang+20 mg·L^-1 cisplatin）， Fe-1 （10% blank serum+20 mg·L^-1 cisplatin+5 μmol·L^-1 Fe-1）， and Buzhong Yiqitang+Fe-1 （10% serum containing Buzhong Yiqitang+20 mg·L^-1 cisplatin+5 μmol·L^-1 Fe-1）. Firstly， PCR Array was used to screen ferroptosis-related genes regulated by Buzhong Yiqitang， and PCBP1 was identified as the target for studying the attenuation of cisplatin resistance by Buzhong Yiqitang. Subsequently， the median inhibitory concentration （IC₅₀） of cisplatin in each group was determined by the cell counting kit-8 （CCK-8） method and the resistance index （RI） was calculated. The ultrastructure of A549/DDP cells in each group was observed by transmission electron microscopy. The protein levels of PCBP1 and glutathione peroxidase 4 （GPX4） were determined by Western blot. The lipid reactive oxygen species （ROS） content in each group was determined by the C11-BODIRY 581/591 fluorescence probe. The ferrous ion assay kit was used to measure the ferrous ion content in each group. The malondialdehyde （MDA） assay kit was used to determine the MDA content in each group. ResultsCompared with model group， the IC₅₀ of cisplatin and the RI of A549/DDP cells decreased in the Buzhong Yiqitang group （P<0.05） but increased in the Fe-1 group （P<0.05）. The IC₅₀ of cisplatin and the RI of A549/DDP cells in the Buzhong Yiqitang+Fe-1 group were lower than those in the Fe-1 group （P<0.05）. Compared with the model group， the Buzhong Yiqitang group showed obvious mitochondrial ferroptosis， while the mitochondrial damage became less obvious after Fe-1 treatment. Compared with that in the Fe-1 group， the mitochondrial ferroptosis was aggravated after the intervention with Buzhong Yiqitang. Compared with blank group， the model group showed down-regulated expression levels of PCBP1 and GPX4 （P<0.05） and increased content of lipid ROS， ferrous ions， and MDA （P<0.05） in A549/DDP cells. Compared with model group， the Buzhong Yiqitang group showed down-regulated expression levels of PCBP1 and GPX4 （P<0.05） and increased content of lipid ROS， ferrous ions， and MDA （P<0.05）， while the Fe-1 group showed up-regulated expression levels of PCBP1 and GPX4 （P<0.05） and reduced content of lipid ROS， ferrous ions， and MDA （P<0.05）. Compared with the Fe-1 group， the Buzhong Yiqitang+Fe-1 group showed down-regulated expression levels of PCBP1 and GPX4 and increased content of lipid ROS， ferrous ions， and MDA （P<0.05）. ConclusionBuzhong Yiqitang attenuated cisplatin resistance in NSCLC by regulating PCBP1 to induce ferroptosis.

In the process of tumor chemotherapy， the emergence of multi-drug resistance （MDR） has always been a thorny problem， which is a result of the joint action of the host， tumor cells， and the immune microenvironment. Tumor cells can escape the toxicity of chemotherapeutic drugs through multiple pathways， being easy to produce drug resistance. MDR greatly restricts the effect of chemotherapeutic drugs on tumor cells and affects their therapeutic effects. Traditional Chinese medicine （TCM） has the unique advantages of multi-target， multi-pathway and individualized treatment. The TCM treatment of tumors emphasizes regulating Yin and Yang， as well as reinforcing healthy Qi and dispelling pathogen. In recent years， TCM has demonstrated remarkable efficacy in the treatment of tumors and the amelioration of multi-drug resistance. TCM not only can target the phenomenon of MDR but also greatly weakens the side effects of the patients after the chemotherapy， thus improving the survival quality and rate of the patients. Accordingly， many patients adopt TCM as an adjuvant therapy during or after chemotherapy. The binding of TCM to targets can reverse the drug resistance of various tumors， which has become an emerging research highlight. From the regulatory mechanism of TCM on MDR of tumors， this paper introduces the mechanisms by which tumor cells continue to grow， proliferate， and metastasize by adjusting the intracellular drug concentration， altering or utilizing the tumor microenvironment， and affecting the cell death mode to achieve the resistance to chemotherapeutic drugs. In this regard， the active ingredients and compound prescriptions of TCM can increase the sensitivity of chemotherapeutic drugs by down-regulating drug transporters， improving the tumor microenvironment， and modulating the drug resistance pathways associated with apoptosis， autophagy， ferroptosis， or pyroptosis. The aim of this paper is to explore more clinical practical value of TCM in the treatment of tumors and provide exploratory ideas and a theoretical basis for the future research on tumors and MDR.

Objectives:To observe the incidence of residual shunt post patent foramen ovale(PFO)closure and the effect of PFO closure in these migraine patients at one year after PFO. Methods:This retrospective study included patients who underwent PFO closure for migraine in the Second Affiliated Hospital Zhejiang University School of Medicine from January 2019 to June 2022,patients were divided into the grade 0 shunt group(n=67),the grade Ⅰ shunt group(n=10),the grade Ⅱ shunt group(n=13)and the grade Ⅲ shunt group(n=16)according to the results of contrast transthoracic echocardiography(cTTE)at 1 year after PFO closure.The incidence of postoperative migraine attacks among different groups of patients were compared.The risk factors of residual shunt after PFO closure were explored. Results:The mean age of enrolled 106 patients with migraine was(35.80±11.70)years,of which 83 patients(78.30%)were female.One year after PFO closure,the migraine attack and rating scale were significantly decreased compared to baseline in the grade 0 shunt group,in the grade Ⅰ shunt group and in the grade Ⅱ shunt group(all P<0.05),but not in the grade Ⅲ shunt group(P>0.05).The rate of significant and complete migraine was significantly higher in the grade 0 shunt group(58.21%),in the gradeⅠ shunt group(60.00%),in the grade Ⅱ shunt group(69.23%)as compared to the grade Ⅲ shunt group(18.75%,P=0.02)at one year after PFO.The rate of grade 0 shunt after PFO closure in patients with the microvesicles appearing in≥6 cardiac cycles in resting state before operation was significantly lower than in patients with the microvesicles appearing within 6 cardiac cycles and no microvesicles in resting state(24.00%vs.83.87%vs.70.00%,P=0.04).Logistic multivariate regression analysis showed that patients with microvesicles appearing beyond 6 cardiac cycles in resting state were more likely to have residual shunts in postoperative cTTE compared to the patients with negative cTTE and microvesicles appearing within 6 cardiac cycles in the cTTE in resting state before operation(OR=0.06,95%CI:0.02-0.23,P<0.01;OR=0.014,95%CI:0.05-0.41,P<0.01). Conclusions:Migraine patients who underwent PFO closure and with grade 0 to grade Ⅱ residual shunt at one year after PFO are most likely to have significant remission of migraine,while the incidence of migraine remission is low in patients with grade Ⅲresidual shunt.The incidence of residual shunt after PFO closure is higher in patients with the microvesicles appearing in 6 cardiac cycles in resting state in the cTTE before operation than in patients with the microvesicles appearing within 6 cardiac cycles and no microvesicles.

ObjectiveTo analyze the effect of standardized training on post competency of rehabilitation therapists, based on World Health Organization rehabilitation competency framework (RCF), and combined with the characteristics of rehabilitation and the requirements of standardized training in China. MethodsFrom 2018 to 2022, a total of 30 rehabilitation therapists who participated in the standardized training were selected. Before and after the standardized training, the closed-book theoretical assessment and Mini-clinical Evaluation Exercise (Mini-CEX) assessment were carried out, and a 360-Degree Evaluation scale was distributed to their teachers, peers and patients. Through multi-dimensional post competency analysis, the data obtained from the scales were combined with the five dimensions of basic theoretical knowledge, clinical practice ability, medical humanities literacy, scientific research and teaching ability, and organizational management ability to analyze the effect of standardized training on post competency of rehabilitation therapists. ResultsAfter training, the therapists improved in theory and case analysis (Z > 2.716, P < 0.05). They also improved in medical interview skills, physical examination, humane care/professionalism, clinical judgment ability and overall clinical level (Z > 2.162, P < 0.05) according to Mini-CEX. The medical ethics, daily work, management ability, social ability, interpersonal communication ability, basic professional ability and operation ability improved (Z > 1.978, P < 0.05) according to the 360-Degree Evaluation scale. The effect of standardized training was significant in basic theoretical knowledge, clinical practice ability and medical humanities literacy by the post competency analysis model. ConclusionThe effect of standardized training of rehabilitation therapists is significant, and the therapists can be competent for daily work in diagnosis and treatment after training.

ObjectiveTo compare the effect of proprioceptive neuromuscular training methods on pain and motor ability of knee in patients with early knee osteoarthritis (KOA) . MethodsFrom November, 2022 to May, 2023, 60 early KOA patients from Beijing Bo'ai Hospital and community were randomly divided into groups A, B and C, with 20 patients in each group. Group A received proprioceptive neuromuscular facilitation (PNF), group B received neuromuscular exercise (NEMEX), and group C received PNF and NEMEX, for six weeks. They were assessed with Visual Analogue Scale for pain (VAS), angle reappearance test, difference of pre-motor reaction time (VM-VL), active range of motion (AROM) of knee flexion, 10-meter walk test (10MWT), and Knee Injury and Osteoarthritis Outcome Score (KOOS) before and after treatment. ResultsAll the indexes improved in all the groups after treatment (|t| > 2.532, P < 0.05). Among the groups, the VAS score was the least in group A, and then groups C and B; the angle reappearance error was the least in group C, and similar in groups A and B; the VM-VL was the least in groups A and C, followed by group B. ConclusionPNF, NEMEX and PNF+NEMEX can relieve the pain and improve the motor function of knee in patients with early KOA, however, PNF is the most effective on relieving pain, and PNF+NEMEX is the most effective on improving knee function.

ObjectiveTo observe the architectural parameter changes of the muscles around the knee in middle-aged and elderly women with early knee osteoarthritis (KOA) by musculoskeletal ultrasound, and to clarify the indicators of muscles that affect early KOA. MethodsFrom January to August, 2022, 20 healthy middle-aged and elderly healthy women (controls) and 20 middle-aged and elderly women with unilateral early KOA (KOA group) were recruited through Beijing Bo'ai Hospital, to measure muscle thickness of the popliteus muscle, the muscle thickness and the pennation angle of the quadriceps, as rectus femoris, vastus intermedius, vastus lateralis, vastus medialis longus and vastus medialis oblique. ResultsCompared with the healthy limb of KOA group, and the controls, the muscle thickness of vastus medialis longus, vastus medialis oblique and popliteus muscle of the affected limb of KOA group became thinner (t > 2.133, P < 0.05); the proportion of thickness of vastus medialis oblique to thickness of vastus lateralis became smaller (t > 3.660, P < 0.05). The pennation angle was smaller in the affected limb of KOA group than in the matched dominant side of the controls (t = 3.101, P < 0.05). Logistic regression analysis showed that the muscle thickness of vastus medialis oblique (OR = 0.235, 95%CI 0.068 to 0.805, P = 0.021) and popliteus muscle (OR = 0.387, 95%CI 0.152 to 0.980, P = 0.045) were related to the onset of early KOA. ConclusionThe thickness of vastus medialis longus, vastus medialis oblique and popliteus muscle decrease, and the balance of the strength of vastus medialis oblique and vastus lateralis weakens in the affected limbs of the middle-aged and elderly women with early KOA. The thickness of vastus medialis oblique and popliteus muscle are protective factors for onset of KOA.

Objective:To explore the effect of "Internet +" nursing clinic in delivery women during puerperium period.Methods:From January to December 2021, 1000 delivery women in the Tianjin Medical University General Hospital were selected as the study objects by convenience sampling. The subjects were randomly divided into observation group and control group, with 500 cases in each group. The control group took routine discharge education and traditional telephone follow-up, and the observation group provided online health guidance to the delivery women through the Careate Q medical platform on the basis of the control group. The incidence of adverse health conditions of the two groups of delivery women and newborns was compared.Results:The incidence of breast-feeding difficulties, abnormal lochia, wound pain, and emotional depression of delivery women during puerperium period in the observation group was lower than that in the control group, and the difference was statistically significant ( P<0.05) . After 6 weeks of discharge, the score of self-management ability of the observation group was higher than that of the control group, and the difference was statistically significant ( P<0.01) . The incidence of neonatal umbilical infection, delayed umbilical cord shedding, defecation and skin abnormalities in the observation group was significantly lower than that in the control group, and the difference was statistically significant ( P<0.01) . The satisfaction of the observation group was higher than that of the control group, with a statistically significant difference ( P<0.01) . Conclusions:The "Internet +" nursing clinic can effectively reduce the incidence of adverse health conditions of delivery women and newborn, improve the satisfaction of delivery women, and is worthy of clinical promotion and application.

Anti-virulence strategy has been considered as one of the most promising approaches to combat drug-resistant bacterial infections. Pore-forming toxins (PFTs) are the largest class of bacterial toxins, inflicting their virulence effect through creating pores on the cell membrane. However, current solutions for eliminating PFTs are mostly designed based on their molecular structure, requiring customized design for different interactions. In the present study, we employed erythroliposome (denoted as RM-PL), a biomimetic platform constructed by artificial lipid membranes and natural erythrocyte membranes, to neutralize different hemolytic PFTs regardless of their molecular structure. When tested with model PFTs, including α-hemolysin, listeriolysin O, and streptolysin O, RM-PL could completely inhibit toxin-induced hemolysis in a concentration-dependent manner. In vivo studies further confirmed that RM-PL could efficiently neutralize various toxins and save animals' lives without causing damage to organs or tissues. In addition, we explored the underlying mechanisms of this efficient detoxification ability and found that it was mainly macrophages in the spleen and the liver that took up RM-PL-absorbed toxins through a variety of endocytosis pathways and digested them in lysosomes. In summary, the biomimetic RM-PL presented a promising system for broad-spectrum and powerful toxin neutralization with a mechanism of lysosome-mediated toxin degradation.

Objective: To understand the prevalence and associated factors of school bullying among primary and secondary school students in Haidian District, and to provide scientific basis for intervention plan. Methods: From September to October 2021, 1 906 primary and secondary school students in Haidian District were selected by stratified cluster random sampling for electronic questionnaire survey,an electronic questionnaire survey was conducted on students by using the questionnaire of the Student Health Status and Influencing Factors Questionnaire. Results: The prevalence of campus bullying among primary and secondary school students in Haidian District was 4.3%, of which primary school (7.6%) > junior middle school (4.1%) > vocational high school (2.5%) > senior high school (1.9%) ( χ 2=23.49, P ＜0.01), boys (5.5%) were more than girls (3.0%) ( χ 2=7.44, P ＜ 0.01 ), students from abnormal families (6.9%) were higher than students from normal families (3.9%) ( χ 2=4.24, P =0.04). Multivariate Logistic regression analysis showed that students in primary school had a higher risk of being bullied in school ( OR =2.13). Abnormal family ( OR = 1.07 ), smoking experience ( OR =2.28), experience of being beaten and scolded by parents( OR =2.49) and fighting behavior ( OR =1.84) were positively correlated with school bullying ( P <0.05). Conclusion Campus bullying is prevalent in primary and secondary schools in Haidian District, which warrents further attention of schools and education departments. Family school partnership and targeted prevention and intervention measures for key populations are expected.