ObjectiveTo explore the mechanism of Shenmai injection in improving cisplatin resistance in non-small cell lung cancer （NSCLC） based on the endoplasmic reticulum stress through protein kinase R-like endoplasmic reticulum kinase （PERK）/activated transcription factor 4 （ATF4）/C/EBP homologous protein （CHOP） signaling pathway. MethodsBALB/c nude mice bearing cisplatin-resistant human lung cancer cell line （A549/cisplatin） were randomly divided into four groups： Blank control group （0.9% sodium chloride）， cisplatin group （5 µg·g^-1cisplatin）， Shenmai injection group （5.2 mg·g^-1 Shenmai injection）， and combination therapy group （5.2 mg·g^-1 Shenmai injection +5 µg·g^-1cisplatin）. The drug intervention lasted for 4 weeks， and the changes in body weight and tumor volume were monitored. Hematoxylin-eosin （HE） staining was performed to observe tumor tissue pathology. Transmission electron microscopy （TEM） was used to assess the morphology of the endoplasmic reticulum. Immunohistochemical assay was conducted to measure the positive expressions of PERK， ATF4， and CHOP in tumor tissues. Western blot quantified the protein expression of immunoglobulin heavy chain binding protein （BIP）， PERK， phosphorylated PERK （p-PERK）， eukaryotic translation initiation factor 2α （eIF2α）， phosphorylated eIF2α （p-eIF2α）， ATF4， CHOP， B-cell lymphoma -2 （Bcl-2）， and Bcl-2 Associated X protein （Bax）. A549/cis cells were divided into blank group： Blank control group （normal culture medium）， cisplatin group （23.3 µmol·L^-1 cisplatin）， Shenmai Injection group （20 g·L^-1 Shenmai injection）， and combination therapy group （20 g·L^-1 Shenmai injection+23.3 µmol·L^-1 cisplatin）. Cell counting kit-8 （CCK-8） method was used to detect cell viability， TEM was used to observe the morphology of endoplasmic reticulum， and Western blot was used to detect endoplasmic reticulum stress and apoptosis-related proteins. ResultsCompared with the cisplatin group， the combination therapy group showed increased body weight （P<0.05）， decreased tumor volume （P<0.05）， and expanded endoplasmic reticulum in tumor cells. The positive expressions of PERK， ATF4， and CHOP increased （P<0.05）. Western blot revealed elevated protein expression levels of BIP， p-PERK/PERK， p-eIF2α/eIF2α， ATF4， CHOP， and Bax （P<0.05）， while Bcl-2 expression decreased （P<0.05）. As shown in the in vitro experiment， compared with the cisplatin group， the combination therapy group exhibited a reduced cell survival rate （P<0.05）. TEM revealed increased endoplasmic reticulum dilation and vesicular degeneration. Western blotting showed increased protein levels of BIP， p-PERK/PERK， p-eIF2α/eIF2α， ATF4， CHOP and Bax （P<0.05）， with decreased Bcl-2 expression （P<0.05）. ConclusionShenmai injection combined with cisplatin has a synergistic antitumor effect in NSCLC， which may be attributed to the activation of endoplasmic reticulum stress response mediated by the PERK/eIF2α/ATF4/CHOP signaling pathway and the induction of tumor cell apoptosis.

Depressive disorder is a mental illness characterized by poor mood and cognitive dysfunction caused by a range of complicated factors. Antidepressants have strong short-term efficacy in clinical application, yet with significant adverse effects and resistance in long-term use. Essential oils are small molecular compounds mainly composed of monoterpenes and sesquiterpenes, most of which are characterized by aromatic odors, easy permeability through the blood-brain barrier, and low toxic side effects. Volatile oil from traditional Chinese medicine can regulate neurotransmitter monoamine, hypothalamic-pituitary-adrenal axis, brain-derived neurotrophic factor, neuroinflammation and oxidative stress, and intestinal microbiota-gut-brain axis to exert an antidepressant effect through multiple pathways and targets. This review summarizes the main antidepressant chemical components of essential oil of traditional Chinese medicine, their pharmacological mechanisms and clinical application, aiming to provide some reference for further development and clinical application of essential oil of traditional Chinese medicine.

Objective:To analyze the effects of SARS-CoV-2 infection and vaccination on virus mutation.Methods:The whole genome sequencing sequences of 2 659 local SARS-CoV-2 specimens from Jiangsu Province in 2023 were selected for analysis, and relevant information such as demographic and clinical characteristics were collected, and the effects of infection and vaccination on the genome-wide mutation rate and S gene′s selective pressure of the virus were analyzed by univariate and multivariate linear regression models.Results:The average age of these infected patients was 55.0 (31.0, 74.0) years, 1 150 cases (43.2%) in the age group of ≥60 years, 1 367 cases (51.4%) were males, 2 044 cases (76.9%) had a history of COVID-19 vaccination, and 1 629 cases (61.3%) had the first-time infection. The clinical symptoms of the infected patients were mainly mild, with a total of 2434 cases (91.5%), and 29 cases (1.1%) with severe symptoms or more. The average substitution rate of SARS-CoV-2 was 9.69 (9.38, 9.98)×10 -4 subs/site/year, and the dN/dS value of the S gene was 6.08 (5.56, 8.66), which was significantly greater than that of 1 ( P<0.001), indicating positive selection. The result of univariate and multivariate linear regression model analysis showed that the SARS-CoV-2 substitution rate was higher in those with vaccination history and reinfection, aged 20-30 years, ≥60 years, and the SARS-CoV-2 substitution rate was lower in males with moderate clinical symptoms and severe disease and above. Those with a history of vaccination and reinfection, aged 50-60 years old, ≥60 years old have smaller S gene dN/dS. Conclusions:Under the immune pressure exerted by vaccination and infection, the genome-wide mutation of SARS-COV-2 accelerated, but the non-synonymous mutation rate of the S gene decreased. The mechanism causing these phenomena needs further study.

Objective:To investigate the pediatricians' needs in the contents of continuing medical education (CME), and the influencing factors of participating in CME, so as to provide references for improving their vocational ability.Methods:Questionnaire survey was carried out for the pediatricians from county-level medical institutions in the nine provinces of China. The questionnaire contents included: basic information, CME contents needs, and influencing factors of participating in CME. SPSS 22.0 was used for chi-square test.Results:A total of 465 questionnaires was recovered, among which 463 were qualified, with a pass rate of 99.6%. Research showed that ① In terms of competency training needs, pediatricians had higher training demand for ability of diagnosis and treatment of children's diseases, pediatrics basic skills and skills related to children's health care, etc. Pediatricians with junior or intermediate title had higher training demand for ability of self-learning and access to learning resources ( P < 0.01); and pediatricians with senior title had higher training demand for teaching ability ( P < 0.05). ② In terms of pediatrics specialty content training needs, pediatricians had higher demand for neonatology, infectious, respiratory, critical medicine, developmental behavior and digestion in order. ③ Regarding the influencing factors of CME, too few opportunities to participate in training, too busy to have time to participate, and defects in curriculum arrangement were the main factors affecting the CME participation of pediatricians. Conclusion:Pediatricians with different professional title had different training needs for CME contents. Lack of CME resources, contradiction between work and study, and curriculum arrangement deficiencies might be the main influencing factors affecting the CME participation of pediatricians working at county-level medical institutions.

Objective:To explore the application effect and feedback of online pediatrics teaching for the clerkship and internship stage of medical students of clinical medicine eight-year program.Methods:In this study, 38 clerkship medical students and 12 internship medical students of clinical medicine eight-year program in pediatrics department of Peking University First Hospital from February to March, 2020 were selected as research objects. They had two weeks of online teaching, including online flipped classroom, case-based learning (CBL), and problem-based learning (PBL). The effect of online teaching, and the feedback from these students were all investigated through the questionnaire survey.Results:All students were satisfied with the overall arrangement of the online teaching and believed that the results exceed [42% (21/50)] or meet [58% (29/50)] their expectations. According to the feedback, network congestion [82% (41/50)] was the biggest problem in online teaching, followed by the inability of effective interaction [20% (10/50)]. Students all believed that the online teaching arrangement was most helpful for the cultivation of theoretical knowledge (Total scores 4.58±0.50), autonomous learning ability (Total scores 4.42±0.58) and clinical reasoning (Total scores 4.42±0.58), but had minimal impact on the skills operation (Total scores 2.68±0.87) and scientific research ability (Total 2.98±0.98). For the ability of communication between doctors and patients, the scores of clerkship students (3.79±0.99) were significantly higher than those of internship students (3.08±0.67), ( P<0.05). Clerkship students considered that online flipped classroom was the most helpful teaching mode, while internship students believed online CBL teaching was the most helpful one. Majority of the students (94%) think it's necessary to keep online teaching in the future. Conclusion:Online teaching of pediatrics is approved by the medical students of clinical medicine eight-year program in the stage of clerkship and internship, and plays an important role in the cultivation of the ability of medical students, but it can't completely replace offline clinical practice.

Objective To evaluate the effects of artemisinin on proliferation,cell cycle and apoptosis of gallbladder cancer cells.Methods Gallbladder carcinoma cell lines (GBC-SD and NOZ) were cultured in vitro.The effects of artemisinin in different concentration on proliferation of the two cell lines in vitro were examined using MTT assay.The cell cycle distribution of GBC-SD and NOZ cells 24 h after treatments with artemisinin(20 μ mol/L) were examined using flow cytometry.The apoptosis of GBC-SD and NOZ cells 24 h after treatments with artemisinin (20 μ mol/L) were examined using Annexin V/PI staining.The expressions of p-ERK1/2,CDK4,cyclin D1,p16,cytochrome C and caspase-3 were examined by Western blot assay.t-test and one way ANOVA were used to evaluate the differences between two groups and more than two groups,respectively.Results The cell proliferation was significantly inhibited by artemisinin,the ICS0 of artemisinin against GBC-SD and NOZ cells were 14.05 μmol/L and 12.42 μmol/L,respectively.Artemisinin induced cycle arrest,and G1 population of GBC-SD and NOZ cells increased to 74.60％ and 78.86％.Cell apoptosis and apoptotic population of GBC-SD and NOZ cells were increased to 15.67％ and 16.51％ after dealt with artemisinin,respectively.In addition,expression of pl6 was increased,and expressions of p-ERK1/2,CDK4 and cyclin D1 were down-regulated by artemisinin(all P ＜0.05).Cytochrome C was released from mitochondria to cytoplasm leading to the activation of caspase-3 and PARP after dealt with artemisinin (P ＜ 0.05).Conclusion The inhibition effect of artemisinin on the proliferation gallbladder cancer cells is accompanied by down-regulation of ERK1/2 signaling pathway,G1 phase arrest and triggering caspase-3-mediate apoptosis.

Objective To evaluate the effects of artemisinin on proliferation,cell cycle and apoptosis of gallbladder cancer cells.Methods Gallbladder carcinoma cell lines (GBC-SD and NOZ) were cultured in vitro.The effects of artemisinin in different concentration on proliferation of the two cell lines in vitro were examined using MTT assay.The cell cycle distribution of GBC-SD and NOZ cells 24 h after treatments with artemisinin(20 μ mol/L) were examined using flow cytometry.The apoptosis of GBC-SD and NOZ cells 24 h after treatments with artemisinin (20 μ mol/L) were examined using Annexin V/PI staining.The expressions of p-ERK1/2,CDK4,cyclin D1,p16,cytochrome C and caspase-3 were examined by Western blot assay.t-test and one way ANOVA were used to evaluate the differences between two groups and more than two groups,respectively.Results The cell proliferation was significantly inhibited by artemisinin,the ICS0 of artemisinin against GBC-SD and NOZ cells were 14.05 μmol/L and 12.42 μmol/L,respectively.Artemisinin induced cycle arrest,and G1 population of GBC-SD and NOZ cells increased to 74.60％ and 78.86％.Cell apoptosis and apoptotic population of GBC-SD and NOZ cells were increased to 15.67％ and 16.51％ after dealt with artemisinin,respectively.In addition,expression of pl6 was increased,and expressions of p-ERK1/2,CDK4 and cyclin D1 were down-regulated by artemisinin(all P ＜0.05).Cytochrome C was released from mitochondria to cytoplasm leading to the activation of caspase-3 and PARP after dealt with artemisinin (P ＜ 0.05).Conclusion The inhibition effect of artemisinin on the proliferation gallbladder cancer cells is accompanied by down-regulation of ERK1/2 signaling pathway,G1 phase arrest and triggering caspase-3-mediate apoptosis.

Objective To develop an intelligent wound therapeutic instrument based on active instillation and negative pressure suction.Methods SCM coordinated peristaltic pumps, solenoid valves and pressure receptor to infuse perfusate into the wound and retained it for a period of time. The perfusate then was eliminated by negative pressure and the wound was kept in the state of negative pressure. The instrument could give out alarm in case of bad tightness, over-high pressure and blocked negative-pressure pipeline.Results Peristaltic pump and central negative pressure were involved in to complete wound perfusion and irrigation, with perfusate controlled quantitatively and negative pressure kept reliable. The pressures in the wound and pipeline could be monitored at real time by the pressure receptor, and timely alarm was implemented when unexpected conditions occurred.Conclusion The instrument behaves well in automation, intelligence and safety, and thus is worth popularizing clinically.

A case of eosinophilic lymphoid granuloma(ELG)was reported and the related literatures were reviewed.ELG is rare in clinic. The etiology and pathogenesis of ELG was unclear.The clinical feature includes enlarged lymph nodes which were always predilected for the head and neck regions,eosinophilic granulocytes and serum IgE rising.Lymphoid tissue hyperplasis formation of lymphoid follicles with active germinal centres are common in pathological examination.There is diffuse infiltration of eosinophils in interfollicular and perivascular zones. Surgery,drug therapy and radiotherapy are all effective for the treatment,but recurrence is often.

Objective:To establish a method based on the iPLEX analysis of MassARRAY mass spectrometry platform to detect multiplex genetic mutations among Chinese lung cancer patients. Methods:We reviewed the related literature and data of lung cancer treatments. We also determined 99 mutation hot spots in 13 target genes, namely, EGFR, KRAS, ALK, FGFR1, FGFR2, FGFR3, PIK3CA, BRAF, PTEN, MET, ERBB2, AKT1, and STK11, which are closely related to the pathogenesis, drug resistance, and metastasis of lung cancer and are associated with relevant transduction pathways. A total of 297 primers comprising 99 paired forward and reverse amplification primers and 99 matched extension primers were designed by using Assay Design in accordance with the mutation label and format requirements of the MassARRAY platform. The detection method was established by analyzing eight cell lines and six lung cancer specimens;the proposed method was then validated through comparisons with a LungCarta kit. The sensitivity and specificity of the proposed method were evaluated by directly sequencing EGFR and KRAS genes in 100 lung cancer cases. Results:The proposed method could detect multiplex genetic mutations in the lung cancer cell lines, and this finding is consistent with that observed using previously reported methods. The proposed method could also detect such mutations in clinical lung cancer specimens;this result is also consistent with that observed by using the LungCarta kit. However, an FGFR2 mutation was detected only by using the proposed method. The measured sensitivity and specificity were 100%and 96.3%, respectively. Conclusion:The proposed MassARRAY technology-based method could detect multiplex genetic mutations among Chinese lung cancer patients. Indeed, the proposed method can be potentially applied to detect mutations in cancer cells.