Dynamic genomic changes in methotrexate-resistant human cancer cell lines beyond DHFR amplification suggest potential new targets for preventing drug resistance.

BACKGROUND: Although DHFR gene amplification has long been known as a major mechanism for methotrexate (MTX) resistance in cancer, the early changes and detailed development of the resistance are not yet fully understood. METHODS: We performed genomic, transcriptional and proteomic analyses of human colon cancer cells with sequentially increasing levels of MTX-resistance. RESULTS: The genomic amplification evolved in three phases (pre-amplification, homogenously staining region (HSR) and extrachromosomal DNA (ecDNA)). We confirm that genomic amplification and increased expression of DHFR, with formation of HSRs and especially ecDNAs, is the major driver of resistance. However, DHFR did not play a detectable role in the early phase. In the late phase (ecDNA), increase in FAM151B protein level may also have an important role by decreasing sensitivity to MTX. In addition, although MSH3 and ZFYVE16 may be subject to different posttranscriptional regulations and therefore protein expressions are decreased in ecDNA stages compared to HSR stages, they still play important roles in MTX resistance. CONCLUSION: The study provides a detailed evolutionary trajectory of MTX-resistance and identifies new targets, especially ecDNAs, which could help to prevent drug resistance. It also presents a proof-of-principal approach which could be applied to other cancer drug resistance studies.

Research progress on biological mechanism of interferon-inducible protein 16 / 中国药理学通报

Interferon γ-inducible protein 16(IFI16)is one member of human pyrin and HIN domain-containing protein(PYHIN)family(also known as interferon-inducible p200 pro-tein family),which is widely present in human organs and tis-sues,and is involved in cell cycle regulation,senescence and ap-optosis,even in immune reaction.The content and localization of IFI16 may change under different physiological and pathological conditions,and recent studies have revealed that it may play an important role in the development of antiviral,tumor,inflammato-ry diseases and other diseases.In this paper,we review its mechanism and the current status of its research in diseases,with the aim of providing a reference for the in-depth study of IFI16.

Application of Ancient Books in Clinical Practice Guidelines and Expert Consensus of Traditional Chinese Medicine： Current Status and Methodological Recommendations / 中医杂志

ObjectiveTo explore the current status and issues regarding the application of ancient books in clinical practice guidelines and expert consensus of traditional Chinese medicine （TCM） published in China， and to provide methodological recommendations for the incorporation of ancient books in the development of TCM guidelines. MethodsWe searched China National Knowledge Infrastructure （CNKI）， WanFang Data， VIP， SinoMed， PubMed， Embase， as well as six industry websites including China Association of Chinese Medicine， National Group Standards Information Platform， and Chinese Association of the Integration of Traditional and Western Medicine，etc. TCM clinical practice guidelines or expert consensus issued during January 1st， 2017， to November 26th， 2022 were searched. Clinical practice guidelines or expert consensus that explicitly referred to ancient books were included， and the content regarding the searching for ancient books， sources of access to ancient books， methods of evaluating the level of evidence， methods of evaluating the level of recommendation， and methods of evaluating the evidence for the ancient books were analysed. ResultsA total of 1,215 TCM clinical practice guidelines or expert consensus were retrieved， with 442 articles explicitly mentioning the application of ancient books， including 300 （67.87%） clinical practice guidelines and 142 （32.13%） expert consensus. Sixty of the 442 publications explicitly reported that ancient books searching had been conducted （13.57%）； among these 60 publications 27 （45.00%） explicitly reported ancient books searching strategies， and the most frequent method was manual searching with a total of 24 articles （40.00%）. The most popular search source was Chinese Medical Dictionary， a TCM classics database， with a total of 18 articles. 197 articles （44.57%） explicitly reported the evaluation criteria for the level of evidence， of which 141 articles （71.57%） involved the evaluation criteria for the ancient books； 413 articles （93.44%） mentioned ancient books in the recommendations， and only the source of formula name was mentioned in 409 （99.03%） of the publications. ConclusionThe current application of ancient books in TCM clinical practice guidelines and expert consensus is limited， with issues of non-standard searching and evaluation methods. Standar-dization and uniformity are needed in evidence grading and recommendation standards. Future research should clarify the scope and methods of applying ancient book， emphasize their integration with modern research evidence， and enhance their value and quality in the development of TCM clinical practice guidelines.

Thinking on ideological and political education in Medical Parasitology teaching / 中国血吸虫病防治杂志

With the deepening reform of ideological and political education, Medical Parasitology teaching needs to update the teaching concept, change the teaching ideas, as well as keep trying to combine ideological and political education with the curriculum content closely. In addition to teaching students’ basic knowledge and practical skills, teachers are needed to cultivate their moral literacy and political awareness through course teaching, so as to provide the basis for students’ subsequent adaptations to social environments and jobs. Currently, the study of ideological and political education in Medical Parasitology teaching is still in the exploratory stage. Therefore, colleges and universities need to carry out effective construction of ideological and political education in Medical Parasitology teaching, in order to achieve good teaching outcomes and provide insights into ideological and political education in teaching.

Study on Quality Evaluation of Honeysuckle Oral Liquid Based on Quality Markers of Anti-Inflammatory Effect / 世界科学技术-中医药现代化

Objective To establish a quality traceability evaluation method for the whole honeysuckle oral solution process by identifying and screening its anti-inflammatory quality markers.Methods UPLC/-TOF-MS was used to analyze the iridoids and phenolic acids in oral solution,and the correlations were constructed by molecular network technology.The HPLC fingerprints of multiple batches of oral solution were established,and similarity analyses were performed to identify key pharmacodynamic molecules.The key anti-inflammatory quality markers were confirmed by the NF-κB dual luciferase assay system.Further,the quantification of 12 quality markers of iridoids and phenolic acids in oral solution was established separately based on the dual-wavelength HPLC technique.The quality of the oral solution was evaluated by examining the extraction and transfer rate of quality markers during the processing of raw materials and preparations and thermal stability.Results A total of 9 iridoids and 6 phenolic acids were identified in the oral solution,and the possible conversion relationships between their components were depicted.Fingerprint analysis of 11 batches of oral liquids showed that the composition of their main peaks was the same,with a similarity of more than 90%.Among them,6 iridoids(loganic acid,secologanoside,secologanic acid,sweroside,secoxyloganin,secologanin)and 6 phenolic acids(neochlorogenic acid,chlorogenic acid,cryptochlorogenic acid,isochlorogenic B,isochlorogenic A,isochlorogenic C)exhibited NF-κB inhibitory activity,which were the main pharmacological components and could be used as quality markers.The traceability of the above 12 quality markers was investigated in a multi-batch process based on the dual-wavelength HPLC method.The thermal stability studies of the raw materials revealed that the contents of their total iridoids and phenolic acids remained stable.Still,some of them would be transformed between components.The production process of the oral solution was stable,and the transfer rates of the iridoids and phenolic acids during the extraction,concentration and preparation were over 76%and 63%,respectively.Conclusion The method is stable,reliable,easy to operate and can evaluate the full honeysuckle oral solution process,which provides an effective means for the quality control of honeysuckle herbs and preparations.

Effect of different lithotomy positions on hemodynamics in patients undergoing laparoscopic total hysterectomy / 中国基层医药

Objective:To analyze the effect of different lithotomy positions on hemodynamics in patients undergoing laparoscopic total hysterectomy.Methods:A total of 50 patients who underwent laparoscopic total hysterectomy at Zhoushan Women and Children's Hospital between January 2020 and June 2021 were included in this study. The patients were randomly divided into a control group and an observation group using a random number table method, with 25 patients in each group. The control group underwent conventional lithotomy position total laparoscopic hysterectomy, while the observation group underwent high and low lithotomy position total laparoscopic hysterectomy. The general surgical indicators, respiratory function indicators, blood gas analysis indicators, hemodynamic levels, incidence of complications, and clinical efficacy were compared between the two groups.Results:The general surgical indicators and airway peak pressure indicators in the observation group were significantly lower than those in the control group (both P < 0.05). There was no statistically significant difference in partial pressure of end-tidal carbon dioxide (PCO 2) and arterial carbon dioxide partial pressure (PaCO 2) between the two groups (both P < 0.05). At 15 minutes after pneumoperitoneum, the PaCO 2 level increased in each group, and the PaCO 2 level in the observation group was significantly higher than that in the control group (all P < 0.05). At the same time, the HCO 3- level decreased in each group, and the HCO 3- level in the observation group was significantly lower than that in the control group (all P < 0.05). At 5 minutes before recovery of body position, heart rate, systolic blood pressure, and diastolic blood pressure in the control group were (76.52 ± 8.61) beats/minute, (113.52 ± 5.36) mmHg (1 mmHg = 0.133 kPa), and (86.91 ± 4.21) mmHg, respectively. At 5 minutes after recovery of body position, heart rate, systolic blood pressure, and diastolic blood pressure in the control group were (89.52 ± 8.61) beats/minute, (106.85 ± 5.63) mmHg, and (80.96 ± 3.65) mmHg, respectively. At 5 minutes before recovery of body position, heart rate, systolic blood pressure, and diastolic blood pressure in the observation group were (76.36 ± 8.61) beats/minute, (112.79 ± 5.28) mmHg, and (86.89 ± 4.54) mmHg. At 5 minutes after recovery of body position, heart rate, systolic blood pressure, and diastolic blood pressure in the observation group were (75.63 ± 6.86) beats/minute, (111.99 ± 5.51) mmHg, and (85.06 ± 3.21) mmHg, respectively. At 5 minutes after recovery of body position, heart rate in the control group was increased and that in the observation group was decreased compared with heart rate measured at 5 minutes before recovery of body position. At 5 minutes after recovery of body position, heart rate in the observation group was significantly lower than that in the control group. Diastolic blood pressure and systolic blood pressure decreased in each group, and the amplitudes of reductions in diastolic blood pressure and systolic blood pressure in the observation group were significantly lower than those in the control group. ( t = 6.04, 3.26, 4.22, all P < 0.05). There was no statistically significant difference in incidence of adverse reactions between the two groups ( P > 0.05). The overall response rate in the observation group was significantly higher than that in the control group ( P < 0.05). Conclusion:Compared with conventional lithotomy position total laparoscopic hysteretsotomy, high and low lithotomy position total laparoscopic hysterectomy takes a shorter duration for total laparoscopic hysterectomy, leads to a shorter length of hospital stay, results in less blood loss, causes fewer postoperative infections, and results in more stable hemodynamics and a lower incidence of complications.

A Comparative Study of the Energy Contribution Characteristics between 1500 m Speed Skating and Cycling Maximal Exercise / 中国运动医学杂志

Objective To explore the differences in energy contribution between 1500 m speed skat-ing and cycling maximal exercise.Methods Eleven professional skaters took the tests of 1500 m speed skating and cycling maximal exercise,respectively.A portable gas analyzer and a blood lactate analyz-er were used to measure and assess the gas metabolism during and 6 minutes after the tests,along with the blood lactate level before and after them.The energy contribution and contribution rates were calculated by using the phosphoric acid-lactic acid-oxygen method.Results There were significant dif-ferences between the two tests in the average accumulated oxygen uptake(5.52±0.99 L vs 5.94±0.75 L,P=0.043,ES=0.481)and the rapid recovery of oxygen uptake after exercise(2.07±0.67 L vs 1.52±0.86 L,P=0.029,ES=0.746).However,no significant differences were found in the rela-tive anaerobic lactic contribution between the two different exercises.Moreover,the relative anaerobic alactic contribution of speed skating was significantly greater than cycling(21.36%±4.12%vs 15.39%±5.89%,P=0.010,ES=1.211),while the relative aerobic contribution was significantly lower than the latter(52.31%±5.45%vs 57.13%±5.12%,P=0.016,ES=0.913).Conclusions The energy contri-bution of 1500 m speed skating is different from the cycling maximal exercise,indicating that the rel-ative aerobic contribution differs among different exercises.Therefore,future training plans should be tailored to the specific energy contribution characteristics of each sport and speed skaters should strengthen their explosive training when taking cycling as the main training method in non-ice periods.

Value of SPECT myocardial perfusion imaging and coronary flow reserve combined with coronary artery calcium score in the diagnosis of obstructive coronary artery disease / 中华核医学与分子影像杂志

Objective:To study the value of myocardial perfusion imaging (MPI) and coronary flow reserve (CFR) combined with coronary artery calcium score (CACS) in the diagnosis of obstructive coronary artery disease (CAD).Methods:From January 2019 to December 2020, 96 confirmed or suspective CAD patients (65 males, 31 females; age: 30-81 years) who completed rest/stress MPI, CFR and CACS defection in Fuwai Central China Cardiovascular Hospital were retrospectively analyzed. Coronary angiography (CAG) was used as the diagnostic standard to calculate the sensitivity and accuracy of MPI, CFR and MPI/CFR combined with CACS in the diagnosis of CAD. The χ2 test was used to compare the diagnostic efficiency of different methods. Results:The diagnostic sensitivity of MPI was 76.06%(54/71), and the accuracy was 75.00%(72/96), while the sensitivity increased to 97.18%(69/71; χ2=13.67, P<0.001) and the accuracy increased to 87.50%(84/96; χ2=4.92, P=0.020) with significant differences after combined with CACS. The sensitivity and accuracy of CFR were 91.55%(65/71)and 87.50%(84/96), which increased to 97.18%(69/71; χ2=2.12, P=0.137) and 89.58%(86/96; χ2=0.21, P=0.411) with no significant differences after combined with CACS. The sensitivity of MPI in the diagnosis of three-vessel CAD was 70.00%(21/30), which increased to 100%(30/30; χ2=7.75, P=0.004) after combined with CACS; while the sensitivity of MPI combined with CACS in the diagnosis of single-vessel and double-vessel CAD were not significantly improved ( χ2 values: 3.29, 1.51, P values: 0.114, 0.416). Conclusion:The combination of MPI and CACS can significantly improve the diagnostic efficiency of CAD, contributed by the improvement of the diagnostic sensitivity in three-vessel disease; whereas the diagnostic efficiency of CFR for CAD is not significantly improved after combined with CACS.

Changes in topological properties of brain functional network after induction of general anesthesia in patients with glioma / 中华麻醉学杂志

Objective:To evaluate the changes in topological properties of brain functional network after induction of general anesthesia in the patients with glioma.Methods:Twenty-two patients scheduled for elective intracranial glioma resection were selected.Resting-state functional magnetic resonance imaging was performed during wakefulness and general anesthesia with endotracheal intubation in patients with glioma. Large-scale functional brain networks of each patient were constructed based on 123 regions of interest in non-surgical hemisphere. Global properties (local efficiency, clustering parameter, shortest path length, global efficiency, small world) and nodal properties (nodal degree, nodal efficiency, and between centrality) in brain functional networks were then compared between wakefulness and general anesthesia.Results:Eighteen patients were finally enrolled. Compared with the status during wakefulness, the local efficiency and clustering parameter on non-surgical side significantly decreased ( P<0.05), no significant change was found in the shortest path length and global efficiency ( P>0.05), and small world was greater than 1 throughout the entire density range; the nodal degree, nodal efficiency and between centrality of nodes located in the medial/mesal regions, such as the medial prefrontal cortex, posterior cingulate gyrus/precuneus, medial temporal lobe, anterior cingulate gyrus, thalamus, amygdala, were significantly reduced ( P<0.05); however, these node parameters increased significantly in the lateral brain regions ( P<0.05) except for the primary auditory and somatosensory cortex, which also decreased significantly after induction of general anesthesia( P<0.05). Conclusions:The functional segregation of brain functional network is widely inhibited after induction of general anesthesia, but the functional integration is still retained. The lateral brain regions show no anticorrelation with the medial brain region during general anesthesia.

Effect of sugammadex on postoperative nausea and vomiting after surgery for intracranial aneurysm / 中华外科杂志

Objective: To investigate the effect of sugammadex on postoperative nausea and vomiting(PONV) after intracranial aneurysm surgery. Methods: Data from intracranial aneurysms patients who met the inclusion and exclusion criteria and underwent interventional surgery in the Department of Neurosurgery, Peking University International Hospital from January 2020 to March 2021 were prospectively included. According to the random number table method, the patients were divided by 1∶1 into the neostigmine+atropine group (group N) and the sugammadex group (group S). Use an acceleration muscle relaxation monitor for muscle relaxation monitoring, and administer neostigmine+atropine and sugammadex to block residual muscle relaxation drugs after surgery. The incidence rates of PONV and severity, the appearance of anesthesia, and the correlation between PONV and postoperative complications were recorded in both groups during five periods after surgery: 0-0.5 hours (T1),>0.5-2.0 hours(T2),>2.0-6.0 hours (T3),>6.0-12.0 hours (T4) and >12.0-24.0 hours (T5). Group comparisons of quantitative data were performed by the independent sample t-test, and categorical data was performed by the χ2 or rank sum test. Results: A total of 66 patients were included in the study, including 37 males and 29 female, aged (59.3±15.4) years (range: 18 to 77 years). The incidence rates of PONV of 33 patients in group S at different time periods of T1, T2, T3, T4, and T5 after surgery were respectively 27.3%(9/33),30.3%(10/33),12.1%(4/33),3.0%(1/33),0(0/33),and the incidence rates of PONV of 33 patients in the group N at different time periods of T1, T2, T3, T4 and T5 after surgery were respectively 36.4%(12/33),36.4%(12/33),33.3%(11/33),6.1%(2/33) and 0(0/33).The incidence of PONV was lower in the group S only in the T3 period after reversal than in the group N (χ2=4.227, P=0.040).However, there was no statistically significant difference in the incidence of PONV between the two groups of patients in other periods (all P>0.05). The recovery time for spontaneous breathing in patients in group S was (7.7±1.4) minutes, the extubation time was (12.4±5.3) minutes, and the safe exit time for anesthesia recovery was (12.3±3.4) minutes; the N groups were (13.9±2.0) minutes, (18.2±6.0) minutes, and (18.6±5.2) minutes, respectively; three time periods in group S were shorter than those in group N, and the differences were statistically significant (all P<0.05). The results regarding the occurrence of complications in patients with different levels of PONV at different time intervals after surgery in the two groups were as follows: in the T3 time period of group N, a significant difference was observed only in the occurrence of postoperative complications among patients with different levels of PONV (χ2=24.786, P<0.01). However, in the T4 time period, significant differences were found in the occurrence of postoperative complications among both the same level and different level PONV patients (χ2=15.435, 15.435, both P<0.01). Significant differences were also observed in the occurrence of postoperative complications among the same level and different level PONV patients in both the T3 and T4 time periods of group S (all P<0.01). Conclusion: Sugammadex can be used to reverse muscle relaxation in patients undergoing intracranial aneurysm intervention surgery,and it does not have a significant impact on the incidence of PONV, it can also optimize the quality of anesthesia recovery and reduce the incidence of complications after intracranial aneurysm embolization surgery.

Analysis of dyslipidemia management status in atrial fibrillation patients with very high and high risk of atherosclerotic cardiovascular disease / 中华心血管病杂志

Objective: To analyze the status of statins use and low-density lipoprotein cholesterol (LDL-C) management in patients with atrial fibrillation (AF) and very high/high risk of atherosclerotic cardiovascular disease (ASCVD) from Chinese Atrial Fibrillation Registry (CAFR). Methods: A total of 9 119 patients with AF were recruited in CAFR between January 1, 2015 to December 31, 2018, patients at very high and high risk of ASCVD were included in this study. Demographics, medical history, cardiovascular risk factors, and laboratory test results were collected. In patients with very high-risk, a threshold of 1.8 mmol/L was used as LDL-C management target and in patients with high risk, a threshold of 2.6 mmol/L was used as LDL-C management target. Statins use and LDL-C compliance rate were analyzed, multiple regression analysis was performed to explore the influencing factors of statins use. Results: 3 833 patients were selected (1 912 (21.0%) in very high risk of ASCVD group and 1 921 (21.1%) in high risk of ASCVD group). The proportion of patients with very high and high risk of ASCVD taking statins was 60.2% (1 151/1 912) and 38.6% (741/1 921), respectively. Attainment rate of LDL-C management target in patients with very high and high risk were 26.7% (511/1 912) and 36.4% (700/1 921), respectively. Conclusion: The proportion of statins use and attainment rate of LDL-C management target are low in AF patients with very high and high risk of ASCVD in this cohort. The comprehensive management in AF patients should be further strengthened, especially the primary prevention of cardiovascular disease in AF patients with very high and high risk of ASCVD.

Determination of biological exposure limit of damage in red blood cells caused by exposure to polycyclic aromatic hydrocarbons using benchmark dose method in general population / 公共卫生与预防医学

Objective To explore the biological exposure limit of blood system damage caused by long-term exposure to polycyclic aromatic hydrocarbons (PAHs) in non-occupational population by using the benchmark dose method, and to provide relevant reference for further improving the assessment of PAHs-induced health damage effects. Methods Adult residents living in downwind direction of a coke-oven plant in Shanxi Province were selected as the research subjects, and the information collected from baseline was used as the control. The metabolites of PAHs in urine were used as exposure biomarker, and the abnormal rate of red blood cell index was used as response biomarker. The relationship between urinary OH-PAHs and the erythrocyte damage rate was analyzed, and the benchmark dose (BMD) and the lower confidence limitation for the benchmark dose (BMDL) were calculated using Bayesian dose-optimizing software. Results The urinary PAH metabolites were mainly naphthalene and fluorene. The detection concentrations of 2-OHFlu and 1-OHPhe in the final year were higher than those in the baseline (P<0.05). With the increase of exposure years, the abnormal rate of red blood cells in the final year was higher than that in the baseline (P<0.05). In addition, the abnormal rate of red blood cells increased with the increase of the concentrations of five metabolites of PAHs in urine, and the chi-square trend test was significant (P<0.05). The benchmark dose (BMD) of OH-PAHs was 0.67 μmol/mol Cr, 0.82 μmol/mol Cr, 1.40 μmol/mol Cr and 0.78 μmol/mol Cr, respectively. The BMD of 2-OHNap in people with barbecue diet habits was 0.23 μmol/mol Cr. The BMD of 2-OHNap in people without barbecue diet habits was 1.44 μmol/mol Cr. Conclusion There is a dose-response relationship between the concentration of PAHs metabolites in urine and the damage of red blood cells. Long-term exposure to PAHs can lead to hematological damage. It is suggested that targeted public health interventions should be formulated to reduce the exposure of the general population to PAHs.

Coronary Heart Disease and Obstructive Sleep Apnea Syndrome： Interpretation and Reflection Based on Simultaneous Treatment of Heart and Lung in Traditional Chinese Medicine / 中国实验方剂学杂志

As the overweight and obese population is growing， the incidence of obstructive sleep apnea is rising， and most of the cases are complicated with coronary heart disease and other cardiovascular diseases. The two diseases affect each other and seriously endanger the patients' health， becoming a major public health problem of global concern. It is of great clinical importance to explore the combination of Chinese and Western medicine in the prevention and treatment of coronary heart disease complicated with obstructive sleep apnea syndrome. Researchers have explored the relationship between the two based on traditional Chinese medicine（TCM） theory and found that the two diseases belong to the TCM disease categories of chest impediment and snoring， respectively， and their co-morbidity is associated with the abnormal physiological functions of the heart and lungs. The failure of the heart to govern blood leads to the generation of blood stasis， and that of the lung to govern Qi movement leads to the generation of phlegm. The accumulation of phlegm and blood stasis in the chest causes chest impediment and snoring due to obstruction of the airway. This paper discusses the internal linkage between the pathogenesis of coronary heart disease and obstructive sleep apnea syndrome in Chinese and Western medicine from the TCM theory of heart-lung correlation. Furthermore， this paper proposes the treatment principles of simultaneously treating the heart and lung and activating blood and resolving phlegm， aiming to provide a theoretical basis for the clinical prevention and treatment of coronary heart disease complicated with obstructive sleep apnea.

An investigation of the incidence of post-traumatic stress disorder, turnover intention and psychological resilience among medical staff in a public hospital in China during the outbreak of the omicron variant in the COVID-19 pandemic in 2022.

Objective: To investigate the incidence of post-traumatic stress disorder (PTSD), turnover intention and psychological resilience of medical staff during the Outbreak of the Omicron Variant in the COVID-19 pandemic in 2022 and to provide a basis for adopting relevant psychological interventions to reduce medical staff turnover. Methods: Using the PTSD Checklist-Civilian Version (PCL-C) and a total score ranging from 17 to 85 points, a total score ≥ 38 indicates significant PTSD symptoms and a diagnosis of PTSD. The Chinese version of the Turnover Intention Scale (TIS) has a total score of 6 to 24 points; the higher the score, the stronger the turnover intention. The Chinese version of the Connor-Davidson Resilience Scale (CD-RISC) has a total score of 0 to 100 points, with higher scores indicating a better level of psychological resilience. A total of 443 front-line medical staff working in Chinese public hospitals and still treating all patients normally during COVID-19 were invited via the internet to complete a survey from 15 May to 30 May 2022 in China. Results: The incidence of PTSD was 14.4%, the total turnover intention score was 13.38 ± 4.08, and the total psychological resilience score was 87.16 ± 18.42. The prevalence of PTSD was higher among medical staff who were married, had children, and were worried about being infected; in addition, the PTSD group had a higher level of education, higher turnover intention, and lower psychological resilience than the non-PTSD group. The total scores for turnover intention and fear of being infected were risk factors for PTSD, while a high total psychological resilience score and high education level were protective factors for PTSD; the differences were statistically significant (all P < 0.05). Conclusion: Post-traumatic stress disorder among Chinese medical personnel was associated with the marital status, childbirth, education level, turnover intention, and psychological resilience. Among these factors, psychological resilience might be exploited as a protective factor.

Detection of an EML4-ALK fusion mutation secondary to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy for lung cancer: a case report.

BACKGROUND: For epidermal growth factor receptor-mutant (EGFR-mutant) advanced non-small cell lung cancer (NSCLC) patients, EGFR-tyrosine inhibitors such as gefitinib, erlotinib, and osimertinib, are recommended as the preferred first-line treatment. Unfortunately, relevant drug resistance is often inevitable and for first and second generation EGFR-tyrosine kinase inhibitors (TKIs), drug resistance most commonly (50-60% of cases) occurs at the secondary point mutation T790M. Second-line treatments may include administering the third generation of EGFR-TKIs, such as osimertinib and almonertinib. In a few relevant studies, rearrangement of the anaplastic lymphoma kinase (ALK) gene was detected in patients with T790M mutation after drug resistance to osimertinib re-occurred following administration as a second-line treatment. The studies concluded that ALK rearrangement is a rare but critical drug resistance mechanism for osimertinib. However, to date, it remains unclear whether almonertinib also triggers the same ALK rearrangement. The current case study is the first one detailing the detection of an ALK rearrangement after almonertinib resistance in advanced EGFR-mutant NSCLC, which contributes to the limited body of literature examining ALK rearrangement as a mechanism of resistance to EGFR-TKIs in advanced EGFR-mutant NSCLC. CASE DESCRIPTION: Herein, we present a 35-year-old female patient with EGFR-mutant advanced NSCLC in the last trimester of pregnancy. The patient was administered multiple treatments, including first-line icotinib and second-line almonertinib. According to the next-generation sequencing (NGS) assay after almonertinib resistance, the development of an EML4-ALK fusion mutation was considered to be a potential mechanism of almonertinib resistance. Subsequently, the patient received a combination of almonertinib and crizotinib, and at the last follow-up, the treatment showed a curative effect and then maintained a one-month stable disease. CONCLUSIONS: This case report suggests that ALK rearrangement may be a potential mechanism of almonertinib resistance. The combination of ALK TKI therapy and EGFR TKI may be a viable strategy for almonertinib-resistant NSCLC patients induced by ALK rearrangement.

Efficacy and Safety of Gefitinib Plus Anlotinib for Patients with EGFR Positive Advanced Non-Small-Cell Lung Cancer: A Retrospective Exploratory Study.

Objective: This study was to investigate the efficacy and safety of gefitinib plus anlotinib for patients with EGFR positive advanced non-small cell lung cancer (NSCLC) in a first-line setting. Methods: A total of 36 patients with previously-untreated EGFR positive advanced NSCLC were included in this study retrospectively. All patients were administered with gefitinib plus anlotinib combination therapy. The efficacy of the patients was evaluated with the change of target lesion using imaging evidence according to RECIST 1.1 criteria and all the patients were followed up regularly. Adverse reactions were collected and documented during the combination administration. Univariate analysis according to the baseline characteristic subgroup was implemented using Log rank test and multivariate analysis was adjusted by Cox regression analysis. Results: All the 36 patients included in our study were available for efficacy and safety analysis. Best overall response of the patients during gefitinib plus anlotinib administration suggested that partial response was observed in 30 patients, stable disease was noted in five patients, and progressive disease was found in one patient, which yielded an objective response rate (ORR) of 83.3% (95% CI=67.2-93.6%) and a disease control rate (DCR) of 97.2% (95% CI=85.5-99.9%). Prognostic data indicated that the median progression-free survival (PFS) of the 36 patients with NSCLC was 15.2 months (95% CI=8.15-22.26). Furthermore, the median overall survival (OS) of the 36 patients was 35.9 months (95% CI=22.77-49.03). Additionally, the most common adverse reactions of the patients with NSCLC were diarrhea (63.9%), fatigue (58.3%), hypertension (50.0%), rash (44.4%), and nausea and vomiting (41.7%). Furthermore, ECOG performance status was associated with PFS of gefitinib plus anlotinib combination therapy in baseline characteristic subgroup analysis. Conclusion: Gefitinib plus anlotinib regimen demonstrated encouraging efficacy and an acceptable safety profile for patients with previously untreated EGFR positive NSCLC preliminarily. The conclusion should be validated in prospective clinical trials subsequently.

Sox10 Gene Is Required for the Survival of Saccular and Utricular Hair Cells in a Porcine Model.

Pathological changes of the cochlea and hearing loss have been well addressed in Waardenburg syndrome (WS). However, the vestibular organ malformation in WS is still largely unknown. In this study, the differentiation and development of vestibular sensory epithelium and vestibular function caused by SOX10 mutation, a critical gene induces WS, have been studied in minature pig model. Degeneration of vestibular hair cells was found in this Sox10 mutation porcine model. Inner ear phenotype of the SOX10+/R109W miniature pigs showed cochlear abnormalities as well as saccular hypofunction. In the mutant pigs, no prominent dissimilarity was shown in the bone structure of the semicircular canals. However, the saccular membrane was collapsed, and the infusion of stereocilia of the hair cells was observed. There were no dark cells in the utricles in the mutant pigs. The density of the utricular hair cells was also significantly lower in the mutant pigs compared to the wild type. Our study demonstrated that the SOX10 gene and melanocytes play important roles in the vestibular organ development. Sox10 mutation disrupts the KIT-DCT signaling pathway, affects the development of melanocytes, and leads to vestibule morphogenesis.

Stasis Caused by Depression and Coronary Heart Disease / 中国实验方剂学杂志

Anxiety and depression are common comorbidities of coronary heart disease and are considered as independent risk factors in addition to traditional cardiovascular risk factors. Anxiety，depression and other mental abnormalities belong to the category of "depressive syndrome" of traditional Chinese medicine，which can lead to stasis of blood due to the lack of Qi flow. "Blood stasis" involves abnormal blood rheology， vascular endothelial dysfunction， chronic inflammatory response， abnormal lipid metabolism and other comprehensive pathological changes， and is the core pathogenesis of coronary heart disease in traditional Chinese medicine. "Depressive syndrome"can aggravate the development of coronary heart disease by promoting blood stasis in multiple ways. Prescriptions and herbs of promoting blood circulation and removing blood stasis can have a clinical effect by promoting blood circulation （improving physiological functions） and removing blood stasis （eliminating pathological changes）. In clinical practice， strengthening the screening of the mental and psychological status of patients with coronary heart disease and providing early and effective psychological interventions and combined Chinese and Western medicine drug treatment can significantly improve the clinical symptoms and prognosis of patients. This article was the first to put forward the academic view of "stasis caused by depression" for the first time，and discuss the modern biological research progress of "depression" in Chinese medicine that promotes blood stasis and aggravates coronary heart disease，in order to provide a basis for the subsequent development of Chinese medicine in the prevention and treatment of coronary heart disease. The aim is to provide a theoretical basis for the subsequent systematic research on the prevention and treatment of coronary heart disease with emotional abnormalities in Chinese medicine.

Comparative analysis of blood components distribution in 24 domestic prefecture-level blood stations / 中国输血杂志

【Objective】 To understand the current situation of blood components distribution in domestic prefecture-level blood stations through analyzing the components distribution data of 24 prefecture-level blood stations in China. 【Methods】 The data of components distribution of 24 blood stations from 2017 to 2020 as well as the data of blood deployment of 24 blood stations from 2019 to 2020 were collected and analyzed. 【Results】 From 2017 to 2020, positive annual growth in red blood cells, plasma and cryoprecipitate was observed in 22, 19 and 15 out of the 24 blood stations, and the annual growth median rate of above three components was 5.24%, 3.80% and 3.25%, respectively. Among the 24 prefecture-level blood stations, 23 carried out the preparation of cryoprecipitate. 【Conclusion】 The distribution of red blood cells, cryoprecipitate and plasma in prefecture-level blood stations is increasing year by year. However, there is a overstock of plasma, and most blood stations need blood employment.