Construction of training program system for hospice care volunteers / 中国实用护理杂志

Objective:To construct the training program system for hospice care volunteers and provide reference for the training of hospice care volunteers in China.Methods:The training program system for hospice care volunteers was initially determined by using the method of literature analysis and investigation, and 16 experts were consulted by two rounds of letters using the method of expert inquiry from May to July 2022, and finally the training program system was established.Results:The effective recovery rate of the two rounds of expert consultation questionnaire was 100%, the expert authority coefficient was 0.88, and the Kendall coordination coefficient was 0.141, 0.131 (both P<0.05). The final training program system for hospice care volunteers contained 7 first-class indicators including training objectives, training objects, training contents, training methods, training hours, training resources and training evaluation, 27 second-class indicators and 92 third-class indicators. Conclusions:The training program system for hospice care volunteers constructed in this study has high reliability and scientificity, and has a good guiding role and reference value for the training of hospice care volunteers.

Age-Related Changes of Biomechanical Properties for Limb Bones in Male Rats / 医用生物力学

Objective To investigate the age-related changes of biomechanical properties for humerus, femur and tibia in male rats and their application values in age estimation. Methods According to different weeks of age, 90 healthy male SD rats were divided into 2, 4, 6, 8, 17, 26, 52, 78 and 104-week groups with 10 rats in eachgroup. After the rats were executed by excessive anesthesia, humerus, femur, and tibia were separated and the attached soft tissues were removed. The length of the above-mentioned bones and the diameter of the middle section (compression site) were measured with vernier caliper, and the three-point bending test was conducted with electronic universal material testing machine to detect the ultimate load and displacement under ultimate load. Results There were significant differences in the ultimate load of humerus, femur and tibia among male rats in different age groups (P<0. 05). With the increase of week age, the ultimate loads of the humerus, femur and tibia increased first and then decreased, and reached the peak value in 52-week age group, showing a strong positive correlation with week age before 52 weeks ( r = 0. 884,0. 933,0. 929, P<0. 05). There was no significant difference in humerus and tibia. The displacement of femur under ultimate load was weakly positively correlated with week age (R= 0. 406,P<0. 05). The age prediction accuracy for automatic linear modeling of ultimate load for humerus, femur, tibia and three above-mentioned bones in rats before 52-week age was 78. 2% , 86. 8% , 84. 1% and 88. 3% , respectively. There was a strong positive correlation between the length of humerus, femur and tibia and the ultimate load (R= 0. 904, 0. 897, 0. 814, P<0. 05). The diameters of humerus, femur and tibia were strongly positively correlated with the ultimate load (R = 0. 759, 0. 814 and 0. 745, P<0. 05). Conclusions The ultimate loads of humerus, femur and tibia in male rats increased first and then decreased with age, and were positively correlated with age before 52 weeks, which could be used for age inference. The highest accuracy of age estimation was ultimate loads of three bones, followed by femur. The length/ middle diameter of humerus, femur and tibia were strongly positively correlated with the ultimate load.

Study on the features of Clostridioides difficile infection among diarrhea patients in Kunming from 2018 to 2020 / 中华流行病学杂志

Objective: We analyze the characteristics of Clostridioides difficile (C. difficile) infection among diarrhea patients in Kunming from 2018 to 2020 and provide evidence for follow-up surveillance and prevention. Methods: A total of 388 fecal samples of diarrhea patients from four sentinel hospitals in Yunnan Province from 2018 to 2020 were collected. Real-time quantitative PCR was used to detect the fecal toxin genes of C. difficile. The positive fecal samples isolated the bacteria, and isolates were identified by mass spectrometry. The genomic DNA of the strains was extracted for multi-locus sequence typing (MLST). The fecal toxin, strain isolation, and clinical patient characteristics, including co-infection with other pathogens, were analyzed. Results: Among the 388 fecal samples, 47 samples with positive reference genes of C. difficile were positive, with a total positive rate of 12.11%. There were 4 (8.51%) non-toxigenic and 43 (91.49%) toxigenic ones. A total of 18 strains C. difficile were isolated from 47 positive specimens, and the isolation rate of positive specimens was 38.30%. Among them, 14 strains were positive for tcdA, tcdB, tcdC, tcdR, and tcdE. All 18 strains of C. difficile were negative for binary toxins. The MLST results showed 10 sequence types (ST), including 5 strains of ST37, accounting for 27.78%; 2 strains of ST129, ST3, ST54, and ST2, respectively; and 1 strain of ST35, ST532, ST48, ST27, and ST39, respectively. Fecal toxin gene positive (tcdB+) results were statistically associated with the patient's age group and with or without fever before the visit; positive isolates were only statistically associated with the patient's age group. In addition, some C. difficile patients have co-infection with other diarrhea-related viruses. Conclusions: The infection of C. difficile in diarrhea patients in Kunming is mostly toxigenic strains, and the high diversity of strains was identified using the MLST method. Therefore, the surveillance and prevention of C. difficile should be strengthened.

Expression and Detection Value of 6 Chlamydia Trachomatis Protein Antibodies in Tubal Factor Infertility / 中山大学学报(医学科学版)

ObjectiveTo further study the pathogenic role of different types of Chlamydia trachomatis （CT） proteins in tubal factor infertility， evaluate the clinical detection value of Chlamydia trachomatis protein antibody in predicting tubal factor infertility. MethodsA total of 58 cases of tubal factor infertility （TFI）， 41 cases of fertile controls （FC） and 18 cases of infertile controls （IFC） were included. For serum detection， first， CT-IgG ELISA kit was used to detect the expression of CT-IgG in serum of three groups of people； then， 6 kinds of Chlamydia trachomatis proteins were expressed and purified in the early stage to establish the antibody test for these proteins， and ELISA detection method was used to detect the expression of their antibodies in the serum of TFI group， FC group and IFC group， respectively； and finally， the antibody OD value of the 6 kinds of Chlamydia trachomatis proteins in the three groups of subjects were statistically described， and CT-IgG was used as the reference standard to draw the receiver operating characteristic curve （ROC curve） of each CT antibody. The Youden Index determines the cutoff value for each antibody. Taking TFI as the reference class， two disordered multiple classification logistic regression models were established with the FC and IFC groups， respectively； and the reference class was used to explore the value of various antibodies and age in predicting TFI， FC and IFC of Chlamydia trachomatis. The back-off method was used to screen the variables. ResultsThe OD value of CT376 antibody in the TFI group was higher than that in the FC group （0.86 vs. 0.60， P=0.026）. The CT376 antibody OD value in the TFI group was higher than that in the IFC group （0.86 vs. 0.64， P=0.026）. The CT443 antibody OD value in the IFC group was higher than that in the TFI group （0.59 vs. 0.34， P=0.036） and higher than that in the FC group （0.59 vs. 0.30， P=0.02）. The multiple classification logistic regression analysis established between TFI and FC showed that CT-IgG ［P<0.001， OR=0.084， 95%CI （0.025， 0.284）］， CT376 antibody ［P=0.068， OR=0.359， 95%CI （0.120， 1.078）］. CT-IgG is an independent risk factor for tubal infertility， and CT376 antibody cannot be an independent risk factor for tubal infertility. The multiple classification logistic regression analysis established between TFI and IFC showed that among infertile patients， CT-IgG ［P<0.05， OR=0.194， 95%CI （0.046， 0.817）］， CT376 antibody ［P<0.05， OR=0.176， 95%CI （0.038， 0.818）］ and CT381 antibody ［P<0.05， OR=0.112， 95%CI （ 0.016， 0.796）］ were independent risk factors for tubal infertility. ConclusionThe expression of CT376 antibody in tubal infertility patients is higher than that in fertile and infertile controls， suggesting that CT-induced tubal factor infertility may be related to CT376. CT-IgG， and CT376 antibodies are meaningful in predicting CT-induced tubal factor infertility.

Efficacy Evaluation of Biejiajianwan in the Treatment of Primary Liver Cancer Based on Real-world Data of Traditional Chinese Medicine / 中国实验方剂学杂志

ObjectiveTo evaluate the efficacy and influencing factors of Biejiajianwan in the treatment of primary liver cancer based on real-world data of traditional Chinese medicine （TCM）. MethodClinical diagnosis and treatment data of patients with primary liver cancer admitted to five Grade-A tertiary hospitals in Henan Province from January 2015 to December 2020 were collected from the medical electronic database. The patients treated with Biejiajianwan for ≥30 days were assigned to the exposure group and those without treatment with Biejiajianwan or treated with Biejiajianwan for <30 days to the non-exposure group. The propensity score matching model was used to balance confounding factors between the two groups according to the 1∶1 genetic matching method. Kaplan-Meier method was used for survival analysis and survival curve plotting. Log-rank was used to test the difference in survival rate between the two groups. Univariate analysis of Biejiajianwan in the treatment of primary liver cancer was performed by Log-rank test combined with the Kaplan-Meier method. The factors with statistical significance （P<0.05） were combined with unbalanced factors by the propensity score matching model， and at the same time， clinical common sense and relevant prognostic factors by literature search were considered， which were subjected to multivariate analysis by Cox proportional hazards regression model. ResultA total of 2 207 electronic cases were collected，including 174 cases in the exposure group （Biejiajianwan group） and 2 033 cases in the non-exposure group. After propensity score matching， there were 174 cases in the exposure group and 174 cases in the non-exposure group. The Kaplan-Meier method was used for survival analysis on the matched data， and the Log-rank test results showed that the survival rate of patients with primary liver cancer in the Biejiajianwan group was higher than that in the control group （χ2=12.193， P<0.01）. Cox proportional hazards regression model analysis showed that the regression coefficient of Biejiajianwan was -0.916 4 with the hazard ratio （HR） ［95% confidence interval （CI）］=0.4 （0.239 5-0.668 0）， P<0.01， and the regression coefficient of radiofrequency ablation treatment was -0.976 5 with HR （95% CI）=0.376 6 （0.172 8-0.821 1， P<0.05）. Fibrinogen （FIB） abnormal regression coefficient was 0.481 4 with HR （95% CI）=1.618 4（1.022 0-2.562 9），P<0.05. ConclusionBiejiajianwan can prolong the survival period of patients with primary liver cancer. Radiofrequency ablation is an independent protective factor for Biejiajianwan in the treatment of primary liver cancer，while abnormal FIB are independent risk factors for Biejiajianwan in the treatment of primary liver cancer.

Prevalence and clinical implications of polypharmacy and potentially inappropriate medication in elderly patients with heart failure: results of six months' follow-up / 老年心脏病学杂志（英文版）

OBJECTIVES@#To investigate the prevalence of polypharmacy and potentially inappropriate medication (PIM) in elderly patients with heart failure (HF) and their impact on readmission and mortality.@*METHODS@#We conducted a study of 274 participants aged 60 years or older with HF. The prevalence of polypharmacy (defined as the use of five or more medications) was calculated, and the 2019 American Geriatrics Society Beers criteria were applied to access PIMs. Medications and PIMs were characterized at admission and discharge, and changes in prescriptions during hospitalization were compared. The impact of polypharmacy and PIM on readmission and mortality were investigated.@*RESULTS@#The median age of this study population was 68 years old. The median number of prescribed drugs was 7 at admission and 10 at discharge. At discharge, 99.27% of all patients were taking five or more drugs. The incidence of composite endpoint and cardiovascular readmission increased with the number of polypharmacy within 6 months. The use of guideline-directed medical therapy reduced the incidence of composite endpoint events and cardiovascular readmission, while the use of non-cardiovascular medications increased the composite endpoint events. The frequency of PIMs was 93.79% at discharge. The incidence of composite endpoint events increased with the number of PIMs. "PIMs in older adults with caution" increased cardiovascular readmission and "PIMs based on kidney function" increased cardiovascular mortality. Several comorbidities were associated with cardiovascular mortality or non-cardiovascular readmission.@*CONCLUSIONS@#Polypharmacy and PIM were highly prevalent in elderly patients with HF, and their use was associated with an increased risk of composite endpoint events, readmission and mortality. Non-cardiovascular medications, "PIMs in older adults with caution", "PIMs based on kidney function" and several comorbidities were important factors associated with hospital readmission and mortality. Our findings highlight the importance of medication optimization in the management of HF in elderly patients.

Discussion on the use of occupational contraindication cardiovascular disease in Technical Specifications for Occupational Health Surveillance (GBZ 188-2014) / 中华劳动卫生职业病杂志

Technical Specifications for Occupational Health Surveillance (GBZ 188-2014) has played an important role in screening occupational contraindications and preventing occupational diseases since its implementation. However, during the use of occupational health examination, we found that the use of occupational contraindication on cardiovascular disease was not "homogenized" due to the differences in the understanding of various physical examination institutions. Therefore, this paper mainly discussed the connotation and quantitative standards of organic heart disease, arrhythmia, hypertension in the occupational contraindication cardiovascular disease in the specification for "homogenization".

Research progress in targeting autophagy of traditional Chinese medicine and natural compounds to regulate atherosclerosis / 中国中药杂志

Atherosclerosis(AS) is the common pathological basis of many ischemic cardiovascular diseases, and its formation process involves various aspects such as vascular endothelial injury and platelet activation. Vascular endothelial injury is the initiating factor of AS plaque. Monocytes are recruited to differentiate into macrophages at the damaged endothelial cells, which absorb oxidized low-density lipoprotein(ox-LDL) and slowly transform into foam cells. Smooth muscle cells(SMCs) proliferate and migrate continuously. As the only cell producing interstitial collagen fibers in the fibrous cap, SMCs largely determine whether the plaque ruptured or not. The amplifying inflammatory response during the formation of AS recruits platelets to adhere to the damaged area of vascular endothelium and stimulates excessive platelet aggregation. Autophagy activity is associated with vascular lesions and abnormal platelet activation, and excessive autophagy is considered to be a negative factor for plaque stability. Therefore, precise regulation of different types of vascular autophagy and platelet autophagy to treat AS may provide a new therapeutic perspective for the prevention and treatment of atherosclerotic ischemic cardiovascular disease. Currently, treatment strategies for AS still focus on lowering lipid levels with high-intensity statins, which often cause significant side effects. Therefore, the development of safer and more effective drugs and treatment modes is the focus of current research. Traditional Chinese medicine and natural compounds have the potential to treat AS by targeted autophagy, and have been playing an increasingly important role in the prevention and treatment of cardiovascular diseases in China. This paper summarizes the experimental studies on different vascular cell types and platelet autophagy in AS, and sums up the published research results on targeted autophagy of traditional Chinese medicine and natural plant compounds to regulate AS, providing new ideas for further research.

Analysis on missed diagnosis or misdiagnosis of anomalous origin of left coronary artery from pulmonary artery by echocardiography from one single medical center / 中华心血管病杂志

Objectives: To analyze the reasons of missed diagnosis or misdiagnosis on anomalous origin of left coronary artery from pulmonary artery (ALCAPA) by echocardiography. Methods: This is a retrospective study. Patients with ALCAPA who underwent surgical treatment in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from August 2008 to December 2021 were included. According to the results of preoperative echocardiography and surgical diagnosis, the patients were divided into confirmed group or missed diagnosis/misdiagnosis group. The results of preoperative echocardiography were collected, and the specific echocardiographic signs were analyzed. According to the experience of the doctors, the echocardiographic signs were divided into four types, namely clear displayed, vague/doubtful displayed, no display and no notice, and the display rate of each sign was calculated (display rate=number of clearly displayed cases/total number of cases×100%). By referring the surgical data, we analyzed and recorded the pathological anatomy and pathophysiological characteristics of the patients, and the rate of missed diagnosis/misdiagnosis of echocardiography in patients with different characteristics was compared. Results: A total of 21 patients were enrolled, including 11 males, aged 1.8 (0.8, 12.3) years (range 1 month to 47 years). Except for one patient with anomalous origin of left anterior descending artery, the others were all originated from the main left coronary artery (LCA). There were 13 cases of ALCAPA in infant and children, and 8 cases of adult ALCAPA. There were 15 cases in the confirmed group (diagnostic accuracy was 71.4% (15/21)), and 6 cases in the missed diagnosis/misdiagnosis group (three cases were misdiagnosed as primary endocardial fibroelastosis, two cases were misdiagnosed as coronary-pulmonary artery fistula; and one case was missed diagnosis). The working years of the physicians in the confirmed group were longer than those in the missed diagnosis/misdiagnosed group ((12.8±5.6) years vs. (8.3±4.7) years, P=0.045). In infants with ALCAPA, the detection rate of LCA-pulmonary shunt (8/10 vs. 0, P=0.035) and coronary collateral circulation (7/10 vs. 0, P=0.042) in confirmed group was higher than that in missed diagnosis/misdiagnosed group. In adult ALCAPA patients, the detection rate of LCA-pulmonary artery shunt was higher in confirmed group than that in missed diagnosis/misdiagnosed group (4/5 vs. 0, P=0.021). The missed diagnosis/misdiagnosis rate of adult type was higher than that of infant type (3/8 vs. 3/13, P=0.410). The rate of missed diagnosis/misdiagnosis was higher in patients with abnormal origin of branches than that of abnormal origin of main trunk (1/1 vs. 5/21, P=0.028). The rate of missed diagnosis/misdiagnosis in patients with LCA running between the main and pulmonary arteries was higher than that distant from the main pulmonary artery septum (4/7 vs. 2/14, P=0.064). The rate of missed diagnosis/misdiagnosis in patients with severe pulmonary hypertension was higher than that in patients without severe pulmonary hypertension (2/3 vs. 4/18, P=0.184). The reasons with an echocardiography missed diagnosis/misdiagnosis rate of≥50% included that (1) the proximal segment of LCA ran between the main and pulmonary arteries; (2) abnormal opening of LCA at the right posterior part of the pulmonary artery; (3) abnormal origin of LCA branches; (4) complicated with severe pulmonary hypertension. Conclusions: Echocardiography physicians' knowledge of ALCAPA and diagnostic vigilance are critical to the accuracy of diagnosis. Attention should be paid to the pediatric cases with no obvious precipitating factors of left ventricular enlargement, regardless of whether the left ventricular function is normal or not, the origin of coronary artery should be routinely explored.

Prediction of vault after implantable collamer lens implantation and its research progress / 国际眼科杂志(Guoji Yanke Zazhi)

Myopia is considered to be a disease occurred under the influence of genetic and environmental factors, and it can only be restored by corrective surgeries. The current surgical methods include laser surgeries and phakic intraocular lens(PIOL)implantation, and PIOL has the advantages of wide range of correction, repeatable procession and small damage to corneal tissue. Furthermore, good visual acuity can be achieved after implantation of intraocular lens. Implantable collamer lens(ICL)is the most common surgical method in this group. The vertical distance between the highest point of the posterior central surface of the implanted lens and the anterior surface of the crystalline lens is called vault. It will cause serious complications if the vault turns out to be abnormal. Up to now, there is no optimal prediction method. This research focuses on vault, discusses the ideal range of postoperative vault, the safety and effectiveness of this surgery, and analyzes the existing prediction methods to provide directions for future clinical research.

Study on preparation and in vivo safety of progesterone cocrystal / 中国药房

OBJECTIVE To prepare progesterone-2-chloro-4-nitroaniline cocrystal （CNA） so as to improve the solubility of progesterone and primarily evaluate the safety of the progesterone cocrystal in vivo. METHODS Using progesterone as the main body and CNA as the ligand， progesterone-CNA cocrystal was prepared with solvent evaporation method. The cocrystal was characterized by X-ray single crystal diffraction， X-ray powder diffraction （XRPD）， differential scanning calorimetry （DSC） and Fourier transform infrared spectroscopy （IR）. The dissolution rate of cocrystal was compared with those of progesterone and physical mixture. Forty-eight female KM mice were randomly divided into normal group （phosphate buffer containing 0.1% dimethyl sulfoxide）， progesterone group （16 mg/kg）， CNA group （9 mg/kg）， progesterone-CNA cocrystal low-dose， medium- dose and high-dose groups （6， 12.5， 25 mg/kg）， with 8 mice in each group. They were given relevant medicine/solvent intramuscularly， once a day， for consecutive 14 d. The safety of cocrystal was evaluated primarily by determining/observing the changes in body weight， organ index， tissue morphology， blood routine indicators， and liver and kidney function indicators. RESULTS The new crystal structure in the X-ray single crystal diffraction results， the new characteristic peak in the XRPD pattern， the change of melting point in the DSC results， and the change of the characteristic peak position in the range of 3 500- 2 750 cm－1 and 1 700-1 250 cm－1 in the infrared spectrum all Δ 基金项目国家重点研发计划项目（No.2022YFC3502100） indicated that progesterone-CNA cocrystal was successfully ＊第一作者 硕士研究生 。研究方向 ：药物制备技术与工艺 。 prepared， and the dissolution rate of cocrystal was more than E-mail：SWB_1221@163.com # 通信作者教授，硕士生导师，博士。研究方向：药物制备技术与 twice that of the progesterone raw material drug. The results of 工艺。E-mail：wuxx-415@126.com in vivo safety experiments showed that the mortality rate of all 中国药房 2023年第34卷第13期 China Pharmacy 2023 Vol. 34 No. 13 · 1567 · groups was zero. Compared with normal group， uterine indexes of mice in progesterone group and progesterone-CNA cocrystal groups were significantly increased （P＞0.05）， and endometrium was also thickened； there was no statistical difference in the changes of body mass， liver and kidney function， liver index， kidney index， the number of leukocyte， lymphocyte and neutrophil in routine blood test among those groups （P＞0.05）， and the morphology of liver and kidney tissue has also no significant difference. However， the number of plasma red blood cells in the progesterone group decreased significantly （P＜0.05）， and there was no statistical significance in the number difference of red blood cells among progesterone-CNA cocrystal groups （P＞0.05）. CONCLUSIONS The progesterone-CNA cocrystal is successfully prepared with good safety in vivo， which significantly improve the solubility of progesterone.

Protective effect of Zhizi Dahuang decoction in a mouse model of alcoholic liver disease / 临床肝胆病杂志

ObjectiveTo investigate the effect of Zhizi Dahuang decoction （ZZDHT） in the treatment of alcoholic liver disease （ALD） by improving oxidative stress in hepatic neutrophils. MethodsNetwork pharmacology was used to obtain the chemical components of ZZDHT and their corresponding action targets and analyze the potential targets and functional pathways of ZZDHT in the treatment of ALD. The non-target metabolomics technology was used to observe the changes in the metabolites of ZZDHT in mouse serum and liver. The mice were given ZZDHT at a dose twice as much as the middle dose concentration by gavage， and serum and liver samples were collected at six time points after gavage （10 minutes， 30 minutes， 1 hour， 2 hours， 4 hours， and 6 hours） and were then mixed for mass spectrometry （administration group with 18 mice）， while the 18 mice in the control group were given an equal volume of normal saline by gavage. Ultra-performance liquid chromatography was used for rapid isolation and identification of the metabolites of ZZDHT in serum and liver tissue， and the effective constituents of ZZDHT were validated. Male C57BL/6J mice， aged 8 weeks， were randomly and equally divided into control group， model group， and low-， middle-， and high-dose ZZDHT groups， with 10 mice in each group. All mice except those in the control group were used to establish a mouse model of ALD （NIAAA model mice）， and at the same time， the mice in the administration groups were given low-， middle-， and high-dose ZZDHT by gavage， while those in the control group and the model group were given an equal volume of normal saline by gavage. The serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and triglyceride （TG） were measured； PCR was used to measure the gene expression levels of related inflammation， oxidative stress， and neutrophil indicators in the liver； ELISA was used to measure the levels of related inflammation and oxidative stress indicators in serum； superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， and malondialdehyde （MDA） were measured to observe the level of oxidative stress in the liver； HE staining， myeloperoxidase staining， and oil red staining were used to observe liver injury， neutrophil infiltration， and lipid deposition. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsA total of 53 active components and 227 target genes were obtained for ZZDHT， and there were 8685 target genes of ALD， resulting in 222 common target genes between these two groups of genes. Core pathways included the interleukin-6 signaling pathway and the TNF signaling pathway. The non-targeted metabolic analysis of ZZDHT obtained 225 metabolites in mouse liver and 227 metabolites in serum， among which there were 126 common metabolites. The core pathways of liver metabolites included glycerolipid metabolism and inflammatory mediator regulation of TRP channels， and the core pathways of serum metabolites included the AMPK signaling pathway and oxidative phosphorylation， all of which were associated with oxidative stress- and inflammation-related pathways. Compared with the model group， the low-， middle-， and high-dose ZZDHT groups had significant reductions in the serum levels of ALT， AST， and TG （all P<0.05）， and the middle-dose ZZDHT group had significant reductions in the levels of Ly6g， Ncf1， Ncf2， IL-6， TNF-α， IL-1β， MDA， 4-HNE， Gp91， and P22 in the liver （all P<0.05）， a significant increase in the level of SOD （P<0.05）， a significant reduction in the serum level of 4-HNE （P<0.05）， and a significant increase in the level of GSH-Px （P<0.05）. There were significant improvements in fat deposition and neutrophil infiltration in the liver of mice in the middle-dose ZZDHT group （both P<0.05）. ConclusionZZDHT significantly reduces oxidative stress and inflammatory response in NIAAA model mice.

The relationship between sleep arousal, ambulatory blood pressure and heart failure in elderly patients with obstructive sleep apnea / 中华老年医学杂志

Objective:To evaluate the relationship between sleep arousal, ambulatory blood pressure and new-onset heart failure(NOHF)in elderly patients with obstructive sleep apnea(OSA).Methods:A total of 584 elderly patients with OSA who were diagnosed and treated in our hospital between March 2015 and March 2019 were prospectively and consecutively selected, with a mean age of(70.1±7.2)years.Polysomnography(PSG)results were obtained at baseline, and the arousal index(AI)was calculated.Based on the quartiles of AI, patients were divided into 4 groups: a low-level group(AI<18.4/h, 186 cases), a low-medium level group(18.4-29.1/h, 177 cases), a medium-high level group(29.2-41.2/h, 137 cases)and a high-level group(>41.2 /h, 84 cases). Participants were followed up for 18 months, the results of ambulatory blood pressure were recorded and compared, and the relationship between AI and the risk of NOHF was analyzed.Results:Compared with the low-level group, patients in the low-medium, medium-high, and high-level groups were older(70.1, 70.3, 73.3 vs.68.7 years, F=2.726, P=0.043)and had more smokers(43.8%, 49.6%, 54.8% vs.38.2%, χ2=8.809, P=0.032), a larger body mass index(26.3, 26.7, 27.6 vs.25.4 kg/m 2, F=2.731, P=0.042), a higher Epworth sleepiness scale score(7.83, 8.50, 9.91 vs.7.64, F=5.124, P=0.018), a higher apnea hypopnea index(23.5, 34.8, 52.7 vs.17.6, F=5.632, P=0.007), lower nocturnal oxygen saturation(80.2, 75.3, 72.1 vs.83.7 mmHg, F=4.811, P=0.024), and higher N-terminal pro-B-type natriuretic peptide(NT-proBNP)levels(317.5, 337.5, 359.2 vs.267.5 pg/L, F=4.307, P=0.033). At the median follow-up(18 months, 14-24 months), the results of ambulatory blood pressure monitoring showed that 24-hour systolic blood pressure(24 h SBP)(147.3, 148.6, 156.2 vs.143.8 mmHg, F=5.4311, P=0.013), 24-hour diastolic blood pressure(24 h DBP)(80.1, 79.5, 83.7 vs.76.5 mmHg, F=5.679, P=0.011)in the low-medium, medium-high and high-level groups were higher than those in the low-level group.The results of survival analysis showed that there were 75(12.8%)cases of NOHF, mostly with preserved ejection fraction(47 cases)or mid-range ejection fraction heart failure(20 cases). The incidences of NOHF were 6.5%, 12.4%, 16.1% and 22.4%, respectively for the low level, low-medium, medium-high and high-level groups, and the risk of NOHF in the low-medium, medium-high and high-level groups was significantly higher than in the low level group(log-rank χ2=11.624, P=0.007). Variables with P<0.2 in the univariate analysis, age and sex were included in the multivariate Cox regression analysis.The results showed that age( HR=1.724, 95% CI: 1.216-3.135), diabetes( HR=1.514, 95% CI: 1.127-3.058), NT proBNP( HR=1.517, 95% CI: 1.232-2.366), nocturnal diastolic blood pressure( HR=2.004, 95% CI: 1.332-4.638), and middle-high AI level( HR=1.611, 95% CI: 1.204-2.967)and high AI level( HR=1.863, 95% CI: 1.272-3.538)were independent factors of NOHF in elderly OSA patients. Conclusions:Sleep arousal in elderly patients with OSA increases blood pressure levels and the risk of NOHF.

Univariate analysis of peripheral neurotoxicity induced by oxaliplatin chemotherapy in patients with colorectal cancer and its prevention and treatment strategies / 中国基层医药

Objective:To analyze the related factors of neurotoxicity induced by oxaliplatin chemotherapy in patients with colorectal cancer and its prevention and treatment strategies.Methods:A total of 300 patients with colorectal cancer treated with oxaliplatin in Zhejiang Cancer Hospital from January 2018 to December 2020 were randomly selected for baseline collection using the convenience sampling method. The occurrence of oxaliplatin-induced peripheral neurotoxicity (OIPN) was statistically analyzed. The factors that affect the occurrence of OIPN were analyzed using univariate analysis.Results:There was a significant difference in OIPN score between patients of different genders, between patients who had different education levels, between patients who had different occupations, and between patients who lived in different long-term residence places ( t = 7.29, 3.39, 2.53, 18.11, all P < 0.05). There was no significant difference in OIPN score between patients adhering to different religion's beliefs, between patients married and not, between patients who lived with and without members, between patients who paid medical costs and not, and between patients who had a previous history of smoking and not ( t = 3.25, 0.37, 0.69, 2.39, 0.15, all P > 0.05). There was a significant difference in OIPN score between patients with different tumor-node-metastasis stages, between patients who received medication via different administration routes, and between patients who received different times of oxaliplatin administration ( t = 8.40, 3.34, 3.49, all P < 0.05). Conclusion:Medical staff should pay attention to the occurrence of OIPN in patients with colorectal cancer treated with oxaliplatin, focus on the patient's factors related to the disease, and take correct and effective coping strategies promptly to reduce the adverse reactions, improve the quality of life, and ensure the therapeutic effect.

Construction and anti-tumor efficiency evaluation of redox-responsive micelles for the co-delivery of IR-780 and 18β-glycyrrhetinic acid / 药学学报

Photothermal therapy (PTT) is a highly effective anti-tumor method. However, when laser radiation was used to ablate tumors, it usually triggers a series of inflammatory reactions, promoting the further development of tumors and affecting the effect of anti-tumor therapy. Therefore, it is an effective method to improve the anti-tumor effect by suppressing the inflammatory response through the precise targeted delivery of anti-inflammatory drug while realizing the photothermal treatment of tumors. To this end, the redox-responsive linker 3,3'-dithiodipropionic acid was used to bond the classic hydrophobic anti-inflammatory drug 18β-glycyrrhetinic acid (18β-GA) and the hydrophilic fragment methoxy-polyethylene glycol (mPEG-NH2) to obtain redox-responsive amphiphilic polymer PEG-DA-GA in this study. Then, photothermal agent IR-780 was encapsulated to prepare redox-responsive polymer micelle PDG/IR-780 NPs. The PDG/IR-780 NPs exhibited uniform particle size of 80.2 ± 5.3 nm and the polydispersity index (PDI) was 0.215 ± 0.079. All animal experiments followed the ethical requirements formulated by the Ethics Committee of Sichuan University. The results showed that PDG/IR-780 NPs could respond to the abundant glutathione (GSH) in tumor cells to promote the disintegration of nanoparticle and the release of 18β-GA, thus significantly improved the killing efficiency on 4T1 cells, when compared with the non-redox-responsive control PSG/IR-780 NPs. When the concentration of 18β-GA was 50 μg·mL-1, the cell viability of 4T1 cells in the PDG/IR-780 NPs group was only (19.29 ± 1.80) %, which was significantly lower than the result of in PSG/IR-780 NPs group (29.30 ± 1.37) %. The results of frozen sections of tumor tissues showed that the designed PDG NPs can promote the tumor-targeted distribution of drugs compared with the free drug group. Eventually, PDG/IR-780 NPs achieved wonderful anti-tumor efficacy on 4T1 triple-negative breast cancer model, revealing the new possibility of the combined therapy strategy of photothermal and anti-inflammatory therapy.

In vitro release study on self-microemulsion of curcumin and piperine / 药学实践杂志

Objective To study the release profile of curcumin and piperine from the compound self-microemulsion. Methods The release of curcumin and piperine in vitro was investigated by dynamic dialysis under the condition of phosphate buffer of pH 4.8 and 7.5 with 0.75% Tween-80. Results The cumulative release rates of curcumin in pH 4.8 and pH 7.5 were 94.85% and 84.38% in 108 h, respectively. The cumulative release rates of piperine were 92.85% and 90.05% in 36 h, separately. Conclusion Curcumin and piperine in self-microemulsion have sustained release properties and released more in the acidic environment similar to the environment in tumors.

Application of double-line mixed teaching in the teaching of medical students in the practice of department of surgical oncology / 中华医学教育探索杂志

Objective:To construct a double-line mixed teaching mode and to explore its application effect on the practice teaching of medical students in the department of surgical oncology.Methods:A total of 80 clinical medicine students were selected and randomly divided into a routine group and a research group, with 40 students in each group. The routine group implemented regular teaching, and the research group developed "double-line mixed teaching" mode. After teaching, the students' theoretical and practical skills assessment results, changes in medical students' abilities and their satisfaction with teaching were compared between the two groups. SPSS 19.0 was used for t test and chi-square test. Results:The theoretical and practical skill assessment scores of the research group were significantly higher than those of the routine group [(91.59±3.65) score vs. (84.67±4.34) scores, (86.05±4.16) scores vs. (74.73± 4.69) scores] ( P<0.05). The scores of medical humanistic spirit, clinical thinking ability, scientific research thinking ability, critical thinking and innovation ability of the two groups after teaching were all higher than those before teaching, and the above-mentioned ability scores of the research group were all higher than those of the routine group after teaching ( P<0.05). The satisfaction rates of the students in the research group regarding teaching content and form, improving self-study ability, strengthening understanding and mastering of knowledge, deepening practical experience, and improving collaboration ability were all higher than those of students in the routine group (87.50% vs. 67.50%; 82.50% vs. 60.00%; 90.00% vs. 67.50%; 92.50% vs. 75.00%; 95.00% vs. 77.50%), and the differences were statistically significant ( P<0.05). Conclusion:Constructing double-line mixed teaching mode in the practice teaching of medical students in the department of surgical oncology can improve the performance of theoretical and practical skills assessment, as well as improve the various abilities of medical students, and can obtain high satisfaction with the teaching mode.

Short needling for knee osteoarthritis with blood stasis obstruction and its effect on serum inflammatory factors / 中国针灸

OBJECTIVE@#To compare the clinical efficacy and its effect on serum levels of tumor necrosis factor α(TNF-α), interleukin 1β(IL-1β), interleukin 6 (IL-6) and prostaglandin E2 (PGE2) between short needling (close-to-bone needling) and conventional acupuncture for knee osteoarthritis (KOA) with blood stasis obstruction.@*METHODS@#A total of 68 KOA patients with blood stasis obstruction were randomized into a short needling group (34 cases, 3 cases dropped off) and a conventional acupuncture group (34 cases, 3 cases dropped off). The same acupoints (Dubi [ST 35], Neixiyan [EX-LE 4], Binzhong [Extra], Liangqiu [ST 34], etc. on the affected side) were selected in the two groups. In the short needling group, short needling technique was adopted, the needles were slowly inserted and the needle bodies were shaken, thus gradually penetrated to the bone. In the conventional acupuncture group, conventional acupuncture was adopted, the needles were penetrated to the muscle. After qi-arrival, Dubi (ST 35) and Neixiyan (EX-LE 4), Zusanli (ST 36) and Liangqiu (ST 34) were connected with CMNS6-1 electronic acupuncture instrument, with disperse-dense wave, 2 Hz/10 Hz in frequency, the current intensity was based on patients' feeling, the needles were retained for 30 min, at the same time, the knee joint was irradiated for 30 min with a special electromagnetic wave apparatus in the two groups. Once every other day, 3 times a week for 4 weeks. Before and after treatment, the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) score, knee joint pain visual analogue scale (VAS) score, inflammatory response related indexes (serum TNF-a, IL-1β, IL-6 and PGE2) and knee joint ultrasound were observed，and the clinical effect was evaluated in the two groups.@*RESULTS@#After treatment，the pain, stiffness, function scores and total scores of WOMAC were decreased as compared with those before treatment in the two groups (P<0.05), except for the pain score, the changes of above scores in the short needling group were greater than the conventional acupuncture group (P<0.05). After treatment, the VAS scores, serum levels of TNF-a, IL-1β, IL-6, PGE2 and knee joint synovium thickness, intra-articular effusion were decreased as compared with those before treatment in the two groups (P<0.05), the levels of TNF-a, IL-1β, IL-6 in the short needling group were lower than the conventional acupuncture group (P<0.05). The total effective rate in the short needling group was 87.1% (27/31), which was superior to 83.9% (26/31) in the conventional acupuncture group (P<0.05).@*CONCLUSION@#Short needling could improve the knee joint function, relieve the pain and inflammatory response, improve the knee joint synovium inflammatory response, reduce the knee joint intra-articular effusion for KOA patients, its effect is better than conventional acupuncture.

Applicability of three nutritional screening tools in patients with liver cirrhosis under the Global Leadership Initiative on Malnutrition criteria / 临床肝胆病杂志

Objective To investigate whether Royal Free Hospital Nutritional Prioritizing Tool (RFH-NPT) is more suitable than Nutritional Risk Screening 2002 (NRS-2002) in nutritional risk screening for patients with liver cirrhosis, as well as the applicability of subjective global assessment (SGA) in the nutritional assessment of patients with liver cirrhosis. Methods A total of 113 patients with liver cirrhosis who were hospitalized in Renmin Hospital of Wuhan University from August 2020 to June 2021 were enrolled. RFH-NPT and NRS-2002 were used for nutritional risk screening, and SGA was used for nutritional assessment. The results of these tools were compared with the Global Leadership Initiative on Malnutrition (GLIM) criteria, and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the three tools. The receiver operating characteristic (ROC) curve was plotted and the area under the ROC curve (AUC) was calculated for each screening tool, and the association between nutritional status and short-term prognosis was analyzed. The independent samples t -test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Spearman correlation analysis was used to analyze the correlation of GLIM criteria with NRS2002, RFH-NPT and SGA. Results According to the GLIM criteria, 69.9% of the patients were diagnosed with malnutrition, and RFH-NPT and NRS2002 screened out that 72.6% and 51.3%, respectively, of the patients had nutritional risk, while SGA assessment showed that 57.5% of the patients had malnutrition. Compared with NRS2002, RFH-NPT had a higher degree of correlation with the GLIM criteria ( r =0.764, P < 0.001), higher sensitivity (94.9%) and NPV (87.1%), and a better predictive value (AUC=0.872, 95% confidence interval [ CI ]: 0.786-0.957). Under the GLIM criteria, SGA had good specificity (88.2%) in the diagnosis of malnutrition in patients with liver cirrhosis, with fair sensitivity (77.2%), good correlation ( r =0.607, P < 0.001), and good predictive value (AUC=0.827, 95% CI : 0.744-0.911). Based on the GLIM criteria, SGA assessment, and RFH-NPT assessment, the patients with nutritional risk or malnutrition tended to have a longer length of hospital stay ( Z= -3.301, -2.812, and -3.813, all P < 0.05) and a higher rehospitalization rate ( χ 2 =3.957, 6.922, and 6.766, all P < 0.05). Based on the GLIM criteria and NRS2002 assessment, the patients with nutritional risk or malnutrition had a significant increase in mortality rate within 3 months ( χ 2 =4.511 and 0.776, both P < 0.05). Conclusion Under the GLIM criteria, RFH-NPT is more suitable than NRS2002 for nutritional risk screening of patients with liver cirrhosis, and SGA also has good applicability in nutritional assessment of patients with liver cirrhosis. In addition, GLIM criteria, SGA, and RFH-NPT are associated with the clinical outcome of patients.

Serum metabolomics of chronic obstructive pulmonary disease with lung-Qi deficiency syndrome / 中国中药杂志

The present study analyzed the potential biomarkers of chronic obstructive pulmonary disease(COPD) with lung-Qi deficiency syndrome by non-targeted metabolomics and explored the biological basis of this syndrome. Blood samples of 96 COPD patients with lung-Qi deficiency syndrome(COPD with lung-Qi deficiency syndrome group) and 106 healthy people(healthy control group) were collected, and the metabolic profiles of both groups were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Multivariate statistical analysis and differential metabolite screening were carried out by using Progenesis QI and Simca-P. Metabolic pathways were constructed through the MetaboAnalyst. Seven potential biomarkers, such as L-cystathionine, protoporphyrinogen Ⅸ, and citalopram aldehyde, were identified. Compared with the results in the healthy control group, the content of citalopram aldehyde, N1-methyl-2-pyridone-5-carboxamide, and 11β,17β-dihydroxy-4-androsten-3-one was significantly up-regulated, while that of the other four compounds such as L-cystathionine, dihydrotestosterone, protoporphyrinogen Ⅸ, and D-urobilinogen was down-regulated. These potential biomarkers involved six metabolic pathways, including cysteine and methionine metabolism, porphyrin and chlorophyll metabolism, drug metabolism of cytochrome P450, steroid hormone biosynthesis, glycine, serine, and threonine metabolism, and nicotinate and nicotinamide meta-bolism. This study is expected to provide a certain scientific basis for the research on traditional Chinese medicine syndrome of COPD with lung-Qi deficiency syndrome from the molecular biology level.