OBJECTIVE To evaluate the comprehensive value of novel oral anticoagulant drugs （NOACs） after major orthopedic surgery. METHODS The evaluation evidence was collected through literature research； evidence and value：impact on decision-making （EVIDEM） framework was introduced to integrate the evaluation process； the multi-criteria decision analysis （MCDA） method was used to construct a multi-dimensional evaluation system； the weights assigned to each evaluation criterion were determined by the combination of Delphi method and analytic hierarchy process， and the rivaroxaban， dabigatran and apixaban were comprehensively evaluated. RESULTS The clinical comprehensive evaluation system of NOACs after major orthopedic surgery was successfully established， and the final clinical comprehensive evaluation weights of NOACs （rivaroxaban， dabigatran， apixaban） after major orthopedic surgery were calculated， with scores of 0.399 7 for rivaroxaban， 0.244 4 for apixaban， and 0.355 9 for dabigatran， indicating that rivaroxaban demonstrated the highest overall clinical value. Among them， rivaroxaban had the highest weight score in the evaluation of pharmaceutical characteristics， cost-effectiveness and other attributes in a single dimension. In terms of efficacy and safety evaluation， apixaban had the highest weighting score. CONCLUSIONS Among NOACs， rivaroxaban is more suitable for routine anticoagulation management after major orthopedic surgery， especially in terms of pharmacological properties， cost-effectiveness and other attributes.

Pure-tone audiometry can be performed to evaluate the type and degree of hearing loss， whose results can be divided into four types including low-frequency descending， high-frequency descending， flat descending and total deafness. The low-frequency descending type of sudden hearing loss （SHL） is more likely to be spleen deficiency and dampness exuberance， the high-frequency descending type is often due to yin deficiency of liver and kidney， the flat descending type is commonly associated with qi and blood depletion， and the type of total deafness is often linked to blood stasis. Our team has further developed a comprehensive diagnostic and therapeutic approach for SHL， emphasizing "the integration of disease and syndrome， the combination of acupuncture and herbal medicine， and dynamically administering treatment". Firstly， it advocates integrating disease diagnosis with syndrome differentiation. Secondly， it recommends combining acupuncture and herbal medicine， with local acupoints such as Ermen （TE 21）， Tinggong （SI 19）， Tinghui （GB 2）， and Yifeng （TE 17） used to unblock the auditory orifice， and herbal prescriptions tailored to the hearing curve patterns. For the low-frequency descending type， it is recommended to fortify the spleen and percolate dampness by taking distal points of spleen channel and stomach channel and using Shenling Baizhu Powder （参苓白术散）. For the high-frequency descending type， the method of nourishing kidney and calming liver is recommended， using distal points of kidney and liver channels and taking Erlong Zuoci Pills （耳聋左慈丸）. Regarding the flat descending type， tonifying qi and nourishing blood is advised， for which acupoints of Conception Vessel， spleen， stomach and large intestine channels can be needled， and Yiqi Congming Decoction （益气聪明汤） can be administered. For the total deafness type， it is recommended to activate blood and dissipate stasis， often with Xuehai （SP 10） and Geshu （BL 17） needled and Tongqiao Huoxue Decoction （通窍活血汤） administered. All these are conducted to treat the root and branch simultaneously. At the same time， it emphasizes the need to consider complex syndrome presentations and disease progression， dynamically analyze the disease causes and mechanisms， and adjust treatment according to the changing syndromes. In conclusion， this article is expected to inspire clinical diagnosis and treatment of SHL.

Through comprehensive and systematic collection of existing evidence,systematic review adopts clinical epidemiological methods,strictly evaluates the quality of evidence,qualitatively or quantitatively combines research results,and finally provides a reliable basis for solving a focused clinical problem.The number of systematic reviews has increased rapidly.With references to the Checklist,this review discussed the typical issues with current systematic reviews in nursing,and highlighted the crucial components for reporting systematic reviews at every essential step.

Objective To summarize and evaluate the characteristics of current recurrent spontaneous abortion(RSA)animal models at home and abroad,and to provide reference and guidance for the standardized preparation of RSA models.Methods"Recurrent spontaneous abortion"and"animal model"were used as co-keywords in CNKI,Wanfang,VIP,PubMed and Web of Science databases to search the RSA animal experimental literature,covering the period up to January 20,2024,and a total of 1 411 articles were collected.The analysis focused on construction methods and essential elements of RSA animal models,the modeling process and result evaluation,as well as the application of these models in pharmacological and pharmacodynamic research.An Excel table was established for systematic analysis and discussion.Results A total of 138 experimental studies were obtained after screening.In constructing RSA animal models,immunological models were the most widely used in Western medicine(96.92％),with the Clark model being the main one(92.31％).In traditional Chinese medicine(TCM)models,70.00％were kidney deficiency-luteal inhibition-syndrome combination models,20.00％were kidney deficiency and blood stasis models,and 10.00％were deficiency-heat syndrome models.Most animals were selected at 6-8 weeks(33.86％)and 8 weeks(32.28％)of age.The majority of animals were paired for mating at 18:00 on the day of cage pairing.In 81.03％of literatures,vaginal plugs were checked once the following morning,with 8:00 being the most common time(17.02％).The most commonly used drug administration cycle was 14 days of continuous gavage after pregnancy.Among the tested drugs,Western drugs were mainly protein-based(29.17％),while TCM drugs were mainly TCM decoction(81.11％).The most frequently used methods for detecting indicators included visual observation of embryos(22.54％),western blot(15.96％),PCR(13.58％),ELISA(12.91％),HE staining(10.80％)and immunohistochemistry(9.39％).Conclusion The etiology of RSA is complex,and corresponding animal models should be established based on different etiologies.Clark model is commonly used in the construction of Western medicine model,while the kidney deficiency-luteal inhibition-syndrome combination model is predominant in TCM.RSA animal model is widely used in related research,but systematic evaluation needs to be strengthened.

Objective:To investigate the association of time in range with metabolic associated fatty liver disease(MAFLD) and advanced liver fibrosis in patients with type 2 diabetes.Methods:This study was a retrospective study. A total of 494 type 2 diabetic patients were recruited in the Department of Endocrinololgy of Henan Provincial People′s Hospital from November 2019 to April 2022. Time in range(TIR) was calculated with continuous glucose monitoring data. Abdominal ultrasound scan was used to diagnose fatty liver. Liver stiffness measurement(LSM) by transient elastography was used to evaluate liver fibrosis. Pearson and multivariate linear regression analysis was used to evaluate the association between TIR and LSM. Multivariate logistic regression analysis was used to analyze the association of TIR with risk of MAFLD and advanced liver fibrosis.Results:Pearson correlation analysis showed that LSM was negatively correlated with TIR( r=-0.86, P<0.001) and was positively correlated with homeostasis model assessment for insulin resistance(HOMA-IR; r=0.48, P<0.001). After adjusting for confounding factors, multivariate linear regression analysis showed that TIR significantly negatively predicted LSM( β=-0.75, P<0.001), and HOMA-IR significantly positively predicted LSM( β=0.21, P=0.025). After adjusting for confounding factors, logistic regression analysis showed that compared with TIR Q4 patients, TIR Q1 patients had an increased risk of MAFLD( OR=1.96, 95% CI 1.07-3.62, P=0.027), advanced liver fibrosis( OR=3.82, 95% CI 1.17-12.50, P=0.027), and HOMA-IR was an independent risk factor for MAFLD( OR=1.22, 95% CI 1.04-1.43, P=0.005) and advanced liver fibrosis( OR=1.26, 95% CI 1.03-1.54, P=0.025). Conclusions:TIR and insulin resistance are independent risk factors for MAFLD and advanced liver fibrosis in patients with type 2 diabetes. TIR has a significant predictive value for MAFLD and advanced liver fibrosis.

ObjectiveTo evaluate the effectiveness and safety of neck seven-line method combined with periauricular acupuncture as salvage treatment for sudden hearing loss in non-acute stage. MethodsSixty-six patients with non-acute stage of sudden hearing loss with a disease duration of 15-90 days were randomly divided into 33 cases each in treatment group and control group. The treatment group was given neck seven-line method combined with acupuncture at periauricular points； the control group used sham acupuncture and sham electroacupuncture at the same points. Both groups were treated 3 times a week for 6 weeks. The pure tone average hearing threshold of impaired frequencies were examined before treatment， after treatment finish and at follow-up （week 10）， and the difference between pure tone average hearing threshold of impaired frequencies before and after treatment was calculated； calculate the proportion of patients with ≥10 dB improvement in pure tone average hearing threshold of impaired frequency after treatment and at follow-up； compare the patients' Tinnitus Evaluation Scale （TEQ） scores， Chinese Medicine Quality of Life Assessment Scale （CQ-11D） health utility values and the difference between before and after treatment， and record the occurrence of adverse events. ResultsThe pure tone average of impaired frequency in the treatment group were （50.57±18.07） dB and （47.70±17.42） dB at post-treatment and follow-up respectively， and （54.38±21.77） dB and （53.36±20.99） dB in the control group at post-treatment and follow-up. Compared with the pre-treatment period， the pure tone average hearing threshold of impaired frequency in the two groups significantly decreased （P＜0.05） at post-treatment and follow-up. The difference of pure tone average hearing threshold of impaired frequency in the treatment group after treatment and at the follow-up visit compared to that before treatment was lower than those in the control group （P＜0.05）. After treatment， 13 patients （39.39%） in the treatment group and 10 patients （30.30%） in the control group showed improvement of ≥10 dB in pure tone average hearing threshold of impaired frequency； at the follow-up visit， 18 patients （54.55%） in the treatment group and 10 patients （30.30%） in the control group showed improvement of ≥10 dB in the pure tone average hearing threshold of impaired frequency， and there was no statistical significance for comparison between groups at the time of post-treatment and follow-up （P＞0.05）. The TEQ score of the treatment group significantly lower than that before treatment （P＜0.05）； the TEQ score of the treatment group and the difference between before and after treatment significantly lower than that of the control group （P＜0.05）. The difference in CQ-11D health utility values and the difference between before and after treatment were not statistically significant between the two groups （P＞0.05）. Eight cases of acupuncture-related adverse events occurred among 66 patients， including subcutaneous haematomas after needling， severe pain during needling and needle fainting， which disappeared after symptomatic treatment and did not affect the following treatment. ConclusionNeck seven-line method combined with periauricular acupuncture could be used as salvage treatment for sudden hearing loss in non-acute stage to improve the pure tone average hearing threshold of impaired frequency， alleviate tinnitus， with safety.

Objective To design a pH-sensitive nintedanib liposomes(Nb-Lips)which targeted the acidic microenvironment of pulmonary fibrosis.The entrapment efficiency(EE%)was optimized by the formulation process.Methods Nintedanib liposomes were prepared by membrane hydration method,and the formulation of nintedanib liposomes were optimized by single factor experiments and response surface method(RSM).The particle size,polymer dispersity index(PDI),Zeta potential and encapsulation rate was investigated by dynamic light scattering technique and microcolumn centrifugation method.The release behavior of nintedanib liposomes in artificial lung fluid with pH 7.4 and artificial lung fluid with pH 5.3 was investigated by dialysis method.Nintedanib liposomes were atomized with a compressed air atomizer and its atomization stability and aerodynamic particle size were investigated.Results The particle size of nintedanib liposomes was(100.651±7.315)nm,the PDI was(0.328±0.026),the zeta potential was(21.633±2.004)mV,and the encapsulation rate was higher than 80%.Compared with nintedanib solution at pH 7.4,the total release of nintedanib liposomes in pH 5.3 artificial lung solution was 60.78%higher,and the release of nintedanib liposomes in pH 5.3 artificial lung solution was 48h delayed,which was much higher than that of nintedanib solution.The data reveals no significant differences in particle size,potential and PDI before and after atomization of nintedanib liposomes,and the encapsulation rate decreased 4.25%.The fine particle fraction of the atomized droplets was 37.49%.Conclusion The response surface method can effectively improve the encapsulation rate of nintedanib liposomes,and successfully prepare nintedanib liposomes that are sensitive to acidic environment,and can be inhaled and released slowly.

OBJECTIVE To identify the influence factors associated with 28-day fatality among COVID-19 hospitalizations and to analyze the interaction between the disease severity at admission and the use of hospital preparations.METHODS A retrospective review of records from COVID-19 hospitalizations aged 18 to 90 who were admitted to the Jiangsu Province Hospital of Chinese Medi-cine from December 15,2022 to January 15,2023 were conducted.Patients who died or were lost to follow-up within 48 h of admis-sion were excluded.Patients were divided into survival and death groups based on their 28-day fatality status.Descriptive statistics were used to characterize the two groups and multivariate logistic regression models were employed to identify factors influencing 28-day fatality risk.The interaction between the severity of illness at admission and the use of hospital preparations was explored through cross-over analysis and hierarchical regression analysis.RESULTS Significant differences were observed between the survival and death groups in terms of severity of illness at admission,hospital preparations usage,steroid therapy,age,platelet count,lactate dehydro-genase levels,and urea(P<0.05.Crossover analysis and hierarchical logistic regression analysis revealed a significant antagonistic interaction between the severity of illness at admission and the use of hospital formulations both before adjustment(RERI=-20.678,95%CI:-33.703～-7.652;APAI=-2.301,95%CI:-4.027～-0.575 and after adjusting for gender,age,clinical characteristics and further adjusting for laboratory parameters(RERI=-5.972,95%CI:-10.564～-1.380;APAI=-2.205,95%CI:-4.131～-0.279,and it was an antagonistic interaction both before(SI=0.279,95%CI:0.157～0.493 and after adjustment(SI=0.222,95%CI:0.095～0.523.CONCLUSION The use of hospital preparations significantly reduces the 28-day fatality risk among COV-ID-19 hospitalizations and a clear antagonistic interaction was observed between the disease severity at admission and the use of hospi-tal preparations.

OBJECTIVE To enrich the polymethoxyflavonoid-rich fraction from Citri Reticulatae Pericarpium using D101 macro-porous resin,and further to analyse the chemical constituents using High-Performance Liquid Chromatography Quadrupole-Time-of-Flight Mass Spectrometry(HPLC-Q-TOF-MS).METHODS Citri Reticulatae Pericarpium extract was adsorbed on D101 macro-porous resin and then eluted with different concentrations of ethanol to enrich the polymethoxyflavonoid-rich fraction;the content of the major flavonoid components was determined by high-performance liquid chromatography(HPLC);and the components were further an-alysed by HPLC-Q-TOF-MS.RESULTS The established HPLC method for the simultaneous determination of seven flavonoids in Citri Reticulatae Pericarpium extract was accurate and reliable.The contents of compounds such as nobiletin and tangeritin were signifi-cantly increased in the polymethoxyflavonoid-rich fraction.Using high resolution mass spectrometry(HRMS),70 and 60 compounds were identified from the Citri Reticulatae Pericarpium extract and the polymethoxyflavonoid-rich fraction,respectively,with 53 polyme-thoxyflavonoids being detected in these two extracts.CONCLUSION The results of this study provide an experimental basis for fur-ther identification of the pharmacological substance basis of the polymethoxyflavonoids in Citri Reticulatae Pericarpium and the estab-lishment of quality control methods.

Purpose To explore the ability of proton density fat fraction(PDFF)and decay constant T2* values in MRI to reflect skeletal muscle aging.Materials and Methods 3T MRI data of skeletal muscle in the middle thigh of 211 healthy adults from the Third Affiliated Hospital of Southern Medical University from August to December 2023 were prospectively collected.Gender,age,height,weight and body mass index(BMI)were recorded.PDFF value and T2* value of thigh skeletal muscle were measured at post-processing workstation,and statistical differences among different age,gender and BMI groups were analyzed.The correlation between PDFF value and T2* value of thigh skeletal muscle and age and BMI was analyzed.Results There were statistically significant differences in PDFF values of thigh skeletal muscle among different age groups(H=18.476-85.619,all P<0.01).There were significantly differences in T2*values of the left and right quadriceps muscles,hamstrings and adductors among different age groups(H=13.342-47.566,all P<0.05).There were statistically significant differences in the PDFF values of right quadriceps,left and right hamstring,adductor and sartor muscles between male and female groups(Z=-4.929--1.626,all P<0.05),while there were statistically significant differences in T2* values of left sartor muscle(Z=-2.971,P=0.003).There was no statistical significance in PDFF value of skeletal muscle of thigh in different BMI groups(P>0.05),but there were statistically significant differences in T2* value of left and right quadriceps muscle,hamstring muscle and adductor muscle(H=9.542-24.495,all P<0.05).There was a moderate positive correlation between age and PDFF value of thigh skeletal muscle(r=0.635,P<0.01),but a slight negative correlation with T2* value of left and right quadriceps,hamstring and sarcoleus(r=-0.451--0.189,all P<0.01).There was a slight positive correlation between BMI and T2* values of thigh skeletal muscle(r=0.317,P<0.01).There was a moderate negative correlation between the PDFF value and T2* value of all thigh skeletal muscles(r=-0.749--0.624,P<0.01).The PDFF and T2* values of the front and back thigh muscles(quadriceps,hamstring)were most significantly correlated with age and BMI.Conclusion PDFF based on MRI can reflect the age-related changes in the microenvironment of thigh skeletal muscle,and is a potential imaging biological marker for accurate and non-invasive quantitative evaluation of thigh skeletal muscle aging.