OBJECTIVE To optimize the extraction process of Shenye buyi formula. METHODS Based on the quality by design （QbD） concept， the contents of rutin， nuciferine， sinapine thiocyanate， liquiritin，and glycyrrhizic acid ammonium salt， as well as the extract yield， were selected as the critical quality attributes （CQAs） for the extraction process of Shenye buyi formula. The fishbone diagram combined with the failure model and effect analysis method was adopted to determine the water addition， extraction time and extraction times as critical process parameters （CPPs）. High-performance liquid chromatography was employed to detect the contents of rutin， nuciferine， sinapine thiocyanate， liquiritin， and glycyrrhizic acid ammonium salt. The analytic hierarchy process-entropy weight method was used to comprehensively assign weights to the content of the five components including rutin and the extract yield. The Box-Behnken response surface method was employed to fit the mathematical model between CQAs and CPPs， screen the operational space of the extraction process， and validate it. RESULTS The optimal operational space of the extraction process was 9.5 to 12 times the amount of water added， the extraction time was 1 to 1.7 hours， and the extraction times were 3. Upon verification，the comprehensive scores of the optimal extraction process within the operational space were 89.79 and 84.93， respectively. CONCLUSIONS The extraction process of the Shenye buyi formula can be applied to the development and production of its granule preparations.

ObjectiveTo explore the dose-effect relationship and safety of high， medium， and low doses of raw Astragali Radix in the modified Huangqi Chifengtang （MHCD） for treating proteinuria in immunoglobulin A （IgA） nephropathy， and to provide scientific evidence for the clinical use of high-dose Astragali Radix in the treatment of proteinuria in IgA nephropathy. MethodsA total of 120 patients with IgA nephropathy， diagnosed with Qi deficiency and blood stasis combined with wind pathogen and heat toxicity， were randomly divided into a control group and three treatment groups. The control group received telmisartan combined with a Chinese medicine placebo， while the treatment groups were given telmisartan combined with MHCD containing different doses of raw Astragali Radix （60， 30， 15 g）. Each group contained 30 patients， and the treatment period was 12 weeks. Changes in 24-hour urinary protein （24 hUTP）， traditional Chinese medicine （TCM） syndrome scores， effective rate， and renal function were observed before and after treatment. Safety was assessed by monitoring liver function and blood routine. ResultsAfter 12 weeks of treatment， 24 hUTP significantly decreased in the high， medium， and low-dose groups， as well as the control group （P<0.05， P<0.01）. The TCM syndrome scores in the high， medium， and low-dose groups also significantly decreased （P<0.01）. Comparisons between groups showed that the 24 hUTP in the high-dose group was significantly lower than in the medium， low-dose， and control groups （P<0.05， P<0.01）， and the 24 hUTP in the medium-dose group was significantly lower than in the control group （P<0.05）. The TCM syndrome scores in the high and medium-dose groups were significantly lower than in the low-dose and control groups （P<0.05， P<0.01）. The total effective rates for proteinuria in the high， medium， low-dose， and control groups were 92.59% （25/27）， 85.19% （23/27）， 60.71% （17/28）， and 57.14% （16/28）， respectively. The effective rates in the high and medium-dose groups were significantly higher than in the low-dose and control groups （χ²=13.185， P<0.05， P<0.01）. The effective rates for TCM syndrome scores in the high， medium， low-dose， and control groups were 88.89% （24/27）， 81.48% （22/27）， 71.43% （20/28）， and 46.43% （13/28）， respectively. The efficacy of TCM syndrome scores in the high and medium-dose groups was significantly higher than in the control group （χ²=14.053， P<0.01）. Compared with pre-treatment values， there was no statistically significant difference in eGFR and serum creatinine in the high and medium-dose groups. However， eGFR significantly decreased in the low-dose and control groups after treatment （P<0.05）， and serum creatinine levels increased significantly in the control group （P<0.05）. No statistically significant differences were observed in urea nitrogen， uric acid， albumin， total cholesterol， triglycerides， liver function， and blood routine before and after treatment in any group. ConclusionThere is a dose-effect relationship in the treatment of IgA nephropathy with high， medium， and low doses of raw Astragali Radix in MHCD. The high-dose group exhibited the best therapeutic effect and good safety profile.

Objective:To assess the sound localization ability of patients with unilateral sudden hearing loss during the early period of treatment, to explore its changing characteristics and to analyze influencing factors.Methods:A total of 22 patients with unilateral sudden sensorineural hearing loss, with onset within 3 days, who were hospitalized at Shandong Provincial ENT Hospital between January and April 2024, were collected in this study. The cohort included 13 males and 9 females, with a mean age of 36.5 years. Among them, 10 suffered in the right ear and 12 in the left ear. Additionally, 15 healthy individuals (8 males and 7 females, mean age 29.2 years) were selected as controls. Pure tone audiometry and sound localization tests were reviewed on the first day, third day, fifth day of admission; the third week after onset, and the pure tone average and the root-mean-square error(RMSE) were used as indicators, respectively. The improvement of the ability of sound localization and pure tone average were assessed by correlation analyses using SPSS, version 27.0, and multiple regression analysis was employed to explore effects that might influence sound localization ability.Results:The pure tone threshold and sound localization ability on the third week of onset were improved compared with those on the initial three instances(the first, third, and fifth days of admission). 9 of the 22 patients (40.91%, 9/22) presented normal sound localization ability whereas their hearing loss had not recurred yet. The Spearman correlation analysis revealed a significant positive correlation between the improvement of sound localization ability and hearing improvement ( r=0.57, P<0.001). Meanwhile, multiple regression analysis showed that hearing threshold was a significant factor for sound localization when there was audible frequency. Vice versa, at this circumstance, ages and vertigo were significant factors. Conclusions:For most of the patients with unilateral sudden hearing loss, ability of sound localization improves with the decrease of hearing threshold. Notably, some patients can restore normal levels of sound localization for white noise, even in the presence of hearing loss at certain frequencies, by relying on binaural acoustic cues provided by residual hearing.

Objective:To investigate the dynamic changes of cellular miRNA expression profiles in EBV latently infected Raji cells upon reactivation with Phorbol ester (TPA).Methods:Total RNA was extracted using TRIzol reagent from Raji cells treated with TPA at different time points (0 h, 24 h, 48 h). Small RNA libraries were constructed and sequenced on an Illumina SE50 platform. Differentially expressed miRNAs were identified, and their target genes were predicted and functionally annotated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out through online tools. Additionally, miRanda and RNAhybrid software were used to predict cellular miRNAs targeting the EBV genome. Real-time RT-qPCR was employed to validate the expression levels of differentially expressed novel miRNAs.Results:High-throughput sequencing identified 1 301 celluar miRNAs, comprising 1 189 known and 112 novel miRNAs. A total of 264 known differentially expressed cellular miRNAs and 13 novel miRNAs were identified through high-throughput miRNA sequencing. Secondary structure prediction revealed that the novel miRNAs exhibited typical pre-miRNA hairpin structures. Stem-loop quantitative real-time PCR (RT-qPCR) validation of Novel_miR_183 and Novel_miR_242 did not exhibit a statistically significant difference ( F=1.407, P=0.370 7 for Novel_miR_183; F=1.277, P=0.397 0 for Novel_miR_242) between the TPA-stimulated and untreated groups. Target gene prediction analysis revealed that the differentially expressed cellular miRNAs were involved in various important biological processes and signaling pathways. Furthermore, 1 189 known cellular miRNAs and 108 novel miRNAs were predicted to target the EBV genome. Conclusions:Treatment of Raji cells with TPA stimulation successfully reactivated Raji cells and significantly altered their miRNA expression patterns. Differentially expressed miRNAs were identified, suggesting that these miRNAs probably play crucial roles in regulating EBV infection and replication by directly targeting the EBV genome.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objective To investigate the microstructural changes of white matter in patients with relapsing-remitting multiple sclerosis(RRMS)and its correlation with clinical functional scores.Methods A total of 20 patients with RRMS(RRMS group)and 20 healthy controls(HC)(HC group)were selected and underwent diffusion tensor imaging(DTI)and expanded disability status scale(EDSS)scores.Patients with RRMS were categorized into two groups based on their EDSS scores,including MS-1 group(motor dysfunction with visual impairment)and MS-2 group(motor dysfunction).Image processing was performed via tract-based spatial statistics(TBSS).Group comparisons were executed using the t-test,while correlations were analyzed utilizing Spearman correlation.Results In the RRMS group,reduced fractional anisotropy(FA)values were accompanied by increased mean diffusivity(MD)and radial diffusivity(RD)values in the forceps major,forceps minor,bilateral cingulum,bilateral uncinate fasciculus,bilateral superior longitudinal fasciculus,bilateral inferior longitudinal fasciculus,bilateral inferior fronto-occipital fasciculus,bilateral corticospinal tract and bilateral anterior thalamic radiation compared with the HC group.Additionally,In the RRMS group,increased axial diffusivity(AD)values were noted in the forceps major,forceps minor,bilateral superior longitudinal fasciculus(temporal),right inferior fronto-occipital fasciculus,bilateral corticospinal tract and right anterior thalamic radiation compared with the HC group.Compared with the MS-2 group,the MS-1 group exhibited higher FA values in the right cingulum(cingulate gyrus part)and higher AD values in the left cingulum(cingulate gyrus part).Correlation analysis revealed negative correlations between the FA values of the forceps major,right superior longitudinal fasciculus and the motor function scores in RRMS group.Conversely,positive correlations were identified between the MD values of the forceps minor,right superior longitudinal fasciculus,right inferior fronto-occipital fasciculus,left corticospinal tract and the RD values of the forceps minor,right cingulum(hip-pocampus),right superior longitudinal fasciculus,and left corticospinal tract,as well as the motor function scores.Conclusion RRMS patients exhibit microstructural damage in white matter and are associated with motor dysfunction,which provides imaging support for the pathological mechanisms underlying motor dysfunction in RRMS patients.

BACKGROUND:Cervical instability is a common orthopedic disease in young and middle-aged people,and is the early manifestation of cervical spondylosis,which has a great impact on the quality of life of patients.Therefore,early diagnosis of cervical instability to implement early intervention has positive clinical and social significance.OBJECTIVE:The clinical prediction model of cervical instability in young and middle-aged people was constructed based on machine learning to realize early screening of cervical instability in young and middle-aged people before X-ray examination.METHODS:From September 2022 to October 2023,155 young and middle-aged adults with cervical instability and 88 with non-cervical instability recruited through recruitment advertisements and spinal department outpatient of Wangjing Hospital,China Academy of Chinese Medical Sciences were selected as research subjects.The research subjects'general information,living and working habits,discomfort symptoms,visual analog scale score,Neck Disability Index,and 36-ltem Short Form Health Survey were collected on site based on questionnaires.The above information was used as predictive factors.After screening,six machine learning algorithms of Support Vector Machine,LightGBM,RandomForest,Logistic,AdaBoost,and XGBClassifier were used to train the model by ten-fold cross-validation method,and the clinical prediction model of cervical instability was constructed.Area under the curve was used as the main evaluation index.Univariate analysis was performed on the predictors,and SHAP method was used to rank the importance of the predictors.Correlation heat maps were used to show the degree of linear correlation between the predictors and the cervical instability.RESULTS AND CONCLUSION:(1)Among the six machine learning models,RandomForest model was chosen as the final prediction model,including nine predictors,such as age,body mass index,neck circumference/neck length,visual analog scale score,Neck Disability Index,bodily pain,general health,vitality,and mental health,area under the curve=0.725 4,and the calibration degree was good.It could be used as a reference tool for early screening of cervical instability in young and middle-aged people.(2)There were significant differences in age,visual analog scale score,Neck Disability Index,bodily pain,general health,and vitality between the two groups(P＜0.05).(3)The order of importance of predictors was age,Neck Disability Index,visual analog scale score,general health,body mass index,vitality,bodily pain,neck circumference/neck length,mental health,among which age,visual analog scale score,Neck Disability Index were positively correlated with cervical instability,while general health,body mass index,vitality,bodily pain,neck circumference/neck length,and mental health were negatively correlated with cervical instability.

Objective:To study the distribution characteristics of current patients with Kashin-Beck disease (KBD) in Molidawa Daur Autonomous Banner (referred to as Morin Banner), and provide suggestions for service management.Methods:Information of KBD current patients in Morin Banner was collected from January 1, 2018 to June 30, 2024 using the "KBD Current Patient Survey System" provided by the Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention. A descriptive study method was used to analyze the basic information and clinical data of current patients.Results:As of June 30, 2024, a total of 6 223 KBD current patients were reported in Morin Banner, and the patients were distributed in 15 townships (towns). There was a statistically significant difference in the prevalence rate of KBD among different townships (towns, χ 2 = 3 069.01, P < 0.001). The minimum age of the KBD current patients was 27 years old, and the maximum was 98 years old, mainly concentrated in the age range of 45 - 74 years old, accounting for 95.7% (5 954/6 223). There was a significant difference in the prevalence rate of KBD among different age groups (χ 2 = 5 912.76, P < 0.001). The male to female ratio was 1.00∶1.14 (2 910 ∶ 3 313), and there was a statistically significant difference in prevalence rate of KBD between genders(χ 2 = 44.38, P < 0.001). The KBD current patients mainly had a primary school education, married, and farmers, accounting for 59.2% (3 685/6 223), 89.8% (5 590/6 223), 93.2% (5 802/6 223), respectively; and the clinical grading of patients is mainly degree Ⅰ. There was a statistically significant difference in the rate of limb disability among patients with different clinical grades (χ 2 = 64.26, P < 0.001). The rate of limb disability in males was higher than that in females (χ 2 = 10.36, P = 0.001). Conclusions:The KBD current patients in Morin Banner are distributed in various township (town), with middle-aged and elderly famers being the main ones. It is necessary to strengthen monitoring of KBD, and pay attention to personalized treatment and management of KBD current patients.

Objective This study aims to investigate the current status and determinants of compassion fatigue symptoms among orthopedic nurses,and to analyze the interrelationships among these determinants to provide references for targeted intervention development.Methods From May to June 2024,a convenience sampling method was employed to recruit orthopedic nurses from 20 tertiary hospitals across 14 provinces and cities in China.The survey instruments encompassed the general demographic information sheet,the Compassion Fatigue Scale,the Social Support Rating Scale,the Nurses' Psychological Capital Questionnaire,and the Professional Identity Questionnaire.The data were analyzed using univariate analysis,Spearman correlation analysis,and multiple linear regression analysis.A structured equation model was also developed.Results Totally 1 397 valid questionnaires were collected,and the effective response rate was 96.94％(1 397/1 441).The average score of compassion fatigue symptoms was 47.41±12.16.The multiple linear regression analysis indicated that professional identity,social support,psychological capital,length of service,and frequency of night shifts per week were independent determinants of compassion fatigue symptoms(P＜0.05).The path analysis demonstrated a good fit with the specified indicators.Psychological capital exhibited a direct mediating effect on compassion fatigue symptoms(β=-0.15,P＜0.05).Furthermore,professional identity(β=1.46,P＜0.001;β=-0.38,P＜0.001)and social support(β=0.14,P＜0.001;β=-0.99,P＜0.001)served as mediators in the relationship between psychological capital and compassion fatigue symptoms.Conclusion The compassion fatigue symptoms among orthopedic nurses are relatively severe.It is imperative for nursing managers to address associated factors of compassion fatigue symptoms among orthopedic nurses and implement effective preventive strategies to mitigate its level.

Objective:To establish a protocol for virus isolation using the mixed method, and evaluate the efficacy of the suspended method and the mixed method in isolating herpes simplex virus (HSV).Methods:Simulated HSV-infected clinical samples were prepared using HSV-1 F strain and CDC-P1 strain. Both the suspended method and the mixed method were used to isolate HSV-1 from these samples. The virus isolation efficiency of the mixed method under various conditions was assessed. These conditions included different multiplicity of infection (MOI), cell seeding densities, and virus adsorption times.The 50% tissue culture infective dose (TCID 50) assay was used for the assessment. The positive rates of virus detection under low viral load conditions were compared between the two methods. Results:Under the conditions of a MOI of 0.005, a virus adsorption time of 15 min, and a cell seeding density of 1×10 6 cell/ml, the mixed method achieved effective isolation of HSV-1. When the virus titer of the sample was 100 TCID 50/ml, the positivity rate of the mixed method reached 100.0%, while the positivity rates of the suspended method were 50.7% (38/75) and 52.0% (39/75) after cultured for 72 h and 96 h, respectively. When the virus titer of the sample was 10 TCID 50/ml, the positivity rate of the mixed method was 100.0%, while the positivity rate of the suspension method was 0. Conclusions:The mixed method exhibits significantly higher efficiency in HSV isolation compared with the suspended method. Under the conditions of high viral load, both the suspended method and the mixed method can be effective in isolating HSV-1. For clinical samples with low viral loads, the mixed method has greater applicability.