As a supplement to randomized controlled trials， observational studies can provide evidence for the effectiveness of traditional Chinese medicine （TCM） treatment measures. They can also study influencing factors of diseases， etiology， and prognosis. However， there is a confounding effect due to the lack of randomization， which seriously affects the causal inference between the study factors and the outcome， resulting in confounding bias. Therefore， identifying and controlling confounding factors are key issues to be addressed in TCM observational studies. According to the causal network and the characteristics of TCM theory， confounding factors can be categorized into measured and unmeasured confounding factors. In addition， attention must be paid to identifying confounding factors and intermediate variables， as well as the interaction between confounding factors and study factors. For methods of controlling confounding factors， measured confounding factors can be controlled by stratification， multifactor analysis， propensity scores， and disease risk scores. Unmeasured and unknown confounding factors can be corrected using instrumental variable methods， difference-in-difference methods， and correction for underlying event rate ratios. Correcting and controlling confounding factors can ensure a balance between groups， and confounding bias can be reduced. In addition， methods such as sensitivity analysis and determination of interactions make the control of confounding factors more comprehensive. Due to the unique characteristics of TCM， observational studies of TCM face unique challenges in identifying and controlling confounding factors， including the ever-changing TCM treatment measures received by patients， the often-overlooked confounding effects in the four diagnostic information of TCM， and the lack of objective criteria for TCM evidence-based diagnosis. Some scholars have already conducted innovative explorations to address these issues， providing a methodological basis for conducting higher-quality TCM observational studies， so as to obtain more rigorous real-world evidence of TCM and gradually develop quality evaluation criteria for OS that are consistent with the characteristics of TCM.

Objective:To analyze clinical and genetic characteristics of congenital hypogonadotropic hypogonadism(CHH) in children.Methods:Clinical data of 0-18 year old CHH patients diagnosed in the Department of Endocrinology, Genetics and Metabolism of Children′s Hospital Affiliated to Zhengzhou University from January 1, 2016 to December 31, 2023 were retrospectively analyzed, including their hormone levels and genetic test results.Results:A total of 95 patients with CHH were included. Among them, 25 were diagnosed before the age of 3, 37 between the ages of 3-14, and 33 were over 14 years old at the time of first diagnosis. The primary manifestations were micropenis(95 cases, 100%) and cryptorchidism(46 cases, 48.5%). The incidence of cryptorchidism was the lowest in the group over 14 years of age. Hormonal analysis revealed that the peak levels of LH following statin B and GnRH stimulation, the peak levels of FSH after GnRH stimulation, and testosterone levels following hCG stimulation were the highest in the infant group. Genetic analysis identified 20 CHH-related genes in 61 out of 77 cases.Double-gene mutation accounted for 7.8%(6/77) and triple-gene mutation accounted for 3.9%(3/77). The most common mutations were FGFR1(18/77, 23.4%), CHD7(12/77, 15.6%), PROKR2(11/77, 14.3%) and ANOS1(6/77, 7.8%). The incidence of cryptorchidism in these four genotypes was 50%, 75%, 45.5% and 83.3%, respectively. The incidence of testicular dysfunction was 22.2%, 16.7%, 27.3%, and 16.7%, respectively, with no statistical significance.Conclusion:The primary manifestation of CHH is micropenis and cryptorchidism. In children with CHH, the incidence of testicular Leydig cell and Sertoli cell dysfunction increased with age in CHH children. FGFR1, CHD7, PROKR2 and ANOS1 were common variants of CHH.

Background:Intestinal microbiota dysbiosis and impaired intestinal barrier,leading to bacterial translocation,are involved in acute pancreatitis(AP)exacerbation.Antimicrobial peptides participate in the regulation of intestinal microbiota,yet their changes and roles in the course of AP are unclear.Aims:To investigate the dynamic changes and significance of antimicrobial peptides in the ileum and pancreas among three classical AP models.Methods:Three AP mouse models were established by using cathelicidin plus lipopolysaccharide(CAE+LPS),sodium taurocholate(N-Tau)and L-arginine(L-Arg),respectively.The pathological changes of pancreatic and ileal tissues were observed and scored.Real-time PCR was applied to detect the expression levels of the proinflammatory cytokines,and antimicrobial peptides including lysozyme(LZM),secretory phospholipase A2(sPLA2),angiogenin 4(Ang4),regenerating islet-derived protein 3(REG3)family,β-defensin family,cathelicidin-related antimicrobial peptide(CRAMP),and glycoprotein 2(GP2)in ileum and/or pancreas.The association between expressions of antimicrobial peptides and the injuries of pancreas and ileum was analyzed.Results:Pancreatic and ileal injuries could be observed in all three AP models in different time points with various degrees.The pathological scores of the CAE+LPS and N-Tau models reached the highest level and then declined from 0-72 h,while those of L-Arg model progressively increased within 72 hours.Compared with the corresponding controls,the mRNA levels of LZM,sPLA2,and Ang4 in ileal tissue,and the mRNA levels of CRAMP,GP2,and β-defensins in pancreatic tissue,were generally downregulated in all three AP models(all P<0.05).CAE+LPS and N-Tau models showed a trend of initial decrease followed by partial recovery,while L-Arg model exhibited a gradual downregulation trend.The mRNA levels of REG3β and REG3γ in ileum upregulated and reached the peak at 48 h or 24 h and downregulated significantly at 72 h in all three AP models(all P<0.05);while in pancreatic tissue,both REG3β and REG3γ were generally upregulated in all three AP models(all P<0.05),but fell back in CAE+LPS and N-Tau models at 72 h.The mRNA levels of ileal β-defensins upregulated significantly in the early stage of the disease(12 h)in all three AP models(all P<0.05),and then gradually decreased.Spearman correlation coefficient analysis showed that the expressions of ileal LZM,sPLA2,and Ang4,as well as the pancreatic CRAMP,GP2,and β-defensins,were significantly negatively correlated with the pancreatic and ileal pathological scores in all three AP models(all P<0.05);but the expression of REG3β in the pancreas was significantly positively correlated with the pancreatic and ileal pathological scores(all P<0.05).Conclusions:The expressions of LZM,sPLA2,and Ang4 in the ileum,as well as the expressions of CRAMP,GP2,β-defensin family,and REG3β in the pancreas of the three classical AP models,dynamically changed with the severity of the disease.Ileal and pancreatic antimicrobial peptides may affect the injuries of pancreas and intestine during AP by regulating intestinal microbiota.

Cytopharmaceutical based on macrophages is a breakthrough in the field of targeted drug delivery. However, it remains a challenge to localize and control drug release while retaining macrophage activity and exerting its immunotherapeutic effect. Herein, a localized light-triggered release macrophage cytopharmaceutical (USIP@M) was proposed, which could utilize the tumor targeting and immunotherapy effects of macrophages to reverse the immune suppression of tumor microenvironment (TME). Amphiphilic block copolymers with ultraviolet (UV)-responsive o-nitrobenzyl groups were synthesized and co-loaded with sorafenib (SF), IMD-0354 (IMD), and upconverting nanoparticles (UCNPs), which were then taken up by macrophages, and the targeted delivery of drugs was realized by using the tumor tropism of macrophages. UCNPs converted near-infrared light with strong penetrability and high safety into UV light, which promoted the photoresponsive depolymerization of block copolymers and production of exosomes from USIP@M, accelerated drug efflux and maintained the activity of macrophages. IMD simultaneously polarized carrier macrophages and tumor-associated macrophages to exert the antitumor effect of macrophages, enhance T cell immunity, and alleviate the immunosuppressive state of TME. Synergistically with the chemotherapeutic effect of SF, it could effectively kill tumors. In conclusion, based on the localized light-triggered release strategy, this study constructed a novel macrophage cytopharmaceutical that could localize and control drug release while retaining the activity of macrophages and exerting its immunotherapeutic effect, which could effectively treat solid tumors.

This study aimed to explore key quality control factors that affected the prognosis of intensive care unit (ICU) patients in Chinese mainland over six years (2015-2020). The data for this study were from 31 provincial and municipal hospitals (3425 hospital ICUs) and included 2 110 685 ICU patients, for a total of 27 607 376 ICU hospitalization days. We found that 15 initially established quality control indicators were good predictors of patient prognosis, including percentage of ICU patients out of all inpatients (%), percentage of ICU bed occupancy of total inpatient bed occupancy (%), percentage of all ICU inpatients with an APACHE II score ⩾15 (%), three-hour (surviving sepsis campaign) SSC bundle compliance (%), six-hour SSC bundle compliance (%), rate of microbe detection before antibiotics (%), percentage of drug deep venous thrombosis (DVT) prophylaxis (%), percentage of unplanned endotracheal extubations (%), percentage of patients reintubated within 48 hours (%), unplanned transfers to the ICU (%), 48-h ICU readmission rate (%), ventilator associated pneumonia (VAP) (per 1000 ventilator days), catheter related blood stream infection (CRBSI) (per 1000 catheter days), catheter-associated urinary tract infections (CAUTI) (per 1000 catheter days), in-hospital mortality (%). When exploratory factor analysis was applied, the 15 indicators were divided into 6 core elements that varied in weight regarding quality evaluation: nosocomial infection management (21.35%), compliance with the Surviving Sepsis Campaign guidelines (17.97%), ICU resources (17.46%), airway management (15.53%), prevention of deep-vein thrombosis (14.07%), and severity of patient condition (13.61%). Based on the different weights of the core elements associated with the 15 indicators, we developed an integrated quality scoring system defined as F score=21.35%xnosocomial infection management + 17.97%xcompliance with SSC guidelines + 17.46%×ICU resources + 15.53%×airway management + 14.07%×DVT prevention + 13.61%×severity of patient condition. This evidence-based quality scoring system will help in assessing the key elements of quality management and establish a foundation for further optimization of the quality control indicator system.
Humans ; China/epidemiology* ; Cross Infection/epidemiology* ; Intensive Care Units/statistics & numerical data* ; Quality Control ; Quality Indicators, Health Care/statistics & numerical data* ; Sepsis/therapy* ; East Asian People/statistics & numerical data*

Objective: To observe the effects of electroacupuncture (EA) with three frequencies (100 Hz, 2 Hz, and 2 Hz/100 Hz) on the apoptosis of neurons and c-Jun N-terminal kinase (JNK) signaling pathway in the hippocampus of rats with vascular dementia (VD), and explore the mechanism of EA intervention for VD. Methods: Fifty male Sprague-Dawley rats were randomly divided into a model group, a sham operation group, a 100 Hz EA group, a 2 Hz EA group, and a 2 Hz/100 Hz EA group, with ten rats in each group. The VD model rats were established by repeated ischemia-reperfusion of bilateral common carotid arteries. The rats in the EA groups received EA intervention at Baihui (GV20), Dazhui (GV14), Geshu (BL17) and Zusanli (ST36), once a day for 14 d. Afterward, Morris water maze was used to examine the learning and memory performances of the rats in each group, hematoxylin-eosin staining to observe the histomorphological changes in the hippocampal CA1 region, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling to test the apoptosis of neurons in the hippocampal CA1 region, and Western blot to detect the protein expression levels of JNK, phosphorylated JNK (p-JNK), Caspase-8, and Caspase-3 in the hippocampus tissue. Results: Compared with the sham operation group, the escape latency of the model group in water maze test was prolonged; the number of crossing the original platform was decreased (P<0.01); the hippocampal neurons were severely damaged and the number of surviving neurons was decreased (P<0.01), whereas the number of apoptotic neurons was increased (P<0.01); the protein expression levels of JNK, p-JNK, Caspase-8, and Caspase-3 in the hippocampus were significantly increased (P<0.01). Compared with the model group, the escape latency of each EA group was significantly shortened; the number of crossing the original platform was significantly increased (P<0.01); the damage of hippocampal neurons was alleviated, the number of surviving neurons was increased (P<0.01), and the number of apoptotic neurons was decreased (P<0.01); the protein expression levels of JNK, p-JNK, Caspase-8, and Caspase-3 in the hippocampus were decreased (P<0.01). The results in the 2 Hz EA group and the 2 Hz/100 Hz EA group were superior to those in the 100 Hz EA group. Conclusion: EA with the three frequencies (100 Hz, 2 Hz, and 2 Hz/100 Hz) can improve the learning and memory performances in VD rats subjected to ischemia-reperfusion, its mechanism may be related to the inhibition of neuronal apoptosis and the regulation of the related protein expression of JNK signaling pathway, and the intervention effects of EA with 2 Hz and 2 Hz/100 Hz are more significant.

Objective To explore the correlation and significance of V312F locus polymorphism of PCSK9 gene in patients with coronary heart disease.Methods We selected 3560 patients with coronary heart disease who came to our hospital from January 2014 to January 2016 as the case group.They were divided into 5 subgroups:angina group,myocardial infarction group,silent myocardial ischemia group,ischemic cardiomyopathy group,and sudden death group,according to their anatomic and pathophysiological features.Data of 1 000 people for physical examination served as the control group.PCR assay combined with direct sequencing method was applied to test V312F locus polymorphism of PCSK9 gene.Logistic regression analysis was used to analyze relationship between V312F locus polymorphism of PCSK9 gene and types of coronary heart disease.The concentration of serum PCSK9 and lipids of the two groups were also measured.Results The serum levels of PCSK9,TC,TG and LDLC and ratio of positive family history in the case group were significantly higher than those in the control group,while the level of HDLC was lower than that of the controls (all P＜0.05).Indexes of sudden death subgroup in the case group showed the most significant changes,while asymptomatic myocardial ischemia subgroup showed the weakest changes.The frequency of genotype TT,GT and allele T in the case group was 3.4％,16.6％ and 11.7％,respectively,which was significantly higher than that in the control group (1.1％,10.2％ and 6.2％) (all P＜0.01).The highest frequency of genotype TT,GT and allele T was found in sudden death subgroup,and the lowest frequency of these indexes was found in asymptomatic myocardial ischemia subgroup (P＜0.05).Results of Logistic regression analysis showed that genotype TT in V312F locus of PCSK9 gene was related to the severity of coronary heart disease (OR =8.463,95％ CI from 3.505 to 17.854,P＜0.001).Conclusion The mutation of V312F (T/G)locus of PCSK9 gene might be related to the severity of coronary heart disease.

Objective To explore the weight for the training target of Applied nursing undergraduate. And find the degree of importance for the indexes of the target , thus highlighting theApplied training objective characteristics. Methods Developed by Bloom's teaching objectives classification theory and educational objectives theory to refined indexes, using Delphi method to establish the Applied nursing undergraduate training objectives. By the importance assignment from experts on each index, using analytic hierarchy process (AHP) method to construct the judgment matrix. Then calculate the weight of each index weight, and test its logical consistency. Results The weight of theattitudes and valueswas 0.56, andknowledgeandabilitywere 0.22. For the secondary indicators, in the values dimension,professional attitudeandideological qualityhad relatively high weight.Under the knowledge dimension, the professional knowledge had the highest weight; and for the ability dimension,communication skillsandapplicationswere heavily maximum. All the random consistency rates (CR) for the indexes were less than 0.10, so there was no logical confusion. ConclusionsAppliednursing undergraduate talents need to combine theory and practice quickly into clinical work. By weight setting, this study provides basis to further quantify and highlight the Applied nursing undergraduate training features, and provides the basis for the application-oriented undergraduate nursing personnel reforms.

Objective To develop the Applied nursing undergraduate students training framework objective, clear the entry of applied training target for undergraduate nursing students. Methods Through literature review and panel discussions, Delphi expert consultation questionnaires were preliminary designed. 23 experts were issued via email and paper questionnaires, conducted two expert advice and analysis. Results A total of 20 valid questionnaires were recovered after two consultation. The expert advice of good scientific reliability:experts had positive reply, and the authority level was 0.857, Kendall were 0.130-0.293, it showed a good level of coordination (P < 0.05). By two rounds of expert advice, three capacity index target level for Applied nursing undergraduate students training were gotten: attitudes, values and basic literacy; knowledge of the target; the ability. The secondary capacity index for target had 15 items, and the third capacity index had 63 items. Conclusions TheAppliednursing undergraduate students training objectives and targets were refined through Delphi which provide the basis for the Applied nursing undergraduate training model and curriculum reform.

Objective To investigate the effect factors for language and memory dominance testing in propofol Wada test in refractory epilepsy patients.Methods From January 2010 to August 2013,total of 23 patients underwent propofol Wada tests for language and memory dominance evaluation.According the performance in language test and memory test,the patients were divided into two groups,respectively:succeed with test or failed in test.The relevant factors including age,duration of epilepsy,handedness,FIQ (full scale of intelligence quotient),lateralization of lesions,language dominance,dose of propofol and the adverse effects of propofol were recorded as independent variables.Logistic regression was adopted to screen the effect factors for memory dominance evaluation.All statistical analyses were processed with SPSS software.Results All 23 patients succeeded with language test,but only 13 patients succeed with memory test.The difference of success ratios between language test and memory test was significant (P=0.001).For memory test,the difference of duration of epilepsy and FIQ in success group and failed group was significantly different (duration of epilepsy:(10.57±4.68) vs (18.30±9.30),P=0.032,FIQ:(81 ±25.33) vs (64.2±10.86),P=0.046).More grade Ⅱ adverse effects of propofol occured in the patients who failed in memory test (P=0.011).Logistic regression results indicated the grade Ⅱ adverse effects of propofol were the main risk factor for memory test failure (OR=28.0,P＜0.01).Conclusions Propofol Wada test is an effective method for language dominance evaluation.However,the effect factors for memory dominance evaluation are much more than language evaluation,such as duration of epilepsy,FIQ and grade Ⅱ adverse effects of propofol,and grade Ⅱ adverse effects of propofol may be the most significant risk factor.