ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

Prescription optimization is a crucial aspect in the study of traditional Chinese medicine （TCM） compounds. In recent years， the introduction of mathematical methods， data mining techniques， and artificial neural networks has provided new tools for elucidating the compatibility rules of TCM compounds. The study of TCM compounds involves numerous variables， including the proportions of different herbs， the specific extraction parts of each ingredient， and the interactions among multiple components. These factors together create a complex nonlinear dose-effect relationship. In this context， it is essential to identify methods that suit the characteristics of TCM compounds and can leverage their advantages for effective application in new drug development. This paper provided a comprehensive review of the cutting-edge optimization experimental design methods applied in recent studies of TCM compound compatibilities. The key technical issues， such as the optimization of source material selection， dosage optimization of compatible herbs， and multi-objective optimization indicators， were discussed. Furthermore， the evaluation methods for component effects were summarized during the optimization process， so as to provide scientific and practical foundations for innovative research in TCM and the development of new drugs based on TCM compounds.

ObjectiveTo investigate the efficacy and mechanism of saffron floral bio-residues（SFB） in the treatment of hyperuricemia（HUA） combined with gouty arthritis（GA） in a compound compatibility setting. MethodScreening candidate control Chinese medicines for compound and SFB based on network target distance calculation and data analysis. After adaptive feeding of 80 SD rats for 7 days， 10 rats were randomly selected as the blank group， while the remaining 70 rats were intraperitoneally injected with 3% potassium oxonate and orally administered with 1% adenine for 14 consecutive days. On the 13^th day， rats were injected with 2.5% sodium urate solution into the right ankle joint cavity to induce swelling of the joint capsule on the opposite side， inducing a HUA combined with GA model. At the same time， the modeling rats were randomly divided into 7 groups， including the model group， benzbromarone group（positive drug， 0.02 g·kg^-1）， Tongfengshu tablets group（9 g·kg^-1）， Tongfengshu granules group（9 g·kg^-1）， SFB granules group（3.6 g·kg^-1）， Plantaginis Semen granules group（3.6 g·kg^-1）， and new formula group（SFB replacing Plantaginis Semen in Tongfengshu granules， 9 g·kg^-1）， with 10 rats in each group. Each treatment group was orally administered with the corresponding drugs according to body weight， while the control and model groups were given equal volume of distilled water by gavage once a day for 14 consecutive days. After 14 days of synchronous administration and modeling， changes in gait， ankle joint swelling and mechanical pain threshold in rats were observed， and serum uric acid， creatinine， urea nitrogen and xanthine oxidase（XOD） were measured. Enzyme-linked immunosorbent assay（ELSIA） was used to detect the levels of tumor necrosis factor（TNF）-α， interleukin（IL）-1β and IL-6 in rat serum， hematoxylin-eosin（HE） staining was used to observe the pathological changes in the liver， kidney and ankle joints of rats， Western blot was used to detect the expression levels of uric acid transporter 1（URAT1）， glucose transporter 9 （GLUT9）， organic anion transporter 1（OAT1）， adenosine triphosphate（ATP） binding cassette transporter G2（ABCG2）， and liver XOD proteins. ResultThrough network pharmacology analysis， Plantaginis Semen was selected as a candidate control herb， and Tongfengshu tablets was used as a compound compatibility environment to explore the efficacy of SFB in reducing blood uric acid levels and treating GA. Animal experiments showed that compared with the blank group， the gait score and joint swelling degree of the model group were significantly increased， and the mechanical pain threshold was significantly decreased（P<0.01）. Compared with the model group， the gait score， joint swelling degree and mechanical pain threshold of rats in each medication group were improved to varying degrees. Biochemical indicators showed that compared with the blank group， the serum uric acid， creatinine， urea nitrogen and XOD levels of the model group were significantly increased（P<0.01）. Compared with the model group， the serum uric acid and XOD levels of rats in each treatment group were significantly decreased（P<0.01）. ELISA results showed that compared with the blank group， the levels of serum TNF-α， IL-1β and IL-6 in the model group were significantly increased（P<0.01）. Compared with the model group， the levels of TNF-α， IL-1β and IL-6 in the benzbromarone group， Tongfengshu tablets group， Tongfengshu granules group and new formula group were significantly reduced（P<0.05，P<0.01）. Western blot results showed that compared with the blank group， the expression levels of URAT1 and GLUT9 proteins in renal tissue and OXD protein in liver tissue of the model group were significantly increased， while the expression levels of renal OAT1 and ABCG2 were significantly decreased（P<0.01）. Compared with the model group， the expression levels of renal URAT1 and GLUT9 in the SFB granules group， Tongfengshu granules group and new formula group were significantly decreased， while the expression levels of renal OAT1 and ABCG2 were significantly increased， and the expression of XOD protein in liver tissue was significantly decreased（P<0.05， P<0.01）. Pathological analysis showed that focal infiltration of neutrophils， cell necrosis and nuclear fragmentation were observed in the liver tissue of the model group， sodium urate deposition crystals and tubular dilation appeared in renal tissue， synovial hyperplasia and inflammatory cell infiltration appeared in ankle joint. Compared with the model group， the abnormal degrees of liver， kidney and ankle joint tissue of rats in each treatment group were alleviated. ConclusionThe new formula of SFB replacing Plantaginis Semen has the same effect in the treatment of HUA combined with GA. This study proposes a new strategy to investigate the efficacy of new resources of Chinese medicine in a compound compatibility environment， which can provide a new demonstration for the research and development of new resources of Chinese medicine.

Objective: The American Heart Association released the Life s Essential 8 (LE 8) for the overall evaluation of cardiovascular health (CVH) on individual level. The present study aimed to describe the overall CVH in Chinese school aged children using LE 8 metrics. Methods: Data of the present analysis came from a national representative multicentered cross sectional study conducted in 7 provinces of China in 2013. The original study used a multistage cluster sampling method. A total of 10 326 children aged 5 to 19 years with complete data of health behaviors and health outcomes were included in the study. Children s health behavior indicators included diet, physical activity, nicotine exposure and sleep health. Health outcome factors included body mass index, fast blood glucose, lipid profile and blood pressure. Results: The median CVH score was 73.3 ( IQR =14.4) in boys and 73.4 ( IQR = 13.5) in girls. Compared to children aged ≤9 years, the health behavior scores were lowest in the 13-15 age group, with boys scoring 7.73 lower (95% CI =-8.35--7.12, P <0.01) and girls scoring 9.15 (95% CI =-9.83--8.48, P <0.01) lower. The ≥16 age group had the lowest health outcome scores, with boys scoring 7.85 (95% CI =-9.07--6.63, P <0.01) lower and girls scoring 6.11 (95% CI =-7.12--5.09, P <0.01) lower. Conclusions Chinese school aged children are generally at a moderate level of cardiovascular health. Specific LE 8 components vary substantially between groups and therefore require targeted intervention strategies.

Objective To construct a machine learning prediction model for postoperative liver injury in patients with non-liver surgery based on preoperative and intraoperative medication indicators.Methods A case-control study was conducted on 315 patients with liver injury after non-liver surgery selected from the databases developed by 3 large general hospitals from January 2014 to September 2022.With the positive/negative ratio of 1 ∶3,928 cases in corresponding period with non-liver surgery and without liver injury were randomly matched as negative control cases.These 1243 patients were randomly divided into the modeling group(n=869)and the validation group(n=374)in a ratio of 7∶3 using the R language setting code.Preoperative clinical indicators(basic information,medical history,relevant scale score,surgical information and results of laboratory tests)and intraoperative medication were used to construct the prediction model for liver injury after non-liver surgery based on 4 machine learning algorithms,k-nearest neighbor(KNN),support vector machine linear(SVM),logic regression(LR)and extreme gradient boosting(XGBoost).In the validation group,receiver operating characteristic(ROC)curve,precision-recall curve(P-R),decision curve analysis(DCA)curve,Kappa value,sensitivity,specificity,Brier score,and F1 score were applied to evaluate the efficacy of model.Results The model established by 4 machine learning algorithms to predict postoperative liver injury after non-liver surgery was optimal using the XGBoost algorithm.The area under the receiver operating characteristic curve(AUROC)was 0.916(95%CI:0.883～0.949),area under the precision-recall curve(AUPRC)was 0.841,Brier score was 0.097,and sensitivity and specificity was 78.95%and 87.10%,respectively.Conclusion The postoperative liver injury prediction model for non-liver surgery based on the XGBoost algorithm has effective prediction for the occurrence of postoperative liver injury.

Objective:To analyze the expression of meiotic recombination 11 homolog A（MRE11A）in T lymphocytes of children with sepsis，and to explore the effect of MRE11A on the function of T lymphocytes in sepsis.Methods:Twenty-four children with sepsis hospitalized in PICU at the First Affiliated Hospital of Guangxi Medical University from December 2021 to April 2022 were selected as sepsis group.During the same period,24 healthy children who underwent outpatient physical examination in our hospital were selected as control group.The gender and age of two groups were collected,and the duration of invasive mechanical ventilation,laboratory examination index and hospitalization time were collected in sepsis group.The peripheral blood samples of sepsis group were collected within 24 hours of admission to PICU,and peripheral blood samples of control group were collected during the study period.Flow cytometry was used to detect the cytoplasmic MRE11A of peripheral blood T lymphocytes in two groups,and the proportion as well as expression of MRE11A positive cells between two groups were compared (expressed by mean fluorescence intensity) .Results:There were 24 cases in sepsis group,including 11 males and 13 females,with a median age of 32.50 (19.00,132.75) months.There were 24 cases in control group,including 14 males and 10 females,with a median age of 57.50 (33.75,102.25) months.There were no significant differences in gender and age between two groups (all P>0.05).The proportion of MRE11A +CD4 +T lymphocytes in sepsis group was lower than that in control group[3.59（2.29，8.87）% vs.99.90（99.03，100.00）%， Z=-5.961， P<0.001 ].The expression of MRE11A in CD4 +T lymphocytes in sepsis group was lower than that in control group[1 663.00（1 557.00，1 777.00）vs.5 689.00（4 415.25，9 567.00）， Z=-5.939， P<0.001].The proportion of MRE11A +CD8 +T lymphocytes in sepsis group was lower than that in control group[3.85（1.87，9.58）% vs.92.15（76.70，96.40）%， Z=-5.856， P<0.001].The expression of MRE11A in CD8 + T lymphocytes in sepsis group was lower than that in control group[1 921.50（1 680.00，2 217.00）vs.4 165.00（2 894.00，9 122.00）， Z=-5.083， P<0.001]. Conclusion:The expression level of MRE11A in the cytoplasm of T lymphocytes in children with sepsis was decreased,which may affect the function of T lymphocytes.

Objective:To explore the changes in serum levels of miR-499 and miR-362 in patients with advanced non-small cell lung cancer (NSCLC) and their relationship with prognosis.Methods:A total of 103 patients with advanced NSCLC at Shanghai University of Medicine & Health Sciences Affiliated Chongming Hospital from January 2020 to October 2021 were selected as the NSCLC group, and 100 healthy volunteers who underwent physical examinations at our hospital during the same period were selected as the control group. Fluorescent quantitative PCR was used to determine and compare the levels of serum miR-499 and miR-362 in the two groups, and the relationship between the two indexes and different clinical characteristics of NSCLC patients was analyzed. According to the clinical outcome of 2-year follow-up, the patients were divided into survival group and death group, and the levels of serum miR-499 and miR-362 were compared between the two groups. The predictive value of miR-499 and miR-362 levels on the prognosis of advanced NSCLC patients were analyzed using receiver operator characteristic (ROC) curves.Results:The serum miR-499 level in the NSCLC group (0.34±0.10) was lower than that in the control group (1.25±0.21), while the miR-362 level (1.13±0.27) was higher than that in the control group (0.63±0.15) ( t=18.26, P<0.001; t=16.32, P<0.001). There were statistically significant differences in serum miR-499 and miR-362 levels among patients with different degrees of differentiation ( t=11.12, P<0.001; t=16.35, P<0.001), TNM staging ( t=13.64, P=0.002; t=8.73, P=0.010) and lymph node metastasis ( t=10.02, P=0.003; t=9.65, P=0.004). The serum miR-499 level in the death group ( n=77) (0.24±0.06) was lower than that in the survival group ( n=26) (0.35±0.09), while the miR-362 level (1.54±0.32) was higher than that in the survival group (1.08±0.21), with statistically significant differences ( t=8.06, P=0.006; t=8.67, P=0.005). ROC curve analysis showed that the sensitivity of miR-499 and miR-362 in predicting the prognosis of advanced NSCLC patients was 73.46% and 75.85%, respectively, with specificity of 64.42% and 65.61%, AUC of 0.739 (95% CI: 0.662-0.805) and 0.743 (95% CI: 0.640-0.793) ; the sensitivity, specificity, and AUC of serum miR-499 combined with miR-362 in predicting the prognosis of advanced NSCLC patients were 87.63%, 85.34%, and 0.875 (95% CI: 0.698-0.897), respectively; the combined prediction of miR-499 and miR-362 for AUC area was higher than the individual prediction ( Z=4.83, P=0.013; Z=5.17, P=0.009) . Conclusion:Advanced NSCLC patients show significant abnormal serum level of miR-499 and miR-362, and as the severity of the disease progressed, the serum level of miR-499 is downregulated more significantly and miR-362 is upregulated more significantly. The combined detection of miR-499 and miR-362 levels has certain predictive value for the prognosis of advanced NSCLC patients.

Objective To investigate the clinical effect of anterolateral mini-incision assisted reduction with InterTan intramedullary nail in the treatment of elderly refractory femoral intertrochanteric fractures to provide reference for clinical treatment.Methods Fifty-eight elderly patients with femoral intertrochanteric fractures admitted and treated in this hospital from August 2020 to April 2023 were selected as the study sub-jects and divided into the observation group and control group accroding to the operation program,29 cases in each group.The observation adopted the anterolateral mini-incision assisted reduction with InterTan intramed-ullary nail,in which there were 6 males and 23 females,the age averaged(86.14±4.98)years old.The control group adopted the closed reduction InterTan intramedullary nail therapy,in which there were 8 males and 21 females,the age averaged(86.33±5.09)years old.The intraoperative bleeding volume,hospitalization dura-tion,incidence rate of fracture related complications,operation time,postoperative fracture reduction quality,postoperative medial cortical support type and postoperative hip joint Harris score were compared between the two groups.Results The two groups obtained the followed up,the follow up time was 6-12 months,with an average(11.45±1.59)months.There were no statistically significant differences in the intraoperative bleed-ing volume,hospitalization duration,incidence rate of fracture related complications between two groups(P＞0.05).The operation time in the observation group was(88.79±29.58)min,which in the control group was(70.66±24.47)min,and there was statistical difference between the two groups(P＜0.05).The excellent and good rate of fracture reduction quality in the observation group was 100.00％,which in the control group was 75.86％,and the difference between the two groups had statistical significance(P＜0.05).The propor-tion of positive and neutral medial cortical support in the observation group was 96.55％,which in control group was 72.41％,and the difference between the two groups was statistically significant(P＜0.05).The hip Harris score in the observation group was(76.33±12.71)points,which in the control group was(68.39±13.17)points,and the difference between the two groups was statistically significant(P＜0.05).Conclusion The eld-erly patients with refractory femoral intertrochanteric fracture are often combined with multiple underlying diseases,and the surgical risk is extremely high.Adopting anterolateral mini-incision assisted reduction with InterTan intramedullary nail fixation treatment could achieve the satisfactory reduction and fixation without increasing obvious trauma and the effect is reliable.

Pathological diagnosis is vital in medicine. Developing and implementing high-quality pathology guidelines and consensus can enhance disease diagnosis accuracy and reduce unnecessary misdiagnosis and missed diagnoses. This article will cover the current status of pathology guidelines and consensus, methods for high-quality development, and the distinctions between them. Additionally, it will provide thoughts and suggestions for promoting their development in China.