OBJECTIVE To investigate the effects of total flavonoids from Carthamus tinctorius L. （TFCTL） on hepatic stellate cell （HSC） activation based on the microRNA （miRNA）-204/NUAK family SNF1-like kinase 1 （NUAK1）/Hippo signaling axis， thereby elucidating the potential mechanism underlying their antifibrotic effects. METHODS The HSC-T6 cells were divided into control group， model group， TFCTL low-concentration group （20 μg/mL）， TFCTL medium-concentration group （40 μg/mL）， and TFCTL high-concentration group （60 μg/mL）. Except for control group， the remaining groups were treated with 5 ng/mL of transforming growth factor-β to induce the activation of hepatic stellate cells， followed by the addition of corresponding drug solutions/culture medium and incubation for 24 hours. Cell apoptosis was assessed， the expression levels of α-smooth muscle actin （α-SMA）， type Ⅰ collagen （Collagen Ⅰ） and proteins associated with the Hippo/Yes-associated protein （YAP） pathway [YAP， large tumor suppressor kinase 1 （LATS1）， and mammalian STE20-like kinase 1 （MST1）] were detected. Additionally， cell transfection was used to investigate the activity of the miRNA-204/NUAK1/Hippo signaling axis at both the genetic and protein levels. RESULTS After intervention with TFCTL， the apoptosis rate of HSC-T6 cells and the protein expressions of MST1 （except for the TFCTL high-concentration group） and LATS1 were significantly increased （P＜0.05）， while the protein expressions of α-SMA， CollagenⅠ， and YAP （except for the TFCTL medium-concentration group） were significantly decreased （P＜0.05）. Further results from cell transfection experiments revealed that after transfection with miRNA-204 mimics， the mRNA it’s protein expressions of α-SMA， CollagenⅠ， NUAK1， and YAP in HSC-T6 cells were significantly decreased （P＜0.05）， while the mRNA and protein expressions of LATS1 and the mRNA expression of MST1 were significantly increased （P＜0.05）. Conversely， the results were opposite following transfection with miRNA-204 inhibitors. CONCLUSIONS TFCTL can exert anti-hepatic fibrosis effects by up-regulating the expression of miRNA-204， thereby down- regulating the expressions of NUAK1， inactivating the Hippo/YAP pathway， which in turn suppresses the activation of HSC and promotes their apoptosis.

ObjectiveTo observe the clinical efficacy and safety of Dizhuo Huayu prescription combined with catgut embedding therapy in patients with nonalcoholic steatohepatitis （NASH） and dyslipidemia and explore the effect of the combined therapy on inflammatory cytokines interleukin （IL）-18 and IL-1β. MethodsA total of 82 patients with NASH and dyslipidemia from the Gastroenterology Department of the First Affiliated Hospital of Henan University of Chinese Medicine were randomly divided into a control group and a treatment group， with 41 patients in each group. The control group received Polyene Polyenylphosphatidylcholine Capsules， while the treatment group received Dizhuo Huayu prescription granules combined with catgut embedding. The treatment duration was 24 weeks for both groups. At weeks 0， 12， and 24， the traditional Chinese medicine （TCM） syndrome score， body mass index （BMI）， liver fat content assessed by Fibroscan （CAP value）， the level of alanine transaminase （ALT）， aspartate aminotransferase （AST）， gamma-glutamyl transferase （GGT）， total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， and free fatty acid （FFA）， and the expression of inflammatory cytokines IL-18 and IL-1β in serum were observed. Adverse reactions in both groups were recorded. ResultsA comparison of the comprehensive therapeutic effects between the two groups after 24 weeks of treatment revealed that the total effective rate was 62.16% （23/37） in the control group and 85.71% （30/35） in the treatment group， with a statistically significant difference （χ² = 5.14， P<0.05）. At weeks 12 and 24 after treatment， the TCM syndrome score， BMI， CAP value， TC， TG， LDL-C， and FFA were all significantly lower in both groups compared to pre-treatment levels， while the HDL-C level significantly increased （P<0.05）. The effect was better at week 24 （P<0.05） than at week 12 （P<0.05）， and the treatment group showed better outcomes than the control group at weeks 12 and 24 after treatment （P<0.05）. After 24 weeks of treatment， both groups exhibited significant reductions in IL-18 and IL-1β levels （P<0.05）. The treatment group demonstrated superior efficacy compared to the control group after treatment （P<0.05）. Both groups experienced decreases in ALT， AST， and GGT levels after treatment （P<0.05）. However， there were no statistically significant differences between the 12-week and 24-week post-treatment values within each group， nor were there significant differences between the two groups. No significant adverse reactions were observed in both groups. ConclusionThe Dizhuo Huayu prescription combined with catgut embedding therapy is safe and effective in treating patients with NASH and dyslipidemia， exhibiting hepatoprotective， anti-inflammatory， lipid-regulating， and weight-reducing effects.

Objective To analyze the value of combined prediction of peripheral blood CD4+,CD3-CD16+CD56+,CD8+,CD19+for the risk of death in patients with Epstein-Barr virus-associated hemophagocytic syn-drome(EBV-HLH).Methods A total of 84 patients with EBV-HLH who were treated in Beijing Friendship Hospital Affiliated to Capital Medical University and Peking University First Hospital from May 2021 to A-pril 2023 were selected and divided into a death group(17 cases)and a survival group(67 cases)according to their survival outcomes within 6 months.The general information and peripheral blood T lymphocyte subsets of the two groups were compared,multivariate Logistic regression analysis was conducted to investigate the influencing factors of death in EBV-HLH patients,and receiver operating characteristic(ROC)curve was used to evaluate the predictive value of peripheral blood T lymphocyte subsets on death in EBV-HLH patients.Results The platelet count,hemoglobin,CD4+and CD3-CD16+CD56+levels in the death group were lower than those in the survival group,while the levels of CD8+and CD19+were higher than those in the survival group(P＜0.05).Multivariate Logistic regression analysis showed that platelet count,hemoglobin,CD4+,and CD3-CD16+CD56+were all independent protective factors for the death of EBV-HLH patients,while CD8+and CD19+were independent risk factors for the death of EBV-HLH patients(P＜0.05).The ROC curve results showed that the area under the curve of combined prediction of CD4+,CD8+,CD19+,CD3 CD16+CD56+for death in EBV-HLH patients was 0.923,with sensitivity and specificity of 94.12％and 80.60％,respectively,which were significantly higher than those predicted by each individual indicator(P＜0.05).Conclusion The abnormal expression of CD4+,CD3-CD16+CD56+,CD8+,and CD19+in peripheral blood of EBV-HLH patients is associated with their survival outcomes,and the combined prediction of CD4+,CD3-CD16+CD56+,CD8+,and CD19+has high reference value for predicting patients'death.

Objective To investigate the expression levels of serum high-mobility group box 1(HMGB1),soluble CD163(sCD163),and prostaglandin E2(PGE2)in patients with hepatitis B virus-related chronic-on-acute liver failure(HBV-ACLF),and to evaluate the value of the three indicators used alone or in combination in predicting prognosis.Methods A total of 76 patients with HBV-ACLF who were hospitalized in Department of Infectious Diseases,The First Affiliated Hospital of Xinxiang Medical University,from July 1,2022 to September 30,2023 were enrolled,and according to the 28-day prognosis,they were divided into survival group with 48 patients and death group with 28 patients.General data were collected,Model for End-Stage Liver Disease(MELD)score was calculated,and ELISA was used to measure the serum levels of HMGB1,sCD163,and PGE2.The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test was used for comparison of categorical data between two groups.The Spearman rank correlation test was used to analyze the correlation of HMGB1,sCD163,and PGE2 with MELD score;the receiver operating characteristic(ROC)curve was used to analyze the value of HMGB1,sCD163,and PGE2 used alone or in combination in predicting the prognosis of HBV-ACLF patients.Results There were significant differences between the two groups in total bilirubin,white blood cell count,the percentage of neutrophils,procalcitonin,serum amyloid A,interleukin-6,serum sodium,and serum creatinine(all P＜0.05).Compared with the survival group,the death group had significantly higher serum levels of HMGB1(Z=-2.997,P=0.003)and sCD163(Z=-2.972,P=0.003),a significantly higher MELD score(t=-6.997,P＜0.001),and a significantly lower serum level of PGE2(Z=-4.909,P＜0.001).The Spearman rank correlation test showed that HMGB1 and sCD163 were positively correlated with MELD score(r=0.431 and 0.319,both P＜0.05),while PGE2 was negatively correlated with MELD score(r=-0.412,P＜0.05).The ROC curve analysis showed that HMGB1,sCD163,and PGE2 used alone had an area under the ROC curve(AUC)of 0.717,0.716,and 0.856,respectively,while the combination of the three indicators had the highest predictive value,with an AUC of 0.930,a sensitivity of 0.778,and a specificity of 0.920.Conclusion Serum HMGB1,sCD163,and PGE2 used alone or in combination have a good reference value in predicting the prognosis of HBV-ACLF patients,and the combination of the three indicators has the highest predictive value,which holds promise for further observation and research.

ObjectiveTo investigate the effect of modified Weijingtang on the pyroptosis of RAW264.7 macrophages via the cysteinyl aspartate-specific protease-1 （Caspase-1）/gasdermin D （GSDMD） pathway. MethodLipopolysaccharide （LPS） was used to induce pyroptosis of RAW264.7 cells. The blank group was treated with the blank serum， and the intervention groups were treated with the sera containing different doses of modified Weijingtang. After 24 h， the viability of cells in different groups was examined by the cell counting kit-8 （CCK-8）. The pyroptosis and morphology of cells in each group were observed by a scanning electron microscope and a phase-contrast microscope， respectively. The mRNA and protein levels of nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3）， Caspase-1， and GSDMD in each group were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. The levels of interleukin （IL）-18 and IL-1β in each group were measured by enzyme-linked immunosorbent assay. ResultUnder the electron microscope， RAW264.7 cells presented the best morphology and structure in the blank group and obvious pyroptosis and leakage of cell contents in the model （LPS） group. Compared with the model group， the intervention groups showed reduced pyroptosis to varying degrees， and the high-dose group had the closest cell morphology and structure to the blank group. Under the optical microscope， RAW264.7 cells were spherical in the blank group and irregular with protrusions in the model group. Compared with the model group， the intervention groups showed improved cell morphology， and the cell morphology in the group with the dose of 20% was the closest to that in the blank group. The mRNA and protein levels of NLRP3， Caspase-1， and GSDMD in the model group were higher than those in the blank group （P<0.05）. Compared with the model group， each intervention group showed down-regulated expression of the above indicators （P<0.05）. Compared with the blank group， the model group presented elevated levels of IL-18 and IL-1β （P<0.05）， which were lowered in the intervention （10%， 20%） groups （P<0.01）. ConclusionModified Weijingtang inhibits the pyroptosis of macrophages by down-regulating the Caspase-1/GSDMD pathway and reducing the release of proinflammatory cytokines.

Objective To accurately encode pelvic organ prolapse and ensure data accuracy.Methods ICD-10 coding analysis was performed in combination with the professional knowledge of the International Classification of Diseases(ICD-10)and specific clinical cases of pelvic organ prolapse.Results Vaginal anterior wall prolapse,regardless of severity,was encoded as N81.1;vaginal posterior wall prolapse,regardless of severity,as N81.6;uterine prolapse grade Ⅰ and Ⅱ,regardless of the presence or absence of vaginal anterior and posterior wall prolapse,as N81.2;uterine prolapse grade Ⅲ,whether the prolapse of the anterior and posterior vaginal walls is combined,or what level of the severity of the prolapse,as N81.3;cervical prolapse staging,regardless of severity or presence of vaginal anterior and posterior wall prolapse,as N81.2.In addition,the N81.-code does not include genital prolapse complicating pregnancy(O34.5),prolapse and hernia of ovary and fallopian tube(N83.4),vaginal fornix prolapse after hysterectomy(N99.3).Conclusion To ensure accurate coding,the composite coding rules must be cross-checked with volume one.ICD-10 failed to reflect the severity of vaginal prolapse in clinical practice.To consider the severity,coding should be extended in the N81.-segment.It is essential for coders to actively acquire clinical knowledge,rein-force professional knowledge,and enhance their responsibility to improve their coding proficiency and ensure data accuracy.

Objective To explore the effects of disuse-induced architectural changes in the osteocytic lacunar-canalicular system(LCS)on the fluid dynamic microenvironment of osteocytes under mechanical stimulus.Methods First,taking the axially loaded mice tibia as the object,a multi-scale model of'whole bone-single osteocyte LCS'was established.Subsequently,pressure gradients and other results obtained from the whole-bone poroelastic finite element model were used as boundary conditions for the single-osteocyte LCS model to calculate the flow velocity and shear stress around osteocytes.Finally,a design of experiment(DOE)method was used to determine the individual and interactive effects of the LCS architectural parameters(lacunar volume,lacunar shape,and canalicular diameter)on the osteocytic fluid dynamic microenvironment within the LCS.Results When the lacunar volume,lacunar shape,and canalicular diameter changed from normal to disused,the flow velocity increased by 5.3%,39.3%,and 37.0%,respectively.The DOE results showed that the lacunar shape and canalicular diameter had a significant effect on fluid velocity and shear stress(P<0.05),with a contribution ratio of 0.38∶0.62,whereas the lacunar volume and interaction of architectural parameters had no significant effects.Conclusions Disuse-induced changes in canalicular diameter and lacunar shape were the main factors affecting the osteocytic fluid dynamic environment within the LCS under mechanical stimulus.Appropriate exercise methods are expected to prevent disuse-induced bone loss caused by space weightlessness and other conditions.

Objective To investigate the relationship between the levels of CD4+/CD8+and D-dimer(D-D)in peripheral blood and the outcome of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis(EBV-HLH).Methods Ninety patients with EBV-HLH who were treated in Beijing Friendship Hospital from September 2021 to August 2023 were included as observation group,and additional 90 patients with infectious mononucleosis(IM)treated in the hospital contemporarily were selected as the control group.The levels of CD4+/CD8+and D-D in peripheral blood were compared between the two groups of patients to examine the correlation between the levels of CD4+/CD8+and D-D in peripheral blood and EBV-DNA load in patients with EBV-HLH,compare the outcome of patients within 3 months in terms of the levels of CD4+/CD8+and D-D in peripheral blood,evaluate the effects of CD4+/CD8+and D-D levels in peripheral blood on the risk of death from EBV-HLH,and analyze the interaction between the levels of CD4+/CD8+and D-D in peripheral blood.Results The patients in observation group showed significantly lower peripheral blood CD4+/CD8+ratio and significantly higher D-D than the patients in control group(P＜0.05).The peripheral blood CD4+/CD8+ratio was negatively correlated with EBV-DNA load(P＜0.05),and D-D was positively correlated with EBV-DNA load(P＜0.05)in EBV-HLH patients.The patients with high peripheral blood CD4+/CD8+ratio were assocaited with lower 3-month mortality rate compared to the patients with low CD4+/CD8+ratio.The patients with high D-D level were associated with higher 3-month mortality rate compared to the patients with low D-D level(P＜0.05).In EBV-HLH patients with low levels of peripheral blood CD4+/CD8+,the risk of death was 6.125 times that of the patients with high levels of CD4+/CD8+.High level D-D was associated with 14.348 times risk of death compared to the patients with low level D-D.CD4+/CD8+and D-D had synergistic effect on death of EBV-HLH patients.Conclusions Peripheral blood CD4+/CD8+levels decreased and D-D levels increased in EBV-HLH patients.Peripheral blood CD4+/CD8+levels and D-D levels and their changes may be useful for predicting the outcome of patients.

Objective To investigate the clinical characteristics of adult secondary hemophagocytic syndrome(sHLH)and analyze the changes and significance of TH17/Treg cells and lymphocyte subsets,providing favorable references for clinical work.Methods 82 a-dult sHLH patients admitted to our hospital from April 2021 to March 2023 were selected.On the second day of admission,we observed their clinical characteristics and detected the levels of TH17/Treg cells(TH17,Treg,TH17/Treg)and lymphocyte subsets(CD3+,CD4+,CD8+,CD19+,CD16+CD56+).The patients were given the HLH-2004 treatment regimen and followed up for 6 months.Ac-cording to the treatment results,they were divided into the survival group(n=57)and fatality group(n=25).The levels of TH17/Treg cells and lymphocyte subsets on the second day of admission between the two groups were compared.The correlation between TH17/Treg cells and lymphocyte subsets and the value of TH17/Treg cells in evaluating the fatality of adult sHLH patients were ana-lyzed.Results All 82 adult sHLH patients had elevated serum beta-2 microglobulin and ferritin levels,and more than 90%of patients had clinical characteristics such as persistent irregular high fever,serous cavity effusion,decreased blood cells,and liver function dam-age.The levels of TH17,TH17/Treg,CD3+,and CD8+T cells on the second day of admission,1 month,2 months,and 3 months after treatment in the survival group were significantly lower than those in the fatality group(P<0.05),while the levels of Treg,CD4+,and CD16+CD56+lymphocytes were the opposite(P<0.05).The area under the reciever operating characteristics curve(AUCROC)of TH17/Treg cells combined with lymphocyte subsets in predicting the fatality of adult sHLH patients was 0.853(95%CI:0.758-0.922),which was higher than that of each individual indicator(P<0.05).Conclusion The clinical characteristics of adult sHLH are complex and diverse,with significant immune dysfunction of TH17/Treg and lymphocyte subsets.The TH17/Treg cells combined with lympho-cyte subsets have high efficacy in predicting the prognosis of adult sHLH patients.

ObjectiveTo compare the neuropsychological development of infants with different types of morphologic cranial deformities. MethodsA total of 954 children aged 0 to 18 months who came to Beijing Children's Hospital from January, 2020 to August, 2021 for cranial measurement and neuropsychological development measurement were selected. They were divided into brachycephaly group, plagiocephaly group, asymmetric brachycephaly group, scaphocephaly group and normal group according to the cranial measurement. The development quotient (DQ) was calculated from Children Neuropsychological Development Scale (0-6). ResultsThere were 449 cases in the normal group, 94 cases in the brachycephaly group, 201 cases in the plagiocephaly group, 82 cases in the asymmetric brachycephaly group and 128 cases in the scaphocephaly group. The detection rate of Developmental Edge and Delay (DQ < 85) for gross motor area was the most in brachycephaly group (60.6%), and it was the most for fine motor (64.6%), language (45.1%), adaption (51.2%) and social behavior areas (48.8%) in the asymmetrical brachycephaly group. The DQ was different among the five groups for all the areas except the language area (F > 14.835, P < 0.001); compared with the normal group, DQ decreased for all the four areas in all the groups except the scaphocephaly group; DQ of the areas of gross motor, fine motor and adaption was more in the plagiocephaly group than in the asymmetric brachycephaly group (P < 0.05), while DQ of the areas of gross motor and fine motor was more in the plagiocephaly group than in the brachycephaly group (P < 0.05). Linear regression analysis showed that, DQ negative linear correlated with the cephalic ratio and cranial vault asymmetry index (|B| > 0.967, P < 0.05). ConclusionAmong four kinds of cranial malformation in infants, the neuropsychological development of the scaphocephaly group is almost normal, and somehow delays for brachycephaly, plagiocephaly and asymmetric brachycephaly, especially in the aspects of gross motor, fine motor, adaption and social behavior. The more serious the cranial deformity, the greater the risk of developmental delay in each functional area.