OBJECTIVE To evaluate the cost-utility of enfortumab vedotin combined with pembrolizumab （PemEV） versus gemcitabine combined with cisplatin or carboplatin （GP） in the first-line treatment of advanced urothelial carcinoma （aUC）. METHODS From the perspective of China’s health system， a dynamic Markov model was established based on the pan-Asian subgroup data from the EV-302 trial. The study timeframe was set at 20 years， with a cycle length of 21 days and a discount rate of 5%. Using total direct medical costs and quality-adjusted life years （QALYs） as outcome measures， the incremental cost- effectiveness ratio （ICER） of the PemEV regimen compared to the GP regimen was calculated. The robustness of the model was validated through sensitivity analysis and scenario analysis， and the price thresholds for enfortumab vedotin and pembrolizumab were estimated under conditions where the PemEV regimen was more cost-effective compared to the GP regimen. RESULTS Cost- utility analysis indicated that compared to the GP regimen， PemEV regimen could generate an additional 2.602 QALYs in aUC patients， but the treatment cost increased by 3 339 703.56 yuan， with an ICER of 1 283 554.39 yuan/QALY. This figure significantly exceeded the willingness-to-pay （WTP） threshold （3 times China’s gross domestic product per capita in 2024， 287 247 yuan/QALY）. The rate parameter of the exponential distribution fitted to the overall survival curve in the PemEV regimen had the greatest impact on ICER， according to the one-way sensitivity analysis. Probabilistic sensitivity analysis suggested that the PemEV regimen had no chance of being more cost-effective than the GP regimen at the current WTP threshold. Scenario analysis revealed that the PemEV regimen consistently lacked cost-utility advantage over the GP regimen， regardless of whether the study model was changed to a partitioned survival model， the study timeframe was set to 5， 10 or 20 years， or the prices of enfortumab vedotin and/or pembrolizumab were reduced by 60%. The prices of enfortumab vedotin and pembrolizumab should be simultaneously reduced by 78.65% （55.71 yuan/mg and 38.26 yuan/mg， respectively） when the PemEV regimen had a cost-utility advantage over the GP regimen. CONCLUSIONS From the perspective of China’s healthcare system， PemEV regimen does not demonstrate a cost-utility advantage over GP regimen in the first-line treatment of aUC.

Objective To summarize and analyze the clinical diagnosis, surgical treatment and prognosis of multiple pulmonary nodules (MPNs). Methods The clinical data of lung cancer patients who received surgical treatment in our hospital from 2018 to 2020 were collected. The short-term efficacy of surgical treatment for MPNs was analyzed. Results A total of 97 patients were enrolled, including 30 males and 67 females with an average age of 56.1±10.0 years at onset ill. There were 62 patients with double lesions, 22 patients with three lesions, 4 patients with four lesions, and 9 patients with more than four lesions. A total of 213 lesions were surgically treated, including 88 pure ground-glass nodules, 81 partially solid nodules, and 7 solid nodules. There were 87 simultaneous surgeries and 10 staged surgeries, with an average operation interval of 5.2 months. The pathological combination type included adenocarcinoma-adenocarcinoma in 96 (99.0%) patients, squamous cell carcinoma-squamous cell carcinoma in 1 (1.0%) patient, and no lymph node metastasis was found. The 2-year disease-free survival (DFS) rate was 92.1%, and the overall survival (OS) rate was 100.0%. Univariate analysis showed that high-risk lesion size>2 cm (P=0.316), residual lesions (P=0.782) and pathological combination type (P=0.913) had statistical effect on the 2-year DFS rate. Conclusion MPNs are mainly diagnosed with multiple primary lung cancers, and the pathological combination is mostly adenocarcinoma-adenocarcinoma combination. Imaging examination is of great help to the surgical approach selection, diagnosis and differential diagnosis of MPNs. During the operation, maximal preservation of lung function and complete resection of high-risk nodules should be taken as the principle, and the prognosis is satisfactory.

To explore the mechanism of spleen- were obtained for the treatment of acute-on-chronic livstrengthening and moisture-nourishing liver prescription er failure, and 244 intersecting target genes and 7 core (JPLSYGF) in the treatment of acute-on-chronic liver target genes were screened. Molecular docking showed failure using network pharmacology and the molecular that the core target genes AKT1, SRC, VEGFA, docking. Methods Relying on TCMSP and Gene- STAT3 , EGFR, MAPK3 , HRAS had good affinity with Cards and other databases, the relevant targets of JPL- quercetin, the main active component in the JPLSYGF in the treatment of acute-on-chronic liver failure SYGF, and had strong binding activity. In addition, in were obtained. String and Cytoscape were used to con- vivo tests verified that the JPLSYGF could reduce the struct PPI networks of targets, core targets were expression of HRAS, EGFR, STAT3 , SRC, and VEGscreened out, and DAVID was used for GO function FA, to delay the progression of acute-on-chronic liver annotation and KEGG pathway enrichment analysis. failure. Conclusions JPLSYGF may act on core tar- The main active ingredients of the traditional Chinese gets such as HRAS, EGFR, STAT3, SRC, VEGFA medicine compound formula for JPLSYGF were select- and so on, to achieve the effect of treating acute-oned with a bioavailability OB value of =Э 30% and a chronic liver failure. drug-like DL^O. 18 as the screening conditions, and.

Due to the high similarity with the lipid layer between human skin keratinocytes, functional cosmetics with layered liquid crystal structure prepared by liquid crystal emulsification technology encapsulating natural active substances have become a hot research topic in recent years. This type of functional cosmetic often has a fresh and natural skin feel, excellent skin barrier repair function and efficient moisturizing effect, etc., showing great potential in cosmetic application. However, the present research on the application of liquid crystal emulsification technology to functional cosmetics is still in the initial stage, and there are fewer relevant reports with reference values. Based on the mentioned above, this review provides a comprehensive summary of functional cosmetics with layered liquid crystal structures prepared by liquid crystal emulsification technology from the following aspects: the structure of human skin, the composition of lamellar liquid crystal, the advantages of liquid crystal emulsification technology containing natural active substances used in the field of functional cosmetics, the preparation process, main components, influencing factors during the preparation and the market functional cosmetics with lamellar liquid crystal structure. Finally, the prospect of the application of liquid crystal emulsification technology in functional cosmetics is presented, to provide useful references for those engaged in the research of liquid crystal emulsification technology-related functional cosmetics.

Animals ; Macaca mulatta ; Optic Disk ; Glaucoma ; Craniocerebral Trauma ; Intraocular Pressure ; Low Tension Glaucoma

There is a bidirectional relationship between intestinal flora and bile acids,and the imbalance of intestinal flora-bile acid axis metabolism is closely related to hypertension.Based on classical TCM literature and clinical practice,this article found that"earth deficiency"is the important pathological basis of hypertension,"wood depression"is the initiating factor of hypertension,and"earth deficiency and wood depression"is the key pathogenesis of hypertension.Combined with the research results of modern medicine and molecular biology,it is considered that the imbalance of intestinal flora and abnormal bile acid metabolism are closely related to the"earth deficiency"and"wood depression"of TCM respectively,and the imbalance of intestinal flora-bile acid axis coincides with the"earth deficiency and wood depression"of TCM in the process of hypertension.It is of great theoretical and practical significance to explore the biological connotation of hypertension"earth deficiency and wood depression"from the perspective of intestinal flora-bile acid axis for guiding TCM to prevent and treat hypertension.

Objective:To explore the diagnostic value of first-trimester and mid-trimester ultrasound in screening fetal pentalogy of Cantrell, and to analyze missed and misdiagnosed cases.Methods:The fetal ultrasound image characteristics of pentalogy of Cantrell diagnosed in the Affiliated Suzhou Hospital of Nanjing Medical University from March 2018 to November 2022 were retrospectively analyzed. The necessary sections and key features of ultrasound images for diagnosing the disease in first-trimester and mid-trimester were summarized. The diagnostic value of ultrasound screenings in first-trimester and mid-trimester was analyzed, and the progression of the disease during pregnancy was understood, the missed diagnosis rate and misdiagnosis rate were calculated, and the reasons for missing diagnosis were analyzed. All fetuses were followed up to birth or induction of labor.Pentalogy of Cantrell was divided into types Ⅰ, Ⅱ, and Ⅲ according to Toyama′s research.Results:Among the 120 190 fetuses, 13 cases of pentalogy of Cantrell were diagnosed by ultrasound in first-trimester and mid-trimester. Ultrasound predominantly showed the fetal heart being malpositioned outside the chest and the fetal abdominal contents bulging outside the abdominal cavity, and the sternumal echo was partially or completely missed in some cases. All 13 cases were confirmed by follow-up, including 1 case of type Ⅱ, and 12 cases of type Ⅲ. In addition, 1 missed case of type Ⅱ pentalogy of Cantrell was followed up after birth. The correct diagnostic rates of fetal pentalogy of Cantrell using standard ultrasound sections during the first-trimester and mid-trimester were 99.9% and 100%, the sensitivity were 88.9% and 100%, the specificity were both 100%, the positive predictive values were both 100%, and the negative predictive values were 99.9% and 100%, respectively.Conclusions:First-trimester and mid-trimester ultrasound screenings have high diagnostic accuracy for pentalogy of Cantrell, and early detection and early diagnosis are of great clinical significance for the guidance of pregnancy outcomes.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Background: Twenty-four-hour urinary free cortisol (UFC) measurement is the initial diagnostic test for Cushing’s syndrome (CS). We compared UFC determination by both direct and extraction immunoassays using Abbott Architect, Siemens Atellica Solution, and Beckman DxI800 with liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, we evaluated the value of 24-hr UFC measured by six methods for diagnosing CS. Methods: Residual 24-hr urine samples of 94 CS and 246 non-CS patients were collected.A laboratory-developed LC-MS/MS method was used as reference. UFC was measured by direct assays (D) using Abbott, Siemens, and Beckman platforms and by extraction assays (E) using Siemens and Beckman platforms. Method was compared using Passing–Bablok regression and Bland–Altman plot analyses. Cut-off values for the six assays and corresponding sensitivities and specificities were calculated by ROC analysis. Results: Abbott-D, Beckman-E, Siemens-E, and Siemens-D showed strong correlations with LC-MS/MS (Spearman coefficient r = 0.965, 0.922, 0.922, and 0.897, respectively), while Beckman-D showed weaker correlation (r = 0.755). All immunoassays showed proportionally positive bias. The areas under the curve were 0.975 for Abbott-D, 0.972 for LCMS/MS, 0.966 for Siemens-E, 0.948 for Siemens-D, 0.955 for Beckman-E, and 0.877 for Beckman-D. The cut-off values varied significantly (154.8–1,321.5 nmol/24 hrs). Assay sensitivity and specificity ranged from 76.1% to 93.2% and from 93.0% to 97.1%, respectively. Conclusions Commercially available immunoassays for measuring UFC show different levels of analytical consistency compared to LC-MS/MS. Abbott-D, Siemens-E, and Beckman-E have high diagnostic accuracy for CS.

Objective To investigate the effects of electroacupuncture on the intestinal NIMA-related kinase 7(NEK7)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathway in mice with Parkinson's disease.Methods According to the randomized number table method,36 C57BL/6 mice were randomly divided into the control group,the model group,and the electroacupuncture group,with 12 mice per group.The Parkinson's disease mouse model was established by gavage of rotenone solution(10 mg/kg)for 28 d.After molding,the electroacupuncture group was stimulated with"Fengfu"(DU17),"Taichong"(LR3),and"Zusanli"(ST36)for 14 d,while the control group and the model group were only treated with immobilization.The motor ability of mice was detected by pole climbing test and hindlimb rating score,the positive expressions of nigral tyrosine hydroxylase(TH)and colon occludin were detected by immunohistochemistry,the histological morphology of colon was observed by hematoxylin-eosin staining,and Western blotting was used to detect the protein expressions of NEK7,NLRP3,Caspase-1,and interleukin-1β(IL-1β).Results Compared with the control group,mice in the model group had lower score on the pole climbing test and a higher hindlimb rating score(P＜0.01);the average optical densities of nigral TH and colon occludin were decreased(P＜0.01);significant inflammatory infiltration was observed in the colonic tissue,and the muscularis propria was thinned;and the protein expressions of NEK7,NLRP3,Caspase-1,and IL-1β in the colonic tissue were elevated(P＜0.01).Compared with the model group,mice in the electroacupuncture group had higher score on the pole climbing test and a lower hindlimb rating score(P＜0.01);the average optical densities of nigral TH and colon occludin were increased(P＜0.01);the degree of inflammatory infiltration of colonic tissues decreased,and the muscularis propria was thickened;and the protein expressions of NEK7,NLRP3,Caspase-1,and IL-1β of colonic tissues were decreased(P＜0.01).Conclusion Electroacupuncture at"Fengfu"(DU17),"Taichong"(LR3),and"Zusanli"(ST36)can improve motor functional impairments in mice with Parkinson's disease,and the mechanism may be through the inhibition of intestinal NEK7/NLRP3 pathway,improving the intestinal barrier damage,relieving the intestinal inflammation,and improving the dopaminergic neuron injury.