Objective To investigate the effects of secukinumab combined with E'xian Huaban decoction on traditional Chinese medicine symptom scores and nailfold microcirculation morphology in patients with plaque psoriasis.Methods A total of 120 patients with plaque psoriasis were selected and randomly divided into monotherapy group(n=60)and combination therapy group(n=60).The monotherapy group received secukinumab treatment,while the combination therapy group was treated with secukinumab plus E'xian Huaban Decoction.Clinical therapeutic efficacy,traditional Chinese medicine symptom scores(including skin lesions,pruritus,rough skin,scales and irritabili-ty),relevant scale[Psoriasisarea and Severity Index(PASI),Dermatology Life Quality Index(DLQI)and Visual Analogue Scale(VAS)]scores,inflammatory factors[interleukin-17(IL-17),interleukin-23(IL-23)and vascular endothelial growth factor(VEGF)]levels and nailfold microcircu-lation morphology(loop tube morphology,blood flow state and loop periphery state)were observed in both groups.Results The overall clinical efficacy rate in the combination therapy group was 95.00％,which was significantly higher than 83.33％ in the monotherapy group(P＜0.05).After treatment,traditional Chinese medicine symptom scores(skin lesions,pruritus,rough skin,scales and irritability),inflammatory factors(IL-17,IL-23 and VEGF)levels,scale(PASI,DLQI and VAS)scores as well as loop tube morphology scores,blood flow state scores and loop periphery state scores were signifi-cantly lower compared to pre-treatment values,and these parameters were significantly lower in the combination therapy group than the monotherapy group(P＜0.05).Conclusion Secukinumab combined with E'xian Huaban Decoction can significantly improve clinical symptoms and signs,and enhancing the clinical therapeutic effect.

Objective:This study aimed to explore the impact of a single Scutellaria baicalensis decoction on the intestinal flora and barrier function in sepsis rats subjected to an endotoxin "second strike."Methods:Twenty-eight healthy adult male SPF-grade SD rats were utilized to develop an acute lung injury model of sepsis induced by an endotoxin "second strike." The rats were randomLy allocated into four groups: sham operation, model, normal dose Scutellaria baicalensis, and high dose Scutellaria baicalensis, with seven rats in each group. Six hours prior to model induction, the normal dose group received 2 mL of Scutellaria baicalensis decoction at 1 g/kg, while the high dose group received 4 g/kg. Both the sham operation and model groups were administered an equivalent volume of normal saline once daily for three consecutive days. Post-experiment, intestinal tissue, blood, and stool samples were collected. HE staining was used to observe intestinal histopathological changes, ELISA to detect serum D-lactic acid and Fn levels, Western blot to measure intestinal tissue NF-κB, and 16S rRNA gene sequencing to analyze intestinal flora. Correlations between intestinal flora and D-lactic acid, Fn, and NF-κB were examined.Results:Compared to the sham operation group, the model group exhibited inflammatory cell infiltration and tissue structure damage in the intestinal tissue, significantly increased NF-κB expression, markedly decreased serum Fn, and elevated D-lactic acid levels. The abundance of Firmicutes and Lactobacillus in the intestine significantly decreased, while Bacteroidota increased ( P<0.05). In contrast, the normal and high dose groups showed significantly reduced serum Fn and D-lactic acid levels, decreased intestinal NF-κB expression, and increased Firmicutes and Lactobacillus abundance ( P<0.05). Bacteroidota levels decreased, and intestinal tissue inflammatory pathology was notably alleviated. No significant differences were observed in Fn, D-lactic acid, and NF-κB expressions between the normal and high dose groups, nor in the abundance of Firmicutes, Bacteroidota, and Lactobacillus. Firmicutes abundance and the Firmicutes/Bacteroidota ratio positively correlated with Fn ( P<0.01) but negatively with D-lactic acid and NF-κB ( P<0.01). Bacteroidota abundance negatively correlated with Fn ( P<0.01) and positively with D-lactic acid and NF-κB ( P<0.01). Conclusions:Alterations in intestinal flora and mucosal barrier damage are implicated in the lung injury of sepsis rats induced by an endotoxin "second strike." Scutellaria baicalensis decoction exerts a protective effect on intestinal function in these rats, potentially by optimizing the abundance of beneficial intestinal flora, preserving the intestinal mucosal barrier, mitigating inflammatory responses, and safeguarding endothelial cell function.

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Objective To explore the communication preferences for advance care planning(ACP)among elderly hospitalized patients and to provide references for improving the ACP implementation rate.Methods Convenience sampling was used to select elderly hospitalized patients from a tertiary hospital in Wenzhou City between April and November 2023.Face-to-face surveys were conducted using a general data collection form and a self-designed questionnaire on ACP communication preferences.Mixed Logit Model,willingness-to-pay analysis,relative importance analysis,and subgroup analysis were employed to explore preferences.Results 204 questionnaires were distributed and 200 valid questionnaires were recovered,with a valid questionnaire response rate of 98.04％.The Mixed Logit Model analysis indicated that key attributes-communication timing,communication form,family participation in ACP communication,legal validity of ACP documents,and out-of-pocket costs-significantly influenced preferences(P＜0.05).Willingness-to-pay analysis showed that changes in communication timing,communication form,and family participation altered patients' willingness to pay.Relative importance analysis ranked the top 3 attributes as commu-nication timing,communication form,and family participation.Subgroup analysis revealed that gender,education level,and residence location affected preferences(P＜0.05).Conclusion Key attributes of ACP communication affect elderly hospitalized patients' preferences and willingness to pay,with variations across subgroups.Healthcare professionals should develop optimal communication programs based on patient preferences and individual characteristics.

Objective:To analyze the clinical characteristics and gene mutations of 4 patients with the male phenotype of 17α-hydroxylase /17, 20-lyase deficiency(17-OHD), in order to improve the recognition and appropriate management of atypical cases.Methods:A retrospective analysis was performed on the clinical features, biochemical findings, and gene mutations of 4 patients with the male phenotype of 17-OHD treated in our hospital between 2018 and 2023.Results:The social gender of all 4 patients with 17-OHD was male. None of the 4 patients had hypertension or hypokalemia, but all had micropenis and gynecomastia. Two patients had adrenal hyperplasia, while adrenal morphology was normal in the other two. One patient had decreased bone mass. There were typical changes in the steroid synthesis-related hormone spectrum: progesterone was significantly elevated in all 4 patients, 17-hydroxyprogesterone was not markedly abnormal, cortisol, dehydroepiandrosterone sulfate(DHEAS) and estradiol levels were low, and testosterone levels were also low.Conclusion:17-OHD is a rare type of congenital adrenal hyperplasia, with the male phenotype being even rarer. Early symptoms are often atypical, resulting in high rates of misdiagnosis and missed diagnosis. Patients without hypertension and hypokalemia are particularly prone to diagnostic confusion. Male patients with unexplained progesterone elevation, poor secondary sexual development, and gynecomastia should undergo timely steroid hormone profiling and genetic testing to avoid misdiagnosis and missed diagnosis.

Objective:To discuss the expression of Rh family C glycoprotein(RHCG)in the esophageal squamous cell carcinoma(ESCC)tissue and its effect on the malignant biological behavior of ESCC cells,and to clarify the value of RHCG as a diagnostic and prognostic marker for the ESCC patients.Methods:A total of 143 ESCC tissue samples and 105 adjacent normal tissue samples were collected.Using immunohistochemical staining method,141 ESCC samples were divided into two groups:RHCG low expression group(immunohistochemistry score≤6)and RHCG high expression group(immunohistochemistry score>6).Immunohistochemical method was used to detect the RHCG protein expression in 143 ESCC tissues and 105 normal tissues,and the relationship between the clinicopathological characteristics of the ESCC patients was analyzed.Receiver operating characteristic(ROC)curve and Kaplan-Meier survival analysis were used to evaluate the value of RHCG in diagnosis and prognosis of the ESCC patients;univariate and multivariate COX regression analysis were used to determine the independent risk factors affecting the prognosis of the ESCC patients.Gene Expression Profiling Interactive Analysis(GEPIA2)database was used to analyze the expression of RHCG mRNA in various tumor tissues.The ESCC TE-1 cells were cultured and transfected in to 6-well cell culture plates with different Lipofectamine2000∶RHCG ratios;the cells in RHCG transfection group were transfected with weights of 2.0,2.5,and 3.0 μg for 24 and 48 h,respectively,and the cells in NC group transfected with empty vector as control.Western blotting method was used to detect the RHCG protein expression level in the TE-1 cells in various groups after transfection at different concentrations and verify the optimal transfection conditions;cell counting kit-8(CCK-8)assay was used to detect the proliferation activities of the TE-1 cells;plate clone formation assay was used to detect the colony formation numbers of the TE-1 cells;Transwell chamber assay was used to detect the numbers of migrating TE-1 cells.Results:Compared with adjacent normal tissue,the RHCG gene expression level in various cancer tissues including ESCC,glioblastoma multiforme,and head and neck squamous cell carcinoma was significantly decreased(P<0.05).RHCG protein was mainly located on the cell membrane of normal esophageal squamous epithelial cells;the RHCG protein expression intensity in ESCC tissues was lower than that in adjacent normal esophageal tissue(χ2=109.373,P<0.001),and the patients in RHCG low expression group had poorer differentiation than those in RHCG high expression group(P=0.041).The area under the curve(AUC)value of RHCG for diagnosing ESCC was 0.86,with sensitivity and specificity of 95.1%and 75.0%,respectively;the Kaplan-Meier survival analysis results showed that compared with high RHCG expression group,the patients in low RHCG expression group had shorter survival time and poorer prognosis[harard ratio(HR)=0.269,95%confidence interval(CI):0.113-0.639,P=0.020];the COX regression analysis results showed that low RHCG expression could serve as an independent risk factor affecting the prognosis of ESCC[HR=4.569,95%CI=1.315-15.877,P=0.017)].The Western blotting results verified that the optimal transfection condition was 3.0 μg RHCG plasmid for 48 h,at which time RHCG overexpression was optimal and RHCG protein expression level was highest.The CCK-8 assay results showed that compared with control group,the proliferation activity in RHCG overexpression group was decreased on the 4th day after cell seeding(P<0.001).In the TE-1 cells,the colony formation number of the TE-1 cells in RHCG over-expression group was lower than that in control group(t=17.70,P<0.001).The Transwell chamber assay results showed that compared with control group,the number of migrating cells in RHCG over-expression group was decreased(t=23.74,P<0.001).Conclusion:RHCG expression is decreased in ESCC tissues and associated with poor prognosis in ESCC patients;overexpression of RHCG can inhibit the proliferation and migration of the TE-1 cells,providing a theoretical basis for RHCG as a novel diagnostic and prognostic marker and therapeutic target for ESCC.

Objective To explore the communication preferences for advance care planning(ACP)among elderly hospitalized patients and to provide references for improving the ACP implementation rate.Methods Convenience sampling was used to select elderly hospitalized patients from a tertiary hospital in Wenzhou City between April and November 2023.Face-to-face surveys were conducted using a general data collection form and a self-designed questionnaire on ACP communication preferences.Mixed Logit Model,willingness-to-pay analysis,relative importance analysis,and subgroup analysis were employed to explore preferences.Results 204 questionnaires were distributed and 200 valid questionnaires were recovered,with a valid questionnaire response rate of 98.04％.The Mixed Logit Model analysis indicated that key attributes-communication timing,communication form,family participation in ACP communication,legal validity of ACP documents,and out-of-pocket costs-significantly influenced preferences(P＜0.05).Willingness-to-pay analysis showed that changes in communication timing,communication form,and family participation altered patients' willingness to pay.Relative importance analysis ranked the top 3 attributes as commu-nication timing,communication form,and family participation.Subgroup analysis revealed that gender,education level,and residence location affected preferences(P＜0.05).Conclusion Key attributes of ACP communication affect elderly hospitalized patients' preferences and willingness to pay,with variations across subgroups.Healthcare professionals should develop optimal communication programs based on patient preferences and individual characteristics.

Objective:To analyze the clinical characteristics and gene mutations of 4 patients with the male phenotype of 17α-hydroxylase /17, 20-lyase deficiency(17-OHD), in order to improve the recognition and appropriate management of atypical cases.Methods:A retrospective analysis was performed on the clinical features, biochemical findings, and gene mutations of 4 patients with the male phenotype of 17-OHD treated in our hospital between 2018 and 2023.Results:The social gender of all 4 patients with 17-OHD was male. None of the 4 patients had hypertension or hypokalemia, but all had micropenis and gynecomastia. Two patients had adrenal hyperplasia, while adrenal morphology was normal in the other two. One patient had decreased bone mass. There were typical changes in the steroid synthesis-related hormone spectrum: progesterone was significantly elevated in all 4 patients, 17-hydroxyprogesterone was not markedly abnormal, cortisol, dehydroepiandrosterone sulfate(DHEAS) and estradiol levels were low, and testosterone levels were also low.Conclusion:17-OHD is a rare type of congenital adrenal hyperplasia, with the male phenotype being even rarer. Early symptoms are often atypical, resulting in high rates of misdiagnosis and missed diagnosis. Patients without hypertension and hypokalemia are particularly prone to diagnostic confusion. Male patients with unexplained progesterone elevation, poor secondary sexual development, and gynecomastia should undergo timely steroid hormone profiling and genetic testing to avoid misdiagnosis and missed diagnosis.

Abstract: Objective To evaluate the impact of meningococcal vaccine immunization on the incidence of meningococcal meningitis, aiming to refine the local immunization strategies and programs. Methods Data on the reported incidence of meningococcal meningitis in Hebei province for 1970-2023 were collected, and interrupted time-series( ITS) analysis was used to quantitatively analyze the levels and slope change of the incidence of meningococcal meningitis before and after vaccine immunization and before and after inclusion in the Expanded Program on Immunization (EPI). Results The annual average reported incidences of meningococcal meningitis in Hebei province before vaccination (1970-1979), before (1980-2007) and after (2008-2023) the inclusion of the vaccine in the EPI were respectively 20.79 per 100 000, 1.66 per 100 000, and 0.018 per 100 000. The interrupted time-series analysis from 1970 to 2023 showed an initial meningitis incidence rate of 24.12 per 100 000 (t=9.86, P<0.05), with an average annual decrease of 1.07 per 100 000 (t=-2.42, P<0.05). After the introduction of the meningococcal vaccine in 1980, the incidence of meningococcal meningitis decreased quickly with an annual average decline of 18.39 per 100 000, showing a significant short-term intervention effect (t=-2.70, P<0.05); however, the rate of decrease slowed over the long term to 0.13 per 100 000, with the long-term intervention effect not being significant (P>0.05). And the incidence was significantly increased due to the outbreak (t=7.80, P<0.05). From 1980 to 2023, the initial level of incidence was 5.13 per 100 000 (t=8.70, P<0.05), and decreased by 0.23/100 000 per year on average (t=-6.42, P<0.05). After the inclusion of the vaccine in the EPI in 2008, the rate of decrease further slowed down to an average of 0.008 per 100,000 per year, with the long-term intervention effect being significant (t=2.50, P<0.05); the impact of epidemic outbreaks on incidence during this period was not statistically significant (P>0.05). Conclusions Meningococcal meningitis vaccination has led to a general downward trend in the incidence of meningitis in Hebei Province, and has flattened the trend of increased incidence caused by outbreaks. Therefore, long-term maintenance in immunization programs on the meningococcal meningitis is necessary. In addition, it is important to strengthen the monitoring of the distribution of epidemic serogroups in patients and healthy carriers, and to adjust immunization strategies timely based on changes in bacterial populations, selecting and promoting vaccines accordingly for the prevalent strains.

AIM:To identify transcriptional differences between the ocular surface ectoderm(OSE)and surface ectoderm(SE)using RNA-seq, and elucidate the OSE transcriptome landscape and the regulatory networks involved in its development.METHODS:OSE and SE cells were differentiated from human embryonic stem(hES)cells. Differentially expressed genes(DEGs)between OSE and SE were analyzed using RNA-seq. Based on the DEGs, we performed gene ontology(GO)analysis, Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis, and protein-protein interaction(PPI)network analysis. Transcription factors(TFs)and hub genes were screened. Subsequently, TF-gene and TF-miRNA regulatory networks were constructed using the NetworkAnalyst platform.RESULTS:A total of 4 182 DEGs were detected between OSE and SE cells, with 2 771 up-regulated and 1 411 down-regulated genes in OSE cells. GO-BP analysis revealed that up-regulated genes in OSE were enriched in the regulation of ion transmembrane transport, axon development, and modulation of chemical synaptic transmission. Down-regulated genes were primarily involved in nuclear division, chromosome segregation, and regulation of cell cycle phase transition. KEGG analysis indicated that up-regulated genes in OSE cells were enriched in signaling pathways such as cocaine addiction, axon guidance, and amphetamine addiction, while down-regulated genes were enriched in proteoglycans in cancer, ECM-receptor interaction, protein digestion and absorption, and cytokine-cytokine receptor interaction. Additionally, compared with SE, 204 TFs(including FOS, EGR1, POU5F1, SOX2, and PAX6)were up-regulated, and 80 TFs(including HAND2, HOXB6, HOXB5, HOXA5, and HOXB8)were down-regulated in OSE cells. Furthermore, we identified 6 up-regulated and 9 down-regulated hub genes in OSE cells, and constructed TF-gene and TF-miRNA regulatory networks based on these hub genes.CONCLUSIONS:The transcriptome characteristics of OSE and SE cells were elucidated through RNA-seq analysis. These findings may provide a novel insight for studies on the development and in vitro directed induction of OSE and corneal epithelial cells.