Objective:To explore the clinical efficacy of Bulleyaconitine A combined with pregabalin in the treatment of herpes zoster neuralgia (HZN), and its effects on serum neuropeptide, interleukin-17 (IL-17), CXC chemokine ligand 10 (CXCL10), and nuclear factor-κB (NF-κB) levels.Methods:A total of 114 HZN patients admitted to the Second Hospital of Tianjin Medical University from January 2021 to December 2022 were selected and divided into observation group ( n=57) and control group ( n=57) by random number table method. The control group was treated with oral pregabalin capsules, and the observation group was treated with Bulleyaconitine A on the basis of the control group for 4 weeks. The clinical efficacy of the two groups was observed. The Visual Analogue Scale (VAS) score for pain, total score of Pittsburgh Sleep Quality Index (PSQI), total score of The MOS 36 Item Short form Health Survey (SF-36), as well as serum neuropeptide [substance P (SP), neuropeptide Y (NPY), β-endorphin (β-EP)] and IL-17, CXCL10, NF-κB levels were compared between the two groups before and after treatment. The occurrence of adverse reactions in the two groups was recorded. Results:The total effective rate of the observation group [82.46%(47/57)] was significantly higher than that of the control group [64.91%(37/57), P<0.05]. Before treatment, there were no significant differences in VAS score, total PSQI score, and total SF-36 score between the two groups (all P>0.05); after treatment, the VAS score and total PSQI score of both groups were significantly decreased (all P<0.05), the total SF-36 score was significantly increased (all P<0.05), and the above indicators in the observation group were better than those in the control group (all P<0.05). Before treatment, there were no significant differences in serum SP, NPY, and β-EP levels between the two groups (all P>0.05); after treatment, serum SP and NPY levels in both groups were significantly decreased (all P<0.05), serum β-EP levels were significantly increased (all P<0.05), and serum SP and NPY levels in the observation group were lower than those in the control group (all P<0.05), serum β-EP levels were higher than those in the control group ( P<0.05). Before treatment, there were no significant differences in serum IL-17, CXCL10, and NF-κB levels between the two groups (all P>0.05); after treatment, serum IL-17, CXCL10, and NF-κB levels in both groups were significantly decreased (all P<0.05), and serum IL-17, CXCL10, and NF-κB levels in the observation group were lower than those in the control group (all P<0.05). There was no significant difference in the adverse reaction rate between the observation group [7.02%(4/57)] and the control group [12.28%(7/57)] ( P>0.05). Conclusions:Bulleyaconitine A combined with pregabalin has good efficacy and safety in the treatment of HZN, which can effectively reduce the degree of neuropathic pain and improve sleep and quality of life. Its mechanism may be related to further regulating the level of neuropeptide and inhibiting the inflammatory state in the body.

McCune-Albright syndrome(MAS) is a postzygotic somatic mutation disorder caused by activating mutations in the GNAS gene, which encodes the α subunit of the stimulatory G protein. Its clinical features typically include polyostotic fibrous dysplasia, cafe-au-lait skin pigmentation, and endocrine hyperactivity, such as Cushing′s syndrome, hyperthyroidism, and growth hormone excess. Here, we report two rare cases of MAS complicated with adrenocorticotropic hormone(ACTH)-independent Cushing syndrome, and provide a review and analysis of previously reported MAS cases associated with Cushing′s syndrome.

Objective To investigate the relationship between the expression levels of serum integrin αMβ2(ITG αMβ2)and gasdermin D(GSDMD)in patients with severe acute pancreatitis(SAP)complicated with acute respiratory distress syndrome(ARDS)and the severity of the disease and its value in predicting prognosis.Methods A total of 147 patients with SAP complicated with ARDS(ARDS group)admitted to the Department of Intensive Care Medicine of the Southwest Jiaotong University Affiliated Hospital(Chengdu Third People's Hospital)from August 2021 to October 2023 were selected.According to the oxygenation index(OI),they were divided into mild group(n=35),moderate group(n=46)and severe group(n=66).According to the 28-day prognosis,they were divided into death group(n=77)and survival group(n=70).Another 147 SAP patients without ARDS at the same time period were selected(non-ARDS group).The expression levels of serum ITG αMβ2 and GSDMD were detected by enzyme-linked immunosorbent assay.Spearman method was used to analyze the correlation between serum ITG αMβ2,GSDMD expression levels and OI in patients with SAP complicated with ARDS.Multivariate Logistic regression was used to analyze the factors of death in patients with SAP complicated with ARDS.Receiver operating characteristic(ROC)curve was used to analyze the value of serum ITG αMβ2,GSDMD expression levels in evaluating the death of patients with SAP complicated with ARDS.Results Compared with the non-ARDS group,the expression levels of serum ITG αMβ2(31.95±8.17 ng/L vs 53.33±12.22 ng/L)and GSDMD(2.25±0.55 ng/ml vs 4.39±1.18 ng/ml)in the ARDS group were increased,and the differences were statistically significant(t=17.637,19.899,all P<0.05).The expression levels of serum ITG αMβ2 and GSDMD in mild group,moderate group and severe group increased in turn,and the differences were statistically significant(F=163.069,194.028,all P<0.05).The expression levels of serum ITG αMβ2 and GSDMD were negatively correlated with OI in patients with SAP complicated with ARDS(r=-0.787,-0.778,all P<0.05).The 28-day mortality rate of 147 SAP patients with ARDS was 52.38%(77/147).Compared with the survival group,the expression levels of serum ITG αMβ2(46.96±10.28 ng/L vs 59.11±10.94 ng/L)and GSDMD(3.74±0.98 ng/ml vs 4.98±1.04 ng/ml)in the death group were increased,and the differences were statistically significant(t=6.920,7.415,all P<0.05).The number of extrapulmonary organ failure≥2,prolonged mechanical ventilation time,increased acute physiological and chronic health assessment II score,and increased ITG αMβ2.and GSDMD were independent risk factors for death in SAP patients complicated with ARDS(Wald χ2=4.297～13.536,all P<0.05),and increased OI was an independent protective factor(Wald χ2=8.346,P<0.05).The combined evaluation AUC of serum ITG αMβ2 and GSDMD expression levels results in a larger area under the curve(AUC)for mortality in SAP patients with ARDS compared to the individual evaluation of SAP complicated with ARDS,which was greater than serum ITG αMβ2 and GSDMD expression levels alone,and the differenes were statistically significant(Z=3.517,3.430,all P<0.05).Conclusion The increase of serum ITG αMβ2 and GSDMD expression levels is related to the progression and poor prognosis of patients with SAP complicated with ARDS.The combined monitoring of serum ITG αMβ2 and GSDMD expression levels has a high evaluation value for the risk of death in patients with SAP complicated with ARDS.

AIM:To appraise the bioequivalence and safety of the test preparation of ritonavir tab-lets and the reference preparation(trade name:Norvir?)in healthy adult subjects under fasting and postprandial conditions.METHODS:This study was a randomized,open-label,single-dose,four-period,fully repeated crossover design bioequivalence study protocol.Thirty-six healthy male and female volunteers were enrolled in the fasting and post-prandial conditions,and a single dose of the test preparation and reference preparation was orally administered.We used liquid chromatography-tan-dem mass spectrometry(LC-MS/MS)to finish the bioassay of the drug concentration of ritonavir in plasma.Pharmacokinetic parameters were statisti-cally analyzed using PhoenixWinNonlin8.1 software(Pharsight,USA)and a non-compartmental model.RESULTS:Under fasting conditions,the pharmacoki-netic parameters of the test and reference prepara-tions:Cmax(792.010±369.282)ng/mL and(856.939±394.427)ng/mL,AUC0-t(6 463.043±2 876.849)ng·mL-1·h and(6 907.690±3 046.132)ng·mL-1·h,AUC0-∞(6 603.617±2 916.352)ng·mL-1·h and(7 051.614±3 093.047)ng·mL-1·h.Here are the pharmacokinetic parameters for both the test prep-aration and the reference preparation in the post-prandial condition:Cmax(574.380±289.566)ng/mL and(615.796±297.382)ng/mL,AUC0-t(5 084.796±2 435.557)ng·mL-1·h and(5 414.167±2 416.952)ng·mL-1·h,AUC0-∞(5 219.144±2 487.793)ng·mL-1·h and(5 551.060±2 490.604)ng·mL-1·h.The 90%confidence interval of the geometric mean ratio of AUC0-t,AUC0-∞,and Cmax for the test preparation and reference preparation lied in the equivalent range of statistics.CONCLUSION:The tested preparation was bioequivalent to the reference preparation un-der fasting and postprandial conditions.

Objective To provide a scoping review of studies on the application of intelligent healthcare for continuity management in liver transplant patients,in order to provide a reference for the future development of intelligent liver transplant management.Methods A systematic search of relevant studies was conducted in PubMed,Embase,CINAHL,Web of Science,Cochrane Library,Scopus,CNKI,Wanfang Database,VIP Database,and CBM from the establishment of the databases to 30 September 2024.Following this search,the included literature was screened,summarized,and analyzed.Results A total of 19 papers were included.The intervention forms included application,intelligent medical device,and remote rehabilitation platform.The content elements included transplant health management,rehabilitation program planning,health data monitoring,telemedicine consultation,psychosocial support,and follow-up supervision.The evaluation indicators included physiological indicators,self-management ability,health-related quality of life,transplantation outcomes,patient satisfaction,and feasibility indicators.Conclusion The application of intelligent healthcare in the continuity management of liver transplantation patients is feasible and effective,and it is recommended that healthcare professionals integrate the diverse practice forms of intelligent healthcare,deepen the content elements and refine the evaluation indicator system based on the actual clinical situation,in order to improve the quality of the continuity management of liver transplantation patients.

Objective To provide a scoping review of studies on the application of intelligent healthcare for continuity management in liver transplant patients,in order to provide a reference for the future development of intelligent liver transplant management.Methods A systematic search of relevant studies was conducted in PubMed,Embase,CINAHL,Web of Science,Cochrane Library,Scopus,CNKI,Wanfang Database,VIP Database,and CBM from the establishment of the databases to 30 September 2024.Following this search,the included literature was screened,summarized,and analyzed.Results A total of 19 papers were included.The intervention forms included application,intelligent medical device,and remote rehabilitation platform.The content elements included transplant health management,rehabilitation program planning,health data monitoring,telemedicine consultation,psychosocial support,and follow-up supervision.The evaluation indicators included physiological indicators,self-management ability,health-related quality of life,transplantation outcomes,patient satisfaction,and feasibility indicators.Conclusion The application of intelligent healthcare in the continuity management of liver transplantation patients is feasible and effective,and it is recommended that healthcare professionals integrate the diverse practice forms of intelligent healthcare,deepen the content elements and refine the evaluation indicator system based on the actual clinical situation,in order to improve the quality of the continuity management of liver transplantation patients.

Oral squamous cell carcinoma(OSCC)accounts for over 90％of oral malignancies,with more than 370 000 new cases and approximately 188 000 deaths annually worldwide.In China,there are roughly 65 000 new cases and 35 000 deaths each year,showing a significant upward trend compared with 2015 statistics.Despite continuous advancements in treatment modalities,the 5-year survival rate remains stagnant at 50％-60％,where tumor heterogeneity and therapy resistance persist as fundamental barriers to precision oncology.To address these critical challenges,this study established a standardized bioban-king protocol for OSCC patient-derived organoids(PDOs)(Patent:Method for constructing an oral squa-mous cell carcinoma organoid bank,ZL202311378598.3).Through groundbreaking optimization of cul-ture media,enzymatic digestion kinetics,and stepwise cryopreservation,we achieved a biobanking suc-cess rate exceeding 95％and pioneered synchronous cultivation of matched primary tumors,lymph node metastases,and adjacent normal mucosa from individual patients,preserving spatial heterogeneity and stromal interactions.Leveraging this platform,we developed high-throughput drug screening:Quantified heterogeneity-driven differential chemoresponse using adenosine triphosphate(ATP)-based viability as-says;We discovered resistance mechanisms:Identified sialylated cancer IgG(SIA-cIgG)-mediated cis-platin resistance(primary/secondary)through PTPN13 suppression,with anti-SIA-cIgG combination therapy demonstrating synergistic efficacy.Besides,we elucidated metastatic drivers:CRISPR-Cas9-edited organoids revealed WDR54 promoted metastasis via H3K4me3/H4K16ac epigenetic reprogramming,activating epithelial-mesenchymal plasticity(EMP)and inducing partial epithelial-mesenchymal transi-tion(pEMT).This"holographic patient-mirroring"platform provided unprecedented resolution for OSCC precision therapy and had been formally incorporated into the Chinese Stomatological Association Techni-cal Guidelines(Technical guideline for establishing patient-derived oral squamous cell carcinoma or-ganoid banks,CHSA 2024-08).Future integration of immune-competent organoids,3D-bioprinted vas-culature,and multi-omics-AI systems will accelerate personalized oncology.These innovations will accelerate clinical translation of personalized therapeutic regimens,ultimately bridging the gap between bench research and bedside application.

Objective To investigate the relationship between the expression levels of serum integrin αMβ2(ITG αMβ2)and gasdermin D(GSDMD)in patients with severe acute pancreatitis(SAP)complicated with acute respiratory distress syndrome(ARDS)and the severity of the disease and its value in predicting prognosis.Methods A total of 147 patients with SAP complicated with ARDS(ARDS group)admitted to the Department of Intensive Care Medicine of the Southwest Jiaotong University Affiliated Hospital(Chengdu Third People's Hospital)from August 2021 to October 2023 were selected.According to the oxygenation index(OI),they were divided into mild group(n=35),moderate group(n=46)and severe group(n=66).According to the 28-day prognosis,they were divided into death group(n=77)and survival group(n=70).Another 147 SAP patients without ARDS at the same time period were selected(non-ARDS group).The expression levels of serum ITG αMβ2 and GSDMD were detected by enzyme-linked immunosorbent assay.Spearman method was used to analyze the correlation between serum ITG αMβ2,GSDMD expression levels and OI in patients with SAP complicated with ARDS.Multivariate Logistic regression was used to analyze the factors of death in patients with SAP complicated with ARDS.Receiver operating characteristic(ROC)curve was used to analyze the value of serum ITG αMβ2,GSDMD expression levels in evaluating the death of patients with SAP complicated with ARDS.Results Compared with the non-ARDS group,the expression levels of serum ITG αMβ2(31.95±8.17 ng/L vs 53.33±12.22 ng/L)and GSDMD(2.25±0.55 ng/ml vs 4.39±1.18 ng/ml)in the ARDS group were increased,and the differences were statistically significant(t=17.637,19.899,all P<0.05).The expression levels of serum ITG αMβ2 and GSDMD in mild group,moderate group and severe group increased in turn,and the differences were statistically significant(F=163.069,194.028,all P<0.05).The expression levels of serum ITG αMβ2 and GSDMD were negatively correlated with OI in patients with SAP complicated with ARDS(r=-0.787,-0.778,all P<0.05).The 28-day mortality rate of 147 SAP patients with ARDS was 52.38%(77/147).Compared with the survival group,the expression levels of serum ITG αMβ2(46.96±10.28 ng/L vs 59.11±10.94 ng/L)and GSDMD(3.74±0.98 ng/ml vs 4.98±1.04 ng/ml)in the death group were increased,and the differences were statistically significant(t=6.920,7.415,all P<0.05).The number of extrapulmonary organ failure≥2,prolonged mechanical ventilation time,increased acute physiological and chronic health assessment II score,and increased ITG αMβ2.and GSDMD were independent risk factors for death in SAP patients complicated with ARDS(Wald χ2=4.297～13.536,all P<0.05),and increased OI was an independent protective factor(Wald χ2=8.346,P<0.05).The combined evaluation AUC of serum ITG αMβ2 and GSDMD expression levels results in a larger area under the curve(AUC)for mortality in SAP patients with ARDS compared to the individual evaluation of SAP complicated with ARDS,which was greater than serum ITG αMβ2 and GSDMD expression levels alone,and the differenes were statistically significant(Z=3.517,3.430,all P<0.05).Conclusion The increase of serum ITG αMβ2 and GSDMD expression levels is related to the progression and poor prognosis of patients with SAP complicated with ARDS.The combined monitoring of serum ITG αMβ2 and GSDMD expression levels has a high evaluation value for the risk of death in patients with SAP complicated with ARDS.

AIM:To appraise the bioequivalence and safety of the test preparation of ritonavir tab-lets and the reference preparation(trade name:Norvir?)in healthy adult subjects under fasting and postprandial conditions.METHODS:This study was a randomized,open-label,single-dose,four-period,fully repeated crossover design bioequivalence study protocol.Thirty-six healthy male and female volunteers were enrolled in the fasting and post-prandial conditions,and a single dose of the test preparation and reference preparation was orally administered.We used liquid chromatography-tan-dem mass spectrometry(LC-MS/MS)to finish the bioassay of the drug concentration of ritonavir in plasma.Pharmacokinetic parameters were statisti-cally analyzed using PhoenixWinNonlin8.1 software(Pharsight,USA)and a non-compartmental model.RESULTS:Under fasting conditions,the pharmacoki-netic parameters of the test and reference prepara-tions:Cmax(792.010±369.282)ng/mL and(856.939±394.427)ng/mL,AUC0-t(6 463.043±2 876.849)ng·mL-1·h and(6 907.690±3 046.132)ng·mL-1·h,AUC0-∞(6 603.617±2 916.352)ng·mL-1·h and(7 051.614±3 093.047)ng·mL-1·h.Here are the pharmacokinetic parameters for both the test prep-aration and the reference preparation in the post-prandial condition:Cmax(574.380±289.566)ng/mL and(615.796±297.382)ng/mL,AUC0-t(5 084.796±2 435.557)ng·mL-1·h and(5 414.167±2 416.952)ng·mL-1·h,AUC0-∞(5 219.144±2 487.793)ng·mL-1·h and(5 551.060±2 490.604)ng·mL-1·h.The 90%confidence interval of the geometric mean ratio of AUC0-t,AUC0-∞,and Cmax for the test preparation and reference preparation lied in the equivalent range of statistics.CONCLUSION:The tested preparation was bioequivalent to the reference preparation un-der fasting and postprandial conditions.

McCune-Albright syndrome(MAS) is a postzygotic somatic mutation disorder caused by activating mutations in the GNAS gene, which encodes the α subunit of the stimulatory G protein. Its clinical features typically include polyostotic fibrous dysplasia, cafe-au-lait skin pigmentation, and endocrine hyperactivity, such as Cushing′s syndrome, hyperthyroidism, and growth hormone excess. Here, we report two rare cases of MAS complicated with adrenocorticotropic hormone(ACTH)-independent Cushing syndrome, and provide a review and analysis of previously reported MAS cases associated with Cushing′s syndrome.