Objective To investigate the potential mechanism of nicotinamide combined with amphotericin B against Candida albicans based on metabolomics. Methods The intracellular metabolites of C. albicans intervened by different drugs including NAM, AmB, and their combination with a proper concentration were analyzed by gas chromatography-mass spectrometry. The differential metabolites were screened by multivariate statistical analysis and identified by searching the NIST database. Results Compared with the control group, the NAM intervention group was hardly separated from it, while the AmB group and NAM+AmB group showed a clear trend of separation. Under the intervention of AmB, 23 metabolites significantly changed compared with the control group, and 28 metabolites remarkably changed after NAM+AmB intervention, including amino acids, organic acids, sugars and other components. Conclusion NAM, as an endogenous metabolite of C. albicans, combined with AmB could enhance the effects of AmB in the original metabolic pathway and changed it to a certain extent. It was speculated that AmB combined with NAM may pose more antifungal effect on Candida albicans by regulating the tricarboxylic acid cycle，interfering with amino acid metabolism and influencing polyamine synthesis.

Based on his extensive clinical experience and the team's mechanistic research, Professor XU Nenggui has proposed the academic concept that "the governor vessel governs the brain and treats cerebral viscus diseases", and established a novel acupuncture approach for encephalopathy treatment centered on the integrated theory of "governor vessel-brain-mind", and developed a staged acupuncture protocol of "governor vessel regulating spirit" for ischemic stroke. This article introduces the academic features of this method in treating post-stroke dysphagia from four aspects: theoretical framework, treatment principles and point selection, mechanistic research, and clinical case studies. In clinical application, the method emphasizes syndrome differentiation based on meridians, harmonization between the conception and governor vessels; precise acupoint selection to treat both form and spirit; stage-specific differentiation with targeted needling. Furthermore, Professor XU integrates basic research with clinical practice, focusing on the neurobiological mechanisms underlying the efficacy of acupuncture in treating post-stroke dysphagia.
Acupuncture Therapy/methods* ; Humans ; Deglutition Disorders/psychology* ; Stroke/complications* ; Meridians ; Acupuncture Points

Objective:To investigate the clinical-epidemiological characteristics of connective tissue diseases (CTD) complicated with pulmonary hypertension in Shanxi province from 2018 to 2021.Methods:This was a cross-sectional study. Data of CTD patients with pulmonary hypertension from 2018 to 2021 were collected from the Shanxi Provincial Health Statistics Direct Reporting System based on inpatient medical records. The demographic and clinical data of patients with different CTD types were analyzed.Results:A total of 1 697 CTD patients with pulmonary hypertension were included, among whom there were 451 cases (26.58%) of Sj?gren′s syndrome, 392 cases (23.10%) of systemic lupus erythematosus, 289 cases(17.03%) of systemic sclerosis, 109 cases (6.42%) of mixed CTD, 69 cases (4.07%) of Takayasu arteritis, and 387 cases (22.80%) of other CTD. The majority of patients were female (1 410 (83.09%)), and 783 cases (46.14%) were aged between 41 and 65 years, and 6 cases (0.35%) were performed right heart catheterization. The prevalence of CTD with pulmonary hypertension increased from 0.06/10 4 in 2018 to 0.20/10 4 in 2021. There were significant differences in the severity of pulmonary hypertension, New York Heart Association (NYHA) functional class, length of hospital stay, medical costs, and clinical outcomes among patients with different CTD subtypes (all P<0.001). Patients with systemic sclerosis had the highest proportion of NYHA functional class Ⅲ/Ⅳ(65.1%(188/289)), the longest length of hospital stays (13 (9, 18) days), the highest average medical costs (13 622.67 (8 636.38, 20 597.75) ￥(RMB)), and the lowest rate of improvement and discharge (51.90%(150/289)). Conclusions:Between 2018 and 2021, Shanxi province, where CTD is more common in Sj?gren′s syndrome, has a high proportion of women, a high proportion of people aged 41-65 years, and a low prevalence of right ventricular catheterization in patients with CTD complicated with pulmonary hypertension. The prevalence of CTD complicated with pulmonary hypertension shows a rising trend in Shanxi province from 2018 to 2021, while patients with systemic sclerosis exhibit the most severe cardiac impairment and poorer clinical outcomes compared to other subtypes.

The preferred treatment for adrenal functional tumors is laparoscopic surgical resection. However, in recent years, various ablation techniques have gradually been applied in the treatment of adrenal tumors. This report presents the successful diagnosis and treatment experience of 4 aldosterone-producing adenomas and 1 cortisol-secreting adenoma treated with a combined cold and hot ablation system at Xi’an Daxing Hospital from Dec. 2023 to Dec. 2024, providing a new treatment approach for clinical exploration.

Post-stroke cognitive impairment(PSCI)is a prevalent and debilitating complication of stroke that significantly hinders recovery and diminishes patients'quality of life.Repetitive transcranial magnetic stimulation(rTMS),a non-invasive neuromodulation technique,has garnered growing interest for its potential to enhance cognitive function in individuals with PSCI.Concurrently,resting-state functional magnetic resonance imaging(rs-fMRI),as a non-invasive neuroimaging technique,has emerged as a valuable tool for assessing spontaneous neural activity and functional connectivity in the brain.By offering in-sights into the neurobiological mechanisms underlying PSCI and the modulatory effects of rTMS,rs-fMRI provides a foundation for advancing precision-targeted interventions.This review aims to highlight recent progress in applying rs-fMRI to evaluate the efficacy and underlying mechanisms of rTMS in the treatment of PSCI.

Cholera toxin B subunit(CTB)can enhance antigen presentation and promote T cell pro-liferation,B cell differentiation and B cell isotype conversion.Moreover,woodchuck hepatitis virus post transcriptional regulatory element(WPRE)can enhance gene expression efficiency by optimi-zing RNA polyadenylation,denuclearization and/or translation.In order to construct porcine epi-demic diarrhea virus like particles(VLPs)chimerized with CTB and WPRE and evaluate their im-munogenicity,the G Ⅱ type PEDV S gene,combined with the elements promoting the protein ex-pression and enhancing immune effects,was synthesized by the company and cloned into pET32a(+).Af-ter double enzyme digestion and gel recovery,the gene named as TSCW was cloned into pFastBacl to construct the recombinant plasmid pFastBac-TSCW.pFastBac-TSCW was further transformed into DH10Bac competent cells to obtain recombinant bacmid Bacmid-TSCW.Subsequently,the Bacmid-TSCW was transfected into sf9 cells to obtain recombinant baculovirus BV-TSCW.After co-infection of BV-TSCW and BV-M into sf9 cells,viral like particles VLP-TSCW was obtained and used to immunize mice to evaluate its immunogenicity.The results showed that the recombi-nant plasmid pFastBac-TSCW and bacmid Bacmid-TSCW were successfully constructed.After transfection of sf9 cells with recombinant baculovirus,significant cytopathic effects were observed.PCR and Western blot results showed that the recombinant baculoviruses existed stably in sf9 cells and the target proteins was also expressed stably.In addition,the electron microscopy results showed that BV-TSCW and BV-M successfully assembled into viral like particles VLP-TSCW.Furthermore,ELISA results indicated that VLP-TSCW induced high level specific antibodies.The above results laid the foundation for further optimization,design and development of PEDV VLPs subunit vaccines.

Objective To develop an ion-pairing reversed-phase high performance liquid chromatography(IP-RP-HPLC)method for the determination of L-methionine sulphoximine(MSX) residues in recombinant protein therapeutics, and to verify and preliminarily apply it, so as to provide a reference for the quality control of related products.Methods A chromatographic analysis method was screened and the mobile phase conditions such as ion-pairing reagent, pH and salt concentration were optimized to develop an IP-RP-HPLC method for the determination of MSX residues in recombinant protein therapeutics. The method was verified for specificity, system applicability, linearity, limit of detection(LOD) and limit of quantitation(LOQ), precision, accuracy and solution stability, by which the residual MSX contents in multiple batches of in-process sample and bulk of recombinant protein therapeutics were determined.Results The chromatographic conditions were determined as follows: using Hypersil GOLDTMC18 column(4. 6 mm × 250 mm, 5 μm) at column temperature of 25 ℃; 50 mmol/L sodium dihydrogen phosphate(containing 5 mmol/L sodium 1-octane sulfonate, pH 2. 0)-acetonitrile(volume fraction of 85 ∶ 15) as mobile phase for isocratic elution at a flow rate of 0. 6 mL/min; detection wavelength of 200 nm; injection volume of 50 μL. The method exhibited good specificity and system applicability. The control substance showed good linearity in the concentration range of 10-100 μg/mL, with a correlation coefficient(R) of 0. 999 95. The LOD and LOQ were 5 and 0. 5 μg/mL, respectively. MSX was not detected in either recombinant protein A or B, and the relative standard deviations(RSDs) of the measured concentrations of six parallel spiked samples were 1. 3% and 1. 1%, respectively, with the recovery rates ranged from 94% to 103%. For recombinant protein A spiked test sample placed at 10 ℃, the RSD of the measured concentrations at 0 h and 12 h were 2. 1%. MSX was not detected in the in-process samples and bulk of recombinant protein A test samples and three batches of recombinant protein B samples.Conclusion The developed IP-RP-HPLC method has the characteristics of simple operation and high sensitivity, and can be used for the quality control of MSX residues in recombinant protein therapeutics.

Post-stroke cognitive impairment(PSCI)is a prevalent and debilitating complication of stroke that significantly hinders recovery and diminishes patients'quality of life.Repetitive transcranial magnetic stimulation(rTMS),a non-invasive neuromodulation technique,has garnered growing interest for its potential to enhance cognitive function in individuals with PSCI.Concurrently,resting-state functional magnetic resonance imaging(rs-fMRI),as a non-invasive neuroimaging technique,has emerged as a valuable tool for assessing spontaneous neural activity and functional connectivity in the brain.By offering in-sights into the neurobiological mechanisms underlying PSCI and the modulatory effects of rTMS,rs-fMRI provides a foundation for advancing precision-targeted interventions.This review aims to highlight recent progress in applying rs-fMRI to evaluate the efficacy and underlying mechanisms of rTMS in the treatment of PSCI.

The preferred treatment for adrenal functional tumors is laparoscopic surgical resection. However, in recent years, various ablation techniques have gradually been applied in the treatment of adrenal tumors. This report presents the successful diagnosis and treatment experience of 4 aldosterone-producing adenomas and 1 cortisol-secreting adenoma treated with a combined cold and hot ablation system at Xi’an Daxing Hospital from Dec. 2023 to Dec. 2024, providing a new treatment approach for clinical exploration.

Cholera toxin B subunit(CTB)can enhance antigen presentation and promote T cell pro-liferation,B cell differentiation and B cell isotype conversion.Moreover,woodchuck hepatitis virus post transcriptional regulatory element(WPRE)can enhance gene expression efficiency by optimi-zing RNA polyadenylation,denuclearization and/or translation.In order to construct porcine epi-demic diarrhea virus like particles(VLPs)chimerized with CTB and WPRE and evaluate their im-munogenicity,the G Ⅱ type PEDV S gene,combined with the elements promoting the protein ex-pression and enhancing immune effects,was synthesized by the company and cloned into pET32a(+).Af-ter double enzyme digestion and gel recovery,the gene named as TSCW was cloned into pFastBacl to construct the recombinant plasmid pFastBac-TSCW.pFastBac-TSCW was further transformed into DH10Bac competent cells to obtain recombinant bacmid Bacmid-TSCW.Subsequently,the Bacmid-TSCW was transfected into sf9 cells to obtain recombinant baculovirus BV-TSCW.After co-infection of BV-TSCW and BV-M into sf9 cells,viral like particles VLP-TSCW was obtained and used to immunize mice to evaluate its immunogenicity.The results showed that the recombi-nant plasmid pFastBac-TSCW and bacmid Bacmid-TSCW were successfully constructed.After transfection of sf9 cells with recombinant baculovirus,significant cytopathic effects were observed.PCR and Western blot results showed that the recombinant baculoviruses existed stably in sf9 cells and the target proteins was also expressed stably.In addition,the electron microscopy results showed that BV-TSCW and BV-M successfully assembled into viral like particles VLP-TSCW.Furthermore,ELISA results indicated that VLP-TSCW induced high level specific antibodies.The above results laid the foundation for further optimization,design and development of PEDV VLPs subunit vaccines.