This article presents a case study of a patient who visited the Geriatric Department of Peking Union Medical College Hospital due to "palpitations, shortness of breath for more than 2 years, limb weakness for 6 months, edema, and nocturnal dyspnea for 2 months". The patient exhibited decreased muscle strength in the limbs and involvement of swallowing and respiratory muscles, alongside complications of heart failure and various arrhythmias which were predominantly atrial. Laboratory tests revealed the presence of multiple autoantibodies and notably anti-mitochondrial antibodies. Following a comprehensive multidisciplinary evaluation, the patient was diagnosed with anti-mitochondrial antibody-associated inflammatory myopathy. Treatment involved a combination of glucocorticoids and immunosuppressants, along with resistance exercises for muscle strength and rehabilitation training for lung function, resulting in significant improvement of clinical symptoms. The case underscores the importance of collaborative multidisciplinary approaches in diagnosing and treating rare diseases in elderly patients, where careful consideration of clinical manifestations and subtle abnormal clinical data can lead to effective interventions.

Objective To design and synthesize novel Hsp90 inhibitors with dual functions of synergistically enhancing the antifungal activity of fluconazole （FLC） against drug-resistant fungi and anti-tumor activity based on the Hsp90 inhibitor Ganetespib. Methods The previous research found that Ganetespib had a good synergistic anti-resistant fungal activity with FLC, with a fractional inhibitory concentration index （FICI） of 0.023 to 0.039. In this study, structural modifications were made to Ganetespib by replacing its indole ring with a phenyl ring containing different substituents to design and synthesize a series of new compounds. The in vitro synergistic anti-resistant fungal activity against C. albicans 0304103 in combination with FLC, anti-tumor activity （against HEL, HL60 and A549 cells）, and Hsp90α inhibition activity were determined to explore their structure-activity relationship and mechanism of action. Results The chemical structures of 19 new compounds were confirmed by ¹H NMR, ¹³C NMR and HRMS. Most of the compounds exhibited strong Hsp90α inhibitory activity, good synergistic activity against drug-resistant fungi in combination with FLC and anti-tumor activity. The substitution of electron-donating groups on the benzene ring was beneficial to enhancing the synergistic activity against drug-resistant fungi in combination with FLC. Among them, compounds F3 and F5 showed excellent synergistic activity against drug-resistant fungi in combination with FLC （FICI were both 0.047） and anti-tumor activity （IC₅₀ were 0.025 to 0.15 μmol/L and 0.021 to 0.23 μmol/L respectively）, and could down-regulate the expression levels of drug resistance genes and efflux pump genes in fungi, inhibit the formation of fungal biofilms, and arrest the cell cycle of HEL cells at G0/G1 phase. Conclusion The novel Hsp90 inhibitors such as F3 and F5 could both effectively exert the dual activities of synergizing with FLC to combat drug-resistant fungi and fight against tumors, which provided a new idea for the development of new drugs with dual functions of synergizing with FLC to combat drug-resistant fungi and fight against tumors.

The culture of suspended Vero cells is facing difficulties such as low cell viability and long doubling time. To investigate the main reasons for the slow growth and low viability of suspended Vero cells, this study conducted transcriptomic analysis of suspended Vero cells (Vero-XF) and adherent Vero cells (Vero-AD) to screen the differentially expressed genes (DEGs) affecting the growth of suspended cells. In addition, epidermal growth factor (EGF) was supplemented to the culture system to improve the growth of Vero-XF. The results showed that compared with the Vero-AD group, the Vero-XF group had 7 376 significant DEGs. Kyoto encyclopedia of genes and genomes enrichment analysis revealed that the DEGs were mainly enriched in the autophagy and mitophagy pathways. Eleven DEGs were selected and verified by quantitative real-time PCR, which showed up-regulated expression of ATG9B, WIPI2, LAMP2, OPTN, Rab7a, and DEPTOR and down-regulated expression of ATG4D, being consistent with the results of transcriptomic analysis. In addition, the Vero-XF group showed significantly up-regulated expression of ATG101, ATG2A, and STX17 and insignificant change in the expression of NBR1, compared with the Vero-AD group. The protein levels of LC3 and P62 in Vero-XF and Vero-AD were determined by Western blotting, which showed up-regulated expression of LC3Ⅱ/Ⅰ and down-regulated expression of P62 in Vero-XF, indicating a higher level of autophagy. Finally, the exogenous supplementation of EGF at 10, 20, and 30 μg/L in the culture system reduced the autophagy level of Vero-XF by 22.35%, 48.15%, and 71.29%, increased the specific growth rate by 15.48%, 33.33%, and 57.14%, and decreased the apoptosis rate by 2.84%, 15.46%, and 16.23%, respectively. The results of this study preliminarily reveal that the activation of autophagy is one of the reasons for the slow growth of Vero-XF, which provides reference for the subsequent culture of suspended Vero cells.
Animals ; Vero Cells ; Autophagy/genetics* ; Chlorocebus aethiops ; Epidermal Growth Factor/pharmacology* ; Gene Expression Profiling ; Transcriptome ; Cell Survival

Objective: To estimate the incidence and mortality of lung cancer in 2021 and their trends from 2014 to 2021 within cancer registration areas of Inner Mongolia Autonomous Region, so as to provide the basis for formulating localized strategies for lung cancer prevention and control. Methods: The data on lung cancer cases in cancer registration areas of Inner Mongolia Autonomous Region in 2021 were collected from the China Cancer Registration, encompassing data from 55 registries within the region. Crude incidence and crude mortality were calculated by genders, urban/rural rareas, and ages. The Chinese population-standardized rate was calculated using the age structure of the standard population from the Fifth National Population Census in 2000, while the world population-standardized rate was calculated using Segi's world standard population. To assess the trends in Chinese population-standardized incidence and mortality of lung cancer from 2014 to 2021, data from nine qualifying cancer registries were analyzed using the average annual percent change (AAPC). Results: In 2021, within Inner Mongolia Autonomous Region, the crude, Chinese population-standardized, and world population-standardized incidences of lung cancer were 58.96/100 000, 31.58/100 000, and 31.50/100 000, respectively. The crude, Chinese population-standardized, and world population-standardized mortalities were 46.48/100 000, 24.65/100 000, and 24.36/100 000 , respectively. The Chinese population-standardized incidence and mortality of lung cancer were 1.59-fold and 1.88-fold higher in males compared to females, and 1.08-fold and 1.10-fold higher in urban areas relative to rural areas. The crude incidence and mortality of lung cancer reached their peaks at age of 80-<85 years (379.91/100 000 and 474.31/100 000, respectively). From 2014 to 2021, the Chinese population-standardized incidence of lung cancer in Inner Mongolia Autonomous Region decreased from 43.28/100 000 to 31.41/100 000, showed a downward trend (AAPC=-3.312%, P<0.05), while the Chinese population-standardized mortality decreased from 31.55/100 000 to 24.11/100 000, showed no statistical significance (P>0.05). The Chinese population-standardized incidence of lung cancer in the group aged ≥75 years and the Chinese age-standardized mortality of lung cancer in the group aged 0-<45 years showed declining trends (AAPC=-4.307%, -7.355%, both P<0.05). Conclusions The disease burden of lung cancer in cancer registration areas of Inner Mongolia Autonomous Region has decreased, showing characteristics where the burden is higher in males than in females and slightly higher in urban areas than in rural areas. The elderly population represents a key group for lung cancer prevention and control.

This study identified blood-entering components of Anshen Dropping Pills and explored their anti-insomnia effects and mechanisms. The main blood-entering components of Anshen Dropping Pills were detected and identified by UPLC-Q-TOF-MS/MS. The rationality of the formula was assessed by using enrichment analysis based on the relationship between drugs and symptoms, and core targets of its active components were selected as the the potential anti-insomnia targets of Anshen Dropping Pills through network pharmacology analysis. Furthermore, protein-protein interaction(PPI) network, Gene Ontology(GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed on the core targets. An active component-core target network for Anshen Dropping Pills was constructed. Finally, the effects of low-, medium-, and high-dose groups of Anshen Dropping Pills on sleep episodes, sleep duration, and sleep latency in mice were measured by supraliminal and subliminal pentobarbital sodium experiments. Moreover, total scores of the Pittsburgh sleep quality index(PSQI) scale was used to evaluate the changes before and after the treatment with Anshen Dropping Pills in a clinical study. The enrichment analysis based on the relationship between drugs and symptoms verified the rationality of the Anshen Dropping Pills formula, and nine blood-entering components of Anshen Dropping Pills were identified by UPLC-Q-TOF-MS/MS. The network proximity revealed a significant correlation between eight components and insomnia, including magnoflorine, liquiritin, spinosin, quercitrin, jujuboside A, ginsenoside Rb_3, glycyrrhizic acid, and glycyrrhetinic acid. Network pharmacology analysis indicated that the major anti-insomnia pathways of Anshen Dropping Pills involved substance and energy metabolism, neuroprotection, immune system regulation, and endocrine regulation. Seven core genes related to insomnia were identified: APOE, ALB, BDNF, PPARG, INS, TP53, and TNF. In summary, Anshen Dropping Pills could increase sleep episodes, prolong sleep duration, and reduce sleep latency in mice. Clinical study results demonstrated that Anshen Dropping Pills could decrease total scores of PSQI scale. This study reveals the pharmacodynamic basis and potential multi-component, multi-target, and multi-pathway effects of Anshen Dropping Pills, suggesting that its anti-insomnia mechanisms may be associated with the regulation of insomnia-related signaling pathways. These findings offer a theoretical foundation for the clinical application of Anshen Dropping Pills.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Tandem Mass Spectrometry/methods* ; Sleep Initiation and Maintenance Disorders/metabolism* ; Mice ; Network Pharmacology ; Male ; Chromatography, High Pressure Liquid ; Humans ; Protein Interaction Maps/drug effects* ; Sleep/drug effects* ; Female ; Adult

Objective:To compare the efficacy and safety of irradiation-incorporated and chemotherapy only-based myeloablative conditioning regimens in haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for patients with high-risk myeloid malignancies.Methods:This study retrospectively collected clinical data from 63 high-risk acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) patients who underwent haplo-HSCT at the Fifth Medical Center of the Chinese PLA General Hospital from January 2015 to December 2019. These patients were classified into the irradiation ( n = 17) and chemotherapy ( n = 46) groups based on different conditioning regimens. The differences between the two groups were compared in terms of hematopoietic reconstitution, cumulative incidence of acute/chronic graft-versus-host diseases (aGVHD and cGVHD), non-relapse mortality (NRM), relapse rate (RR), overall survival (OS), and disease-free survival (DFS), followed by the analysis of prognostic factors. Results:The median follow-up time for the irradiation and chemotherapy groups was 78.5 and 72.3 months, respectively. The median time for neutrophil engraftment was 14.0 days in the irradiation group and 14.5 d in the chemotherapy group, and for platelet engraftment was 15.0 and 13.0 d, respectively. As a result, the two groups showed no statistically significant differences in hematopoietic reconstitution ( P > 0.05). The cumulative incidence of aGVHD and cGVHD was higher in the irradiation group compared to the chemotherapy group, yet showing no statistically significant differences ( P > 0.05). Specifically, the cumulative incidence of grade Ⅱ-Ⅳ aGVHD within 100 d was 29.4% and 21.7% for the irradiation and chemotherapy groups, respectively. The cumulative incidence of grade Ⅲ-Ⅳ aGVHD was 23.5% and 13.0%, respectively. The cumulative incidence of severe cGVHD within five years was 11.8% in the irradiation group and 8.7% in the chemotherapy group. In terms of long-term survival, the cumulative 5\|year RR and NRM were 20.2% and 28.4% in the irradiation group, 5.9% and 23.9% in the chemotherapy group, respectively, showing no statistically significant differences ( P > 0.05). The 5-year DFS and OS rates were 73.9% and 47.7% in the irradiation group, and 81.1% and 54.4% in the chemotherapy group, respectively, without statistically significant differences ( P > 0.05). Notably, the irradiation group manifested more favorable DFS and OS survival curves compared to the chemotherapy group. The survival curves indicate that the irradiation-incorporated regimen exhibited better trends in OS, DFS, and cGVHD-free relapse-free survival (GRFS). However, multivariate analysis did not reveal that irradiation conditioning is an independent prognostic factor affecting survival [ HR = 0.532 (0.163-1.735), 0.370 (0.091-1.516), 0.683 (0.248-1.882), P > 0.05]. Conclusions:In haplo-HSCT for high-risk myeloid malignancies, the irradiation-incorporated conditioning regimen demonstrates lower RR and NRM, higher DFS and OS, and potentially superior survival outcomes compared to the chemotherapy only-based regimen. Therefore, the irradiation-incorporated conditioning regimen may be preferentially considered in haplo-HSCT.

Type 2 diabetes mellitus is a metabol-ic disease characterized by high blood sugar levels.Traditionally,amino acids are primarily viewed as the basic building blocks for proteins and peptide synthesis.However,in recent years,amino acids have gained increased attention as signaling mole-cules that play crucial roles in the maintenance and regulation of metabolic homeostasis.It has been found that there is a close correlation between the metabolism of branched-chain and/or aromatic amino acids and the occurrence or development of type 2 diabetes mellitus.Furthermore,there have been successive reports on the regulation mecha-nism involved.This article will focus on the meta-bolic processes,mechanisms and clinical value of branched-chain and aromatic amino acids in type 2 diabetes mellitus.It will also summarize and pro-vide an outlook on the current state of amino acid metabolism in the treatment of diabetes mellitus,with the aim of offering new ideas for the treat-ment of type 2 diabetes mellitus.

Aim To investigate the effect of oroxylin A(OA)on apoptosis in Ishikawa cell line of endometrial cancer and the underlying mechanism through the phosphatidylinositol-3 kinase/protein kinase B(PI3K/AKT)signaling pathway.Methods Ishikawa cells were treated with different concentrations of OA(0,4,8,10,12,and 20 μmol·L-1)for 24 h-72 h,the cell viability was detected by CCK-8 assay,apoptosis was detected by flow cytometry,and the protein ex-pression levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),PI3K/AKT,recombinant cytochrome P450 1B1(CYP1B1),and catechol-O-methyltransferase(COMT)were detected by Western blot technique.Results OA inhibited the prolifera-tion of Ishikawa cells in a concentration-and time-de-pendent manner.Compared with the blank control group,the expression of Bax protein increased signifi-cantly,while the expression of Bcl-2 protein decreased significantly with the increase of OA concentration.The expression of COMT protein increased significant-ly,while the expression of CYP1B1 protein decreased significantly.PI3K/AKT:IGF-1(PI3 K agonist)sup-plementation reversed the effect,the expression of COMT protein significantly decreased,and the expres-sion of CYP1B1 protein significantly increased.Con-clusions OA exerts anti-tumor effects in Ishikawa cells of endometrial cancer,which may be related to cell apoptosis mediated by the inhibition of the PI3K/AKT signaling pathway.

Type 2 diabetes mellitus is a metabol-ic disease characterized by high blood sugar levels.Traditionally,amino acids are primarily viewed as the basic building blocks for proteins and peptide synthesis.However,in recent years,amino acids have gained increased attention as signaling mole-cules that play crucial roles in the maintenance and regulation of metabolic homeostasis.It has been found that there is a close correlation between the metabolism of branched-chain and/or aromatic amino acids and the occurrence or development of type 2 diabetes mellitus.Furthermore,there have been successive reports on the regulation mecha-nism involved.This article will focus on the meta-bolic processes,mechanisms and clinical value of branched-chain and aromatic amino acids in type 2 diabetes mellitus.It will also summarize and pro-vide an outlook on the current state of amino acid metabolism in the treatment of diabetes mellitus,with the aim of offering new ideas for the treat-ment of type 2 diabetes mellitus.

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.