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 retrospectively analyze the detection results of alanine aminotransferase (ALT) unqualified repeat blood donors in Guangzhou, so as to provide evidence for further expanding the repeat blood donor pool, reducing the rate of blood discarding and improving the qualified rate of blood test. [Methods] Blood donors with unqualified ALT in Guangzhou Blood Center from January 2018 to April 2024 were selected as the research objects. The past blood donation and population characteristics were analyzed according to the number of blood donations and ALT unqualified times. [Results] Among repeat blood donors with previous ALT disqualification, 99.5% to 99.7% did not have reactive markers for transfusion-transmitted diseases (TTD), which was higher than the rate among first-time blood donors with unqualified ALT (95.8%) (P<0.05). The rate of single-item ALT disqualification in repeat blood donors was higher in males than in females (P<0.05); it also varied by age (18-25 years > 26-35 years > 36-45 years > over 45 years) (P<0.05); and by quarter (third and fourth quarters > first and second quarters) (P<0.05). The ALT unqualified rate was significantly higher whole blood donors than that of platelet donors and returning blood donors (P<0.05). The overall ALT level (51.0 U/L), individual ALT level (56.0 U/L) and individual ALT unqualified rate (66.7%) of repeat blood donors with multiple ALT disqualifications were higher than those of repeat blood donors with single-item ALT disqualifications (26.0 U/L, 38.5 U/L, and 33.3%, respectively) (P<0.05). Moreover, as the number of ALT disqualifications increased, the overall level of ALT in repeat blood donors also increased (P<0.05), and the average level of individual ALT and individual ALT unqualified ratio tended to increase. Repeat blood donors with frequent ALT disqualifications had higher ALT levels (69.0 U/L). [Conclusion] The ALT unqualified rates of repeat blood donors were mostly non-specific elevation without TTD. Repeat blood donors with multiple ALT disqualifications tend to have continuous high ALT. Moreover, and with the increase of ALT disqualifications times, the overall ALT levels the average individual ALT levels and individual ALT unqualified rates showed an increasing trend.

[摘 要] 目的：探究包被蛋白复合体β1亚基（COPB1）在食管鳞状细胞癌（ESCC）中的表达，及其对ESCC细胞恶性生物学行为的影响、作用机制及临床意义。方法：采用2014～2018年间在河北医科大学第四医院生物样本库中82例ESCC组织及癌旁组织，常规培养正常食管鳞状上皮细胞HEEC和食管癌细胞KYSE-150、KYSE-170、Eca109、TE1、KYSE-30、KYSE-450，用转染试剂将pcDNA3.1-vector（空载体）、pcDNA3.1-COPB1载体，si-NC和si-COPB1转染至KYSE-150、TE1细胞中，记为NC、COPB1-OE、si-NC和si-COPB1组。用数据库数据分析COPB1 mRNA在泛癌组织中的表达及其表达与免疫细胞浸润的关系，qPCR法检测ESCC组织和细胞中COPB1、PIK3CB、CD68、CD163、CD206、ARG1、IL-10 mRNA水平表达情况，WB法检测ESCC组织和各组细胞中的COPB1、PI3K、CD68、CD163、CD206、p-AKT蛋白表达，克隆形成实验和MTS实验检测各组细胞的增殖能力，划痕愈合实验和Transwell实验检测各组细胞的迁移和侵袭能力，免疫组织化学染色（IHC）法检测ESCC组织中COPB1和CD206蛋白表达。以人单核细胞白血病细胞（THP-1）构建巨噬细胞模型，用佛波酯（PMA）和IL-3和IL-4和ESCC细胞上清液诱导巨噬细胞转型，用qPCR和WB法检测CD68和CD206m RNA和蛋白的表达。结果：COPB1在泛癌组织和ESCC组织中均呈高表达且与淋巴结转移和TNM分期有关联（均P < 0.01），COPB1高表达的ESCC患者总生存期短（P < 0.05），COPB1是潜在的ESCC的诊断标志物。COPB1在KYSE-150和TE1细胞中也呈高表达（均P < 0.05），过表达或敲减COPB1可明显抑制或促进KYSE-150和TE1细胞的增殖能力、迁移和侵袭能力（均P < 0.05）。COPB1表达变化诱导的差异表达基因主要富集于PI3K/AKT通路（均P < 0.001）, COPB1可促进PI3K/AKT通路的活化（P < 0.05），COPB1高表达可导致M2型巨噬细胞浸润增加（P < 0.05），COPB1高表达促进TAM/M2极化（P < 0.05）。结论：COPB1在ESCC组织中呈高表达，其可激活PI3K/AKT通路及调控肿瘤免疫微环境促进 ESCC发生发展，COPB1有望成为ESCC诊断和预后的生物标志物及治疗靶点。

Objective To establish the method of infrared fingerprint,TLC identification and content determination of phenolic acid components of Yao medicine Calonyction muricatum(Linn)G.Methods The infrared fingerprint of 10 batches of Calonyction muricatum(Linn)G were established by infrared spectroscopy.The spectral datas were analyzed by similarity analysis,infrared spectroscopy(HCA),principal component analysis(PCA)and Partial-least-squares discriminant analysis(PLS-DA).Chlorogenic acid,heterochlorogenic acid A and caffeic acid of Calonyction muricatum(Linn)G were identified by TLC.The contents of neochlorogenic acid,chlorogenic acid,caffeic acid,cryptochlorogenic acid,isochlorogenic acid A and C were determined simultaneously by HPLC method.Results It could be suggested that organic acids,flavonoids and other compounds of Calonyction muricatum(Linn)G by infrared spectroscopy and nine common peaks were calibrated by infrared fingerprint;the similarity evaluation was above 0.999;the results of cluster analysis(CA)and principal component analysis(PCA)showed that it could be clustered into 2 categories,including S1,S2 and S3 were clustered into one categoriy and the rest were one.5 differential components(VIP>1)were selected by Partial-least-squares discriminant analysis;the test and control samples of TLC showed consistent locations the spots were clear,with good separation degree;the six components of Calonyction muricatum(Linn)G showed good linear relationship(r≥0.999 2),average sample recovery rate 97.77%-102.59%,and RSD less than 2.90% .Conclusion The TLC and infrared fingerprint were simple and stable,and the results of the six components were reliable,which can lay a scientific foundation for the quality control of the materials.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

OBJECTIVE To analyze the metabolites of Zhideke granules and speculate its metabolic pathway in rats in vivo. METHODS Male SD rats were randomly divided into blank group and administration group （Zhideke granules， 9.45 g/kg）； they were given ultrapure water or relevant medicine， twice a day， every 6-8 h， for 3 consecutive days. Serum， urine and feces samples of rats were collected， and their metabolites were identified by UPLC-Q-Exactive-MS technique after intragastric administration of Zhideke granules； their metabolic pathways were speculated. RESULTS After intragastric administration of Zhideke granules， 16 prototype components （i.g. irisflorentin， baicalin， chlorogenic acid） and 11 metabolites （i.g. hydration products of kaempferol or luteolin， methylation products of chlorogenic acid， and hydroxylation products of baicalin） were identified in serum， urine and feces of rats. Among them， 8 prototype components and 4 metabolites were identified in serum samples； 10 prototype components and 7 metabolites were identified in urine samples； 8 prototype components and 5 metabolites were identified in the fecal samples. CONCLUSIONS The metabolites of Zhideke granules in rats mainly include baicalin， irisflorentin，chlorogenic acid， and the main metabolic pathways included methylation， hydroxylation， glucuronidation.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

OBJECTIVE: Anemoside B4 (AB4), the most abundant triterpenoidal saponin isolated from Pulsatilla chinensis, inhibited influenza virus FM1 or Klebsiella pneumoniae-induced pneumonia. However, the anti-SARS-CoV-2 effect of AB4 has not been unraveled. Therefore, this study aimed to determine the antiviral activity and potential mechanism of AB4 in inhibiting human coronavirus SARS-CoV-2 in vivo and in vitro. METHODS: The cytotoxicity of AB4 was evaluated using the Cell Counting Kit-8 (CCK8) assay. SARS-CoV-2 infected HEK293T, HPAEpiC, and Vero E6 cells were used for in vitro assays. The antiviral effect of AB4 in vivo was evaluated by SARS-CoV-2-infected hACE2-IRES-luc transgenic mouse model. Furthermore, label-free quantitative proteomics and bioinformatic analysis were performed to explore the potential antiviral mechanism of action of AB4. Type I IFN signaling-associated proteins were assessed using Western blotting or immumohistochemical staining. RESULTS: The data showed that AB4 reduced the propagation of SARS-CoV-2 along with the decreased Nucleocapsid protein (N), Spike protein (S), and 3C-like protease (3CLpro) in HEK293T cells. In vivo antiviral activity data revealed that AB4 inhibited viral replication and relieved pneumonia in a SARS-CoV-2 infected mouse model. We further disclosed that the antiviral activity of AB4 was associated with the enhanced interferon (IFN)-β response via the activation of retinoic acid-inducible gene I (RIG-1) like receptor (RLP) pathways. Additionally, label-free quantitative proteomic analyses discovered that 17 proteins were significantly altered by AB4 in the SARS-CoV-2 coronavirus infections cells. These proteins mainly clustered in RNA metabolism. CONCLUSION Our results indicated that AB4 inhibited SARS-CoV-2 replication through the RLR pathways and moderated the RNA metabolism, suggesting that it would be a potential lead compound for the development of anti-SARS-CoV-2 drugs.

Epithelial splicing regulatory protein 1(ESRP1)is an epithelial cell-specific splicing factor that in-volved in selective splicing and translation of multiple genes.ESRP1 regulates signaling pathways that affect cell proliferation and tumor growth via mediating target genes and regulating cyclic RNA cyclization and biogenesis in a variety of cancers,including head and neck squamous cell carcinoma,carcinoma of colon,and prostate cancer.Through integrating and analyzing the link between ESRP1 and related cancers,provide new ideas for the treatment of tumor cells in which ESRP1 as a key factor.