As one of the most common malignant tumors， digestive system tumors exhibit an increase in the incidence and mortality year by year. Its pathogenesis is complex， making it difficult to carry out early prevention. Autophagy is a process in which cells use lysosomes to degrade their organelles and macromolecules to maintain cellular homeostasis under the regulation of autophagy-related genes. Cellular autophagy has a dual regulatory effect on the tumor microenvironment， which always affects the occurrence and development of digestive system tumors. Therefore， the effect and mechanism of action of cellular autophagy on digestive system tumors have become a hot topic in tumor therapy in recent years. Meanwhile， the remarkable research results of targeted autophagy drugs indicate that cellular autophagy may become an important target for anti-digestive system tumors. Traditional Chinese medicine （TCM） has been widely used in the comprehensive treatment of digestive system tumors with good efficacy. A variety of active ingredients in TCM， such as flavonoids， glycosides， terpenoids， quinones， and alkaloids， can increase the expression of autophagy-associated proteins microtubule-associated protein 1 light chain 3 （LC3）Ⅱ/Ⅰ， autophagy-related gene （ATG）5， ATG7， inhibit the expression of autophagy-related protein p62 ， and induce autophagy in digestive system tumor cells， thereby exerting the anti-digestive system tumor effect. By summarizing the research results in recent years on the modulation of cell autophagy by active ingredients in TCM to fight against digestive system tumors， this paper analyzed the relevant signaling pathways， regulatory factors， and functional characteristics of cell autophagy modulation， so as to elucidate the mechanism by which active ingredients of TCM induce autophagy and to provide ideas and references for clinical application.

As one of the most common malignant tumors， digestive system tumors exhibit an increase in the incidence and mortality year by year. Its pathogenesis is complex， making it difficult to carry out early prevention. Autophagy is a process in which cells use lysosomes to degrade their organelles and macromolecules to maintain cellular homeostasis under the regulation of autophagy-related genes. Cellular autophagy has a dual regulatory effect on the tumor microenvironment， which always affects the occurrence and development of digestive system tumors. Therefore， the effect and mechanism of action of cellular autophagy on digestive system tumors have become a hot topic in tumor therapy in recent years. Meanwhile， the remarkable research results of targeted autophagy drugs indicate that cellular autophagy may become an important target for anti-digestive system tumors. Traditional Chinese medicine （TCM） has been widely used in the comprehensive treatment of digestive system tumors with good efficacy. A variety of active ingredients in TCM， such as flavonoids， glycosides， terpenoids， quinones， and alkaloids， can increase the expression of autophagy-associated proteins microtubule-associated protein 1 light chain 3 （LC3）Ⅱ/Ⅰ， autophagy-related gene （ATG）5， ATG7， inhibit the expression of autophagy-related protein p62 ， and induce autophagy in digestive system tumor cells， thereby exerting the anti-digestive system tumor effect. By summarizing the research results in recent years on the modulation of cell autophagy by active ingredients in TCM to fight against digestive system tumors， this paper analyzed the relevant signaling pathways， regulatory factors， and functional characteristics of cell autophagy modulation， so as to elucidate the mechanism by which active ingredients of TCM induce autophagy and to provide ideas and references for clinical application.

[Objective] To perform genetic analysis on samples with weak agglutination and mixed agglutination of ABO blood group antigens in neonates, and to investigate the molecular biological characteristics of ABO subtypes in neonates. [Methods] Serological identification of ABO blood group was performed by tube method and microcolumn gel method. The ABO exons 2-7 were amplified by PCR, and the amplified products were sequenced by Sanger sequencing method to determine the genotype. [Results] Among the ABO blood group serological results of 14 neonates, 8 cases showed weakened A antigen, and 6 cases showed weakened B antigen. Seven samples were identified with ABO subtype alleles, with genotypes as A102/B101+c.538C>T, Aw26/B102, A205/O02, A205/B101(2 cases), Aw26/O02, B(A)06/O01, B101/O01(3 cases), A102/O01(2 cases), A102/B101 and B101/O02. Additionally, three other family members were also found to carry B(A)06 allele in a pedigree investigation. [Conclusion] For samples showing weakened antigens in ABO blood type identification of neonates, it is necessary to consider the possibility of ABO subtype in addition to age factors, and genetic testing can be used to prevent missed detection of ABO subtypes in neonates.

As a common malignant tumor of the respiratory system， the incidence and mortality of lung cancer are still rising year by year. Its pathogenesis is complex， the prognosis is poor， and it seriously affects human physical and mental health. Although existing Western medical treatments can inhibit tumor growth to a certain extent and relieve patients' painful symptoms， problems such as postoperative recurrence and metastasis， numerous adverse reactions， and the tendency to develop drug resistance make the overall therapeutic effect unsatisfactory. Therefore， it is urgent to seek more efficient and safer treatments. Adenosine monophosphate-activated protein kinase （AMPK） signaling pathway can regulate the growth， differentiation， apoptosis， and autophagy of lung cancer cells， and is extensively involved in the occurrence and development of lung cancer， thus being regarded as an important target for anti-lung cancer therapy. Traditional Chinese medicine （TCM） exerts anti-lung cancer effects through multiple pathways， mechanisms， and targets， with advantages such as preventing postoperative recurrence and metastasis， alleviating the adverse reactions of radiotherapy and chemotherapy， and improving quality of life. TCM has therefore become a key approach in current anti-lung cancer treatment. Studies have found that active components of Chinese medicine， including flavonoids， saponins， polyphenols， and terpenes， as well as Chinese medicine compound prescriptions such as Guiqi Yiyuan extract， Qingzao Jiufei decoction， and Yiqi Fuzheng formula， have significant regulatory effects on AMPK and its interacting signaling pathways. These effects include inducing autophagy and apoptosis of lung cancer cells， modulating macrophage polarization， inhibiting epithelial-mesenchymal transition， reversing drug resistance， and blocking the cell cycle， thereby exerting anti-lung cancer activity. This article reviews and summarizes recent studies on the anti-lung cancer effects of TCM， and discusses the mechanisms by which TCM regulates the AMPK signaling pathway in the treatment of lung cancer， with the aim of providing ideas and references for the development of new clinical anti-lung cancer drugs.

As a common malignant tumor of the respiratory system， the incidence and mortality of lung cancer are still rising year by year. Its pathogenesis is complex， the prognosis is poor， and it seriously affects human physical and mental health. Although existing Western medical treatments can inhibit tumor growth to a certain extent and relieve patients' painful symptoms， problems such as postoperative recurrence and metastasis， numerous adverse reactions， and the tendency to develop drug resistance make the overall therapeutic effect unsatisfactory. Therefore， it is urgent to seek more efficient and safer treatments. Adenosine monophosphate-activated protein kinase （AMPK） signaling pathway can regulate the growth， differentiation， apoptosis， and autophagy of lung cancer cells， and is extensively involved in the occurrence and development of lung cancer， thus being regarded as an important target for anti-lung cancer therapy. Traditional Chinese medicine （TCM） exerts anti-lung cancer effects through multiple pathways， mechanisms， and targets， with advantages such as preventing postoperative recurrence and metastasis， alleviating the adverse reactions of radiotherapy and chemotherapy， and improving quality of life. TCM has therefore become a key approach in current anti-lung cancer treatment. Studies have found that active components of Chinese medicine， including flavonoids， saponins， polyphenols， and terpenes， as well as Chinese medicine compound prescriptions such as Guiqi Yiyuan extract， Qingzao Jiufei decoction， and Yiqi Fuzheng formula， have significant regulatory effects on AMPK and its interacting signaling pathways. These effects include inducing autophagy and apoptosis of lung cancer cells， modulating macrophage polarization， inhibiting epithelial-mesenchymal transition， reversing drug resistance， and blocking the cell cycle， thereby exerting anti-lung cancer activity. This article reviews and summarizes recent studies on the anti-lung cancer effects of TCM， and discusses the mechanisms by which TCM regulates the AMPK signaling pathway in the treatment of lung cancer， with the aim of providing ideas and references for the development of new clinical anti-lung cancer drugs.

Gastrointestinal tumors （GTs）， including colorectal cancer， gastric cancer， liver cancer， pancreatic cancer， and esophageal cancer， are increasing in incidence worldwide and have become one of the major diseases threatening human health. Tumor stem cells （TSCs）， an undifferentiated subpopulation within tumor tissues， possess biological characteristics such as self-renewal， multidirectional differentiation， high tumorigenicity， and resistance to radiochemotherapy. They play an important role in the occurrence， progression， recurrence， and metastasis of GTs and have increasingly become a research hotspot in GT treatment. Although modern medicine has made remarkable progress， there remain many problems in therapeutic approaches targeting TSCs. In this context， traditional Chinese medicine （TCM）， with its favorable safety profile and multi-target mechanisms， has shown potential advantages and value in regulating TSCs. It can reduce TSC drug resistance， enhance the sensitivity of tumor cells to chemotherapeutic agents， inhibit tumor growth and metastasis， and has shown unique advantages in improving the quality of life and prolonging the survival of GT patients. Studies have found that active components of Chinese medicine， such as terpenoids， polyphenols， flavonoids， glycosides， and quinones， and Chinese medicine compound formulas， including Zuojin pills， Sijunzi decoction， Biejiajian pills， and Xuanfu Daizhe decoction， can inhibit TSCs-related signaling pathways such as the Notch signaling pathway， the Wnt/β-catenin signaling pathway， the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway， and the Hippo signaling pathway. They also reduce the expression of TSC surface markers， including sex-determining region Y-box 2 （SOX2）， sex-determining region Y-box 9 （SOX9）， octamer-binding transcription factor 4 （OCT4）， prominin-1 （CD133）， cluster of differentiation 44 （CD44）， cluster of differentiation 24 （CD24）， and thyroid transmembrane protein 1 （CD90）， thereby hindering TSC differentiation， accelerating their metabolic processes， improving the tumor microenvironment， and consequently inhibiting GT growth. This study collects and analyzes recent research on the regulation of TSCs by TCM in the treatment of GT， aiming to provide a new theoretical basis for tumor therapy with TCM， expand its application in the comprehensive treatment of GT， and offer new therapeutic ideas and methods for clinical practice.

BACKGROUND: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke. METHODS: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes. RESULTS: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P  <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P  <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P  <0.01). CONCLUSIONS: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes. REGISTRATION ClinicalTrials.gov , NCT03222024.
Humans ; Male ; Female ; Prospective Studies ; Ischemic Stroke/mortality* ; Aged ; Middle Aged ; Aged, 80 and over ; Stroke ; Brain Ischemia

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Objective: To explore the positive rate and distribution characteristics of unexpected antibodies in hospitalized children. Methods: A total of 22 336 hospitalized pediatric patients admitted to Henan Children's Hospital from August 2018 to September 2022 were selected as the research subjects, and their relevant clinical data were collected. Blood samples of the patients were subjected to blood type identification and unexpected antibody screening. For samples with positive screening results, further antibody specificity identification was conducted using panel cells. The distribution patterns of unexpected antibodies across different genders, age groups, blood types, and disease categories were analyzed, and inter-group differences were compared. Results: Of the 22 336 patients, 286 (1.3%) tested positive for unexpected antibodies. The most frequently identified specificities belonged to the MNS blood group system (45.1%, 129/286), followed by the Rh system (24.5%, 70/286) and antibodies of undetermined specificity (24.5%, 70/286). Less common specificities included those from the P blood group system (2.4%, 7/286), Lewis blood group system (1.4%, 4/286), mixed antibodies from multiple systems (0.9%, 3/286), drug-induced antibodies (0.7%, 2/286), and LW blood group system (0.3%, 1/286). Within the MNS blood group system, anti-M was the most prevalent (129 cases). In the Rh blood group system, anti-E (30 cases, 10.5%) and anti-D (28 cases, 9.8%) were the main antibodies detected; other antibodies included anti-DE (4 cases, 1.4%), anti-DC (3 cases, 1.0%), anti-Ec (3 cases, 1.0%), and anti-c (2 cases, 0.7%). Only anti-P was identified in the P blood group system (7 cases), while anti-Lea was found in the Lewis blood group system (4 cases) and anti-LW in the LW blood group system (1 case). Mixed antibodies from multiple systems consisted of anti-D+Fy , anti-e+Fy , and anti-Le +P , with 1 case (0.3%) each. Among the antibodies with undefined specificity, 26 cases were autoantibodies. All drug-induced antibodies were anti-CD38 (2 cases). The distribution of unexpected antibodies showed statistically significant differences among different genders, ages, and ABO blood types (P<0.05). Regarding age distribution, Rh blood group antibodies associated with hemolytic disease of the fetus and newborn (HDFN) were predominant in the 0-1 month group, which differed significantly from all other age groups (P<0.001). In contrast, anti-M was predominant in children over 1 year of age (89.0%), while anti-E was detected in only 3 cases (10.0%) in children over 3 years old. After Bonferroni correction (α' = 0.003 3), a statistically significant difference was observed only between the 6-17 year group and the 1-3 year group (P=0.003). Among ABO blood types, type B had the highest antibody detection rate. Following Bonferroni correction (α' ≈ 0.008 3), a significant difference in detection rates was found solely between type B and type O blood (P=0.005), with no statistically significant differences among other blood types (P>0.008 3). Conclusion: In hospitalized pediatric patients, unexpected antibodies were mainly distributed in the MNS and Rh blood group systems, with anti-M being the most commonly detected specificity and anti-E the most prevalent within the Rh system.. Sex, age and blood type significantly influence the development of unexpected antibodies. Clinically, it is necessary to pay attention to the prenatal monitoring of unexpected antibodies in pregnant women, so as to achieve homotypic transfusion of other Rh antigens as early as possible.

AIM: To investigate the relationship between vascular smooth muscle cell (VSMC) injury, organelle stress response and autophagic cell death (autophagy) and ferroptosis induced by the chemical hypoxia inducer cobalt chloride (CoCl2) through the bioinformatics analysis and in vitro cell experimentation. METHODS: The dataset GSE119226 of VSMC treated with cobalt chloride was acquired from the gene expression database (GEO). The R language was used to investigate the relationship between CoCl2 treatment and organelle stress response (Golgi stress, endoplasmic reticulum stress) and two forms of cell death (ferroptosis and autophagic cell death). With primary cultured rat VSMC (rVSMC) and CoCl2-induced anoxia model, the changes in cell viability were detected by CCK-8 method, and reactive oxygen species (ROS) levels were measured using DCFH-DA method. The expression levels of HIF-1α (a key molecule in hypoxia), Golgi stress markers GM130 and p115, endoplasmic reticulum stress markers GRP78 and CHOP, autophagy markers LC3-II / LC3-I and Beclin1, and ferroptosis markers GPx4 and xCT were detected by Western blot. The effect of inducing or inhibiting organelle stress and cell death on the CoCl2-induced cell damage was also observed. RESULTS: Differentially expressed genes analysis of GSE119226 dataset showed that CoCl2 treatment of VSMCs had significant effects on organelle function and stress response, autophagy and ferroptosis-related genes, in which endoplasmic reticulum stress, protein processing in endoplasmic reticulum, regulation of Golgi to plasma membrane protein transport, autophagy / autophagic cell death, and ferroptosis pathways were remarkably enriched. The results of in vitro experiment showed that compared with normal rVSMC, cell viability was significantly decreased after CoCl2 treatment, as well as HIF-1α protein expression and ROS levels in rVSMCs were increased. In rVSMC treated with Co-Cl2, the expression levels of Golgi structural proteins GM130 and p115 (reflecting the occurrence of Golgi stress) were decreased, while the markers GRP78 and CHOP (reflecting the occurrence of endoplasmic reticulum stress) were increased. At the same time, CoCl2 treatment also reduced the expression of autophagy markers LC3-II/LC3-I and Beclin1 (indicating the decrease levels of autophagy), while the expression of ferroptosis markers GPx4 and xCT were decreased (indicating the occurrence of ferroptosis). Compared with CoCl2 treatment group, induced Golgi stress, endoplasmic reticulum stress, or ferroptosis could further reduce cell viability, while inhibition of these processes could improve cell viability. On the other hand, increasing the level of autophagy can improve the cell viability. CONCLUSION: Hypoxia induced by cobalt chloride can lead to VSMC injury. Golgi stress, endoplasmic reticulum stress, ferroptosis, and the reduction of autophagy level play an important role in it. Inhibition of organelle stress response and ferroptosis, or increase of autophagy level can improve VSMC injury caused by cobalt chloride.