ObjectiveThis study aimed to investigate the intervention effect of Renqing Mangjue on the malignant transformation of gastric mucosal epithelial cells induced by N-methyl-N′-nitro-N-nitrosoguanidine （MNNG） and to explore its molecular mechanism in preventing precancerous lesions of gastric cancer based on the cyclic guanosine monophosphate （cGMP）/protein kinase G （PKG）/mitogen-activated protein kinase （MEK）/extracellular signal-regulated kinase （ERK） signaling pathway. MethodsHuman gastric mucosal epithelial cells （GES-1） were initially induced by MNNG to establish a precancerous cell model （MC cells）. The effective concentration of MNNG for inducing malignant transformation in GES-1 cells was screened using the cell proliferation activity decection （CCK-8） assay， and the effective concentration of Renqing Mangjue for inhibiting the proliferation of transformed GES-1 cells was also determined. GES-1 cells were divided into a blank control group， a model group， and treatment groups with Renqing Mangjue at concentrations of 1， 3， 10， and 30 mg·L^-1. Furthermore， the effects of Renqing Mangjue on the migratory ability and epithelial-mesenchymal transition （EMT） characteristics of GES-1 malignant transformed cells were evaluated using Transwell migration assays， wound healing assays， and real-time quantitative reverse transcription polymerase chain reaction （Real-time PCR）. Additionally， candidate chemical components and target sites of Renqing Mangjue were obtained from the TCMIP v2.0 database， and disease targets at various stages of gastric cancer precursors were sourced from the Gene Expression Omnibus （GEO） database. Pathway enrichment analysis was performed using the Metascape database to predict the potential mechanisms of action of Renqing Mangjue. Finally， the protective mechanism of Renqing Mangjue against gastric cancer precursors was validated through Western blot analysis. ResultsAt a concentration of 20 μmol·L^-1， MNNG exhibited an inhibition rate of approximately 50% on GES-1 cells （P<0.01）， and at this concentration， the GES-1 cells displayed biological characteristics indicative of malignant transformation. In contrast， Renqing Mangjue had no significant effect on the proliferation of normal GES-1 cells， but significantly inhibited the proliferation of MC cells （P<0.01） and markedly reduced their migratory capacity （P<0.01）. Moreover， it also increased the mRNA expression level of E-cadherin during the EMT process （P<0.05）， while inhibiting the expression of both N-cadherin and the transcription factor Snail mRNA （P<0.05， P<0.01）. Network predictions suggested that Renqing Mangjue may prevent gastric cancer precursors through modulating the cGMP/PKG and MAPK/ERK signaling pathways. Furthermore， Western blot results indicated that Renqing Mangjue upregulated the expression of PKG and NPRB （B-type natriuretic peptide receptor） proteins in the cGMP/PKG pathway （P<0.01）， while downregulating the expression of the downstream proteins MEK and ERK （P<0.05， P<0.01）. ConclusionIn summary， Renqing Mangjue can prevent gastric cancer precursors by inhibiting the proliferation and migration of malignant transformed GES-1 cells， thereby delaying the EMT process. The underlying mechanisms may be related to the activation of the cGMP/PKG pathway and the inhibition of the MEK/ERK signaling pathway.

ObjectiveTo investigate the protective effects and mechanisms of Bushen Zhuyun prescription （BSZY） on abortion rats with kidney deficiency-corpus luteum inhibition syndrome. MethodsAn abortion rat model with kidney deficiency-corpus luteum inhibition syndrome was constructed. Pregnant mice aged 8-10 weeks were randomly divided into a control group （Control）， a model group （Model）， low-dose BSZY （BSZY-L）， medium-dose BSZY （BSZY-M）， and high-dose BSZY （BSZY-H） groups （2.57， 5.14， 10.28 g·kg^-¹）， and a Zishen Yutai Pill （ZSYT） group （1.575 g·kg^-¹）. Hematoxylin-eosin （HE） staining was used to evaluate histopathological changes in ovarian and decidual tissue of rats in each group. Enzyme-linked immunosorbent assay （ELISA） was employed to measure levels of estrogen （E₂）， progesterone （P）， luteinizing hormone （LH）， prolactin （PRL）， and follicle-stimulating hormone （FSH） in serum. The candidate targets of BSZY were obtained from the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP） v2.0 databases， while disease targets for recurrent spontaneous abortion （RSA） were retrieved from GeneCards， DrugBank， Online Mendelian Inheritance in Man （OMIM）， and Therapeutic Target Database （TTD）. The intersection targets were identified by the Venny 2.1.0 platform. Pathway enrichment analysis was conducted based on the Metascape database to predict the potential mechanisms of BSZY. Additionally. Western blot was used to verify the effects of BSZY on the expression of estrogen receptor （ERα）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） and explore its protective mechanism on RSA rats. ResultsCompared with the control group， the model group exhibited significantly decreased uterine， ovarian， and embryonic wet weights （P<0.05， P<0.01）， with an abortion rate of 57.18%. The ovarian tissue showed varying degrees of reduction in primordial follicles， primary follicles， mature follicles， and corpora lutea， along with a large number of atretic follicles. The endometrium was thinner， and decidual tissue exhibited cellular edema and disorganized arrangement. In contrast， compared with the model group， the BSZY groups at all doses and the ZSYT group demonstrated increased uterine， ovarian， and embryonic wet weights， along with a reduced abortion rate. The number of primordial follicles， primary follicles， mature follicles， and corpora lutea increased， while atretic follicles decreased. The endometrium thickened， and decidual tissue displayed normal cellular structure with tight arrangement. Additionally， the model group showed significantly decreased levels of E₂， P， PRL， and FSH in serum （P<0.05， P<0.01）， along with a decreasing trend in LH level. In contrast， the BSZY groups at all doses exhibited significantly elevated levels of E₂， P， LH， PRL， and FSH in serum （P<0.05， P<0.01）. Network pharmacology predictions suggested that BSZY may exert protective effects against abortion in rats by activating the ERα/PI3K/Akt signaling pathway. Western blot results confirmed that BSZY significantly upregulated the expression of ERα， PI3K， and p-Akt proteins （P<0.05， P<0.01）. ConclusionBSZY has a protective effect on the abortion rats with kidney deficiency-corpus luteum inhibition syndrome， possibly by activating the ERα/PI3K/Akt signaling pathway to reduce ovarian apoptosis and regulate endocrine function， thereby lowering the abortion rate.

OBJECTIVE: To compare the protective effects of electroacupuncture (EA) and transcutaneous electrical acupoint stimulation (TEAS) during pregnancy on maternal immune activation (MIA)-induced adverse pregnancy outcomes, fetal developmental defects, and neuropsychological behavior abnormalities in offspring mice. METHODS: Eighty pregnant C57BL/6 mice were randomly divided into 5 groups: control, model, EA, TEAS, and sham-stimulation groups, 16 mice in each group. MIA models were replicated on the day 12.5 of pregnancy via tail intravenous injection with polyinosinic-polycytidylic acid. On the second day of modeling success, in the EA and TEAS groups, the interventions were delivered at bilateral "Zusanli" (ST36), with a frequency of 2 Hz, a current of 0.5 mA, and for 20 min each day in the pregnant mice; and the interventions lasted 6 days. Body mass and fertility indexes of pregnant mice, and the development indexes of offspring mice were recorded. Liquid phase suspension chip technology was used to detect the levels of cytokines and chemotactic factors in the serum of pregnant mice and and fetal brain of offspring mice. Flow cytometry was adopted to detect the proportion of the subgroups and subtypes of spleen T lymphocytes and macrophages in pregnant mice. Using the open field test, prepulse inhibition (PPI) test and Morris water maze, the spatial learning and memory were assessed in offspring mice. Immunofluorescence staining was used to detect microglial count in the medial prefrontal cortex (mPFC) in offspring mice. RESULTS: Compared with the control group, the model group showed a reduced body mass of pregnancy mice (P<0.01), smaller litter size and fewer live births (P<0.01, P<0.05), the increase in dead birth and the decrease in offspring survival rate (P<0.05, P<0.01). When compared with model group, in the EA group and the TEAS group, the body mass of pregnancy mice rose (P<0.05), litter size and live births increased (P<0.05, P<0.01), the dead birth was reduced and the offspring survival rate higher (P<0.05). In comparison with the control group, the model group showed the increase in the levels of monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), γ-interferon (IFN-γ) in the serum of pregnant mice, and spleen M1 macrophage proportion (P<0.01, P<0.05), and the decrease in spleen M2 macrophages of pregnant mice (P<0.01); and the increase in MCP-1 and IL-6 in fetal brain of offspring mice (P<0.05). Compared with the model group, the EA group and the TEAS group showed the decrease in MCP-1, IL-6 and IFN-γ, and spleen M1 macrophage proportion (P<0.01, P<0.05), and the increase in spleen M2 macrophages of pregnant mice (P<0.01, P<0.05) ; and the decrease in MCP-1 and IL-6 in fetal brain of offspring mice (P<0.05). Compared with the control group, in the model group, the total movement distance, escape incubation were extended (P<0.05, P<0.01), the frequency of entering the central area and crossing the platform decreased, and the activity duration in central area was shortened (P<0.05, P<0.01), the average speed rose (P<0.05), PPI%, the percentage of target quadrant swimming time in the total time and that of target quadrant swimming distance in the total distance were reduced (P<0.05, P<0.01) in offspring mice. When compared with the model group, in the EA group and TEAS group, the total movement distance and escape incubation were shortened, the average speed was reduced (P<0.05), PPI% and the frequency of crossing the platform increased (P<0.05, P<0.01); the percentage of target quadrant swimming time in the total time and that of target quadrant swimming distance in the total distance rose (P<0.05, P<0.01) in the offspring mice. In the EA group, the frequency of entering the central area and the activity duration in central area were higher (P<0.05, P<0.01); and in the the TEAS group, the activity duration in central area were longer (P<0.05). When compared with the control group, in the model group, microglial count in mPFC was elevated in offspring mice (P<0.05). In comparison with the model group, the EA group and the TEAS group showed the decrease of microglial count in mPFC (P<0.05). CONCLUSION EA and TEAS at "Zusanli" (ST36) during pregnancy effectively improve in the pregnancy outcomes and fetal brain developmental abnormalities induced by infection, and attenuate neurodevelopmental defects and mental disorders of offspring mice through inhibiting inflammatory activation of microglia in mPFC.
Animals ; Female ; Pregnancy ; Electroacupuncture ; Acupuncture Points ; Mice ; Mice, Inbred C57BL ; Humans ; Male

The diagnosis of hematological disorders is currently established from the combined results of different tests, including those assessing morphology (M), immunophenotype (I), cytogenetics (C), and molecular biology (M) (collectively known as the MICM classification). In this workflow, most of the results are interpreted manually (i.e., by a human, without automation), which is expertise-dependent, labor-intensive, time-consuming, and with inherent interobserver variability. Also, with advances in instruments and technologies, the data is gaining higher dimensionality and throughput, making additional challenges for manual analysis. Recently, artificial intelligence (AI) has emerged as a promising tool in clinical hematology to ensure timely diagnosis, precise risk stratification, and treatment success. In this review, we summarize the current advances, limitations, and challenges of AI models and raise potential strategies for improving their performance in each sector of the MICM pipeline. Finally, we share perspectives, highlight future directions, and call for extensive interdisciplinary cooperation to perfect AI with wise human-level strategies and promote its integration into the clinical workflow.

Objective To explore the clinical efficacy of two procedures in thoracoscopic anterior mediastinal tumor resection. Methods A retrospective study was conducted on patients who underwent thoracoscopic anterior mediastinal tumor resection at the Department of Thoracic Surgery, the 910th Hospital of Joint Logistics Support Force from October 2016 to January 2024. Patients were divided into two groups according to the surgical approach: a modified approach group (bilateral intercostal ports+two subcostal ports) and a classic subxiphoid approach group (one subxiphoid port+two subcostal ports). Perioperative data and postoperative improvement of myasthenia gravis (MG) subgroup were compared between the two groups. Results A total of 55 patients were included, including 27 males and 28 females with a mean age of (49.4±15.1) years. There were 23 patients in the modified approach group and 32 patients in the classic subxiphoid approach group. The modified approach group had shorter operation time [(129.0±20.5) min vs. (148.9±16.7) min, P<0.001], less intraoperative blood loss [(63.0±16.6) mL vs. (75.0±10.8) mL, P<0.001], shorter postoperative drainage tube removal time [(3.1±0.4) d vs. (3.9±0.6) d, P<0.001] and shorter postoperative hospital stay [(4.2±0.4) d vs. (5.0±0.6) d, P<0.001), and lower proportion of intraoperative cardiac dysfunction [4 (17.4%) vs. 14 (43.8%), P=0.040]. There was no statistical difference in maximum diameter of tumor resected [(4.5±1.7) cm vs. (4.0±0.9) cm, P=0.193] and postoperative drainage volume [(396.4±121.5) mL vs. (399.9±161.3) mL, P=0.932]. There was 1 patient of perioperative collateral injury in the modified approach group (pericardial injury), and 6 patients in the classic subxiphoid approach group (1 patient of diaphragm injury, 1 patient of liver contusion, 4 patients of pericardial injury). There was no statistical difference in pain scores at 24 h, 48 h and 72 h after surgery (P>0.05). The postoperative improvement of MG symptoms in the modified approach group was better than that in the classic subxiphoid approach group at 1 year after surgery (complete stable remission rate: 77.8% vs. 50.0%; effective rate: 100.0% vs. 91.6%). No conversion to open chest surgery occurred in either group, and there were no postoperative rehospitalizations or deaths related to surgery within 30 days after surgery in both groups. Conclusion The modified approach is safe and controllable with more open surgical field and more reliable complete resection range than the classic subxiphoid approach group.

Objective:To analyze the clinical, genetic, and bioinformatic characteristics of 3 children diagnosed with GM1 gangliosidosis type Ⅰ, and to conduct a literature review.Methods:From January 2020 through December 2022, a detailed examination, encompassing whole-exon sequencing and the evaluation of β-galactosidase enzymatic function, was undertaken for 3 pediatric inpatients at Xi′an Children′s Hospital. Each child presented with distinct clinical features: recurrent seizures, developmental delays, and hypotonia. Concurrently, computational tools MutaBind2 and PyMOL were employed to prognosticate the potential impact of identified genetic mutations.Results:All 3 children experienced severe developmental delay or regression in infancy, accompanied by epilepsy. Serum alkaline phosphatase and aspartate aminotransferase were significantly increased. Furthermore, the serum β-galactosidase activity was 1.59%, 3.47%, 1.96%,respectively. Brain magnetic resonance imaging revealed poor myelination and X-ray examinations demonstrated beak-like changes in the anterior edge of the lumbar spine. All 3 children carried compound heterozygous variants in the GLB1 gene. The c.148T>C variant had not been previously reported, while the c.785G>T, c.1438A>G and c.304C>G variants were only present in 1 case. It was predicted that the mutated protein exhibited reduced binding affinity, with an interrupted hydrogen bond or the formation of a significant steric hindrance with the neighboring residues. Combined with the literature evidence, it was hypothesized that the mutations could potentially impact the overall structure and stability of the GLB protein, leading to a decrease in enzyme activity. Conclusions:The diagnosis and classification of GM1 ganglioside storage disease need to integrate the clinical features, exome sequencing and β-galactosidase activity assay. Bioinformatics analysis is helpful to predict the effect of mutations on protein structure and function.

To promote the development of the prescription-based processing of Chinese herbal pieces,the China Association of Chinese Medicine published the social organization standard of the Standard for Prescription-based Processing of Chinese Herbal Pieces(T/CACM 1367-2021)in June 2021.The standard was led by the First Affiliated Hospital of Henan University of Chinese Medicine and Jiangsu Province Hospital of Chinese Medicine.It was jointly drafted by 28 Traditional Chinese medical institutions across the country.This paper introduced the standards in detail to promote the implementation and propel the inheritance and innovation of the processing of Chinese herbal pieces.

Objective To investigate the expression and role of the Sonic Hedgehog (Shh) signaling pathway in intestinal mucosal barrier injury in rats with severe acute pancreatitis (SAP). Methods A total of 48 Sprague-Dawley rats were divided into sham-operation group (Sham group), SAP model group (SAP group), SAP+Shh signaling pathway-specific agonist purmorphamine group (PUR+SAP group), and SAP+Shh signaling pathway-specific antagonist cyclopamine group (CYC+SAP group) using a random number table, with 12 rats in each group, and each group was further divided into 12-hour and 24-hour subgroups, with 6 rats in each subgroup. Rats were given retrograde injection of 5% sodium taurocholate into the pancreatic and bile ducts to establish a model of SAP, and rats in the intervention groups were given intraperitoneal injection of 0.69 mg/kg purmorphamine and 0.69 mg/kg cyclopamine before modeling. Related samples were collected at 12 and 24 hours after modeling. HE staining was used to observe the pathological changes of the pancreas and the ileum; ELISA was used to measure the serum levels of amylase, lipase, diamine oxidase (DAO), and endotoxin-core antibody (EndoCAb); the TUNEL method was used to observe the apoptosis of intestinal epithelial cells; Western blot was used to measure the expression levels of Shh, Ptch1, and Gli1 in ileal tissue. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups and further comparison between two groups. Results Compared with the Sham group, the SAP group had significant increases in the pathological scores of pancreatic and ileum tissue, the serum levels of lipase, amylase, DAO, and EndoCAb, the apoptosis of intestinal epithelial cells, and the protein expression levels of Shh, Ptch1, and Gli1 in ileal tissue (all P < 0.05). Compared with the SAP group, the PUR+SAP group had significantly alleviated pathological injury and dysfunction of the pancreas and intestine, a significant reduction in the apoptosis of intestinal epithelial cells, and significant increases in the protein expression levels of Shh, Ptch1, and Gli1 in ileal tissue (all P < 0.05). Compared with the SAP group, the CYC+SAP group had significant aggravation of the pathological injury and dysfunction of the pancreas and intestine, a significant increase in the apoptosis of intestinal epithelial cells, and significant reductions in the protein expression levels of Shh, Ptch1, and Gli1 in ileal tissue (all P < 0.05). Conclusion The Shh signaling pathway may be involved in intestinal mucosal barrier injury in SAP and exerts a protective effect.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC, OMIN: 604004) caused by mutations in the MLC1 gene, is an rare autosomal recessive disorder. More patients are with infancy and young children onset, whereas adult cases are rare. Only 2 patients from 1 family have been reported in domestic adult cases. Now a 58-year-old female MLC patient is reported. The clinical manifestations of the patient included large head circumference, slow responses, walking difficulties, seizures and paroxysmal loss of consciousness. The result of whole exome sequencing revealed a homozygous insertion mutation c.920_943dup in the MLC1 gene. The mutation in this patient has not been reported in the Human Gene Mutation Database.

Objective:To investigate the clinical characteristics and pathogen spectrum of acquired immunodeficiency syndrome (AIDS) patients complicated with pulmonary filamentous fungal infection in Guangdong Province, so as to provide evidences for improving the diagnosis and treatment.Methods:A total of 143 AIDS patients with pulmonary filamentous fungal infection hospitalized in Guangzhou Eighth People′s Hospital, Guangzhou Medical University from January 2016 to December 2018 were included. The filamentous fungi cultured in bronchoalveolar lavage fluid of these patients were identified with morphological and molecular biological methods. And their clinical characteristics were analyzed. Nonparametric Kruskal-Wallis H test and chi-square test were used for statistical analysis. Results:Among the 143 patients, 116(81.1%) had fever, 104(72.7%) had cough, 83(58.0%) had expectoration, and 59(41.3%) had anhelation. The CD4 + T lymphocyte count was 22.0(9.3, 60.8) cells/μL and 118(82.5%) cases were below 100.0 cells/μL. The white blood cell counts decreased in 52(36.4%) cases and increased in 18(12.6%) cases, anemia was found in 109(76.2%) cases, platelet count decreased in 29(20.3%) cases. Sixty-four (44.8%) cases were positive for galactomannan test. Chest computed tomography showed diffuse infection of both lungs in 114(79.7%) cases, miliary changes in 12(8.4%) cases, pleural effusion in 44(30.8%) cases, and enlargement of pleural and (or) mediastinal lymph nodes in 45(31.5%) cases. After receiving antifungal therapy, 124 (86.7%) cases were cured or improved, and 19 (13.3%) cases were discharged automatically or died of disease deterioration. Among the 143 strains of filamentous fungi, there were 56 strains of Aspergillus species pluralis (39.2%, including 24 strains of Aspergillus fumigatus), 37 strains of Talaromyces marneffei ( T. marneffei) (25.9%), 22 strains of Penicilium species pluralis (15.4%), and 28 strains of other genera of filamentous fungi (19.6%). The median CD4 + T lymphocyte counts in patients infected with Aspergillus species pluralis, T. marneffei, Penicilium species pluralis and other genera were 24.5, 15.0, 53.5 and 22.0 cells/μL, respectively, and the difference was statistically significant ( H=11.282, P=0.010). The proportions of AIDS patients with different pulmonary filamentous fungal infection of CD4 + T lymphocyte count ≤50.0 cells/μL in descending order were T. marneffei group (89.2%(33/37)), Aspergillus species pluralis group and other genera group (67.9%(38/56), 67.9%(19/28)), and Penicillium species pluralis group (54.5%(12/22)), and the difference was statistically significant ( χ2=9.296, P=0.026). Conclusions:The clinical manifestations of pulmonary filamentous fungal infection in AIDS patients in Guangdong Province are not specific. The pathogenic spectrum contains various genera, and T. marneffei and Aspergillus fumigatus are dominant, which could be correlated with CD4 + T lymphocyte count.