Heterotypic cell-in-cell structures(heCICs)mediate unique non-autonomous cell death,which are widely involved in a variety of important pathological processes,such as tumorigenesis,pro-gression and clinical prognosis.Methylenetetrahydrofolata dehydrogenase 2(MTHFD2),one of the key enzymes of one-carbon metabolism,is highly expressed in a variety of tumor cells.In this study,in order to investigate the effect of MTHFD2 on the formation of heCICs,liver cancer cells and immune cells were first labeled separately by live cell dyes,and the heCIC model was established by using fluorescence mi-croscopy for cell imaging and analysis.After transiently knocking down MTHFD2 in cells by RNAi,we found that the ability of PLC/PRF/5 and Hep3B to form heCICs with immune cells was significantly in-creased(all P＜0.01).MTHFD2 recombinant expression plasmid was constructed by the homologous re-combination method,and MTHFD2 overexpression cell lines were further constructed.Then,the effect of MTHFD2 overexpression on the ability to form heCICs was detected by co-culturing the overexpression cell lines with immune cells.The results showed that the rate of heCIC formation was significantly re-duced after overexpression of MTHFD2(all P＜0.001).In conclusion,this study demonstrated that MTHFD2 is a negative regulator of heCIC formation,providing a research basis for targeting MTHFD2 to promote heCIC formation and enhance the in-cell killing of immune cells.

Decoction is a classical dosage form of traditional Chinese medicines. In the process of decocting, various complex components produce physical interactions and chemical reactions, among which physical interactions include van der Waals force, hydrogen bond, electrostatic interaction, π-π stacking, etc., and chemical reactions include Maillard reaction, oxidation reaction, hydrolysis reaction, degradation reaction, polymerization reaction, etc. New substances and original ingredients from chemical reactions can be further activated. These effects form the basis of particle formation in the broth. The sizes of the particles in decoctions range from nanoscale to micron scale, mostly composed of polysaccharide, protein matrix, wrapped in water insoluble molecules, can increase the dispersion of insoluble components and the stability of unstable components, as well as reduce the volatile components and toxic components of volatile components, and ultimately achieve the purpose of efficient absorption and toxicity reduction. From the angle of physical change and chemical reaction in the process of decoction, this paper expounds the formation mechanism of particles in decoction, expounds the research method of particles, analyzes the components in particles and the interaction between components, and then explains the pharmacodynamic characteristics of traditional Chinese medicine decoction, which provides the foundation for the modernization of Chinese decoction.

OBJECTIVE: To screen the prognostic biomarkers of metabolic genes in patients with multiple myeloma (MM), and construct a prognostic model of metabolic genes. METHODS: The histological database related to MM patients was searched. Data from MM patients and healthy controls with complete clinical information were selected for analysis.The second generation sequencing data and clinical information of bone marrow tissue of MM patients and healthy controls were collected from human protein atlas (HPA) and multiple myeloma research foundation (MMRF) databases. The gene set of metabolism-related pathways was extracted from Molecular Signatures Database (MSigDB) by Perl language. The biomarkers related to MM metabolism were screened by difference analysis, univariate Cox risk regression analysis and LASSO regression analysis, and the risk prognostic model and Nomogram were constructed. Risk curve and survival curve were used to verify the grouping effect of the model. Gene set enrichment analysis (GSEA) was used to study the difference of biological pathway enrichment between high risk group and low risk group. Multivariate Cox risk regression analysis was used to verify the independent prognostic ability of risk score. RESULTS: A total of 8 mRNAs which were significantly related to the survival and prognosis of MM patients were obtained (P<0.01). As molecular markers, MM patients could be divided into high-risk group and low-risk group. Survival curve and risk curve showed that the overall survival time of patients in the low-risk group was significantly better than that in the high risk group (P<0.001). GSEA results showed that signal pathways related to basic metabolism, cell differentiation and cell cycle were significantly enriched in the high-risk group, while ribosome and N polysaccharide biosynthesis signaling pathway were more enriched in the low-risk group. Multivariate Cox regression analysis showed that the risk score composed of the eight metabolism-related genes could be used as an independent risk factor for the prognosis of MM patients, and receiver operating characteristic curve (ROC) showed that the molecular signatures of metabolism-related genes had the best predictive effect. CONCLUSION Metabolism-related pathways play an important role in the pathogenesis and prognosis of patients with MM. The clinical significance of the risk assessment model for patients with MM constructed based on eight metabolism-related core genes needs to be confirmed by further clinical studies.
Humans ; Cell Cycle ; Multiple Myeloma/genetics* ; Prognosis ; Risk Factors

OBJECTIVE: JieZe-1 (JZ-1), a Chinese herbal prescription, has an obvious effect on genital herpes, which is mainly caused by herpes simplex virus type 2 (HSV-2). Our study aimed to address whether HSV-2 induces pyroptosis of VK2/E6E7 cells and to investigate the anti-HSV-2 activity of JZ-1 and the effect of JZ-1 on caspase-1-dependent pyroptosis. METHODS: HSV-2-infected VK2/E6E7 cells and culture supernate were harvested at different time points after the infection. Cells were co-treated with HSV-2 and penciclovir (0.078125 mg/mL) or caspase-1 inhibitor VX-765 (24 h pretreatment with 100 μmol/L) or JZ-1 (0.078125-50 mg/mL). Cell counting kit-8 assay and viral load analysis were used to evaluate the antiviral activity of JZ-1. Inflammasome activation and pyroptosis of VK2/E6E7 cells were analyzed using microscopy, Hoechst 33342/propidium iodide staining, lactate dehydrogenase release assay, gene and protein expression, co-immunoprecipitation, immunofluorescence, and enzyme-linked immunosorbent assay. RESULTS: HSV-2 induced pyroptosis of VK2/E6E7 cells, with the most significant increase observed 24 h after the infection. JZ-1 effectively inhibited HSV-2 (the 50% inhibitory concentration = 1.709 mg/mL), with the 6.25 mg/mL dose showing the highest efficacy (95.76%). JZ-1 (6.25 mg/mL) suppressed pyroptosis of VK2/E6E7 cells. It downregulated the inflammasome activation and pyroptosis via inhibiting the expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (P < 0.001) and interferon-γ-inducible protein 16 (P < 0.001), and their interactions with apoptosis-associated speck-like protein containing a caspase recruitment domain, and reducing cleaved caspase-1 p20 (P < 0.01), gasdermin D-N (P < 0.01), interleukin (IL)-1β (P < 0.001), and IL-18 levels (P < 0.001). CONCLUSION JZ-1 exerts an excellent anti-HSV-2 effect in VK2/E6E7 cells, and it inhibits caspase-1-dependent pyroptosis induced by HSV-2 infection. These data enrich our understanding of the pathologic basis of HSV-2 infection and provide experimental evidence for the anti-HSV-2 activity of JZ-1. Please cite this article as: Liu T, Shao QQ, Wang WJ, Liu TL, Jin XM, Xu LJ, Huang GY, Chen Z. The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro. J Integr Med. 2023; 21(3): 277-288.
Caspase 1/metabolism* ; Inflammasomes/pharmacology* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Pyroptosis ; Simplexvirus/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Herpes Simplex/drug therapy* ; Humans

Established in 2017, the Screening Cohort for Asian Nomadic descendants in China (Scan-China) has benefited over 180,000 members of a multi-ethnic population, particularly individuals of Mongolian descent compared with the general population (Han ethnicity), in the Inner Mongolia Autonomous Region, China. This cohort study aims to evaluate the effectiveness of cancer screening and serve as a real-world data platform for cancer studies. The 6 most prevalent cancers in China are considered—namely, breast, lung, colorectal, gastric, liver and esophageal cancer. After baseline cancer risk assessments and screening tests, both active and passive follow-up (based on the healthcare insurance database, cancer registry, the front page of hospital medical records, and death certificates) will be conducted to trace participants’ onset and progression of cancers and other prevalent chronic diseases. Scan-China has preliminarily found a disproportionately lower screening participation rate and higher incidence/mortality rates of esophageal and breast cancer among the Mongolian population than among their Han counterparts. Further research will explore the cancer burden, natural history, treatment patterns, and risk factors of the target cancers.

Bayesian network Meta-analysis was performed to evaluate the efficacy and safety of different Chinese patent medicines in the treatment of dilated cardiomyopathy. The PubMed, EMbase, Cochrane Library, CNKI, Wanfang, and VIP were searched for the randomized controlled trial(RCT) from the inception to May 2023. The quality of the included RCT was evaluated by the Cochrane risk of bias assessment tool, and the data were analyzed by RStudio 3.6.3 calling the "gemtc" package. A total of 96 RCTs involving 8 452 patients, 11 Chinese patent medicines, and 8 outcome indicators were included. Network Meta-analysis is described as follows.(1)In terms of improving clinical total effective rate, except Yixinshu Capsules + conventional western medicine, Shexiang Baoxin Pills + conventional western medicine, and Xinshuai Mixture + conventional western medicine, the other Chinese patent medicines combined with conventional western medicine were superior to conventional western medicine alone, and Shenqi Yiqi Dropping Pills + conventional western medicine had the best effect.(2)In terms of improving left ventricular ejection fraction(LVEF), except Yixinshu Capsules + conventional western medicine and Shensong Yangxin Capsules + conventional western medicine, other Chinese patent medicines combined with conventional western medicine outperformed conventional western medicine alone, and Shexiang Baoxin Pills + conventional western medicine had the best effect.(3)In terms of reducing left ventricular end-diastolic dimension(LVEDD), Getong Tongluo Capsules + conventional western medicine, Xinshuai Mixture + conventional western medicine, Huangqi Mixture + conventional western medicine, Tongxinluo Capsules + conventional western medicine, Wenxin Granules + conventional western medicine, and Qili Qiangxin Capsules + conventional western medicine were better than conventional western medicine alone, and Wenxin Granules + conventional western medicine had the best effect.(4)There was no significant difference in reducing left ventricular end-systolic diameter(LVESD) between Chinese patent medicines combined with conventional western medicine and conventional western medicine alone.(5)In terms of improving 6-minute walking trail(6MWT), Yangxinshi Tablets + conventional western medicine, Yixinshu Capsules + conventional western medicine, Shenqi Yiqi Dropping Pills + conventional western medicine, Wenxin Granules + conventional western medicine, and Qili Qiangxin Capsules + conventional western medicine were superior to conventional western medicine alone, and Shenqi Yiqi Dropping Pills + conventional western medicine had the best effect.(6)In reducing brain natriuretic peptide(BNP), Xinshuai Mixture + conventional western medicine ourperformed conventional western medicine alone.(7)In reducing hypersensitive C-reactive protein(hs-CRP), Shenqi Yiqi Dropping Pills + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine outperformed conventional western medicine alone, and Qili Qiangxin Capsules + conventional western medicine had the best effect.(8)In terms of safety, adverse reactions were reported in both groups. In conclusion, Chinese patent medicine combined with conventional western medicine were more effective in the treatment of dilated cardiomyopathy. The combinations relieve clinical symptoms and improve cardiac function indexes, and thus can be used according to the patients' conditions in clinical practice. However, limited by the quality and sample size of the included studies, the conclusion remains to be verified by multi-center, large-sample, and high-quality RCT in the future.
Humans ; Bayes Theorem ; Cardiomyopathy, Dilated/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Natriuretic Peptide, Brain ; Network Meta-Analysis ; Nonprescription Drugs/therapeutic use* ; Stroke Volume ; Ventricular Function, Left

Objective:To investigate the relationship between the level of anti Mullerian hormone (AMH) and antral follicle count (AFC) and oocytes number in patients with in vitro fertilization (IVF). Methods:372 patients with primary infertility who received IVF and embryo transfer (IVF-ET) treatment in the Affiliated Hospital of Guizhou Medical University from January 2020 to December 2020 were prospectively selected as the study subjects. According to the oocytes obtained, the patients were divided into low ovarian response group (LOR group, the number of oocytes obtained ≤5, n=37), normal group (NOR group, the number of oocytes obtained was 6-15, n=292) and high ovarian response group (HOR group, the number of oocytes obtained >15, n=43). The levels of AMH and AFC in the three groups were observed. The relationship between AMH, AFC with LOR and HOR was observed by multivariate logistic analysis. The sensitivity, specificity, optimal cut-off value and area under the curve (AUC) of AMH and AFC for predicting LOR and HOR were calculated by receiver operating characteristic (ROC) curve. Results:There were significant difference in AMH, AFC and oocyte number among the three groups (all P<0.05). The AMH, AFC and oocyte number in NOR group were higher than those in LOR group, and AMH, AFC and oocyte number in HOR group were higher than those in LOR and NOR group (all P<0.05). The results of binary multivariate analysis showed that AFC and AMH were protective factors of LOR (all P<0.05), while AFC and AMH were risk factors of HOR ( P<0.05). The sensitivity and specificity of AMH and AFC in predicting LOR were 83.8% and 75.7%, 65.7% and 84.2%, respectively. The sensitivity of AMH or AFC positive as the standard for predicting LOR was 94.6%, and the specificity of AMH and AFC was 91.6%. The sensitivity and specificity of positive AMH and AFC in predicting HOR were 69.8% and 74.4%, 69.6% and 83.6%, respectively. The sensitivity of AMH or AFC positive as the standard for predicting HOR was 93.0%, and the specificity of AMH and AFC positive as the standard for predicting HOR was 93.0%. Conclusions:AMH and AFC are significantly correlated with oocyte number in patients with primary infertility. Flexible application of AMH and AFC is beneficial to better predict the number of oocytes obtained, which provides a reference for clinical development of individualized ovarian stimulation program.

Objective: The surgical reconstruction strategy for scar contracture deformity in chin and neck was explored, aiming to obtain better aesthetic outcome. Methods: A retrospective observational study was conducted. From December 2017 to April 2021, 34 patients with scar contracture deformity in chin and neck after burns were hospitalized in the Department of Plastic Surgery of the First Affiliated Hospital of Army Medical University (the Third Military Medical University), aged 12-54 years, including 13 males and 21 females, 4 cases with chin affected only, 7 cases with neck affected only, and 23 cases with both chin and neck affected. The scar areas were 48-252 cm². All the patients were treated by operation with expanded flaps, following the "MRIS" principle of matching of the color and thickness of the repair flaps (match), reconstructing of the aesthetic features of subunits (reconstruction), design of incision according to the plastic principle (incision), and prevention of the surgical incision scar (scar). The rectangular or kidney shaped skin and soft tissue expander (hereinafter referred to as the expander) with rated capacity of 80-400 mL was embedded in the first stage, which was routinely expanded to 3-5 times of the rated capacity of the expander. In the second stage, scar resection and expanded flap excision were performed to repair the secondary wound, and the flap donor site was sutured directly. The expansion ratio of the expander (with average value being calculated), the type of flaps used, the reconstruction of local aesthetic morphology, the appearance of postoperative incision, the survival of flap, and the situation of donor and recipient sites observed during follow-up were recorded. Results: Among the 34 patients, the average expansion ratio of the implanted expander was 3.82 times of the rated capacity of the expander. Three cases were repaired by the expanded local pedicled flap only, 19 cases by the expanded shoulder and/or chest perforator pedicled flap only, 10 cases by the expanded local pedicled flap combined with the expanded shoulder and/or chest perforator pedicled flap, and 2 cases by the expanded local pedicled flap combined with the expanded free flap of the second intercostal perforator of internal thoracic artery. After scar resection, the shapes of lower lip and chin-lip groove were reconstructed in 10 cases, chin process reconstruction and chin lengthening were performed in 16 cases, and the cervico-mental angle and mandibular margin contour were reconstructed in 28 cases. The surgical incision was concealed, most of which were located at the natural junction or turning point of the chin and neck subunits. The vertical incision of neck was Z-shaped or fishtail-shaped. All the expanded flaps in 34 patients survived after operation, of which 8 patients had minor necrosis at the edge or tip of the expanded flaps 1-3 days after operation and healed after dressing change. During the follow-up of 3-18 months, little difference in color and thickness between the expanded flap and the skin of chin and neck was observed, and the aesthetic shape of chin and neck was significantly improved, with mild scar hyperplasia of surgical incision. Conclusions: Reconstruction of scar contracture deformity in chin and neck by using expanded flaps based on the "MRIS" principle is beneficial to improve the quality of surgery and achieve better aesthetic outcome.
Chin/surgery* ; Cicatrix/surgery* ; Contracture/surgery* ; Female ; Free Tissue Flaps ; Humans ; Male ; Perforator Flap ; Reconstructive Surgical Procedures ; Skin Transplantation ; Surgical Wound ; Treatment Outcome

Objective:To investigate the clinical value of nutritional indexes including body mass index (BMI), albumin (ALB), nutrition risk screening 2002 (NRS 2002) and the nutrition risk in critically ill score (NUTRIC) in 28-day prognosis of patients with sepsis related acute kidney injury (AKI).Methods:A prospective cohort study was conducted. Patients with sepsis treated in the emergency intensive care unit (EICU) of China Rehabilitation Research Center from December 1, 2018 to December 1, 2020 were observed for 7 days. Patients with sepsis related AKI were enrolled in this study. The gender, age, BMI, basic diseases, shock, number of affected organs, length of hospital stay, ALB, mechanical ventilation (MV) and vasoactive drug use, sequential organ failure score (SOFA), rapid sequential organ failure score (qSOFA) and acute physiology and chronic health evaluationⅡ(APACHEⅡ) were recorded. The NRS 2002 score and NUTRIC score were calculated. Cox regression model was used to analyze the risk factors of 28-day mortality in patients with sepsis related AKI. The receiver operator characteristic curves (ROC curves) were drawn and the areas under the ROC curves (AUC) were calculated, and the value of BMI, ALB, NRS 2002 score and NUTRIC score was analyzed to predict 28-day mortality in patients with sepsis related AKI. Kaplan Meier survival curves were used to analyze the effects of NRS 2002 score and NUTRIC score stratification on the 28 day prognosis of patients with sepsis related AKI.Results:A total of 140 patients with sepsis related AKI were enrolled, including 73 survival patients and 67 died patients within 28 days. The 28-day mortality was 47.9% (67/140). BMI in the survival group was significantly higher than that in the death group [kg/m 2: 22.0 (19.5, 25.6) vs. 20.7 (17.3, 23.9), P < 0.05], and NRS 2002 score and NUTRIC score were significantly lower than those in the death group [NRS 2002 score: 5 (4, 6) vs. 7 (6, 7), NUTRIC score: 6 (5, 7) vs. 7 (6, 9), both P < 0.05]. The ALB of the survival group was slightly higher than that of the death group, but the difference was not statistically significant. Cox regression analysis showed that NRS 2002 score and NUTRIC score were independent risk factors for 28-day death in patients with sepsis related AKI. ROC curve analysis showed that NUTRIC score had the strongest predictive ability for 28-day death [AUC = 0.785, 95% confidence interval (95% CI) was 0.708-0.850], followed by NRS 2002 score (AUC = 0.728, 95% CI was 0.647-0.800), but there was no significant difference between them. Compared with NRS 2002 score, the predictive ability of BMI and ALB was poor. Kaplan-Meier curve analysis showed that the prognosis of patients with NRS 2002 score≥5 was significantly worse than that of patients with NRS 2002 score < 5 (28-day cumulative survival rate: 42.1% vs. 75.6%, Log-Rank test: 2 = 11.884, P = 0.001), and the prognosis of patients with NUTRIC score≥6 was significantly worse than that of patients with NUTRIC score < 6 (28-day cumulative survival rate: 40.4% vs. 86.1%, Log-Rank test: 2 = 19.026, P = 0.000). Conclusions:Patients with sepsis related AKI have high nutritional risk. Both NRS 2002 score and NUTRIC score have good predictive value for the prognosis of patients with sepsis related AKI, while BMI and ALB have low predictive value. Due to the complex calculation of NUTRIC score, NRS 2002 score may be more suitable for emergency department.

OBJECTIVES: To investigate the mutation rate of the RAS gene and its clinical significance in children with acute lymphoblastic leukemia. METHODS: A retrospective analysis was performed on the medical data of 120 children with newly diagnosed acute lymphoblastic leukemia, who were admitted to the Third Affiliated Hospital of Zhengzhou University from January 2015 to January 2020 and underwent next-generation sequencing. The clinical and molecular features were analyzed. The impact of RAS gene mutation on the overall survival rate was evaluated in these children. RESULTS: Among the 120 children, 35 (29.2%) had RAS gene mutation, 30 (25.0%) had KRAS gene mutation, and 5 (4.2%) had both NRAS and KRAS gene mutations. All NRAS mutations and 71% (25/35) of KRAS mutations were located at the 12th and 13th codons. RAS gene mutation was detected in 35 (33.3%) out of 105 children with B-lineage acute lymphoblastic leukemia, but it was not detected in those with acute T lymphocyte leukemia. Of all the children, 11 (9.2%) were lost to follow-up, and among the 109 children followed up, 16 (14.7%) died. The children with RAS gene mutation had a significantly lower 2-year overall survival rate than those without RAS gene mutation (P<0.05). The prognosis of children with RAS gene mutation combined with WT1 overexpression and WBC>50×10⁹/L at diagnosis was worse (P<0.05). CONCLUSIONS RAS gene mutation is commonly observed in children with B-lineage acute lymphoblastic leukemia and may have an adverse effect on prognosis.
Child ; Genes, ras ; Humans ; Mutation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Prognosis ; Retrospective Studies