Objective:Synchronous mucinous metaplasia and neoplasia of the female genital tract (SMMN-FGT) occurring at multiple sites during the same period of time is extremely rare, and the aim of this study was to investigate the clinicopathologic features of SMMN-FGT and its relationship with prognosis.Methods:We retrospectively analyzed the clinicopathological features and follow-up records of 25 cases of SMMN-FGT diagnosed from January 2012 to October 2022 in the case database of Obstetrics and Gynecology Hospital of Fudan University.Results:The median age at onset was 46 years old, respectively. Clinical manifestations included irregular vaginal bleeding or drainage, pelvic pain, and ovarian cysts, etc. Germline genetic test confirmed Peutz-Jeghers syndrome (P-J syndrome) in two patients. All patients underwent surgery, and 13 patients had postoperative adjuvant radiotherapy and/or chemotherapy. The most frequent site of lesion was the cervix (21 cases), with 11, 10 and 16 cases occurring in the endometrium, fallopian tubes and ovaries, respectively. Six cases involved three sites simultaneously, and only one case had all four sites involved at the same time. Among the 9 cases with P53 mutation phenotype, 6 cases had gastric-type mucinous adenocarcinoma, 2 cases had lobular endocervical glandular hyperplasia, and 1 case had mucinous adenocarcinoma, whereas all the minimally deviated adenocarcinomas had wild phenotype of P53. The median follow-up time was 59 months, during which 3 cases died and 6 cases developed local recurrence or distant metastasis. According to our analysis, postoperative recurrence or metastasis was correlated with the FIGO stage of the disease, the number of lesion sites and the severe degree of the uterine lesions ( P＜0.05). Conclusions:SMMN-FGT has a relatively good clinical prognosis, and even advanced patients can benefit from surgery and adjuvant therapy. In young patients, the ovaries may be preserved if no evidence of lesions are seen after adequate evaluation. In SMMN-FGT, gastric-type mucinous adenocarcinoma occurring in the cervix may have a better prognosis than gastric-type mucinous adenocarcinoma of the cervix alone, so the accurate diagnosis of SMMN-FGT is critical for clinical management.

Background::Homoharringtonine (HHT) is an effective anti-inflammatory, anti-viral, and anti-tumor protein synthesis inhibitor that has been applied clinically. Here, we explored the therapeutic effects of HHT in a mouse heart transplant model.Methods::Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver, kidney, and hematology. A mouse heart transplantation model was constructed, and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan–Meier analysis, immunostaining, and bulk RNA sequencing analysis. The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells (Tregs) differentiation. Results::HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo. Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days ( P <0.001) without non-immune toxicity. The allografts had long-term survival after continuous HHT treatment for 28 days. HHT significantly reduced lymphocyte infiltration in the graft, and interferon-γ-secreting CD4 + and CD8 + T cells in the spleen ( P <0.01). HHT significantly increased the number of peripheral Tregs (about 20%, P <0.001) and serum interleukin (IL)-10 levels. HHT downregulated the expression of T cell receptor (TCR) signaling pathway-related genes ( CD4, H2-Eb1, TRAT1, and CD74) and upregulated the expression of IL-10 and transforming growth factor (TGF) -β pathway-related genes and Treg signature genes ( CTLA4, Foxp3, CD74, and ICOS). HHT increased CD4 + Foxp3 + cells and Foxp3 expression ex vivo, and it enhanced the inhibitory function of inducible Tregs. Conclusions::HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels, thereby promoting mouse heart allograft acceptance. These findings may have therapeutic implications for organ transplant recipients, particularly those with viral infections and malignancies, which require a more suitable anti-rejection medication.

Objective:To explore the relationship between depressive symptoms and filial piety in adult-child caregivers of disabled elderly,and the mediating effect of mutuality on the relationship.Methods:Totally 383 adult-child caregivers were assessed with the Center for Epidemiological Studies Depression Scale(CES-D),Dual Filial Piety Scale(DFPS)and Mutuality Scale(MS).The SPSS macro program Process was used to test the mediation model.Results:The CES-D scores were negatively correlated with the reciprocal filial piety scores and the MS scores(r=-0.49,-0.48,Ps＜0.01)and positively correlated with the authoritarian filial piety scores(r=0.37,P＜0.01).The MS scores were positively correlated with the reciprocal filial piety scores(r=0.76,P＜0.01),and negatively correlated with the authoritarian filial piety scores(r=-0.84,P＜0.01).Reciprocal filial piety scores were negatively associated with CES-D scores(β=-0.67).In addition,MS scores partly mediated the relationship between reciprocal filial piety scores and CES-D scores,the value of mediating effect was 22.89％.Conclusion:The depressive symptoms are correlated with filial piety and mutuality among adult-child caregivers of disabled eld-erly.

Objective:Synchronous mucinous metaplasia and neoplasia of the female genital tract (SMMN-FGT) occurring at multiple sites during the same period of time is extremely rare, and the aim of this study was to investigate the clinicopathologic features of SMMN-FGT and its relationship with prognosis.Methods:We retrospectively analyzed the clinicopathological features and follow-up records of 25 cases of SMMN-FGT diagnosed from January 2012 to October 2022 in the case database of Obstetrics and Gynecology Hospital of Fudan University.Results:The median age at onset was 46 years old, respectively. Clinical manifestations included irregular vaginal bleeding or drainage, pelvic pain, and ovarian cysts, etc. Germline genetic test confirmed Peutz-Jeghers syndrome (P-J syndrome) in two patients. All patients underwent surgery, and 13 patients had postoperative adjuvant radiotherapy and/or chemotherapy. The most frequent site of lesion was the cervix (21 cases), with 11, 10 and 16 cases occurring in the endometrium, fallopian tubes and ovaries, respectively. Six cases involved three sites simultaneously, and only one case had all four sites involved at the same time. Among the 9 cases with P53 mutation phenotype, 6 cases had gastric-type mucinous adenocarcinoma, 2 cases had lobular endocervical glandular hyperplasia, and 1 case had mucinous adenocarcinoma, whereas all the minimally deviated adenocarcinomas had wild phenotype of P53. The median follow-up time was 59 months, during which 3 cases died and 6 cases developed local recurrence or distant metastasis. According to our analysis, postoperative recurrence or metastasis was correlated with the FIGO stage of the disease, the number of lesion sites and the severe degree of the uterine lesions ( P＜0.05). Conclusions:SMMN-FGT has a relatively good clinical prognosis, and even advanced patients can benefit from surgery and adjuvant therapy. In young patients, the ovaries may be preserved if no evidence of lesions are seen after adequate evaluation. In SMMN-FGT, gastric-type mucinous adenocarcinoma occurring in the cervix may have a better prognosis than gastric-type mucinous adenocarcinoma of the cervix alone, so the accurate diagnosis of SMMN-FGT is critical for clinical management.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Autologous ozonized blood transfusion(AOBT) is a therapy of re-transfusion of 100-200 mL of autologous blood after shaking and agitation with appropriate amount of oxygen-ozone in vitro. The oxidation of blood through the strong oxidation of ozone can enhance the non-specific immune response of the body, regulate the internal environment and promote health. This therapy has been increasingly applied in clinical practice, while no unified standard for the operation process in terms of ozone concentration, treatment frequency and treatment course had been established. This operation process of AOBT is primarily explored in order to standardize the operation process and ensure its safety and efficacy.

As an important part of tumor microenvironment, neutrophils are poorly understood due to their spatiotemporal heterogeneity in tumorigenesis. Here we defined, at single-cell resolution, CD44-CXCR2- neutrophils as tumor-specific neutrophils (tsNeus) in both mouse and human gastric cancer (GC). We uncovered a Hippo regulon in neutrophils with unique YAP signature genes (e.g., ICAM1, CD14, EGR1) distinct from those identified in epithelial and/or cancer cells. Importantly, knockout of YAP/TAZ in neutrophils impaired their differentiation into CD54+ tsNeus and reduced their antitumor activity, leading to accelerated GC progression. Moreover, the relative amounts of CD54+ tsNeus were found to be negatively associated with GC progression and positively associated with patient survival. Interestingly, GC patients receiving neoadjuvant chemotherapy had increased numbers of CD54+ tsNeus. Furthermore, pharmacologically enhancing YAP activity selectively activated neutrophils to suppress refractory GC, with no significant inflammation-related side effects. Thus, our work characterized tumor-specific neutrophils in GC and revealed an essential role of YAP/TAZ-CD54 axis in tsNeus, opening a new possibility to develop neutrophil-based antitumor therapeutics.
Humans ; Animals ; Mice ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Stomach Neoplasms/pathology* ; Neutrophils/pathology* ; Signal Transduction/genetics* ; YAP-Signaling Proteins ; Tumor Microenvironment ; Hyaluronan Receptors/genetics*

Objective:To investigate the relationship between the activation level of Nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome and the change of cognitive functions in patients with acute ischemic stroke.Methods:A total of 88 patients with acute ischemic stroke in Department of Neurology from October 2018 to July 2020 were selected as case group and 100 healthy physical examinees were selected as control group.Peripheral blood of the case group and the control group was collected, and peripheral blood mononuclear cells (PBMCs) were isolated by centrifugation.Then the NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1 and interleukin-1β (IL-1β) expression were detected by Western blot.The cognitive function of patients with acute ischemic stroke was detected by Montreal Cognitive Assessment (MoCA). The differences in expression levels of NLRP3, ASC, Caspase-1 and IL-1β were compared between the case group and the control group.Pearson correlation analysis was used to analyze the correlation between expression levels of NLRP3, ASC, Caspase-1, IL-1β and MoCA score.Logistic multivariate regression was used to analyze the relationship between expression levels of NLRP3, ASC, caspase-1, IL-1β and the cognitive dysfunction.Results:(1)Western blot results showed that NLRP3, ASC, Caspase-1 and IL-1β expressions in PBMCs cells in the case group were higher than those in the control group (all P<0.05). (2)The expression level of NLRP3 in stroke patients with hypertension, hyperlipidemia, National Institutes of Health Stroke Scale (NIHSS) score ≥ 8 points was significantly higher than that in patients without hypertension, hyperlipidemia and NIHSS score<8 points ( P<0.05); (3)The incidence of cognitive dysfunction in the case group was 34.09% (30/88). The MoCA scores of the cognitive dysfunction group and the non-cognitive dysfunction group were 20 (24, 28) and 27 (26, 28) points respectively, and the difference between the groups was statistically significant ( P<0.05); (4)Pearson correlation analysis showed that NLRP3, ASC, caspase-1 and IL-1β expression in PBMCs cells were negatively correlated with MoCA scores ( r=-0.426, -0.396, -0.417, -0.320 respectively, all P<0.05). (5)Logistic regression analysis showed that hyperlipidemia, NIHSS scores, frontotemporal lobe infarction, and NLRP3 expression were the influencing factors for the occurrence of cognitive dysfunction (all P<0.05). Conclusion:Patients with acute ischemic stroke have high activated NLRP3 inflammasome, and its activation degree is closely related to the condition and the occurrence of cognitive dysfunction after stroke.Targeted inhibition or regulation of NLRP3 inflammasome activation may become a new idea of neuroprotection for acute ischemic stroke.

Objective:To analyze the clinical characteristics of gastrointestinal symptoms and liver function injury in patients with coronavirus disease 2019 (COVID-19).Methods:From January 23, 2020 to February 29, 2020, the medical records of 251 patients with COVID-19 admitted to the West Campus of the Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, were collected. The proportion of the patients with gastrointestinal symptoms including anorexia, nausea and vomiting, diarrhea and abdominal pain were analyzed respectively. The patients were divided into common type (76 cases), severe type (65 cases) and critical type (110 cases). The incidence of liver function injury and the changes of liver function parameters such as total bilirubin (TBil), direct bilirubin (DBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), albumin and globulin of the patients with different clinical types and with or without gastrointestinal symptoms were analyzed. Mann-Whitney U test, Chi square test and Fisher′s exact test were used for statistical analysis. Results:The main gastrointestinal symptoms of patients with COVID-19 were anorexia (33.9%, 85/251), diarrhea (12.0%, 30/251), nausea and vomiting (7.6%, 19/251) and abdominal pain (1.2%, 3/251). 143 patients (57.0%) had liver function injury, the rate of liver function injury in critical type patients was 75.5% (83/110), which was higher than that of common type patients (40.8%, 31/76) and severe type patients (44.6%, 29/65), and the differences were statistically significant ( χ2=22.765 and 16.865, both P<0.01). There was no significant difference in the proportion of patients with liver function injury between common type and severe type patients ( P>0.05). There was no statistically significant difference in the proportion of liver function injury between patients with gastrointestinal symptoms and those without gastrointestinal symptoms (57.8%(67/116) vs. 56.3%(76/135), P>0.05). The median values of TBil, DBil, ALT, AST, ALP, GGT, LDH and globulin level of critical type patients were 13.5 μmol/L, 4.9 μmol/L, 44.5 U/L, 50.0 U/L, 64.0 U/L, 41.0 U/L, 527.0 U/L and 33.6 g/L respectively. The proportions of critical type patients with TBil level >34.2 μmol/L, DBil level>13.6 μmol/L, ALT level>80 U/L and AST level>80 U/L were 7.3% (8/110), 7.3% (8/110), 17.3% (19/110) and 17.3% (19/110), respectively. These results were all higher than those of common type patients (9.5 μmol/L, 2.9 μmol/L, 28.5 U/L, 28.5 U/L, 54.0 U/L, 25.5 U/L, 225.5 U/L, 30.1 g/L, 0, 0, 6.6% (5/76) and 2.6% (2/76) ) and severe type patients (10.4 μmol/L, 3.4 μmol/L, 30.0 U/L, 31.0 U/L, 49.0 U/L, 25.0 U/L, 284.0 U/L, 30.7 g/L, 0, 0, 6.2% (4/65) and 1.5% (1/65)), and the differences were statistically significant ( Z=-4.264, -5.507, -4.000, -6.558, -3.112, -4.333, -4.858, -3.873, Fisher′s exact test, Fisher′s exact test, χ2=4.574, 9.620; Z=-3.060, -3.850, -3.923, -5.005, -9.495, -7.651, -3.853, -2.725, Fisher′s exact test, Fisher′s exact test, χ2=4.425, 10.169; all P<0.01). The median values of pre-albumin level, albumin level and the albumin to globulin ratio of critical type patients were 85.3 g/L, 28.2 g/L and 0.8, which were all lower than those of common type patients (157.3 g/L, 32.3 g/L and 1.1, respectively) and severe type patients (133.6 g/L, 31.6 g/L and 1.1, respectively), and the differences were statistically significant ( Z=-6.631, -3.647, -4.924, -4.503, -5.283 and -3.903, all P<0.01). The median albumin level of patients with diarrhea was lower than that of patients without diarrhea (28.2 g/L vs. 30.5 g/L), the proportion of diarrhea patients whose TBil level >20.0 to 34.2 μmol/L was higher than that of patients without diarrhea (70.0%, 21/30 vs. 10.9%, 24/221), and the differences were statistically significant ( Z=-2.182, χ2 =62.788; both P<0.05). Conclusions:Anorexia is the most common digestive symptom in COVID-19 patients, and the incidences of abdominal pain is low. The incidence of liver function injury of critical type patients is high. There is no significant correlation between gastrointestinal symptoms and liver function injury, and patients with diarrhea have lower albumin levels.

Objective To investigate the association between the plasma levels of 20 amino acids and the risk of diabetes in middle-aged and elderly population.Methods This study was a part of the Chinese multi-provincial cohort study conducted in communities of Shougang.In 2007 and 2012,the population was investigated for diabetes and other risk factors.Blood samples collected from 475 people were tested for various amino acid levels by liquid chromatography-tandem mass spectrometry.A multivariate logistic regression analysis was used to analyze the association between plasma amino acid levels and diabetes risk.Results The age of the selected population at baseline was (58.7±6.3) years,and the blood glucose level at baseline was (5.68 ± 1.34) mmol/L.Among them,56 (11.79％) subjects were diabetes.Multivariate logistic regression analyses showed that after adjusting for age,gender,body mass index,systolic blood pressure and dyslipidemia,individuals with plasma branched-chain amino acid (valine,leucine and isoleucine) and cysteine in the highest tertile levels were at high risk of diabetes with the ORs of 3.61 (95％ CI 1.48-8.80),3.27 (95％ CI 1.34-7.99),2.46 (95％ CI 1.04-5.84) and 2.09 (95％ CI 1.02-4.27),respectively.After 5 years' followed up,5.73％ (24/419) subjects developed diabetes.Compared with those in the lowest tertile,individuals with plasma branched-chain amino acid (total concentration),phenylalanine,and tyrosine levels at baseline in the highest tertile had 3.69 times,3.61 times and 4.14 times higher risk to develop new diabetes,respectively.In contrast,individuals with plasma glycine level in the highest tertile had only 76％ (OR 0.24,95％ CI 0.06-0.91) risk for the development of diabetes compared with those with plasma glycine level in the lowest tertile.Conclusions The increase in plasma branched-chain amino acid and cysteine levels is significantly associated with an increase in incident diabetes.Subjects with higher levels of branched-chain amino acids and aromatic amino acids (phenylalanine,tyrosine) had a significantly higher risk of developing new-onset diabetes,while those with higher glycine levels had a significantly lower risk of developing diabetes in 5 years.