Purpose To explore the application and clini-copathological significance of molecular classification in endome-trial cancer(EC)of WHO(2020)tumors of the female repro-ductive system.Methods Sixty-two EC patients were collected and categorized into four subgroups,namely POLE mutation type,mismatch repair deficient(MMRd)type,non-specific molecular spectrum(NMSP)type,and p53 mutation type,based on WHO molecular classification tested by PCR and im-munohistochemistry.The correlation among four molecular sub-groups and their clinicopathological features were analyzed.Re-sults The molecular classification was distributed as follows:3(4.8％)cases were POLE-mutated,15(24.2％)cases MMRd,36(58.1％)cases NSMP and 8(12.9％)cases p53 abnormal expression.There were no significant differences a-mong POLE-mutated and infiltration depth,grade,lymph vascu-lar space invasion and other pathological factors such as lymph node metastasis and FIGO stage(P＞0.05).Among 15 patients with MMRd,the proportion of FIGO stage Ⅱ+Ⅲ significantly increased.One case showed abnormal overexpression of p53 pro-tein,while two cases showed complete loss of expression in MMRd subgroup.36 cases of NSMP were associated with low histopathological grade(Grade Ⅰ+Ⅱ)(P＜0.05),and no significant differences were observed among NSMP and other clinicopathological factors(P＞0.05).The p53 abnormal ex-pression in 8 cases was related to high histopathological grade(Grade Ⅲ)(P＜0.05),and the rate of lymph node metastasis and FIGO stage Ⅱ+Ⅲ significantly increased in patients with p53 abnormal expression,and although the difference was not statistically significant(P＞0.05).Conclusion The molecu-lar subgroups of EC have certain clinical application value,the cases with MMRd and p53 abnormal expression may have poor prognosis than these with POLE-mutated and NSMP.

ObjectiveTo establish a qualitative analysis method for the chemical constituents of the reference sample of Xiao Xumingtang， and to establish the fingerprint of 15 batches of Xiao Xumingtang， so as to evaluate the quality consistency among batches. MethodAccording to the key information of Xiao Xumingtang in the Key Information Table of Ancient Famous Classical Formulas（25 Formulas）， the reference sample of this formula was prepared， and it was detected by ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）. The chemical components were identified by self-constructed database， consulting relevant literature， and comparing with the reference substances， and the components were assigned by comparing with single drug samples and negative samples lacking single drug. The fingerprint of the reference sample of Xiao Xumingtang was established using high performance liquid chromatography（HPLC）， and the common peaks were assigned and identified through single drug samples and negative samples lacking single drug. ResultBased on the information of MS fragments， relevant literature， and database retrieval， a total of 64 compounds were identified and inferred from the reference sample of Xiao Xumingtang， including 31 flavonoids， 8 terpenoids， 12 triterpenoid saponins， 2 phthalides， 3 phenylpropanoids， 2 gingerols， 5 alkaloids， and 1 cyanoside. Among them， 21 were derived from Scutellariae Radix， 10 from stir-fried Glycyrrhizae Radix et Rhizoma， 9 from Ginseng Radix et Rhizoma， 8 from Paeoniae Radix Alba， 4 from Saposhnikoviae Radix， 3 from Stephaniae Tetrandrae Radix， 3 from Chuanxiong Rhizoma， 2 from Aconiti Lateralis Radix Praeparata， 2 from Zingiberis Rhizoma Recens， 1 from Ephedrae Herba， and 1 from Armeniacae Semen Amarum. The established HPLC fingerprint of the reference sample of Xiao Xumingtang had 23 common peaks， among which， peaks 1 and 2 were derived from Paeoniae Radix Alba， peaks 3 and 7 from Saposhnikoviae Radix， peaks 4， 8 and 9 from Stephaniae Tetrandrae Radix， peaks 10， 17， 18， 20 and 21 from stir-fried Glycyrrhizae Radix et Rhizoma， peaks 11-16， 19 and 22 from Scutellariae Radix， peak 5 from Chuanxiong Rhizoma， peak 23 from Zingiberis Rhizoma Recens， peak 6 was the common component of stir-fried Glycyrrhizae Radix et Rhizoma and Scutellariae Radix. A total of 10 compounds including albiflorin（peak 1）， paeoniflorin（peak 2）， cimicifugoside（peak 3）， 5-O-methylvisammioside（peak 7）， baicalin（peak 11）， sec-O-glucosylhamaudol（peak 13）， oroxylin A-7-O-β-D-glucuronide（peak 15）， wogonoside（peak 16）， glycyrrhizic acid（peak 21） and 6-gingerol（peak 23） were identified. The similarities of 15 batches of reference samples were>0.999， indicating that the reference samples had good consistency. ConclusionThrough the identification of the chemical constituents in the reference sample of Xiao Xumingtang， it is clear that the composition of the samples is mainly composed of flavonoids and triterpenoid saponins. The established fingerprint can basically reflect the overall chemical characteristics of the reference sample of Xiao Xumingtang， which can provide a basis for the quality research of its compound preparations.

AIM:To investigate the effects of sodium hydrosulfide(NaHS)on hexokinase 2(HK2)-nucleo-tide-binding oligomerization domain-like receptor protein 3(NLRP3)-gasdermin D(GSDMD)pathway and pyroptosis in-duced by lung ischemia/reperfusion(I/R)in rats.METHODS:Male Sprague-Dawley rats were divided into 6 groups:control group,control+NaHS group,I/R group,low-dose NaHS+I/R(L+I/R)group,medium-dose NaHS+I/R(M+I/R)group,and high-dose NaHS+I/R(H+I/R)group,with 6 rats in each group.The NaHS was administered via intraperi-toneal injection at 1.5 mL,30 min before modeling.The left lung tissues were collected 30 min after ischemia and 1 h af-ter reperfusion,and the wet/dry weight ratio and total lung water content were recorded.Hematoxylin-eosin(HE)staining was used to examine lung tissue morphological changes.The levels of malondialdehyde(MDA),myeloperoxidase(MPO)and lactate in lung tissues were measured with test kits.ELISA was employed to determine the levels of interleukin-1β(IL-1β)and IL-18.The expression of glycolysis-and pyroptosis-related indicators was analyzed by Western blot,qRT-PCR and immunofluorescence staining.RESULTS:Compared with control group,the rats in NaHS group showed no signifi-cant differences in all laboratory tests(P>0.05).The rats in I/R group exhibited significant lung injury,oxidative stress,increased lactate level,and up-regulated glycolysis and pyroptosis(P<0.05 or P<0.01).Compared with I/R group,the indicators in L+I/R group showed a downward trend(P<0.01)or no difference(P>0.05),while those in M+I/R group dis-played a significant reduction(P<0.05 or P<0.01).However,the indexes in H+I/R group exhibited no significant dif-ferences in these tests(all P>0.05).CONCLUSION:A moderate dose(56 μmol·L-1·kg-1)of NaHS mitigated the oc-currence of pyroptosis by inhibiting the HK2-NLRP3-GSDMD pathway,thus contributing to the attenuation of lung I/R in-jury in rats.

Objective:To construct a novel dual-specific antibody targeting human CD123 (CD123 DuAb) and study its effects in acute myeloid leukemia (AML) .Methods:Based on the variable region of the CD123 monoclonal antibody independently developed at our institution, the CD123 DuAb expression plasmid was constructed by molecular cloning and transfected into ExpiCHO-S cells to prepare the antibody protein. Through a series of in vitro experiments, its activation and proliferation effect on T cells, as well as the effect of promoting T-cell killing of AML cells, were verified.Results:① A novel CD123 DuAb plasmid targeting CD123 was successfully constructed and expressed in the Expi-CHO eukaryotic system. ②The CD123 DuAb could bind both CD3 on T cells and CD123 on CD123 + tumor cells. ③When T cells were co-cultured with MV4-11 cells with addition of the CD123 DuAb at a concentration of 1 nmol/L, the positive expression rates of CD69 and CD25 on T cells were 68.0% and 44.3%, respectively, which were significantly higher than those of the control group ( P<0.05). ④Co-culture with CD123 DuAb at 1 nmol/L promoted T-cell proliferation, and the absolute T-cell count increased from 5×10 5/ml to 3.2×10 6/ml on day 9, and CFSE fluorescence intensity decreased significantly. ⑤ With the increase in CD123 DuAb concentration in the culture system, T-cell exhaustion and apoptosis increased. When the CD123 DuAb was added at a concentration of 1 nmol/L to the culture system, the proportion of CD8 + PD-1 + LAG-3 + T cells was 10.90%, and the proportion of propidium iodide (PI) - Annexin Ⅴ + T cells and PI + Annexin Ⅴ + T cells was 18.27% and 11.43%, respectively, which were significantly higher than those in the control group ( P<0.05). ⑥ The CD123 DuAb significantly activated T cells, and the activation intensity was positively correlated with its concentration. The expression rate of CD107a on T cells reached 16.05% with 1 nmol/L CD123 DuAb, which was significantly higher than that of the control group ( P<0.05). ⑦The CD123 DuAb promoted cytokine secretion by T cells at a concentration of 1 nmol/L, and the concentration of IFN-γ and TNF-α in the supernatant of the co-culture system reached 193.8 pg/ml and 169.8 pg/ml, respectively, which was significantly higher than that of the control group ( P<0.05). ⑧When CD123 DuAb was added at a concentration of 1 nmol/L to the co-culture system of T cells and CD123 + tumor cells, the killing intensity of T cells significantly increased, and the residual rates of CD123 + MV4-11 cells, CD123 + Molm13 cells, and CD123 + THP-1 cells were 7.4%, 6.7%, and 14.6% on day 3, respectively, which were significantly lower than those in the control group ( P<0.05) . Conclusion:In this study, a novel CD123 DuAb was constructed and expressed. In vitro experiments verified that the DuAb binds to CD123 + tumor cells and T cells simultaneously, promotes T-cell activation and proliferation, and facilitates their anti-leukemia effect, which provides a basis for further clinical research.

Objective To analyze the prevalence trend of chronic hepatitis C and liver function impairment in Taixi area from 2018 to 2021, and to provide theoretical basis for preventing liver function impairment in hepatitis C patients in Taixi area. Methods The data of hepatitis C cases reported in Taixi were downloaded from the infectious disease reporting Information management system of Chinese Center for Disease Control and Prevention, and the epidemiological characteristics of hepatitis C were analyzed by descriptive epidemiological methods. The clinical data including gender, age, place of residence, smoking history, drinking history, therapeutic drugs, genotyping and other clinical data were collected from HIS system of the hospital. Patients were divided into liver function injury group and control group according to whether they had liver function injury. Univariate analysis and logistic regression were used to analyze the factors of liver function injury in hepatitis C patients in Taixi area. Results Among the 550 cases reported from 2018 to 2021, there were no deaths, including 292 males and 258 females. The male cases were more than the female cases, and the average age was (53.47±5.74) years old. There was no significant difference in the composition of male and female cases among different age groups (χ²=1.472,P>0.05). From 2018 to 2021, the proportion of patients aged 40 to 59 was significantly higher than that of patients aged 20 to 39 and ≥60. The occupation composition was mainly farmers, accounting for 44.36% (244/550), and 287 cases (52.18%) lived mainly in rural areas. From 2018 to 2021, 129 (23.45%) of 550 patients with hepatitis C had liver function injury. ALT, AST and GGT values in the liver function injury group were significantly higher than those in the control group (P<0.05). The ALB value of liver function injury group was significantly lower than that of control group (P<0.05). There were statistically significant differences between the two groups in mean age, drinking history, diabetes mellitus, genotyping, HCV-RNA viral load, CD4+CD25+Treg (P<0.05). CD4+CD25+Treg>5%, genotype 1b and high load of HCV-RNA were independent risk factors for liver function impairment in hepatitis C patients in Taixi area (P<0.05). Conclusion The incidence of hepatitis C was high in Taixi area from 2018 to 2021, and patients with CD4+CD25+Treg<5%, genotype 1b and high load of HCV-RNA had a high risk of liver function impairment. Therefore, active treatment should be carried out to reduce the occurrence of liver function injury.

Objective:The nasal swell body（NSB） consists of the nasal septal cartilage, nasal bone, and swollen soft tissue, all of which are visible during endoscopic and imaging examinations. Although the function of the NSB remains uncertain, there is evidence to suggest that it plays a vital role in regulating nasal airflow and filtering inhaled air. Based on anatomical and histological evidence, it is hypothesized that the NSB is indispensable in these processes. This study aims to investigate the impact of NSB on nasal aerodynamics and the deposition of allergen particles under physiological conditions. Methods:The three-dimensional （3D） nasal models were reconstructed from computed tomography （CT） scans of the paranasal sinus and nasal cavity in 30 healthy adult volunteers from Northwest China, providing basis for the construction of models without NSB following virtual NSB-removal surgery. To analyze the distribution of airflow in the nasal cavity, nasal resistance, heating and humidification efficiency, and pollen particle deposition rate at various anatomical sites, we employed the computed fluid dynamics（CFD） method for numerical simulation and quantitative analysis. In addition, we created fully transparent segmented nasal cavity models through 3D printing, which were used to conduct bionic experiments to measure nasal resistance and allergen particle deposition. Results:①The average width and length of the NSB in healthy adults in Northwest China were （12.85±1.74） mm and （28.30±1.92） mm, respectively. ②After NSB removal, there was no significant change in total nasal resistance, and cross-sectional airflow velocity remained essentially unaltered except for a decrease in topical airflow velocity in the NSB plane. ③There was no discernible difference in the nasal heating and humidification function following the removal of the NSB; ④After NSB removal, the deposition fraction（DF） of Artemisia pollen in the nasal septum decreased, and the DFs post-and pre-NSB removal were（22.79±6.61）% vs （30.70±12.27）%, respectively; the DF in the lower airway increased, and the DFs post-and pre-NSB removal were（24.12±6.59）% vs （17.00±5.57）%, respectively. Conclusion:This study is the first to explore the effects of NSB on nasal airflow, heating and humidification, and allergen particle deposition in a healthy population. After NSB removal from the healthy nasal cavities: ①nasal airflow distribution was mildly altered while nasal resistance showed no significantly changed; ②nasal heating and humidification were not significantly changed; ③the nasal septum's ability to filter out Artemisia pollen was diminished, which could lead to increased deposition of Artemisia pollen in the lower airway.
Adult ; Humans ; Cross-Sectional Studies ; Nasal Cavity/surgery* ; Allergens ; Pollen ; Artemisia ; Hydrodynamics

In 2022,breast cancer ranks the first in incidence among all malignant tumors worldwide,and it's high recurrence and fatality rate has posed serious threat to human life and health.Triple negative breast cancer(TNBC)is known for its poor prognosis among all types of breast cancer,and is often associated with elevated expression of epidermal growth factor receptor(EGFR).EGFR is widely expressed on the surface of various cells.The signaling pathway mediated by EGFR is mainly involved in cell growth,proliferation and differentiation.EGFR overexpression is often closely related to tumor invasion,metastasis and prognosis.Therefore,elucidating the roles of EGFR in TNBC and developing prevention and treatment strategies correspondingly are helpful to prevent and control the occurrence of breast cancer,and improve patients'quality of life.This review summarizes the research progress in the roles of EGFR,the treatment strategies and drug resistance in TNBC,in order to provide more refence for treating and improving the prognosis of breast cancer.

Dynasore is a small molecule that inhibits the GTPase activity of dynamin and mitochondria-related proteins both in vitro and in vivo,consequently preventing bacteria and viruses from entering cells via endocytic processes,impeding infection and spread of the pathogen.Dynasore is able to participate in cell survival,proliferation and apoptosis through a variety of dynamin protein-independent mechanisms such as reducing reactive oxygen species production,inhib-iting ferroptosis,lowering dynamin-related protein 1 activity to reduce mitophagy,and deeply engaging in vascular endo-thelial growth factor pathway.Here based on the molecular mechanisms and signaling pathways of dynasore involving in diseases,this review summarizes the role of dynasore in microbial infections,neurodegenerative diseases,and tumors.

Objective To investigate the effect of dapagliflozin on metabolic markers, hepatic fat content, and autonomic nervous function in patients with type 2 diabetes mellitus (T2DM) and metabolic associated fatty liver disease (MAFLD). Methods A total of 90 patients with T2DM and MAFLD who were admitted to The Second Affiliated Hospital of Zhengzhou University from October 2019 to October 2020 were enrolled and randomly divided into control group and dapagliflozin group, with 45 patients in each group. All patients were given conventional treatment before enrollment; the patients in the control group were treated with the original hypoglycemic regimen, and those in the dapagliflozin group were given dapagliflozin in addition to the treatment in the control group. The treatment cycle was 24 weeks. General information was collected before and after treatment, and the two groups were compared in terms of the changes in body mass index (BMI), glycosylated hemoglobin (HbA1c), fasting blood glucose (FPG), blood lipids, serum uric acid (SUA), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), liver function, liver fat content, and heart rate variability after treatment. The paired t -test was used for comparison of normally distributed continuous data within each group, and the independent samples t -test was used for comparison between groups; the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data within each group, and the Mann-Whitney U test was used for comparison between groups. The Chi-square test was used for comparison of categorical data between two groups. Results A total of 43 patients in the dapagliflozin group and 40 patients in the control group completed the study. After 24 weeks of treatment, the dapagliflozin group had significant reductions in BMI, HbA1c, FBG, triglyceride (TG), SUA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), HOMA-IR, and liver fat content ( t =8.781, 8.765, 8.813, 3.485, 6.199, 5.694, 3.428, 6.492, and 4.925, all P < 0.05) and significant increases in high-density lipoprotein cholesterol, standard deviation of all normal R-R intervals (SDNN), standard deviation of average NN intervals (SDANN), root mean square of successive differences, percent of the number whose difference between adjacent NN interval are more than 50 ms (pNN50), high frequency (HF), and low frequency (LF) ( t =-2.055, -6.307, -7.696, -3.388, and -7.928, Z =-3.339 and -3.309, all P < 0.05), while the control group had significant reductions in HbA1c, FBG, and HOMA-IR ( t =9.220, 7.214, and 3.340, all P < 0.05). Compared with the control group after treatment, the dapagliflozin group had significantly lower levels of BMI, HbA1c, TG, SUA, HOMA-IR, ALT, AST, and liver fat content ( t =-4.055, -2.670, -2.056, -2.496, -3.976, -3.703, -2.123, and -5.184, all P < 0.05) and significantly higher levels of SDNN, SDANN, pNN50, LF, and HF ( t =4.136, 5.433, and 5.971, Z =-2.333 and -2.010, all P < 0.05). Conclusion For patients with T2DM and MAFLD, dapagliflozin can reduce BMI, HbA1c, TG, SUA, and liver fat content, improve insulin resistance and liver function, reduce the activity of sympathetic nerve, and regulate autonomic nerve function.

Objective:To investigate the manifestations of liver injury in hospitalized patients with coronavirus disease 2019 (COVID-19), to investigate the prognosis indicators of the disease, and to provide the reference for clinical diagnosis and treatment.Methods:From January 10 to February 14, 2020, at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, the data of 333 hospitalized patients with COVID-19 were collected. The changes of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), direct bilirubin (DBil), indirect bilirubin (IBil) and albumin of the first liver function test after admission and the reexaminations of liver function test during hospitalization period in patients with liver injury were retrospectively analyzed. Student t test and Chi-square test were used for statistical analysis. Results:Liver injury occurred in 39.6% (132/333) of COVID-19 patients. There was no statistically significant difference in the rate of liver injury between patients in intensive care unit (ICU) and in general ward (45.6%, 26/57 vs. 38.4%, 106/276; χ2=1.026, P>0.05). 67.4% (89/132) of COVID-19 patients with liver injury presented with increased ALT or AST level on admission. During hospitalization, the level of ALT was higher than that of the first examination after admission ((60.28±50.44) U/L vs. (42.25±32.21) U/L), and the difference was statistically significant ( t=-3.230, P<0.05). The levels of ALT and AST of 71.2% (94/132) patients were both <80 U/L, which indicated that most of the patients showed mild liver injury. The patients with elevated level of TBil, DBil and IBil accounted for 3.9% (13/333), 5.4% (18/333) and 2.4% (8/333) of the COVID-19 patients, respectively. The albumin level of COVID-19 patients with liver injury during hospitalization was lower than that of the first examination after admission ((31.8±5.1) g/L vs. (33.7±5.4) g/L), and the difference was statistically significant ( t=2.712, P<0.05). The albumin levels at first examination on admission and reexamination during hospitalization of patients in ICU were both significantly lower than those of patients in general ward ((29.3±3.7) g/L vs. (34.8±5.1) g/L and (27.6±2.8) g/L vs. (32.9±5.1) g/L), and the differences were statistically significant ( t=4.928 and 4.783, both P<0.05). Conclusions:The incidence of liver injury in COVID-19 patients is high. A slight increase in aminotransferase levels is particularly common. Bilirubin abnormality is relatively rare and mild. The level of albumin may be one of the indicators for the severity and prognosis of COVID-19.