AIM:To investigate the therapeutic effect of menstrual blood-derived endometrial stem cells(MenSCs)on chemotherapy-induced intestinal mucositis and flora disorders in mice,and to explore the potential mecha-nism.METHODS:The mice were randomly divided into 3 groups including normal treatment,cisplatin(Cis)treatment and Cis+MenSC treatment,with 10 mice in each group.To induce intestinal mucositis,the mice were treated with Cis(2 mg·kg-1·d-1)by intraperitoneal injection for 5 consecutive days.Control mice for normal group were received equal vol-umes of normal saline.For Cis+MenSC treatment,MenSCs(1×106)was transplanted into the mice of Cis treated mice through tail vein.The performances and weight changes of mice were examined during the experiment.After the treat-ment,the small intestine and colon were isolated for subsequent HE staining,the ratio of F4/80 and IL-6 positive cells in small intestine were detected by immunohistochemical staining,and the expression of tight junction,inflammation and apoptosis related proteins was detected by Western blot.16S rDNA amplicon sequencing was performed to detect the diver-sity and richness of intestinal flora in mice.RESULTS:Compared to the Cis group,the MenSCs-treated mice showed sig-nificantly increased body weight,relieved intestinal lymphocytes infiltration,alleviated intestinal villous edema,and or-derly arranged glands in intestinal tissues.Further analysis indicated that MenSCs transplantation significantly up-regulat-ed the expression of intestinal tight junction related proteins ZO-1 and occludin in Cis-treated mice(P＜0.05).Subse-quently,MenSCs transplantation significantly inhibited the macrophages infiltration in intestinal tissues(P＜0.01),down-regulated the expression of pro-inflammatory factors IL-1 and IL-6 and pro-apoptotic protein Bax(P＜0.01),while up-regu-lated anti-inflammatory factor IL-10 and anti-apoptotic protein Bcl-2(P＜0.01).Additionally,further microflora sequenc-ing indicated that MenSCs transplantation prevented mice from Cis-induced intestinal flora disorder,and significantly re-duced the abundance of harmful bacteria such as isenbergiella tayi and Anaerotruncus colihominis(P＜0.01).At the same time,the abundance of beneficial bacteria Lactobacillus apodemi was increased(P＜0.05),thereby restoring the composi-tion and function of healthy intestinal flora.CONCLUSION:MenSCs transplantation alleviates the chemotherapy-in-duced damage of intestinal structure,relieves the symptoms of chemotherapy-induced mucositis and restores the homeosta-sis of intestinal flora in mice.

Objective To explore the optimal postoperative adjuvant regimens for patients with stage IB lung adenocarcinoma.Methods We respectively analyzed the data of 653 patients undergoing surgery for stage IB lung adenocarcinoma in our hospital from January,2013 to December,2021.The 5-year disease-free survival(DFS)and overall survival(OS)rates were compared among the patients receiving postoperative adjuvant therapy with epidermal growth factor-tyrosine kinase inhibitors(EGFR-TKIs group,n=111),chemotherapy(CT group,n=108)and clinical observation(CO group,n=434).Results In TKIs,CT,and CO groups,the 5-year DFS rates were 92.8%,80.7%,and 81.7%,respectively,significantly higher in TKIs group than in CO group(P<0.01).The 3-year OS rates of the 3 groups were 96.8%,97.1%,and 91.7%,respectively.Subgroup analysis showed that in TKIs,CT,and CO groups,the 5-year DFS rates of patients with with T3-4 cmN0M0 were 92.6%,84.0%,and 81.4%,respectively,significantly higher in TKIs group than in CO group(P<0.05);the 5-year DFS rates of T2ViscPlN0M0 patients were 95.1%,71.4%,and 83.5%,respectively.Multivariate COX regression analysis showed that age(P<0.05;HR=0.631,95%CI:0.401-0.993),solid nodules(P<0.01;HR=7.620,95%CI:3.037-19.121),micropapillary or solid component(P<0.05;HR=1.776,95%CI:1.010-3.122),lymphovascular invasion(P<0.05;HR=2.981,95%CI:1.198-7.419),and adjuvant therapy(P<0.01)were independent predictors of DFS.The most common adverse effects included rashes,paronychia,and diarrhea for TKIs and hematological suppression and gastrointestinal reactions for chemotherapy,and TKIs were associated with a higher incidence of grade 3 or above adverse effects(44.4%vs 9.0%).Conclusion Adjuvant therapy with TKIs helps improve DFS in patients with stage IB(T3-4cmN0M0)lung adenocarcinoma but not in patients with T2ViscPlN0M0.Adjuvant chemotherapy does not improve DFS or OS in patients with stage IB lung adenocarcinoma.

Objective To evaluate the performance of a clinical-radiomics model for differentiating focal organizing pneumonia(FOP)and lung adenocarcinoma(LUAD).Methods We retrospectively analyzed the data of 60 patients with FOP confirmed by postoperative pathology at the First Medical Center of the Chinese PLA General Hospital from January,2019 to December,2022,who were matched with 120 LUAD patients using propensity score matching in a 1∶2 ratio.The independent risk factors for FOP were identified by logistic regression analysis of the patients'clinical data.The cohort was divided into a training set(144 patients)and a test set(36 patients)by random sampling.Python 3.7 was used for extracting 1835 features from CT image data of the patients.The radiographic features and clinical data were used to construct the model,whose performance was validated using ROC curves in both the training and test sets.The diagnostic efficacy of the model for FOP and LUAD was evaluated and a diagnostic nomogram was constructed.Results Statistical analysis revealed that an history of was an independent risk factor for FOP(P=0.016),which was correlated with none of the hematological findings(P>0.05).Feature extraction and dimensionality reduction in radiomics yielded 30 significant labels for distinguishing the two diseases.The top 3 most discriminative radiomics labels were GraylevelNonUniformity,SizeZoneNonUniformity and shape-Sphericity.The clinical-radiomics model achieved an AUC of 0.909(95%CI:0.855-0.963)in the training set and 0.901(95%CI:0.803-0.999)in the test set.The model showed a sensitivity of 85.4%,a specificity of 83.5%,and an accuracy of 84.0%in the training set,as compared with 94.7%,70.6%,and 83.3%in the test set,respectively.Conclusion The clinical-radiomics nomogram model shows a good performance for differential diagnosis of FOP and LUAD and may help to minimize misdiagnosis-related overtreatment and improve the patients'outcomes.

Objective To explore the optimal postoperative adjuvant regimens for patients with stage IB lung adenocarcinoma.Methods We respectively analyzed the data of 653 patients undergoing surgery for stage IB lung adenocarcinoma in our hospital from January,2013 to December,2021.The 5-year disease-free survival(DFS)and overall survival(OS)rates were compared among the patients receiving postoperative adjuvant therapy with epidermal growth factor-tyrosine kinase inhibitors(EGFR-TKIs group,n=111),chemotherapy(CT group,n=108)and clinical observation(CO group,n=434).Results In TKIs,CT,and CO groups,the 5-year DFS rates were 92.8%,80.7%,and 81.7%,respectively,significantly higher in TKIs group than in CO group(P<0.01).The 3-year OS rates of the 3 groups were 96.8%,97.1%,and 91.7%,respectively.Subgroup analysis showed that in TKIs,CT,and CO groups,the 5-year DFS rates of patients with with T3-4 cmN0M0 were 92.6%,84.0%,and 81.4%,respectively,significantly higher in TKIs group than in CO group(P<0.05);the 5-year DFS rates of T2ViscPlN0M0 patients were 95.1%,71.4%,and 83.5%,respectively.Multivariate COX regression analysis showed that age(P<0.05;HR=0.631,95%CI:0.401-0.993),solid nodules(P<0.01;HR=7.620,95%CI:3.037-19.121),micropapillary or solid component(P<0.05;HR=1.776,95%CI:1.010-3.122),lymphovascular invasion(P<0.05;HR=2.981,95%CI:1.198-7.419),and adjuvant therapy(P<0.01)were independent predictors of DFS.The most common adverse effects included rashes,paronychia,and diarrhea for TKIs and hematological suppression and gastrointestinal reactions for chemotherapy,and TKIs were associated with a higher incidence of grade 3 or above adverse effects(44.4%vs 9.0%).Conclusion Adjuvant therapy with TKIs helps improve DFS in patients with stage IB(T3-4cmN0M0)lung adenocarcinoma but not in patients with T2ViscPlN0M0.Adjuvant chemotherapy does not improve DFS or OS in patients with stage IB lung adenocarcinoma.

Objective To evaluate the performance of a clinical-radiomics model for differentiating focal organizing pneumonia(FOP)and lung adenocarcinoma(LUAD).Methods We retrospectively analyzed the data of 60 patients with FOP confirmed by postoperative pathology at the First Medical Center of the Chinese PLA General Hospital from January,2019 to December,2022,who were matched with 120 LUAD patients using propensity score matching in a 1∶2 ratio.The independent risk factors for FOP were identified by logistic regression analysis of the patients'clinical data.The cohort was divided into a training set(144 patients)and a test set(36 patients)by random sampling.Python 3.7 was used for extracting 1835 features from CT image data of the patients.The radiographic features and clinical data were used to construct the model,whose performance was validated using ROC curves in both the training and test sets.The diagnostic efficacy of the model for FOP and LUAD was evaluated and a diagnostic nomogram was constructed.Results Statistical analysis revealed that an history of was an independent risk factor for FOP(P=0.016),which was correlated with none of the hematological findings(P>0.05).Feature extraction and dimensionality reduction in radiomics yielded 30 significant labels for distinguishing the two diseases.The top 3 most discriminative radiomics labels were GraylevelNonUniformity,SizeZoneNonUniformity and shape-Sphericity.The clinical-radiomics model achieved an AUC of 0.909(95%CI:0.855-0.963)in the training set and 0.901(95%CI:0.803-0.999)in the test set.The model showed a sensitivity of 85.4%,a specificity of 83.5%,and an accuracy of 84.0%in the training set,as compared with 94.7%,70.6%,and 83.3%in the test set,respectively.Conclusion The clinical-radiomics nomogram model shows a good performance for differential diagnosis of FOP and LUAD and may help to minimize misdiagnosis-related overtreatment and improve the patients'outcomes.

MAGED4B belongs to the melanoma-associated antigen family; originally found in melanoma, it is expressed in various types of cancer, and is especially enriched in glioblastoma. However, the functional role and molecular mechanisms of MAGED4B in glioma are still unclear. In this study, we found that the MAGED4B level was higher in glioma tissue than that in non-cancer tissue, and the level was positively correlated with glioma grade, tumor diameter, Ki-67 level, and patient age. The patients with higher levels had a worse prognosis than those with lower MAGED4B levels. In glioma cells, MAGED4B overexpression promoted proliferation, invasion, and migration, as well as decreasing apoptosis and the chemosensitivity to cisplatin and temozolomide. On the contrary, MAGED4B knockdown in glioma cells inhibited proliferation, invasion, and migration, as well as increasing apoptosis and the chemosensitivity to cisplatin and temozolomide. MAGED4B knockdown also inhibited the growth of gliomas implanted into the rat brain. The interaction between MAGED4B and tripartite motif-containing 27 (TRIM27) in glioma cells was detected by co-immunoprecipitation assay, which showed that MAGED4B was co-localized with TRIM27. In addition, MAGED4B overexpression down-regulated the TRIM27 protein level, and this was blocked by carbobenzoxyl-L-leucyl-L-leucyl-L-leucine (MG132), an inhibitor of the proteasome. On the contrary, MAGED4B knockdown up-regulated the TRIM27 level. Furthermore, MAGED4B overexpression increased TRIM27 ubiquitination in the presence of MG132. Accordingly, MAGED4B down-regulated the protein levels of genes downstream of ubiquitin-specific protease 7 (USP7) involved in the tumor necrosis factor-alpha (TNF-α)-induced apoptotic pathway. These findings indicate that MAGED4B promotes glioma growth via a TRIM27/USP7/receptor-interacting serine/threonine-protein kinase 1 (RIP1)-dependent TNF-α-induced apoptotic pathway, which suggests that MAGED4B is a potential target for glioma diagnosis and treatment.
Humans ; Tumor Necrosis Factor-alpha ; DNA-Binding Proteins/metabolism* ; Ubiquitin-Specific Peptidase 7 ; Cisplatin ; Temozolomide ; Transcription Factors ; Glioma ; Cell Proliferation ; Melanoma ; Cell Line, Tumor ; Apoptosis ; Nuclear Proteins/genetics*

The mesencephalic astrocyte-derived neurotrophic factor (MANF) has been recently identified as a neurotrophic factor, but its role in hepatic fibrosis is unknown. Here, we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl₄. MANF deficiency in either hepatocytes or hepatic mono-macrophages, particularly in hepatic mono-macrophages, clearly exacerbated hepatic fibrosis. Myeloid-specific MANF knockout increased the population of hepatic Ly6C^high macrophages and promoted HSCs activation. Furthermore, MANF-sufficient macrophages (from WT mice) transfusion ameliorated CCl₄-induced hepatic fibrosis in myeloid cells-specific MANF knockout (MKO) mice. Mechanistically, MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation. Pharmacologically, systemic administration of recombinant human MANF significantly alleviated CCl₄-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout (HKO) mice. This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a "brake" on the upstream of NF-κB pathway, which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment.

OBJECTIVE: To analyze the clinicopathological characteristics and risk factors of 4L lymph node metastasis in left non-small cell lung cancer. METHODS: We retrospectively analyzed the data of 134 patients undergoing surgical resection of left non-small cell lung cancer and 4L lymph node dissection, including 60 patients with squamous cell carcinoma (SCC) and 74 with lung adenocarcinoma (ADC). The clinicopathological characteristics of the patients were analyzed, and logistic regression analysis was used to identify the predictors of station 4L metastasis. RESULTS: Of these patients, 16.4% (22/134) presented with station 4L metastasis. The patients with SCC and ADC showed significant differences in age, gender, smoking history, neoadjuvant chemotherapy, tumor size, tumor location and type, visceral pleural invasion, Ki-67 index, 4L metastasis and pathological TNM stage (stage Ⅱ). The rate of station 4L metastasis was significantly lower in SCC group than in ADC group. Univariate analysis revealed that pathological types (SCC or ADC), visceral pleural invasion, lymphovascular invasion, tumor markerabnormality, and station 5 to 10 metastasis were all high-risk factors for station 4L metastasis. Multivariate analysis suggested that the pathological type (OR=0.120, CONCLUSIONS In patients with left non-small cell lung cancer, station 4L metastasis is not rare and is more likely to occur in patients with lung adenocarcinoma. Dissection of the 4L lymph nodes should be performed in cases with low risk of damages of the adjacent tissues and high risk of station 4L metastasis.
Carcinoma, Non-Small-Cell Lung/pathology* ; Humans ; Lung Neoplasms/pathology* ; Lymph Node Excision ; Lymph Nodes/pathology* ; Lymphatic Metastasis ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Risk Factors

Objective To analyze the differences in immune system between Npc1 gene mutant (Npc1-/ -) and wild-type (Npc1+/ +) mice for better understanding the pathogenesis of Niemann-Pick disease type C1 (NPC1) from an immunological perspective and providing reference for NPC1 treatment in clinic.Methods Body, thymus and spleen weight of Npc1-/ -and Npc1+/ + mice aged (14±2) days, (42±2) days and (63±2) days (Day14±2 , Day42±2 and Day63±2 ) were recorded and the associated organ index were calcu-lated. White blood cell count in peripheral blood of mice aged Day42±2 was examined by routine blood test. Expression of cytokines at mRNA level in mouse peripheral blood was detected by qPCR. Percentages of CD4+, CD8+ and CD19+ lymphocytes in peripheral blood and spleen of mice aged Day42±2 were measured by flow cytometry. Apoptosis and senescence of spleen in mice aged Day63±2 were examined by immunofluores-cence and β-galactosidase staining. Results Compared with Npc1+/ + mice, there was no significant differ-ence in the weight of spleen and thymus in Npc1-/ - mice aged Day14±2; the weight of spleen in Npc1-/ - mice aged Day42±2 significantly increased, but the weight of thymus showed a significant decrease; furthermore, both the weight of spleen and thymus in Npc1-/ - mice aged Day63±2 significantly decreased; and the body weight of Npc1-/ - mice of each age group significantly decreased. Moreover, compared with Npc1+/ + mice, the absolute number of lymphocytes in the peripheral blood of Npc1-/ - mice aged Day42±2 showed no signifi-cant difference, but the percentage in whole white blood cells significantly decreased due to the significantly increased neutrophils. Expression of cytokines ( IL-1, IL-2, IFN-γ, TNF-α, IL-4, granzyme A and granzyme B) at mRNA level in the peripheral blood leukocytes of Npc1-/ - mice aged Day42±2 was abnormal as compared with that in Npc1+/ + mice. The number of T (CD4+ and CD8+) lymphocytes in Npc1-/ - mice aged Day42±2 significantly decreased, while the number of B (CD19+) lymphocytes increased significantly as com-pared with those in the Npc1+/ + mice. Compared with Npc1+/ + mice, apoptosis and senescence of the spleen in Npc1-/ - mice aged Day63±2 aggravated significantly. Conclusion The abnormal lipid metabolism triggered by Npc1 gene mutation causes severe immune dysfunction in Npc1-/ - mice. Therefore, immune dysfunction should be taken into full consideration when treating patients with NPC1, which might help improve the life quality and prolong the survival time.

[Objective] Analyzing and summarizing the compatibility characters and the clinical applications of theAngle Medicinesof Aconite, in order to enlighten the modern applications. [Methods] According to the theories of classical prescriptions, arranging the compatibility characteristics and clinical applications of theAngle Medicinesof Aconite, there are three kinds ofAngle Medicines, including theAngles Medicineas independent prescriptions, theAngle Medicinesas the main part of prescriptions and theAngle Medicineas the combinations of prescriptions. At last, listing two cases of theAngle Medicinesof Aconite as the examples of clinical experience to demonstrate theAngle Medicines. [Results]This article sorted out 7 pairs ofAngle Medicinesof Aconite as the first kind, 8 pairsAngle Medicinesof Aconite as the second kind, and theAngle Medicinesof Aconite as combinations. In clinic, we use the Aconite, fried ginger and Licorice to treat long-term diarrhea, use Aconite, Semen Coicis and Patrinia to treat the hypogastralgia, and we gain the good effects, which can declare the clinical practicability of theAngle Medicines. [Conclusions]There are a lot of compatibility knowledge in classical prescriptions. Comprehending and grasping the compatibility characters and the clinical applications of the Angle Medicinesof Aconiteare is very unique and ingenious for modern clinic.