Abnormal expression of CMTM4 protein is closely related to tumour occurrence,development and prognosis.Although the important role of CMTM4 in tumours has been gradually manifested,its spe-cific mechanism of action in cervical cancer remains unclear.The aim of this study was to investigate the relationship between CMTM4 expression and clinicopathological features in cervical cancer and study its mechanism.Immunohistochemistry and Western blot were used to detect the expression level of CMTM4 in cancer tissues and paracancerous tissues,and it was found that CMTM4 was significantly under-ex-pressed in cervical cancer tissues(P＜0.001).The chi-square test analysed the relationship between high and low CMTM4 expression and the clinical and pathological characteristics of cervical cancer pa-tients and results found that CMTM4 expression was correlated with the number of births,HPV infection status,pathological type,FIGO stage and lymph node metastasis.Data from Western blot and RT-qPCR found that CMTM4 protein and mRNA levels in HaCaT cells were significantly higher than that of C-33A cells,HeLa cells,U14 cells,and HT-3 cells.Among them,the most significant change in CMTM4 ex-pression was observed in C-33A cells,so the C-33A cell line was selected for subsequent overexpression experiments.CCK-8 analysis found that the proliferation ability of C-33A cervical cancer cells in the pcDNA-CMTM4 group was significantly lower than that in the pcDNA-NC group(P＜0.001).Flow cy-tometry and Western blot results indicated that CMTM4 overexpression promoted apoptosis(P＜0.001),significantly increased Bax(P＜0.001)and cleaved caspase 3(P＜0.05)protein levels,and significant-ly decreased Bcl-2 protein level(P＜0.01).Western blot results further found that CMTM4 overexpres-sion significantly reduced the protein levels of p-PI3K(P＜0.001)and p-AKT(P＜0.01),but did not affect the protein levels of PI3K and AKT(P＞0.05).The above findings indicated that CMTM4 gene expression was down-regulated in cervical cancer,and CMTM4 overexpression inhibited cervical cancer cell proliferation and induced apoptosis by inhibiting the PI3K/AKT pathway.Therefore,CMTM4 may be used as a biological marker for screening cervical cancer.

OBJECTIVE: To investigate the clinical characteristics and prognosis of primary pulmonary lymphoma (PPL). METHODS: The clinical data of 17 patients with PPL admitted to Gansu Provincial Hospital from January 2013 to June 2023 were collected, and their clinical characteristics and prognosis were retrospectively analyzed and summarized. RESULTS: The median age of the 17 patients was 56 (29-73) years old. There were 8 males and 9 females. According to Ann Arbor staging system, there were 9 patients with stage I-II and 8 patients with stage III-IV. There were 14 patients with IPI score of 0-2 and 3 patients with IPI score of 3-4. All 17 patients had symptoms at the initial diagnosis, most of the first symptoms were cough, and 6 patients had B symptoms.Among the 17 patients, there were 8 cases of diffuse large B-cell lymphoma (DLBCL), 5 cases of mucosa-associated lymphoid tissue (MALT) lymphoma, 1 case of gray zone lymphoma (GZL), and 3 cases of Hodgkin's lymphoma (HL). 15 patients received chemotherapy, of which 3 cases received autologous hematopoietic stem cell transplantation(ASCT) and 3 cases received radiotherapy; 2 patients did not receive treatment. The median number of chemotherapy courses was 6(2-8). The short-term efficacy was evaluated, 12 patients achieved complete remission (CR) and 3 patients achieved partial remission (PR). The age, pathological subtype, sex, Ann Arbor stage, β₂-microglobulin(β₂-MG) level, lactate dehydrogenase(LDH) level were not correlated with CR rate (P >0.05), while IPI score was correlated with recent CR rate (P < 0.05 ). The median follow-up time was 31(2-102) months. One of the 12 CR patients died of COVID-19, and the rest survived. Among the 3 patients who did not reach CR, 1 died after disease progression, while the other 2 survived. One of the 2 untreated patients died one year after diagnosis. Both the median progression-free survival (PFS) time and overall survival (OS) time of the 17 patients were both 31 (2-102) months. CONCLUSION The incidence of PPL is low, and the disease has no specific clinical manifestations, which is easily missed and misdiagnosed. The pathological subtypes are mainly MALT lymphoma and DLBCL, and the treatment is mainly combined chemotherapy. The IPI score is related to the treatment efficacy.
Humans ; Middle Aged ; Male ; Female ; Adult ; Prognosis ; Aged ; Lung Neoplasms/therapy* ; Retrospective Studies ; Neoplasm Staging ; Lymphoma/therapy* ; Lymphoma, Large B-Cell, Diffuse

Abnormal expression of CMTM4 protein is closely related to tumour occurrence,development and prognosis.Although the important role of CMTM4 in tumours has been gradually manifested,its spe-cific mechanism of action in cervical cancer remains unclear.The aim of this study was to investigate the relationship between CMTM4 expression and clinicopathological features in cervical cancer and study its mechanism.Immunohistochemistry and Western blot were used to detect the expression level of CMTM4 in cancer tissues and paracancerous tissues,and it was found that CMTM4 was significantly under-ex-pressed in cervical cancer tissues(P＜0.001).The chi-square test analysed the relationship between high and low CMTM4 expression and the clinical and pathological characteristics of cervical cancer pa-tients and results found that CMTM4 expression was correlated with the number of births,HPV infection status,pathological type,FIGO stage and lymph node metastasis.Data from Western blot and RT-qPCR found that CMTM4 protein and mRNA levels in HaCaT cells were significantly higher than that of C-33A cells,HeLa cells,U14 cells,and HT-3 cells.Among them,the most significant change in CMTM4 ex-pression was observed in C-33A cells,so the C-33A cell line was selected for subsequent overexpression experiments.CCK-8 analysis found that the proliferation ability of C-33A cervical cancer cells in the pcDNA-CMTM4 group was significantly lower than that in the pcDNA-NC group(P＜0.001).Flow cy-tometry and Western blot results indicated that CMTM4 overexpression promoted apoptosis(P＜0.001),significantly increased Bax(P＜0.001)and cleaved caspase 3(P＜0.05)protein levels,and significant-ly decreased Bcl-2 protein level(P＜0.01).Western blot results further found that CMTM4 overexpres-sion significantly reduced the protein levels of p-PI3K(P＜0.001)and p-AKT(P＜0.01),but did not affect the protein levels of PI3K and AKT(P＞0.05).The above findings indicated that CMTM4 gene expression was down-regulated in cervical cancer,and CMTM4 overexpression inhibited cervical cancer cell proliferation and induced apoptosis by inhibiting the PI3K/AKT pathway.Therefore,CMTM4 may be used as a biological marker for screening cervical cancer.

Objective:To analyze the prognostic nutritional index(PNI),controlling nutritional status(CONUT)and fibrinogen/albumin ratio(FAR)levels in elderly patients with multiple myeloma(MM)and their prognostic impact.Methods:The clinical data of 74 elderly MM patients diagnosed in Gansu Provincial Hospital from January 2020 to July 2022 were retrospectively analyzed.The optimal cut-off values for PNI,CONUT score and FAR were obtained by receiver operating characteristic(ROC)curve,which were used for grouping patients.The correlation of above three indexes with clinical parameters such as sex,serum calcium(Ca),β2-microglobulin(β2-MG),serum creatinine(Cr)in elderly MM patients were analyzed.The survival rates of patients with different levels of each index were compared.Univariate and multivariate analysis of the impact of clinical indicators on the prognosis of patients were performed.Results:The optimal cut-off values for PNI,CONUT score and FAR were 39.775,3.5 and 0.175,respectively,according to which the patients were divided into high and low group.Statistical analysis showed that there were significant differences in albumin level among different groups(all P＜0.05).In addition,there was a significant difference in hemoglobin between high-PNI group and low-PNI group(P＜0.05),while in sex distribution between high-FAR and low-FAR group(P＜0.05).The survival rate of elderly MM patients with increased PNI,decreased CONUT score and FAR was higher(all P＜0.05).Univariate and multivariate analysis showed that β2-MG,Cr,PNI,CONUT score and FAR were independent prognostic factors for elderly MM patients.Conclusion:PNI,CONUT score and FAR are related to some clinical indicators of elderly MM patients,and have an impact on the prognosis.

Objective:To analyze the clinical characteristics and occurrence of thrombotic/bleeding events of patients with myeloproliferative neoplasm(MPN),and explore the main influencing factors,and create a risk prediction.Methods:The clinical data of 126 MPN patients with BCR-ABL fusion gene negative in the Department of Hematology of Gansu Provincial Hospital from January 2016 to September 2021 were collected,and their clinical characteristics,occurrence of thrombotic/bleeding events and main influencing factors were analyzed and summarized retrospectively.Then,a risk prediction model for thrombotic/bleeding events in MPN patients was constructed.Results:Among 126 MPN patients,50 patients(39.7％)had experienced thrombotic/bleeding events,including 44 patients(34.9％)with thrombotic events and 6 patients(4.8％)with bleeding events.Among thrombotic diseases,cerebral thrombosis was the most common(23/44,52.3％),followed by 9 cases of limb artery thrombosis mainly characterized by finger and toe tip artery ischemia,occlusion and gangrene(9/44,20.5％).Bleeding events included intracerebral hemorrhage and gastrointestinal hemorrhage.Univariate analysis showed that hypertension,hyperhomocysteinemia,white blood cell(WBC)≥10 × 109/L,hematocrit(HCT)≥49％,platelet(PLT)≥600 × 109/L and JAK2V617F gene mutation were risk factors for thrombotic/bleeding events in MPN patients,while CALR gene mutation was a protective factor.Multivariate analysis showed that hypertension and PLT ≥ 600 × 109/L were independent risk factors for thrombotic/bleeding events in MPN patients.The goodness of fit of the constructed risk prediction model was 0.872,and the area under the ROC curve was 0.838.The model was validated with clinical data,the sensitivity,specificity and accuracy was 78.85％,87.83％and 84.13％,respectively.Conclusion:The risk of thrombotic/bleeding events in MPN patients with high WBC count,hypertension and hyperhomocysteinemia is higher.Controlling hypertension and hyperhomocysteinemia and reducing WBC and PLT counts are helpful to prevent thrombotic/bleeding events and improve the life quality of patients.

The aberrant expression of CMTM4 protein has been implicated in tumorigenesis,develop-ment,and prognosis;however,its precise role and underlying mechanism in cervical cancer remain elu-sive.We aimed to investigate the expression level of CMTM4 in cervical cancer and its regulatory effect and molecular mechanism on MDSCs differentiation and immune cell function.Firstly,immunohisto-chemical (IHC) staining and Western blot analysis were employed to assess the expression level of CMTM4 in cervical cancer tumors and adjacent tissues.The results revealed a significant decrease in the expression level of CMTM4 in cervical cancer tissues compared to adjacent tissues (P<0.01) .Differenti-ation of MDSCs in tumor samples from cervical cancer patients was assessed using flow cytometry,with CD45,CD11b,and Ly6G used as markers for M-MDSCs,and CD45,CD11b,and Ly6C used as mark-ers for G-MDSCs.The percentage of M-MDSCs and G-MDSCs in the blood of cervical cancer patients was significantly higher than that observed in healthy volunteers (P<0.01) .Furthermore,flow cytometry a-nalysis demonstrated that high expression of CMTM4 increased the proportion of CD3+CD4+T cells and CD3+CD8+T cells in the blood of cervical cancer patients (P<0.01),while also promoting the activa-tion ratio of Th1 and Th17 cells (P<0.05) .Conversely,it inhibited the activation ratio of Th2 and Treg cells (P<0.05 or P<0.01) .The percentage of CD8+PD-1+T cells and CD8+PD-L1+T cells within tumor tissues was determined by flow cytometry analysis which showed that high expression levels of CMTM4 suppressed their presence within tumor tissues (P<0.05) .The in vitro studies demonstrated that overexpression of CMTM4 in HeLa cells significantly suppressed the generation of MDSCs (P<0.01),while overexpression of PD-1 in HeLa cells further enhanced the generation of MDSCs (P<0.05) .Additionally,ELISA was employed to measure the levels of Th1,Th2,Th17,and Treg cyto-kines.It was observed that CMTM4 overexpression in HeLa cells reduced IL-10 secretion by T cells (P<0.01),but increased IFN-γ and TNF-α secretion (P<0.01),both of which were reversed by PD-1 overexpression (P<0.05 or P<0.01) .In conclusion,low expression of CMTM4 in cervical cancer leads to abnormal differentiation of MDSCs and immune escape of tumors.CMTM4 influences the activation of tumor T cells by regulating the PD-1/PD-L1 pathway.Thus,CMTM4 may be a potential target for the treatment of cervical cancer.

Objective To analyze risk factors and pathogenic characteristics of intestinal colonization of carbape-nem-resistant Enterobacterales(CRE)in patients from intensive care unit(ICU).Methods A total of 392 ICU pa-tients who underwent intestinal CRE screening in a tertiary hospital in Changzhou from March to December,2023 were divided into the colonization group(n=42)and the non-colonization group(n=350)according to the screening results.Clinical data of patients,including age,gender,underlying diseases,malignant tumors,radiotherapy,chemotherapy,infection before the last screening,antimicrobial use,and invasive procedures were collected for the analysis on risk factors and pathogenicity.Results Among 42 patients with positive CRE screening results,44 CRE strains were detected,mainly Klebsiella pneumoniae(65.91％),followed by Escherichia coli(15.91％)and En-terobacter cloacae(13.64％).The average time from admission in ICU to positive screening results of intestinal CRE in the colonization group was 14 days.Long term use of carbapenem antibiotics(OR=1.47,95％CI:1.31-1.65),mechanical ventilation(OR=1.14,95％CI:1.06-1.22),and Enterobacterales infection(OR=10.10,95％CI:3.28-32.09)were independent risk factors for intestinal CRE colonization.Patients who received carbap-enem antibiotics for ≥15 days(x2=167.52,P＜0.001)and those who received mechanical ventilation for ≥15 days(x2=101.03,P＜0.001)had higher risks for intestinal CRE colonization.Conclusion In clinical practice,it is necessary to improve pathogen detection,treat Enterobacterales infection timely,choose carbapenem antibiotics carefully,shorten treatment course,actively evaluate indications for mechanical ventilation,and wean off ventilator timely.

Objective:To verify the effect of Fu′s massage combined with physical therapy technology in rapidly relieving neck and low back pain caused by long-haul flight.Methods:Forty-two male volunteers were divided into 8, 12, 16, 24 and 48 h groups according to the simulated flying hours. After the completion of the simulated long-haul flight, the 5 groups of volunteers were immediately treated with Fu′s massage combined with physical factors for neck and low back pain. The Visual Analogue Scale (VAS) was used to evaluate the cervical and lumbar pain of volunteers after simulated flight and after treatment, and the treatment effect was before treatment analyzed.Results:There were significant differences in the VAS scores of cervical and lumbar regions before treatment among volunteers with different flying hours ( H=-30.15, -28.25, both P<0.001). The VAS scores of cervical and lumbar regions of volunteers in the 24 h and 48 h groups were higher than those in the 8 h group ( P=0.002, <0.001, =0.002, <0.001). The VAS scores of cervical and lumbar regions of volunteers in the 48 h group were higher than those in the 12 h group ( P=0.016, 0.001). The VAS score of cervical region of volunteers in the 48 h group was higher than that in the 16 h group ( P=0.033). After the intervention of Fu's massage combined with physical therapy, the VAS scores of cervical and lumbar regions in each group were lower than those before treatment, and the differences were significant ( t/ Z=-3.00-17.00, all P<0.05 or 0.01). Conclusions:Fu′s massage manipulation combined with physical treatment can effectively relieve the neck and low back pain caused by long-haul flight, which can be widely used as a relief method.

OBJECTIVE: To retrospectively analyze the clinical efficacy of anterior cruciate ligament (ACL) reconstruction combined with anterolateral complex repair and ACL reconstruction combined with ALL reconstruction in the treatment of anterior cruciate ligament injuries with high-grade pivot shift. METHODS: From January 2018 to June 2022, 49 patients combined ACL and ALL injuries with high-grade pivot shift were retrospectively studied from three hospitals, 29 of them underwent ACL reconstruction with anterolateral complex repair (repair group), including 23 males and 6 females with an average age of (27.5±4.8) years old, ranged from 20 to 37 years old;the injured sides were 13 on the left and 16 on the right, and 11 patients were suffered with meniscus injury. The other 20 patients underwent ACL and ALL reconstruction (reconstruction group) including 17 males and 3 females with the mean age of (27.1±4.5) years old, ranged from 20 to 38 years old;the injured sides were 8 on the left and 12 on the right, and 6 patients were suffered with meniscus injury. Knee stability (pivot shift test, KT-2000), range of motion, knee function (Lysholm scoring scale, Cincinnati sports activity scale (CSAS) scoring scale, and Tegner activity level score between two groups were compared. RESULTS: A total of 49 patients were followed up, the repair group receiving 13 to 20(15.3±1.8) months and the reconstruction group receiving 12 to 21(16.0±2.2) months. There was no statistically significant difference in the preoperative pivot shift test grading distribution between two groups (P>0.05). At the last postoperative follow-up, there were 24 patients with grade 0 and 5 patients with grade 1 in the repair group, and there were 18 patients with grade 0 and 2 patients with grade 1 in the reconstruction group, there is no significant difference in the distribution of axial shift test grading between two groups(P>0.05). The preoperative KT-2000 tibial displacement of two groups were (9.39±0.77) mm (repair group) and (9.14±0.78) mm (reconstruction group) respectively, with no statistically significant difference (P>0.05). At the final postoperative follow-up, there were 24 patients with KT-2000 tibial displacement <3 mm and 5 patients with 3 to 5 mm in the repair group, while 18 patients with <3 mm and 2 patients with 3 to 5 mm in the reconstruction group, KT-2000 tibial displacement distribution of two groups was no significant difference (P>0.05), but the KT-2000 tibial displacement in the reconstruction group (1.30±0.86) mm was significantly smaller than that in the repair group (1.99±1.11) mm (P<0.05). The final postoperative follow-up range of motion of the contralateral side knee between two groups was no significant difference (P>0.05). The range of motion of the suffering knee in the repair group was less than that in the reconstruction group (P<0.05). There was no significant difference in preoperative Lysholm and CSAS scores between two groups (P>0.05). At the final postoperative follow-up, both groups showed significant improvement in Lysholm and CSAS scores, while the Lysholm and CSAS scores of the reconstruction group were better than those of the repair group, and the difference was statistically significant (P<0.05). Significant differences was found in Tegner scores between two groups, which 16 patients in the repair group returned to their pre-injury activity level, and 17 patients in the reconstruction group returned to their pre-injury level (P<0.05). CONCLUSION Compared to anterolateral complex repair, combined ACL and ALL reconstruction in the treatment of ACL injuries with high-grade pivot shift results in better knee joint function and stability. This is advantageous in reducing the risk of ACL reconstruction failure.
Humans ; Male ; Female ; Adult ; Anterior Cruciate Ligament Reconstruction/methods* ; Anterior Cruciate Ligament Injuries/surgery* ; Young Adult ; Retrospective Studies ; Anterior Cruciate Ligament/surgery* ; Range of Motion, Articular

The aberrant expression of CMTM4 protein has been implicated in tumorigenesis,develop-ment,and prognosis;however,its precise role and underlying mechanism in cervical cancer remain elu-sive.We aimed to investigate the expression level of CMTM4 in cervical cancer and its regulatory effect and molecular mechanism on MDSCs differentiation and immune cell function.Firstly,immunohisto-chemical (IHC) staining and Western blot analysis were employed to assess the expression level of CMTM4 in cervical cancer tumors and adjacent tissues.The results revealed a significant decrease in the expression level of CMTM4 in cervical cancer tissues compared to adjacent tissues (P<0.01) .Differenti-ation of MDSCs in tumor samples from cervical cancer patients was assessed using flow cytometry,with CD45,CD11b,and Ly6G used as markers for M-MDSCs,and CD45,CD11b,and Ly6C used as mark-ers for G-MDSCs.The percentage of M-MDSCs and G-MDSCs in the blood of cervical cancer patients was significantly higher than that observed in healthy volunteers (P<0.01) .Furthermore,flow cytometry a-nalysis demonstrated that high expression of CMTM4 increased the proportion of CD3+CD4+T cells and CD3+CD8+T cells in the blood of cervical cancer patients (P<0.01),while also promoting the activa-tion ratio of Th1 and Th17 cells (P<0.05) .Conversely,it inhibited the activation ratio of Th2 and Treg cells (P<0.05 or P<0.01) .The percentage of CD8+PD-1+T cells and CD8+PD-L1+T cells within tumor tissues was determined by flow cytometry analysis which showed that high expression levels of CMTM4 suppressed their presence within tumor tissues (P<0.05) .The in vitro studies demonstrated that overexpression of CMTM4 in HeLa cells significantly suppressed the generation of MDSCs (P<0.01),while overexpression of PD-1 in HeLa cells further enhanced the generation of MDSCs (P<0.05) .Additionally,ELISA was employed to measure the levels of Th1,Th2,Th17,and Treg cyto-kines.It was observed that CMTM4 overexpression in HeLa cells reduced IL-10 secretion by T cells (P<0.01),but increased IFN-γ and TNF-α secretion (P<0.01),both of which were reversed by PD-1 overexpression (P<0.05 or P<0.01) .In conclusion,low expression of CMTM4 in cervical cancer leads to abnormal differentiation of MDSCs and immune escape of tumors.CMTM4 influences the activation of tumor T cells by regulating the PD-1/PD-L1 pathway.Thus,CMTM4 may be a potential target for the treatment of cervical cancer.