Objective:To explore the relationship between perceived stigma and self-transcendence meaning of life among male college students who have sex with men with HIV,and the role of fear of negation evaluation,seeking for meaning,perspective change in it.Methods:A total of 474 male college students who had sex with men with HIV were selected and tested with the simplified Berger HIV Stigma Scale(BHSS),Fear of Negative Evalua-tion Rating Scale(FNE),Chinese Meaning in Life Questionnaire(C-MLQ),Meaning-focused Coping Questionnaire(MFCQ),and Self-transcendence Meaning of Life Scale(SMLS).Results:The BHSS total scores were negatively correlated with the SMLS total scores(r=0.69,P＜0.001).The FNE scores and the seeking for meaning scores were mediating variables between the BHSS total scores and the SMLS total scores,with estimated effects of-0.13 and-0.11,respectively.The FNE score and seeking for meaning score played a chain mediating role in the total scores of BHSS and SMLS,with estimated effects of-0.16,the perspective change score played a moderating role in the score of the seeking for meaning and the SMLS total score(β=0.07,P＜0.05).Conclusion:Fear of negation evaluation and seeking for meaning play a mediating role between perceived stigma and self-transcendence meaning of life,as well as the moderating effect of perspective change between the search for meaning and self-transcendence meaning of life.

Objective:To observe the effects of electroacupuncture(EA)combined with Western medication on lower-limb motor function and blood circulation in patients with cerebral infarction-induced hemiplegia in the acute stage. Methods:One hundred eligible patients with acute ischemic stroke accompanied by lower-limb motor dysfunction were allocated to an observation group and a control group using the random number table method,with 50 cases in each group.The control group received routine Western medications for treatment,and the observation group received additional EA intervention.After 2-week and 4-week treatments,the improvement of lower-limb motor function was assessed using the Fugl-Meyer assessment scale for lower extremity(FMA-LE),and changes in the peak blood flow velocities of the posterior tibial(PT)and dorsalis pedis(DP)arteries on the affected side were detected using Doppler. Results:Three cases dropped out during the study,so there were 48 cases in the observation group and 49 in the control group collected for statistical analysis.The FMA-LE score and the peak blood flow velocities of PT and DP arteries increased after 2-week and 4-week treatments in both groups compared with the pre-treatment baseline(P<0.05).After 2-week treatments,the FMA-LE score and the peak blood flow velocities of PT and DP arteries showed no significant differences between the two groups(P>0.05).After 4-week treatments,compared with the control group,the FMA-LE score was higher(P<0.05),and the peak blood flow velocities of PT and DP arteries on the affected side were larger in the observation group(P<0.05). Conclusion:EA combined with Western medication can significantly improve the motor function and blood flow velocity of the affected lower limb in patients with acute cerebral infarction accompanied by hemiplegia.

Objective To study the possibility of salivary microbiota model to diagnose laryngopharyngeal re-flux(LPR).Methods A case-control study was applied to enroll 34 patients as case group who showed significant efficacy after 8 weeks of proton pump inhibitor treatment from February 2022 to November 2022.And 47 healthy volunteers matched by age,gender and body mass index with the case group were enrolled as the control group.Their salivary samples were collected before medication,and the salivary microbiota was detected by 16S rDNA se-quencing.Bioinformatics analysis was conducted on the sequencing results to compare species differences at the ge-nus level.A total of 24 patients and 33 cases in the control group were selected as train set and the rest as test set.Random forest method was used to classify data and ten fold cross validation was applied to select the optimal bacte-rial genus combination to construct a diagnostic model.The probability of disease(POD)index was calculated and receiver operating characteristic curve(ROC)was used to evaluate the diagnostic model in diagnosis of LPR.SPSS 18.0 software was utilized for statistical analysis.Results Compared with the control group,there was a statistical difference in the relative abundance of 22 genera in saliva between the case group and the control group(P＜0.05).A diagnostic model consisting of 6 genera was constructed,namely Lactobacillus,Novosphingobium,Bacillus,Pseudoalteromonas,Ralstonia and Phocaeicola.The area under the ROC curve of the test set was 0.843,the sensi-tivity of the diagnostic model was 60.0％,the specificity was 87.71％,and the Kappa value was 0.470.Conclusion The bacterial combination diagnostic model constructed from saliva microbiota based on microbiome and machine learning can effectively distinguish LPR patients from healthy individuals,which has potential clinical application value.

Objective To investigate the protective effect of 5-hydroxy-6,7-dimethoxyflavone(5-HDF),a compound extracted from Elsholtzia blanda Benth.,against lung injury induced by H1N1 influenza virus and explore its possible mechanism of action.Methods 5-HDF was extracted from Elsholtzia blanda Benth.using ethanol reflux extraction and silica gel chromatography and characterized using NMR and MS analyses.In an A549 cell model of H1N1 influenza virus infection(MOI=0.1),the cytotoxicity of 5-HDF was assessed using MTT assay,and its effect on TRAIL and IL-8 expressions was examined using flow cytometry;Western blotting was used to detect the expression levels of inflammatory,apoptosis,and ferroptosis-related proteins.In a mouse model of H1N1 influenza virus infection established by nasal instillation of 50 μL H1N1 virus at the median lethal dose,the effects of 30 and 60 mg/kg 5-HDF by gavage on body weight,lung index,gross lung anatomy and lung histopathology were observed.Results 5-HDF exhibited no significant cytotoxicity in A549 cells within the concentration range of 0-200 μg/mL.In H1N1-infected A549 cells,treatment with 5-HDF effectively inhibited the activation of phospho-p38 MAPK and phospho-NF-κB p65,lowered the expressions of IL-8,enhanced the expression of anti-ferroptosis proteins(SLC7A11 and GPX4),and inhibited the expressions of apoptosis markers PARP and caspase-3 and the apoptotic factor TRAIL.In H1N1-infected mice,treatment with 5-HDF for 7 days significantly suppressed body weight loss and increment of lung index and obviously alleviated lung tissue pathologies.Conclusion 5-HDF offers protection against H1N1 influenza virus infection in mice possibly by suppressing H1N1-induced ferroptosis,inflammatory responses,and apoptosis via upregulating SLC7A11 and GPX4,inhibiting the activation of phospho-NF-κB p65 and phospho-p38 MAPK,and decreasing the expression of cleaved caspase3 and cleaved PARP.

Objective To investigate the protective effect of 5-hydroxy-6,7-dimethoxyflavone(5-HDF),a compound extracted from Elsholtzia blanda Benth.,against lung injury induced by H1N1 influenza virus and explore its possible mechanism of action.Methods 5-HDF was extracted from Elsholtzia blanda Benth.using ethanol reflux extraction and silica gel chromatography and characterized using NMR and MS analyses.In an A549 cell model of H1N1 influenza virus infection(MOI=0.1),the cytotoxicity of 5-HDF was assessed using MTT assay,and its effect on TRAIL and IL-8 expressions was examined using flow cytometry;Western blotting was used to detect the expression levels of inflammatory,apoptosis,and ferroptosis-related proteins.In a mouse model of H1N1 influenza virus infection established by nasal instillation of 50 μL H1N1 virus at the median lethal dose,the effects of 30 and 60 mg/kg 5-HDF by gavage on body weight,lung index,gross lung anatomy and lung histopathology were observed.Results 5-HDF exhibited no significant cytotoxicity in A549 cells within the concentration range of 0-200 μg/mL.In H1N1-infected A549 cells,treatment with 5-HDF effectively inhibited the activation of phospho-p38 MAPK and phospho-NF-κB p65,lowered the expressions of IL-8,enhanced the expression of anti-ferroptosis proteins(SLC7A11 and GPX4),and inhibited the expressions of apoptosis markers PARP and caspase-3 and the apoptotic factor TRAIL.In H1N1-infected mice,treatment with 5-HDF for 7 days significantly suppressed body weight loss and increment of lung index and obviously alleviated lung tissue pathologies.Conclusion 5-HDF offers protection against H1N1 influenza virus infection in mice possibly by suppressing H1N1-induced ferroptosis,inflammatory responses,and apoptosis via upregulating SLC7A11 and GPX4,inhibiting the activation of phospho-NF-κB p65 and phospho-p38 MAPK,and decreasing the expression of cleaved caspase3 and cleaved PARP.

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 study the effect of Musashi-2 ( MSI2 ) overexpression on the imbalance of proliferation and apoptosis of human ovarian granulosa cell line (KGN) induced by dihydrotestosterone (DHT) ． Methods: The gene expression profiles of human ovarian granulosa cells ( GCs) in primary culture were statistically analyzed to screen the differentially expressed genes．pcDNA3. 1-MSI2 eukaryotic expression plasmid was constructed and transiently transfected into the KGN cells，and the overexpression effect of MSI2 was detected by Quantitative Real-time PCR (RT-qPCR) and Western blot．After overexpressing MSI2 in DHT induced KGN cells，MTT colorimetry and Edu staining were used to detect the proliferation of cells in each group，and flow cytometry ( FCM) was further used to detect the apoptosis of cells in each group. Results: The mRNA expression level of MSI2 gradually decreased during the primary culture of human ovarian GCs．And pcDNA3. 1-MSI2 was successfully constructed and transfected into KGN cells to improve the mRNA and protein expression levels of MSI2．Then MTT，EdU and FCM results showed that compared with the blank group，DHT induction could significantly reduce the proliferation rate and increase the apoptosis rate of KGN cells (P ＜0. 05) ．However，after MSI2 overexpression，the proliferation rate of KGN cells increased and the apoptosis rate decreased (P ＜0. 05) ，which were close to the blank group. Conclusion Overexpression of MSI2 can effectively alleviate the imbalance of proliferation and apoptosis of KGN cells induced by DHT，indicating that MSI2 plays an important role in GCs growth and follicle development.

Acidosis, regardless of hypoxia involvement, is recognized as a chronic and harsh tumor microenvironment (TME) that educates malignant cells to thrive and metastasize. Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression, the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy. Here, chemical-induced and transgenic mouse models for colon, liver and lung cancer were established, respectively. miR-7 and TGF-β2 expressions were examined in clinical tissues (n = 184). RNA-seq, miRNA-seq, proteomics, biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis. Our data show that lung cancer is sensitive to the increased acidification of TME, and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5p. TGF-β2 is a direct target of miR-7-5p. The reduced expression of miR-7-5p subsequently increases the expression of TGF-β2 which enhances the metastatic potential of the lung cancer. Indeed, overexpression of miR-7-5p reduces the acidic pH-enhanced lung cancer metastasis. Furthermore, the human lung tumor samples also show a reduced miR-7-5p expression but an elevated level of activated TGF-β2; the expressions of both miR-7-5p and TGF-β2 are correlated with patients' survival. We are the first to identify the role of the miR-7/TGF-β2 axis in acidic pH-enhanced lung cancer metastasis. Our study not only delineates how acidification directly affects tumorigenesis, but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer (NSCLC) treatment. Our study opens an avenue to explore the pH-sensitive subcellular components as novel therapeutic targets for cancer treatment.

Objective To study the irradiation dose of organs at risk (OAR) in involved field radiation and extended field radiation in patients with thoracic esophageal cancer who received intensity modulated radiotherapy (IMRT). Methods A total of 40 patients with thoracic esophageal cancer were treated with IMRT. The involved field, extended field, and OAR were outlined to generate IMRT plans. The conformity index (CI) and homogeneity index (HI) of planning target volume (PTV) and the irradiation parameters of OAR were evaluated for the two plans. Paired t-test was used for comparison of irradiation parameters. Results The PTV of both plans received the prescribed dose. There were no significant differences in CI and HI of PTV between the two groups (P = 0.317, 0.130). There were significant differences in average lung dose, lung V₅, lung V₂₀, lung V₃₀, spinal cord D_mean, heart D_mean, heart D_max, heart V₃₀, heart V₄₀, and heart V₆₀ between the two groups (P < 0.01). Conclusion Compared with the extended field, the involved field can reduce the irradiation dose of ORA in patients with thoracic esophageal cancer, thus reducing the risk of radiation.

Objective To evaluate the value and short-term efficacy of Miccoli for cervical lymph node dissection in patients with thyroid papillary carcinoma.Methods From Mar.2017 to Jan.2018,15 patients with thyroid papillary carcinoma received cervical lymph node dissection in Department of Thyroid and Breast Surgery of Nanjing Chinese Traditional Medicine Hospital,and they were divided into open surgery group (8 cases) and Miccoli surgery group (7 cases).The operation time,incision length,intraoperative blood loss,total number of dissection lymph nodes,incidence of postoperative complications and length of hospital stay between the two groups were analyzed.These groups were followed up for 6 months after surgery,in terms of neck comfort,incidence of enlarged lymph nodes in the cervical region and blood thyroglobulin level.Results There was no obvious difference between the two groups in intraoperative blood loss(P=0.651),total number of dissection lymph nodes(P=0.887),the incidence of postoperative complications(P=0.52),incidence of intumescent lymph node(P=1.000) and blood thyroglobulin level(P=0.826) after 6 months.The operation time of Miccoli group was longer than that of the open group(P=0.001),but the incision length(P=0.001),length of hospital stay(P=0.001)and postoperative neck comfort(P=0.001)were superior to those of the open surgery group.Conclusion Miccoli operation can be used to perform cervical lymph node dissection for PTC patients,which can achieve the curative effect of open surgery,without increasing the risk of postoperative complications,and the postoperative neck comfort was better.