Abstract: Objective　To predict the potential distribution of talaromycosis marneffei (TSM) and analyze its driving factors, so as to provide evidence for the surveillance and prevention of this disease. Methods　The data of all laboratory-confirmed, non-duplicating TSM published in the English and Chinese literature from the first case in January 1964 to December 2018 was collected. A Maxent ecology model using environmental variables, Rhizomys distribution and HIV/AIDS epidemic was developed to forecast ecological niche of TSM worldwide, as well as identify the driving factors. Results　A total of 705 articles (477 in Chinese and 228 in English) were obtained during the study period. After excluding imported cases, a total of 100 foci information were included in the model. The area under the receiver operating characteristic (ROC) curve (AUC) of the model was 0.997 for the training set and 0.991 for the test set. Maxent model revealed that Rhizomys distribution, mean temperature of warmest quarter, precipitation of wettest month, HIV/AIDS epidemic and mean temperature of driest quarter were the top 5 important variables affecting TSM distribution. In addition to identifying traditional TSM endemic areas (South of the Yangtze River in China, Southeast Asian, North and Northeast India), other potential endemic areas were also identified, including parts of the North of the Yangtze River, Central America, West Coast of Africa, East Coast of South America, the Korean Peninsula and Japan. Conclusion　Our finding has discovered hidden high-risk areas and provided insights about driving factors of TSM distribution, which will help inform surveillance strategies and improve the effectiveness of public health interventions against TM infections.

The PRR11 gene (Proline Rich 11) has been implicated in lung cancer; however, relationship between PRR11 and immune infiltration is not clearly understood. In this study, we used The Cancer Genome Atlas (TCGA) data to analyze the lung adenocarcinoma patients; PRR11 gene expression, clinicopathological findings, enrichment, and immune infiltration were also studied. PRR11 immune response expression assays in lung adenocarcinoma (LUAD) were performed using TIMER, and statistical analysis and visualization were conducted using R software. All data were verified using Gene Expression Profiling Interactive Analysis (GEPIA), and the Human Protein Atlas (HPA). We found that PRR11 was an important prognostic factor in patients with LUAD. PRR11 expression was correlated with tumor stage and progression. Gene Set Enrichment Analysis (GSEA) showed that PRR11 was enriched in the cell cycle regulatory pathways. Immune infiltration analysis revealed that the number of T helper 2 (Th2) cells increased when PRR11 was overexpressed. These results confirm the role of PRR11 as a prognostic marker of lung adenocarcinoma by controlling the cell cycle and influencing the immune system to facilitate lung cancer progression.
Humans ; Prognosis ; Adenocarcinoma of Lung/genetics* ; Lung Neoplasms/genetics* ; Biological Assay ; Cell Cycle

Objective:To investigate the efficacy and safety of comprehensive therapy in the treatment of advanced unresectable hepatocellular carcinoma.Methods:Clinical data of 34 patients with primary liver cancer admitted to Peking Union Medical College Hospital from Nov 2018 to Dec 2020 initially evaluated as unresectable were treated firstly by combined therapy and then underwent reevaluation for further management.Results:A total of 34 patients completed the integrative treatment, and no serious adverse events occurred. Among them, 6 patients were evaluated as partial remission, and underwent successful tumor resection, tumors in 7 patients were stable, and 21 patients suffered from disease progression.Conclusion:After comprehensive therapy, unresectable tumors in some patients could reduce and be rendered resection.

Objective:To investigate the application of continuous intracranial pressure (ICP) combined with regional cerebral oxygen saturation (rScO 2) monitoring in patients with hypertensive intracerebral hemorrhage before and after operation of the removal hematoma through small bone window and the effect on the prognosis of patients. Methods:The clinical data of 37 patients with supratentorial hypertensive intracerebral hemorrhage admitted to the neurosurgical intensive care unit of the people′s Hospital of Inner Mongolia Autonomous Region from April 2018 to October 2020 were retrospectively analyzed.ICP monitoring and near infrared spectroscopy (NIRS) were used to monitor the intracranial pressure and rScO 2 concentration before and after the operation, and the changes of intracranial pressure and rScO 2 before and after the operation were analyzed.According to Glasgow Outcome Score (GOS), patients with GOS score>3 were classified as good prognosis group (21 cases), and those with GOS score ≤3 were classified as poor prognosis group (16 cases). Results:The postoperative intracranial pressure((15.80±6.70) mmHg)of patientswith hypertensive intracerebral hemorrhage was lower than that before operation((20.40±5.80) mmHg), and the difference was statistically significant( t=3.226, P=0.002). The postoperative rScO 2 ((62.31±3.85)% )of patientswith hypertensive intracerebral hemorrhage was higher than that before operation((59.73±3.13)%), and the difference was statistically significant( t=3.171, P=0.002). The decrease of intracranial pressure in patients with good prognosis((6.53±2.21) mmHg)was more obvious than that in patients with poor prognosis((4.24±2.30) mmHg). The concentration of rScO 2 increased in both groups.But in the group with good prognosis, the rScO 2 increased((3.99±2.34)%)was significantly higher than that in poor prognosis group((2.32±2.25)%). Six months after operation, there were significant differences in preoperative and postoperative intracranial pressure and rScO 2 between good prognosis group and poor prognosis group, and the difference was statistically significant( t=3.090, 2.176; P=0.004, 0.036). Conclusion:Small bone window evacuation of intracerebral hematoma can significantly reduce the concentration of intracranial pressure and increase the concentration of rScO 2 in patients with intracerebral hemorrhage.The changes of intracranial pressure and rScO 2 before and after operation have potential value in judging the prognosis of patients.

Adult ; Beijing ; HIV Infections/diagnosis* ; HIV Testing ; Health Promotion ; Homosexuality, Male ; Humans ; Internet ; Male ; Self-Testing

AIM:To investigate the stemness of mouse triple-negative breast cancer (TNBC) 4T1 cells induced by doxorubicin (DOX) and the underlying mechanism.METHODS:The 4T1 cells and MDA-MB-468 cells were treated with DOX at different concentrations (0, 0.05, 0.1 and 0.5μmol/L) for 24 h, and the shape and viability of the cells were observed.The concentration of DOX at 0.1μmol/L was chosen as the optimal concentration for the following experiments.The 4T1 cells and MDA-MB-468 cells resistant to DOX were established by continuous stimulation with DOX for 4 weeks, and named as 4T1-DOX and MDA-MB-468-DOX.Sphere formation assay was used to detect the stemness of 4T1cells and MDA-MB-468 cells.The expression of CD133 was observed by immunofluorescence staining.The expression of CD44 was analyzed by flow cytometry.The protein levels of Stat3, phosphorylated Stat3 (p-Stat3) and Oct-4 were determined by Western blot.RESULTS:The sphere formation ability of the 4T1-DOX cells was stronger than that of the 4T1control cells.The 4T1-DOX cells expressed high levels of the stemness markers CD133 and CD44 as compared with the 4 T1 cells (P<0.05).Furthermore, the 4T1-DOX cells exhibited enhanced activation of Stat3 (p-Stat3) and increased expression of Oct-4 (P<0.05) , while the expression of total Stat3 had no obvious variation.In addition, when activation of Stat3 was inhibited by WP1066, the protein levels of p-Stat3, Oct-4 and CD44 were down-regulated (P<0.05).Furthermore, inhibition of Stat3 phosphorylation reduced the sphere formation ability of the 4T1-DOX cells (P<0.05).CONCLUSION:DOX induces the stemness of mouse TNBC 4T1 cells through Stat3-Oct-4 signaling pathway.

Background: Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS) in remission. The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7 mg and 14 mg) in the subgroup of Chinese patients with relapsing MS included in the TOWER study. Methods: TOWER was a multicenter, multinational, randomized, double-blind, parallel-group (three groups), placebo-controlled study. This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7 mg (n = 51), teriflunomide 14 mg (n = 43), or placebo (n = 54). Results: Of the 148 patients in the intent-to-treat population, adjusted annualized relapse rates were 0.63 (95% confidence interval [CI]: 0.44, 0.92) in the placebo group, 0.48 (95% CI: 0.33, 0.70) in the teriflunomide 7 mg group, and 0.18 (95% CI: 0.09, 0.36) in the teriflunomide 14 mg group; this corresponded to a significant relative risk reduction in the teriflunomide 14 mg group versus placebo (-71.2%, P = 0.0012). Teriflunomide 14 mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio: 0.319, P = 0.1194). There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs; 72.2% in the placebo group, 74.5% in the teriflunomide 7 mg group, and 69.8% in the teriflunomide 14 mg group); corresponding proportions for serious adverse events were 11.1%, 3.9%, and 11.6%, respectively. The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia, increased alanine aminotransferase, and hair thinning. Conclusions: Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial. Teriflunomide has the potential to meet unmet medical needs for MS patients in China. Trial Registration ClinicalTrials.gov, NCT00751881; https://clinicaltrials.gov/ct2/show/NCT00751881?term=NCT00751881&rank=1.
China ; Crotonates ; administration & dosage ; adverse effects ; therapeutic use ; Double-Blind Method ; Drug Administration Schedule ; Humans ; Immunosuppressive Agents ; administration & dosage ; adverse effects ; therapeutic use ; Multicenter Studies as Topic ; Multiple Sclerosis ; drug therapy ; metabolism ; Proportional Hazards Models ; Toluidines ; administration & dosage ; adverse effects ; therapeutic use

The aim of this paper was to observe the effect of Feiliuping Gao and its combination with different types of drugs intervention on the expression of PI3K/AKT/NF-κB in lung metastatic microenvironment, and to reveal the advantage of Chinese medicine intervention time on the key molecule in lung metastatic microenvironment. The mouse model of Lewis lung carcinoma was established, and lung tissues were collected at 14 days, 21 days and 28 days after the intervention of Feiliuping Gao, and the expressions of PI3K, AKT and NF-κB were detected by immunohistochemistry and Western blot. At 14 days, there was no significant difference in PI3K expression between each group and the control group. The expression of AKT protein was significantly inhibited in the celecoxib (CLB) group, the Feiliuping Gao (FLP) combination with cyclophosphamide (FLP+CTX) group, and the Feiliuping Gao combination with celecoxib (FLP+CLB) group (<0.05). The inhibition of AKT protein expression in FLP+CLB group was superior. The FLP+CLB group can inhibit the expression of NF-κB protein (<0.05). At 21 days, compared with the control group, the expression of PI3K was inhibited in FLP group and the FLP+CTX group (<0.05), while the expression of PI3K was best inhibited in the FLP+CLB group (<0.001). Only the FLP+CLB group could significantly inhibit the expression of AKT protein (<0.01). The FLP+CTX group had the best effect in inhibiting the expression of NF-κB protein (<0.001). At 28 days, compared with the control group, the expression of PI3K and AKT was inhibited in the FLP+CLB group (<0.001). Feiliuping ointment combination with celecoxib has an advantage in regulating the expression of PI3K/AKT/NF-κB molecules in lung metastatic microenvironment.
Animals ; Carcinoma, Lewis Lung ; pathology ; Drugs, Chinese Herbal ; pharmacology ; Lung ; Mice ; NF-kappa B ; metabolism ; Neoplasm Metastasis ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Signal Transduction

Objective The treatment methods for blood blister-like aneurysm remain controversial due to its special patholog-ical structure,the risk of post-operative rebleeding and the high rate of recurrence. The arm of this paper is to access the feasibility and effectiveness of overlapping stent-assisted coiling in the treatment of blood blister-like aneurysms of the internal carotid artery. Methods Form January 2014 to December 2016,we treated 15 patients with blood blister-like aneurysm of the internal carotid artery by stent-assisted coiling in the Department of Neurosurgery,5 with two Enterprise tents,3 with three Enterprise tents,4 with Enter-prise+LVIS tents,and 3 with two LVIS tents. We determined the rate of immediate embolization of aneurysms by Raymond-Roy Occlu-sion Classification(RROC)and analyzed the clinical characteristics,postoperative complications,and follow-up data. Results All the coils and stents were successfully implanted. RROC showed 9 cases of gradeⅠ(60%),4 cases of gradeⅡ(27%),and 2 cases of gradeⅢimmediate occlusion(13%),with the parent arteries unobstructed in all the cases. Thrombosis in the stent was found in 2 cases intraoperatively,slight stent migration in 1 case,and internal carotid artery dissection in the petrous segment in another,but no cer-ebral vasospasm or aneurysm rupture in any case.Delayed cerebral in-farct was observed in 2 cases postoperatively. The patients were fol-lowed up for 2 weeks to 28 months,which showed that 11 of them were cured,2 remained stable and 2 developed further thrombosis,with an MRS score of 0-2 in 12 cases,4 in 1 case,5 in 1 case, and 6 in 1case. Conclusion Overlapping stent-assisted coiling is effective for the treatment of blood blister-like aneurysm by reduc-ing the risks of rebleeding and recurrence.

Objective To investigate the clinical features of patients with acute ST-segment elevation myocardial infarction (STEMI) comorbid with diabetes mellitus (DM) and to analyze the prognosis within 12 months after primary percutaneous coronary intervention (pre-PCI). Methods A total of 375 STEMI patients were divided into the diabetes group (n=140) and the normal blood glucose group(n=235) according to whether they met the diagnostic criteria of DH. The clinical data,characteristics of coronary artery lesions,type of stent implant,rate of coronary slow flow or no-reflow after pre-PCI, and the prognosis within 12 months after PCI of the two groups were investigated.Results Patient in the diabetes group presented with higher mean age ,higher comorbid rates of hypertension , hyperlipidemia and heart function of Killip class Ш and above than patients in the normal blood glucose group (all P<0.05). patients in the diabetes group had higher rates of slow reflow /no-reflow after PCI(12.9% vs.5.5%,P=0.013),higher percentages of 3-ressel disease(40.7% vs. 28.9%,P=0.019)and lef t main lesions(13.6% vs. 7.2%,P=0.044). The in-hospital mortality rates(6.4% vs.1.7%,P=0.020),revascularization rates within 12 months(7.9% vs.0.9%,P=0.001)and incidence of heart failure(7.9% vs. 2.6%,P=0.017)were all higher in the diabetes group. Conclusions STEMI patients comorbid with DM were relatively older, had higher comorbidities of hypertension,hyperlipidemia, three-vessel disease, left main coronary lesions and higher mortality during hospitalization. No significant increase in cardiac death and recurrent myocardial infarction were deserved during the follow-up period. These patients may benefit more from early intervention.