Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

Objective To investigate the influencing factors associated with bleeding complications in patients with obstructive jaundice treated with percutaneous transhepatic cholangial drainage(PTCD).Methods Clinical data of 1 042 patients with obstructive jaundice,who received PTCD at the Affiliated Hospital of Guizhou Medical University,the Xiangya Second Hospital of Central South University,and the Affiliated Cancer Hospital of Guizhou Medical University of China between January 2015 and January 2021,were collected.The risk factors related to PTCD bleeding complications were retrospective analyzed.Results The location where the drainage tube forming loop had a statistically significant effect on PTCD bleeding complications(P＜0.01).Compared with the loop-forming within the common bile duct,the loop-forming within the left and right hepatic duct would increase the risk of postoperative bleeding by 155.6％(OR=2.556,95％CI:1.251-5.225),the loop-forming within the lower order branch of the left and right hepatic duct would increase the risk of postoperative bleeding by 414.4％(OR=5.144,95％CI:2.618-10.106).The difference in the risk degree of postoperative bleeding between different drainage ways after successful puncturing was statistically significant(P＜0.05).Compared with the external drainage method,internal-external joint drainage method would increase the risk degree of postoperative bleeding by 159.1％(OR=2.591,95％CI:1.102-6.091).Preoperative platelet count and preoperative total bilirubin level were the independent risk factors for bleeding complications of PTCD(P＜0.05).For each unit increase in preoperative platelet count,the probability of developing postoperative bleeding complications would decrease by 0.2％(OR=0.998,95％CI:0.995-1.000),and a preoperative platelet count level＜228 ×109/L would have an impact on the postoperative bleeding.For each unit increase in preoperative total bilirubin,the probability of developing postoperative bleeding complications would increase by 0.3％(OR=1.003,95％CI:1.001-1.004),and a preoperative total bilirubin＞264.4 μmol/L would have an impact on the postoperative bleeding.Conclusion The loop-forming location of draining tube and the drainage method are the independent risk factors for PTCD bleeding complications.The closer the loop-forming location to the tertiary branches is,the greater the risk of bleeding would be.The bleeding risk of internal-external joint drainage method is higher than that of external drainage method.The preoperative total bilirubin and preoperative platelet count are the independent risk factors for bleeding complications of PTCD.The preoperative total bilirubin level is positively correlated with bleeding risk,while the preoperative platelet count level is negatively correlated with the bleeding risk.(J Intervent Radiol,2024,33:500-506)

Objective To explore characteristics of co-infection of Chlamydia pneumoniae(Cpn)and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),and identify their effect on SARS-CoV-2-induced inflammatory response.Methods Patients with coronavirus disease 2019(COVID-19)who received treatment in a hospital in Chenzhou City from December 20,2022 to February 20,2023 were selected.According to the severity of COVID-19,severe and critical cases were classified as the severe symptom group,while mild and moderate cases were classified as the mild symptom group.Meanwhile,according to the age of patients(≥18 years old as adults,＜18 years old as juveniles),they were divided into the adult severe symptom group,adult mild symptom group,juvenile severe symptom group,and juvenile mild symptom group.Propensity score was adopted to match age,gender,and under-lying diseases of patients in severe symptom and mild symptom group in a 1∶1 ratio.Bronchoalveolar lavage fluid(BALF),throat swabs,and serum specimens of patients were collected.Cpn IgG/IgM antibody was detected by enzyme-linked immunosorbent assay(ELISA),levels of 12 common cytokines(including interleukin-8[IL-8])in BALF were detected by flow cytometry,differences among groups were compared.Results A total of 102 patients were included,with 61 severe and critical(severe symptom)patients,as well as 41 mild and moderate(mild symp-tom)patients.There were 71 patients aged ≥18 years and 31 juvenile patients aged＜18 years.There were 39 pa-tients in the adult severe symptom group and 32 in the adult mild symptom group,and 30 pairs were successfully matched through propensity score analysis.There were 22 patients in the juvenile severe symptom group and 9 in the juvenile mild symptom group,and 8 pairs were successfully matched through propensity score analysis.Among COVID-19 patients,the positive rates of Cpn IgG and IgM were 36.27％(n=37)and 8.82％(n=9),respective-ly,with 1 case positive for both Cpn IgG and IgM.The level of interferon(IFN)-α in serum specimens from adult patients with severe symptom combined with positive Cpn IgG was higher than that of IgG negative patients(P=0.037).There was no statistically significant difference in the levels of other cytokines in BALF and serum speci-mens between the two groups of patients(all P＞0.05).The levels of IL-8 and IL-17 in serum specimens of patients with positive Cpn IgG in the adult mild symptom group were both higher than those in Cpn IgG negative patients(both P＜0.05).The levels of IL-8 in both BALF and serum specimens from Cpn IgM positivity patients in the ju-venile mild symptom group were higher than those from patients with negative Cpn IgM(both P＜0.05).Logistic regression analysis results showed that Cpn IgG and IgM positivity were not risk factors for the development of se-vere COVID-19.Conclusion Combined Cpn infection is not a risk factor for the development of severe symptom in COVID-19 patients,and Cpn infection has limited impact on the secretion of inflammatory factors caused by SARS-CoV-2.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To explore the long-term effect of endoscopic radiofrequency ablation for the treatment of unresectable ampullary carcinoma.Methods:Clinical data of patients with ampullary carcinoma who received endoscopic radiofrequency ablation in the Third Affiliated Hospital of Naval Medical University from January 2012 to May 2019 were retrospectively collected, including basic information, frequency of radiofrequency ablation, the type of biliary stent, postoperative complications, and follow-up. Kaplan-Meier method was used to analyze the survival of patients after endoscopic radiofrequency ablation. Relationship between frequency of radiofrequency ablation, type of biliary stent and overall survival time was analyzed.Results:A total of 50 patients were enrolled, including 31 males and 19 females, aged 73.0±9.7 years. Twenty-five patients (50.0%) underwent 1 radiofrequency ablation treatment, while 25 patients (50.0%) underwent radiofrequency ablation treatments more than twice. Postoperative complications occurred in 6 patients (12.0%), all of which were mild symptoms. The average follow-up was 22.3 months, with a total of 39 (78.0%) deaths, 5 (10.0%) lost to follow-up, and 6 (12.0%) surviving. The median overall survival time was 16.9 (95% CI: 9.1-24.8) months, with cumulative survival rates of 62.0%, 38.5%, 27.0%, and 12.6% at 1, 2, 3, and 5 years, respectively. The median overall survival time of those treated with radiofrequency ablation ≥2 times showed a trend of prolongation compared to patients treated once, but the difference was not statistically significant [26.7 (95% CI: 9.7-43.7) months VS 12.6 (95% CI: 4.9-20.3) months, χ2=3.049, P=0.081]. Plastic stents were used in 32 patients (64.0%) and metal stents in 18 patients (36.0%). There was no significant difference in median overall survival time between patients using metal and plastic stents [17.1 (95% CI: 6.1-28.0) months VS 15.9 (95% CI: 6.9-24.9) months， χ2=0.029， P=0.865]. Conclusion:Endoscopic radiofrequency ablation is a safe treatment for unresectable ampullary carcinoma, and multiple consecutive treatments may increase the survival benefit.

Objective:To investigate the efficacy of endoscopic stent placement for patients with Bismuth type Ⅳ hilar cholangiocarcinoma.Methods:Data of 229 patients with unresectable Bismuth type Ⅳ hilar cholangiocarcinoma who successfully underwent endoscopic stent placement at the Department of Endoscopy, the Third Affiliated Hospital of Naval Medical University from January 2002 to January 2019 were retrospectively analyzed. Outcomes included clinical success rate, complication incidence, stent patency period and overall survival time. The patency of stents and overall survival time of patients were estimated by using the Kaplan-Meier method. The independent predictors for stent patency and overall survival of patients were analyzed by a multivariate Cox proportional regression model.Results:The overall clinical success rate was 78.2% (179/229). The incidence of early cholangitis after endoscopic retrograde cholangiopancreatography was 20.5% (47/229). The median stent patency and overall survival time were 5.7 (95% CI: 4.8-6.7) months and 5.1 (95% CI: 4.2-6.0) months, respectively. Further multivariate Cox regression analysis showed that metal stent ( P<0.001, HR=0.452, 95% CI: 0.307-0.666) and bilateral stents with bilateral angiography ( P=0.036, HR=0.644, 95% CI: 0.427-0.971) were independent predictors of stent patency; total bilirubin>200 μmol/L ( P=0.001, HR=1.627, 95% CI: 1.208-2.192), metal stent ( P=0.004, HR=0.636, 95% CI: 0.467-0.866) and antitumor therapy ( P<0.001, HR=0.439, 95% CI:0.308-0.626) were independent predictors of overall survival. Conclusion:There is high incidence of cholangitis in patients with unresectable Bismuth type Ⅳ hilar cholangiocarcinoma treated with endoscopic stenting. Longer stent patency can be achieved with metal stent placement and bilateral drainage. In addition, metal stent for drainage and antitumor therapy can also help increase the survival benefit.

Objective: To examine the clinical feasibility of mixed reality navigation (MRN) technology based on multimodal imaging for the resection of intracranial eloquent lesions. Methods: Fifteen patients with intracranial eloquent lesions admitted to the Department of Neurosurgery, the First Medical Center, People's Liberation Army General Hospital from September 2020 to September 2021 were retrospectively enrolled. There were 7 males and 8 females, aged (50±16) years (range: 16 to 70 years). Postoperative pathological diagnosis included meningioma (n=7), metastatic carcinoma (n=3), cavernous hemangioma, glioma, ependymoma, aneurysmal changes and lymphoma (n=1, respectively). The open-source software was used to perform the three-dimensional visualization of preoperative images, and the self-developed MRN system was used to perform the fusion and interaction of multimodal images, so as to formulate the surgical plan and avoid damaging the eloquent white matter fiber tracts. Traditional navigation, intraoperative ultrasound and fluorescein sodium angiography were used to determine the extent of lesion resection. The intraoperative conditions of MRN-assisted surgery were analyzed, and the setup time and localization error of MRN system were measured. The changes of postoperative neurological function were recorded. Results: MRN based on multimodal imaging was achieved in all patients. The MRN system setup time (M(IQR)) was 36 (12) minutes (range: 20 to 44 minutes), and the localization error was 3.2 (2.0) mm (range: 2.6 to 6.7 mm). The reliability of eloquent white matter fiber tracts localization based on MRN was rated as "excellent" in 11 cases, "medium" in 3 cases, and "poor" in 1 case. There were no perioperative death and no new impairment in motor, language, or visual functions after operation. Transient limb numbness occurred in 1 patient after operation, and recovered to the preoperative state in 2 weeks after operation. Conclusion: The MRN system based on multimodal imaging can improve the surgical accuracy and safety, and reduce the incidence of iatrogenic neurological dysfunction.
Humans ; Augmented Reality ; Reproducibility of Results ; Retrospective Studies ; Multimodal Imaging

Objective: To investigate the functional changes of key gut microbiota (GM) that produce lipopolysaccharide (LPS) in atrial fibrillation (AF) patients and to explore their potential role in the pathogenesis of AF. Methods: This was a prospective cross-sectional study. Patients with AF admitted to Beijing Chaoyang Hospital of Capital Medical University were enrolled from March 2016 to December 2018. Subjects with matched genetic backgrounds undergoing physical examination during the same period were selected as controls. Clinical baseline data and fecal samples were collected. Bacterial DNA was extracted and metagenomic sequencing was performed by using Illumina Novaseq. Based on metagenomic data, the relative abundances of KEGG Orthology (KO), enzymatic genes and species that harbored enzymatic genes were acquired. The key features were selected via the least absolute shrinkage and selection operator (LASSO) analysis. The role of GM-derived LPS biosynthetic feature in the development of AF was assessed by receiver operating characteristic (ROC) curve, partial least squares structural equation modeling (PLS-SEM) and logistic regression analysis. Results: Fifty nonvalvular AF patients (mean age: 66.0 (57.0, 71.3), 32 males(64%)) were enrolled as AF group. Fifty individuals (mean age 55.0 (50.5, 57.5), 41 males(82%)) were recruited as controls. Compared with the controls, AF patients showed a marked difference in the GM genes underlying LPS-biosynthesis, including 20 potential LPS-synthesis KO, 7 LPS-biosynthesis enzymatic genes and 89 species that were assigned as taxa harbored nine LPS-enzymatic genes. LASSO regression analysis showed that 5 KO, 3 enzymatic genes and 9 species could be selected to construct the KO, enzyme and species scoring system. Genes enriched in AF group included 2 KO (K02851 and K00972), 3 enzymatic genes (LpxH, LpxC and LpxK) and 7 species (Intestinibacter bartlettii、Ruminococcus sp. JC304、Coprococcus catus、uncultured Eubacterium sp.、Eubacterium sp. CAG:251、Anaerostipes hadrus、Dorea longicatena). ROC curve analysis revealed the predictive capacity of differential GM-derived LPS signatures to distinguish AF patients in terms of above KO, enzymatic and species scores: area under curve (AUC)=0.957, 95%CI: 0.918-0.995, AUC=0.940, 95%CI 0.889-0.991, AUC=0.972, 95%CI 0.948-0.997. PLS-SEM showed that changes in lipopolysaccharide-producing bacteria could be involved in the pathogenesis of AF. The key KO mediated 35.17% of the total effect of key bacteria on AF. After incorporating the clinical factors of AF, the KO score was positively associated with the significantly increased risk of AF (OR<0.001, 95%CI:<0.001-0.021, P<0.001). Conclusion: Microbes involved in LPS synthesis are enriched in the gut of AF patients, accompanied with up-regulated LPS synthesis function by encoding the LPS-enzymatic biosynthesis gene.
Aged ; Atrial Fibrillation/complications* ; Cross-Sectional Studies ; Gastrointestinal Microbiome ; Humans ; Lipopolysaccharides ; Male ; Middle Aged ; Prospective Studies

Objective:To investigate the characteristics of blood glucose fluctuation and risk factors in type 2 diabetic patients with asymptomatic hypoglycemia.Methods:From September 2018 to July 2021, 342 patients with type 2 diabete mellitus who were hospitalized in the Department of Endocrinology of Hefei Hospital Affilitated to Anhui Medical University were enrolled for a retrospective study. The mean amplitude of glycemic excursions(MAGE), coefficient of variation (CV), 24 hour mean blood glucose level (MG), and time in range (TIR) were obtained by continuous glucose monitoring (CGM). According to the results of CGM and whether the patients have hypoglycemia symptoms, they were divided into three groups: no hypoglycemia group, symptomatic hypoglycemia group, and asymptomatic hypoglycemia group. The differences in blood glucose fluctuations were compared among the three groups. Multivariate logistic regression analysis was used to evaluate the risk factors in type 2 diabete mellitus patients with asymptomatic hypoglycemia. The predictive value of MAGE for asymptomatic hypoglycemia was analyzed by receiver operating characteristic (ROC) curve.Results:Compared with the non-hypoglycemia group, the TIR in asymptomatic hypoglycemia group was higher ( Z=-2.042, P=0.041). The asymptomatic hypoglycemia group had lower MG, higher MAGE and CV compared with the other two groups(all P<0.05). Multivariate logistic regression analysis showed that urinary albumin/creatinine ratio (UACR), MAGE, and CV were the risk factors for asymptomatic hypoglycemia, while MG was the protective factor. After adjustment for other risk factors, MAGE was still associated with asymptomatic hypoglycemia ( OR=1.111, 95% CI 0.999-1.235, P=0.049). The sensitivity and specificity of MAGE in predicting asymptomatic hypoglycemia were 0.769 and 0.776, respectively. Conclusions:Patients with asymptomatic hypoglycemia present with larger TIR and MAGE. MAGE, UACR, and CV were risk factors for asymptomatic hypoglycemia. Moreover, MAGE has some predictive value for the occurrence of asymptomatic hypoglycemia.

Aim To explore the effeet of chemogenetic designer reeeptors exclusively activated by designer drugs( DREADD) mediated inhibition of glutamatergic neurons in paraventricular nucleus of hypothalamus (PVN ) on myocardial ischemia-reperfusion injury in mice.Methods Mice were catheterized in PVN by stereotaxic technique, followed by recover}' for three days in individual cages.The mice were then received the inhibitory virus rAAV CaMK E cx-hM4d (Gi)-EG- FP-WPRE-hGHpA or the control vims rAAV CaMK H a - E GF P- W PRE - h GH pA in the PVN nucleus.Three weeks after virus infection, myocardial ischemia-reperfusion injury ( IR) was performed by ligating the left anterior descending coronary artery for 1 h and then releasing it for 2 h.Clozapine N-oxide (CNO) 2 mg •kg 1 was injected intraperitoneally 1 h before IR, to induce inhibition of glutamatergic neurons in PVN by specifically binding to the hM4D receptor ( Gi).TTC staining was used to measure the infarct size, and ELISA was used to measure the serum cTnl concentration.During experiments, the ECG was recorded by PowerLab system.Western blot was used to detect the pro-survival kinase ERK and cleaved caspase-3 proteins in heart tissues, and the expressions of EGFP, CaMKII and c-fos in PVN were examined under fluorescence microscope.Results The glutamatergic neurons in PV N were specifically infected by AAV vectors.When compared with sham group, the ratio of IS/AAR, serum cTnl, c-fos in PVN, and cleaved caspase-3 protein all increased in IR group , but the pERK level decreased.However, hM4D ( Gi) DREADD mediated inhibition of PVN glutamatergic neurons significantly reduced IS/AAR, cTnl concentration and c-fos expression in PVN, as well as the decrease of cleaved caspase-3 and the increase of pERK in heart tissues.Conclusion Chemogenetic DREADD mediated inhibition of glutamatergic neurons in paraventricular nu- cleus of hypothalamus ( PVN) reduces myocardial is- chemia-reperfusion injury in mice.