Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

Active Suppression of Quantum Dephasing in Resonantly Driven Ensembles.

We have used quantum control to suppress the impact of random atom positions on coherent population transfer within atom pairs, enabling the observation of dipole-dipole driven Rabi oscillations in a Rydberg gas with hundreds of atoms. The method exploits the reduced coupling-strength sensitivity of the off-resonant Rabi frequency, and coherently amplifies the achievable population transfer in analogy to quasi-phase-matching in nonlinear optics. Simulations reproduce the experimental results and demonstrate the potential benefits of the technique to other many-body quantum control applications.

Efficient Creation of Ultracold Ground State

We report the creation of ultracold ground state ^{6}Li^{40}K polar molecules with high efficiency. Starting from weakly bound molecules, stimulated Raman adiabatic passage is adopted to coherently transfer the molecules to their singlet rovibrational ground state |X^{1}Σ^{+},v=0,J=0⟩. By employing a singlet stimulated Raman adiabatic passage pathway and low-phase-noise narrow-linewidth lasers, we observed a one-way transfer efficiency of 96(4)%. Held in an optical dipole trap, the lifetime of the ground state molecules is measured to be 5.0(3) ms. The large permanent dipole moment of LiK is confirmed by applying a dc electric field on the molecules and performing Stark shift spectroscopy of the ground state. With recent advances in the quantum control of collisions, our work paves the way for exploring quantum many-body physics with strongly interacting ^{6}Li^{40}K molecules.

Notch signaling regulates Th17 cells differentiation through PI3K/AKT/mTORC1 pathway and involves in the thyroid injury of autoimmune thyroiditis.

PURPOSE: Autoimmune Thyroiditis (AIT) is the most common thyroid disease; however, there were no measures to prevent the progression of the disease. The present study attempts to identify that Notch signaling regulates the differentiation of T helper 17 (Th17) cells by activating downstream Phosphatidylinositol-3 kinase/protein kinase/mechanistic target of rapamycin complex 1 (PI3K/AKT/mTORC1) pathway participating in the thyroid injury of the experimental autoimmune thyroiditis (EAT). METHODS: In vivo experiments, mice were randomly divided into 4 groups: a control group, an EAT group, and two groups with LY294002 treatment (pTg plus 25 mg/kg or 50 mg/kg LY294002, respectively). The degrees of thyroiditis were evaluated, and the percentage of Th17 cells, expression of interleukin-17A (IL-17A), and the main components of the Notch-PI3K signaling pathway were detected in different groups. In vitro experiments, two different dosages of LY294002 (25 and 50 µM) were used to intervene splenic mononuclear cells (SMCs) from EAT mice to further evaluate the regulatory effect of Notch-PI3K pathway on Th17 cells. RESULTS: Our data demonstrate that the infiltration of Th17 cells and the expressions of IL-17A, Notch, hairy and split 1 (Hes1), p­AKT (Ser473), p­AKT (Thr308), p­mTOR (Ser2448), S6K1, and S6K2 increased remarkably in EAT mice. After PI3K pathway was blocked, the degrees of thyroiditis were significantly alleviated, and the proportion of Th17 cells, the expression of IL-17A, and the above Notch-PI3K pathway-related molecules decreased in a dose-dependent manner. Additionally, the proportion of Th17 cells was positively correlated with the concentration of serum thyroglobulin antibody (TgAb), IL-17A, and Notch-PI3K pathway-related molecules mRNA levels. CONCLUSIONS: Notch signal promotes the secretion of IL-17A from Th17 cells by regulating the downstream PI3K/AKT/mTORC1 pathway through Hes-Phosphatase and tensin homolog (PTEN) and participates in thyroid autoimmune damage, and the PI3K pathway inhibitor may play important effects on AIT by affecting Th17 cells differentiation.

[Correlation between the distribution of airborne pollen and the positive sIgE test in patients with allergic rhinitis in Taiyuan City in spring from 2022 to 2023].

This study was to investigate the relationship between spring pollen distribution concentration, species and the detection results of air-borne pollen allergens in Taiyuan City, Shanxi Province during March to May 2022 and March to May 2023.A retrospective study was conducted in the Otorhinolaryngology Head and Neck Surgery Clinic of the First Hospital of Shanxi Medical University.Pollen particles will be monitored by gravity sedimentation method on the roof of the outpatient department of the First Hospital of Shanxi Medical University in downtown Taiyuan from March to May 2022-2023, and pollen species and quantity will be observed and recorded under an optical microscope.The air-borne pollen allergen detection results of all allergic rhinitis patients in the otolaryngology Head and Neck surgery Department of the First Hospital of Shanxi Medical University were extracted from the relevant outpatient system. SPSS software and Pearson correlation analysis were used to compare the correlation between the allergens and the dominant air-borne pollen monitoring results. Results are as follows: (1)A total of 18 species of spring pollen in Taiyuan City were monitored in 2022-2023, with 101 177.5 grains, and the dominant airborne pollen was poplar (16.69%) and pine (29.06%) pollen. The pollen of poplar (11.96%), elm (7.89%) and cypress (8.68%) were dominant in early spring; Pine (25.16%) pollen predominated in late spring. The two peaks of pollen dispersal in Taiyuan were in late March (15 479 grains) and early and mid May (15 094/15 343 grains).(2) The positive rates of allergens in serum specific IgE detection were: wormwood (46%, 248/541 cases), tree combination (26%, 143/541 cases), ragweed (19%, 101/541 cases), humulus scandens (9%, 49/541 cases).(3)There was a linear positive correlation between the positive rate of air-borne pollen allergens in allergic rhinitis patients in the Department of Otolaryngology Head and Neck Surgery in the First Hospital of Shanxi Medical University and the dominant air-borne pollen concentration in the same period (P<0.05, r=0.999). In conclusion, two spring pollen dispersal peaks were formed in late March and early to mid May in Taiyuan City, and the dominant air-borne pollens were poplar and pine pollens. The positive rate of air borne pollen allergen sIgE showed that wormwood allergy was the highest.There was a positive correlation between the concentration of air-borne pollen and the positive rate of air-borne pollen allergens in patients with allergic rhinitis in the Department of otorhinolaryngology and head and neck surgery in Taiyuan in 2022 and 2023.The monitoring of pollen distribution in spring can provide an important scientific basis for clinical workers to formulate prevention and treatment plans for patients with allergic rhinitis in the season, and provide data reference for the epidemiological investigation of allergic diseases in Taiyuan in the future.

Development and multicenter validation of a novel radiomics-based model for identifying eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: Reliable noninvasive methods are needed to identify endotypes of chronic rhinosinusitis with nasal polyps (CRSwNP) to facilitate personalized therapy. Previous computed tomography (CT) scoring system has limited and inconsistent performance in identifying eosinophilic CRSwNP. We aimed to develop and validate a radiomics-based model to identify eosinophilic CRSwNP. METHODS: Surgical patients with CRSwNP were recruited from Tongji Hospital and randomly divided into training (n = 232) and internal validation cohort (n = 61). Patients from two additional hospitals served as external validation cohort-1 (n = 84) and cohort-2 (n = 54), respectively. Data were collected from October 2013 to May 2021. Eosinophilic CRSwNP was determined by histological criterion. The least absolute shrinkage and selection operator and the logistic regression (LR) algorithm were used to develop a radiomics model. Univariate and multivariate LR were employed to build models based on CT scores, clinical characteristics, and the combination of radiological and clinical characteristics. Model performance was evaluated by assessing discrimination, calibration, and clinical utility. RESULTS: The radiomics model based on 10 radiomic features achieved an area under the curve (AUC) of 0.815 in the training cohort, significantly better than the CT score model based on ethmoid-to-maxillary sinus score ratio with an AUC of 0.655. The combination of radiomic features and blood eosinophil count had a further improved performance, achieving an AUC of 0.903. The performance of these models was confirmed in all validation cohorts with satisfying predictive calibration and clinical application value. CONCLUSIONS: A CT radiomics-based model is promising to identify eosinophilic CRSwNP. This radiomics-based method may provide novel insights in solving other clinical concerns, such as guiding personalized treatment and predicting prognosis in patients with CRSwNP.

[Efficacy observation and compliance analysis of pollen allergen drops in seasonal allergic rhinitis].

To study the efficacy and compliance analysis of pollen allergen drops in the treatment of allergic rhinitis. The method of single-center controlled was used to analyze the dates' results. From July 2021 to September 2021, 80 patients with seasonal allergic rhinitis were referred to the clinic of otorhinolaryngology in First Hospital of Shanxi Medical University.40 patients received sublingual immunotherapy (SLIT group), and the other 40 patients received symptomatic drug treatment as the control group. The total rhinoconjunctivitis symptom score (TRSS), the visual analogue scale(VAS), total medication score (TMS) and combined scores of medication and rhinoconjunctivitis symptoms (CSMRS) of the patient before the start of the treatment and after the first year of the treatment were compared to assess the efficacy of sublingual immunotherapy of Artemisia pollen. Follow the shedding during the study, the safety of the drug and the causes for compliance analysis were analyzed and recorded. The results of comparison with TRSS, VAS, TMS and CSMRS in two groups in the period of pretherapy were as follows: TRSS(12.393±3.023, 12.450±3.029, t=-0.077, P=0.939), VAS(8.357±1.026, 8.400±0.982, t=-0.173, P=0.862), TMS(3.214±0.568, 3.175±0.501, t=0.301, P=0.764), CSMRS (5.286±0.680, 5.253±0.677, t=0.199, P=0.843), there was no significant difference (P>0.05); lower observed symptom scores were got in the post-treatment pollen peak SLIT group compared to the control group, TRSS(3.964±1.551, 7.750±2.169, t=-7.918, P<0.05), VAS(2.893±0.956, 5.175±1.481, t=-8.286, P<0.05), TMS (1.821±0.863, 3.175±0.501, t=-8.163, P<0.05), CSMRS (2.489±0.921, 4.468±0.601, t=-10.723, P<0.05), and the differences between the groups were statistically significant (P<0.05); the SLIT group significantly reduced all symptom scores at the first peak compared to the starting, TRSS(12.393±3.023, 3.964±1.551, t=20.576, P<0.05), VAS (8.357±1.026, 2.893±0.956, t=30.070, P<0.05), TMS (3.214±0.568, 1.821±0.863, t=7.151, P<0.05), CSMRS(5.286±0.680, 2.489±0.921, t=14.533, P<0.05) and there was statistical difference (P<0.05). No significant adverse reactions occured during medication in the SLIT group. A total of 12 cases were shed in the SLIT group, so the compliance rate was 70%. The four reasons were that patients considered the course was long (4 cases, 33%); the drugs were expensive (3 cases, 25%); patients were busy with their work and life (3 cases, 25%); patients were affected by the outbreak (2 cases, 17%). In summary, Artemisia pollen sublingual drops may improve the symptoms of the patients who got allergic rhinitis caused by Artemisia pollen after the treatment for one year. However, due to the lack of sufficient understanding of immunotherapy or the difficulty in adhering to standardized medication, the compliance with sublingual immunotherapy is still poor, the compliance with sublingual immunotherapy needs to be further improved through patient education.

[The efficacy of thin struct bare stents for the treatment of spontaneous isolated dissection of the superior mesenteric artery].

Objective: To examine the safety and effectiveness of thin struct bare stents for the treatment of spontaneous isolated dissection of the superior mesenteric artery (SIDSMA). Methods: The data of 32 patients admitted to First Hospital of Jiaxing (20 cases) and Jinling Hospital (12 cases) with SIDSMA from January 2016 to January 2021 were retrospectively analyzed. There were 27 males and 5 females, aging (54.8±9.4) years (range: 36 to 75 years). All patients were treated with thin struct bare stents. Controllable spring coils were used to fulfill the false lumen in 2 cases. Symptoms, vascular remodeling pattern at the SIDSMA lesion, and patency of the stents were observed during follow-up. Results: The surgical success rate was 100%. According to the length of the lesions and stents, the number of stents implanted was 1 in 17 cases, 2 in 11 cases and 3 in 4 cases. The angiography showed that blood flow in the stent was smooth and that the false lumen disappeared or weakened. The numerical rating scale for abdominal pain decreased from 6.1±1.5 (range: 4 to 10) preoperatively to 1.0 (1.0) (range: 0 to 3) 1 hour postoperatively (W=528, P<0.01). The compression rate of the true lumen of the superior mesenteric artery decreased from (92.3±6.7)% (range: 25% to 94%) preoperatively to 0.8 (1.2)% (range: 0 to 3.2%) 1 month postoperatively (W=528, P<0.01). The primary patency rate of CT angiography at 1 month postoperatively was 100%. The vascular remodeling rate was (92.3±6.7)% (range: 80% to 100%). All patients were followed for (46.3±17.0) months (range: 24 to 76 months). The cumulative patency rates in 1, 2 and 5 years were all 100%. Conclusion: The use of thin struct bare stents for SIDSMA is safety and efficacy.

[Effect of miR-96-5p targeting IRS1 on apoptosis of PC12 cells induced by aluminum maltol].

Objective: To investigate the effect and mechanism of miR-96-5p on apoptosis of PC12 cells induced by maltol aluminum. Methods: In January 2021, PC12 cells at logarithmic growth phase were divided into blank control group and low, medium and high dose group. Cells in each group were treated with 0, 100, 200 and 400 µmol/L maltol aluminum for 24 hours respectively. Cells were collected and cell apoptosis rates were detected by flow cytometry, miR-96-5p and insulin receptor substrate 1 (IRS1) mRNA expressions were detected by qRT-PCR, and the protein expression levels of cysteine protease 3 (Caspase3) 、activated cysteine protease 3 (Cleaved-caspase3) 、IRS1、phosphorylated protein kinase B (p-AKT) and phosphorylated glucose synthesis kinase 3ß (p-GSK3ß) were detected by western blotting. The target binding relationship between miR-96-5p and IRS1 was detected by double luciferase reporter gene experiment. The miR-96-5p inhibitor cells and negative control cells were constructed after transfecting PC12 cells with miR-96-5p inhibitor for 24 hours. The cells were divided into blank control group, negative control group, aluminum exposure group, aluminum exposure+negative control group, aluminum exposure+miR-96-5p inhibition group, and miR-96-5p inhibition group. After transfecting PC12 cells with miR-96-5p inhibition and IRS1 siRNA for 24 h, the cells were divided into aluminum exposure+miR-96-5p inhibition+negative control group and aluminum exposure+miR-96-5p inhibition+IRS1 inhibition group. The control group was cultured in complete culture medium, and cells in the aluminum exposure group were treated with 200 µmol/L maltol aluminum for 24 hours. Cells in each group were collected and the apoptosis rate, miR-96-5p and IRS1 mRNA expression levels, as well as protein expression levels of Caspase3, Cleaved-caspase3, IRS1, p-AKT, and p-GSK3ß were measured. Results: After 24 hours of exposure, compared with blank control group and low-dose group, the apoptosis rates, relative expressions of Caspase3 and Cleaved-caspase3 proteins, and relative expressions of miR-96-5p in the medium and high-dose groups of PC12 cells were significantly increased, while the relative expression levels of IRS1 mRNA, IRS1, p-AKT and p-GSK3ß proteins were significantly decreased (P<0.05). Targetscan prediction and double luciferase report experiment both proved that IRS1 was a direct target gene of miR-96-5p. In the transfection experiment, compared with the aluminum exposure group, the apoptosis rate, the relative expressions of Caspase3 and Cleaved-caspase3 proteins, the relative expression of miR-96-5p in the aluminum exposure+miR-96-5p inhibition group were significantly decreased, while the relative expression levels of IRS1 mRNA and IRS1, p-AKT and p-GSK3ß proteins were significantly increased (P<0.05). In the IRS1 low expression experiment, compared with the aluminum exposure+miR-96-5p inhibition+negative control group, the apoptosis rate, the relative expressions of Caspase3 and Cleaved-caspase3 proteins in the aluminum exposure+miR-96-5p inhibition+IRS1 inhibition group were significantly increased, while the relative expression levels of IRS1 mRNA and IRS1, p-AKT and p-GSK3ß proteins were significantly decreased (P<0.05) . Conclusion: The increased expression of miR-96-5p and the targeted inhibition of IRS1 may be one of the mechanisms of apoptosis of PC12 cells induced by maltol aluminum exposure.

[Effect of fully covered self-expandable metal stents completely inserted into the common bile duct in the treatment of benign biliary stricture].

Objective: To investigate the safety and efficacy of fully covered self-expandable metal stents(FCSEMS) completely inserted into the common bile duct in the treatment of benign biliary stricture(BBS). Methods: From December 2018 to December 2020, 22 cases of BBS treated by FCSEMS completely inserted into the common bile duct were analyzed retrospectively in the cholelithic center of Shanghai East Hospital Affiliated to Tongji University, including 12 males and 10 females, with average ages of (50.9±8.6) years. Results: All 22 cases of FCSEMS insertion were successful. The average indwelling time was (221.9±19.8) d. There were no complications of enterobiliary reflux such as liver abscess, acute cholangitis, and common bile duct obstruction. FSCEMS proximal displacement occurred in 2 cases (9.1%) with the removal time of 62 min and 115 min, respectively. There was no FCSEMS proximal displacement in 20 cases (90.9), with an average removal time of (29.7±6.3) min. All the 22 cases were followed up for 16.0 (8.0, 25.3) months, and there was no recurrence of stenosis. Conclusion: FCSESM completely inserted into the common bile duct is an effective method for the treatment of BBS, which can avoid the occurrence of enterobiliary reflux.

[Clinical observation of microsurgical removal of the hemilateral tuberculum sellae meningiomas through contralateral eyebrow arch approach].

The current study aimed to investigate the clinical feasibility of microscopic resection of hemilateral tuberculum sellae meningiomas (TSM) via the contralateral eye brow arch approach. The clinical data of 34 patients with TSM who underwent microsurgery from January 2016 to June 2021 in the Neurosurgery Department of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine and the First Affiliated Hospital of Henan University were collected and reviewed. The postoperative visual acuity improvement rate was 88.5% (23/26), and the total tumor resection rate was 88.2% (30/34); the postoperative visual acuity improvement in patients with total tumor resection was better than that of patients with partial resection [90.9% (20/22) vs 3/4]. Meanwhile, the postoperative visual acuity improvement in patients with the superior optic nerve and laterl-superior optic nerve was better than that of patients with the lateral optic nerve type (12/14, 8/8 vs 3/4). Supraorbital skin numbness occurred in 3 cases after operation, and the symptoms disappeared during follow-up; 2 cases had mild disturbance of hormone level, and urine output of 2 cases increased after operation, which returned to normal level after symptomatic treatment; 1 case had subcutaneous effusion which was absorbed after treatment. There were no complications such as olfactory disturbance and intracranial infection. During follow-up for 3-60 (33±6) months, recurrence occurred in 2 cases and reoperation was performed. For the hemilateral TSM, according to the preoperative evaluation of the origin of the TSM and the side with visual impairment, the contralateral eyebrow approach is selected to fully expose the tumor base below the optic nerve. It is beneficial to fully resect the tumor under direct vision, and the symptoms of postoperative visual impairment are significantly improved, indicating that the current surgical method can be used in the clinical setting.

[Proliferative lesions with mesonephric features in the gynecologic tract: a clinicopathological analysis of sixteen cases].

Objective: To investigate the clinicopathological features of proliferations with mesonephric features (PMF) of the gynecologic tract. Methods: A retrospective analysis was performed on the clinical and pathological data of 16 cases with PMF that were diagnosed from October 2016 to January 2022 at a single institution. The relevant literature was reviewed. Results: Among the 16 cases, with an average of 53 years (31-68 years), there were 5 cases of mesonephric hyperplasia, 4 cases of mesonephric adenocarcinoma and 7 cases of mesonephric-like adenocarcinoma. The five cases of mesonephric hyperplasia were located in the lateral wall of the cervix and composed of simple tubules with growth patterns of diffuse or lobular clusters, without obvious stromal reaction. Four cases of mesonephric adenocarcinoma consisted of a mixture of papillary, cribriform, solid and other architectures, the nuclei resembling these of papillary thyroid carcinoma, and strong fibroproliferative reaction. They were located deep in the cervical and vaginal stroma. One of the tumors showed atypical mesonephric hyperplasia adjacent to the tumor. Five uterine and two ovarian mesonephric-like adenocarcinoma cases had similar histological morphology with mesonephric adenocarcinoma, but no mesonephric remnants/mesonephric hyperplasia were found near the tumors. In addition, four (4/5) uterine mesonephric-like adenocarcinoma cases originated from the endometrium with secondary involvement of myometrium, including one case with clear demarcation between the normal endometrium and the neoplastic glands. One (1/5) uterine mesonephric-like adenocarcinoma case was mainly located in the deep myometrium, along with adenomyosis around the tumor, without mesonephric remnants. Two ovarian mesonephric-like adenocarcinoma cases were associated with endometriotic cyst/endometrioid cystadenoma, including one case with an abrupt transition between normal epithelium and atypical mesonephric cells within the single individual cyst directly adjacent to tumor. All mesonephric hyperplasia and mesonephric adenocarcinoma cases were positive for GATA3, PAX8 and CD10 in a varying degree, and negative for ER, PR and TTF1. Although mesonephric-like adenocarcinoma showed a considerable overlap of immunohistochemical expression with mesonephric adenocarcinoma, seven mesonephric-like adenocarcinoma cases were positive for TTF1 and negative for GATA3. Conclusions: PMF is a class of rare proliferative lesions with morphological and immunophenotypic characteristics of mesonephric duct. Its commonly involved site, microscopic morphology, associated benign and/or atypical lesions, and immunophenotype may contribute to its diagnosis and differential diagnosis.

[Primary ovarian squamous cell carcinoma: clinicopathological features and prognostic analysis of fifteen cases].

Objective: To assess the clinical features and treatment outcomes in patients with primary ovarian squamous cell carcinoma (POSCC). Methods: Fifteen patients with primary ovarian squamous cell carcinoma diagnosed from January 2009 to December 2018 in Cancer Hospital of the University of Chinese Academy of Sciences were collected. The expression of p16, hMLH1, hMSH2, hMSH6 and PMS2 in POSCC was detected by immunohistochemistry, and the status of high-risk human papillomavirus (HPV) by RNAscope test. Results: Squamous cell carcinoma with different degrees of differentiation was found in 15 cases, including three cases with high differentiation and 12 cases with medium to low differentiation. There were four cases with in situ squamous cell carcinoma, four cases with teratoma, one case with endometrial carcinoma/atypical hyperplasia, and one case with endometriosis. p16 was expressed in five cases (5/15), indicating coexisting high-risk HPV infection. There was no high-risk HPV infection in the remaining 10 cases, and p16 staining was negative. There was no deficient mismatch repair protein in all cases. The overall survival time (P=0.038) and progression free survival (P=0.045) of patients with high-risk HPV infection were longer than those without HPV infection. Conclusions: POSCC is more commonly noted in postmenopausal women and often occurs unilaterally. Elevated serological indexes CA125 and SCC are the most common finding. Morphologically, the tumors show variable degrees of differentiation, but the current data suggest that the degree of differentiation cannot be used as an independent prognostic index. High-risk HPV infection may be associated with the occurrence of POSCC, and that the prognosis of POSCC patients with HPV infection is better than that of patients without infection.

[Clinical characteristics and outcomes of acute respiratory distress syndrome caused by severe Chlamydia psittaci pneumonia].

Objective: To investigate the clinical characteristics and outcomes of acute respiratory distress syndrome (ARDS) caused by Chlamydia psittaci pneumonia. Methods: From June 2016 to January 2021, 10 cases were diagnosed as severe Chlamydia psittaci pneumonia induced ARDS in Intensive Care Unit of Respiratory and Critical Care Medicine Department (RICU) of Beijing Chao-Yang Hospital Affiliated to Capital Medical University. We collected the clinical data including clinical features, laboratory tests, imaging and outcomes of the patients. Results: The pathogenic diagnosis was confirmed by metagenomic Next-generation Sequencing (mNGS) in these 10 patients, with a median age of 59 (46, 67) years. In addition to high fever, cough and dyspnea, the patients also had multiple organ involvement. Six patients had elevated peripheral leukocyte count, 10 cases had increased type B natriuretic peptide, 7 cases had increased aspartate aminotransferase/alanine aminotransferase, 9 cases had hyponatremia and 3 cases had elevated creatinine. The imaging findings were bilateral consolidation with air bronchogram and infiltrates, and pleural effusion were found in 5 cases. All cases were combined with respiratory failure. Six patients received invasive mechanical ventilation. Nine patients received moxifloxacin and one patient was administrated with Azithromycin. All the patients were improved and discharged after the treatment, and the mean duration of RICU stay was 13.5 (11, 16.7) days. One month follow-up of nine patients showed significant improvement in lung lesions. Conclusions: Severe Chlamydia psittiaci pneumonia may be complicated with respiratory failure and/or multiple organ involvement. For severe pneumonia with an exposure history of sick birds, the possibility of Chlamydia psittaci infection should be considered. mNGS may help etiological diagnosis. All patients in this study had a good prognosis after targeted treatment.

[Comparison of the efficacy of irreversible electroporation and conversional resection for locally advanced pancreatic cancer].

Objective: To compare the short-term and long-term prognosis of irreversible electroporation(IRE) and conversional resection for locally advanced pancreatic cancer(LAPC). Methods: The clinical and pathological data of 98 LAPC patients who underwent IRE or conversional resection at the Department of Pancreatobiliary Surgery,Sun Yat-sen University Cancer Center from August 2015 to December 2020 were retrospectively collected and analyzed.The study comprised of 53 males and 45 females, with age(M(IQR)) of 57.5(13.5)years old(range:20 to 87 years old). Fifty-three patients received IRE treatment(IRE group) and 45 patients received surgical resection(resection group). The differences of clinical and pathological data between both groups were not significant(all P<0.05). The Mann-Whitney U test was used for quantitative data and the χ2 test was used for categorical data.Survival was analyzed using Kaplan-Meier method and compared using Log-rank test. Results: The operation time and intraoperative blood loss were 5.0(2.4)hours and 50(100) ml in the IRE group,respectively,which were significantly less than those of resection group(7.0(3.3)hours and 400(200)ml,both P<0.05).The hospital stay and hospitalization cost were 9.0(3.0)days and 79 154 (83 738) yuan in the IRE group,respectively,which were also significantly less than those in the resection group(16.0(8.5)days and 109 557(37 795)yuan,both P<0.05).The complication rate of IRE group was significantly lower than that of the resection group(18.8% vs. 55.6%,χ2=14.270,P<0.01).The median overall survival(OS) time of IRE group was 28.9 months(95%CI:23.2 to 34.6 months),with the 1-,2-,and 3-year OS rates of 91.6%,61.7%,and 24.6%,respectively.The median survival of OS of resection group was 27.1 months(95%CI:20.9 to 33.3 months),with the 1-,2-,and 3-year OS rates of 81.8%,53.9%,and 30.3%,respectively.There was no significant difference in OS between the two groups(χ2=0.900,P=0.760).The median progression free survival(PFS) time of IRE group was 18.0 months(95%CI:14.7 to 21.3 months),with the 1-,2-,and 3-year PFS rates of 68.3%,29.7%,and 9.9%,respectively.The median survival of PFS of resection group was 11.1 months(95%CI:6.1 to 16.2 months),with the 1-,2-,and 3-year PFS rates of 45.2%,21.9%,and 14.6%,respectively.There was no significant difference in PFS between the two groups(χ2=1.850,P=0.170). Conclusion: IRE can achieve similar survival for LAPC and may has less complications compared to those with conversion resection.

Structural determination of arginine-linked cisplatin complexes via IRMPD action spectroscopy: arginine binds to platinum via NO- binding mode.

Cisplatin, (NH3)2PtCl2, has been known as a successful metal-based anticancer drug for more than half a century. Its analogue, Argplatin, arginine-linked cisplatin, (Arg)PtCl2, is being investigated because it exhibits reactivity towards DNA and RNA that differs from that of cisplatin. In order to understand the basis for its altered reactivity, the deprotonated and sodium cationized forms of Argplatin, [(Arg-H)PtCl2]- and [(Arg)PtCl2 + Na]+, are examined by infrared multiple photon dissociation (IRMPD) action spectroscopy in the IR fingerprint and hydrogen-stretching regions. Complementary electronic structure calculations are performed using density functional theory approaches to characterize the stable structures of these complexes and to predict their infrared spectra. Comparison of the theoretical IR spectra predicted for various stable conformations of these Argplatin complexes to their measured IRMPD spectra enables determination of the binding mode(s) of Arg to the Pt metal center to be identified. Arginine is found to bind to Pt in a bidentate fashion to the backbone amino nitrogen and carboxylate oxygen atoms in both the [(Arg-H)PtCl2]- and [(Arg)PtCl2 + Na]+ complexes, the NO- binding mode. The neutral side chain of Arg also interacts with the Pt center to achieve additional stabilization in the [(Arg-H)PtCl2]- complex. In contrast, Na+ binds to both chlorido ligands in the [(Arg)PtCl2 + Na]+ complex and the protonated side chain of Arg is stabilized via hydrogen-bonding interactions with the carboxylate moiety. These findings are consistent with condensed-phase results, indicating that the NO- binding mode of arginine to Pt is preserved in the electrospray ionization process even under variable pH and ionic strength.

Effect of congenital heart disease on the recurrence of cough variant asthma in children.

BACKGROUND: The research into the recurrence of cough variant asthma (CVA) in congenital heart disease (CHD) are few in number. The purpose of this study is to investigate the effect of CHD on the risk of the recurrence of CVA. METHODS: This study was a retrospective cohort study of 489 children with CVA aged between one and 14 years, of whom 67 had CHD complicated with CVA and 134 had CVA without CHD at a ratio of 1:2 according to age, sex and index year. The adjusted hazard ratio (aHR) of CVA recurrence in both the CHD cohort and the non-CHD cohort was determined by multivariate analysis using the Cox proportional hazard regression model. RESULTS: Adjusting for CHD classification, Mycoplasma pneumonia (MP) infection and immunoglobulin E (IgE) sensitization, the recurrence hazard of CVA in the complex congenital heart disease (CCHD) group (aHR = 3.281; 95% CI 1.648-6.530; P < 0.01) was significantly higher than that in the simple congenital heart disease group (aHR = 2.555; 95% CI 1.739-3.752; P < 0.01). Further, children with IgE sensitization (aHR = 2.172; 95% CI 1.482-3.184; P < 0.01) had a higher recurrence hazard of CVA than those without IgE sensitization, and children with MP infection (aHR = 1.777; 95% CI 1.188-2.657; P < 0.01) had a higher recurrence hazard of CVA than those without the MP infection. CONCLUSION: The hazard of recurrent CVA is higher in children with CHD, especially in the CCHD children. In addition, those children with IgE sensitization or a MP infection had an increased hazard of recurrent CVA.

Specific PCR-based detection of Phomopsis heveicola the cause of leaf blight of Coffee (Coffea arabica L.) in China.

Coffee (Coffea arabica L.) is currently grown in many tropical and subtropical areas countries and is a major traded commodity for the developing world. Coffee leaf blight, caused by Phomopsis heveicola, is one of the most important fungal diseases dangerous to coffee crops in China. This study aimed to develop a PCR-based diagnostic method for detecting P. heveicola in planta. Specific primers (CPHF/CPHR) were designed based on sequence data of region of internal transcribed spacer (ITS1 and ITS4) of P. heveicola. The efficiency and specificity of CPHF/CPHR were established by PCR analysis of DNA from P. heveicola strains isolated from China and fungal isolates of other genera. A single amplification product of 318 bp was detected from DNA P. heveicola isolates. No amplification product was observed with any of the other fungal isolates tested. The specific primers designed and employed in PCR detected P. heveicola up to 3 pg from DNA isolated. This is the first report on the development of a species-specific PCR assay for identification and detection of P. heveicola. Thus, the PCR-based assay developed was very specific, rapid and sensitive tool for the detection of pathogen P. heveicola.

Comparative efficacy of respiratory personal protective equipment against viral respiratory infectious diseases in healthcare workers: a network meta-analysis.

OBJECTIVE: With the epidemic of coronavirus disease 2019 (COVID-19), the healthcare workers (HCWs) require proper respiratory personal protective equipment (rPPE) against viral respiratory infectious diseases (VRIDs). It is necessary to evaluate which type of mask and manner of wearing is the best suitable rPPE for preventing the VRID. STUDY DESIGN: A Bayesian network meta-analysis was performed to comprehensively analyze the protective efficacy of various rPPE. METHODS: This network meta-analysis protocol was registered in an international prospective register of systematic reviews (CRD42020179489). Electronic databases were searched for cluster randomized control trials (RCTs) of comparing the effectiveness of rPPE and wearing manner in preventing HCWs from VRID. The primary outcome was the incidence of laboratory-confirmed viral respiratory infection reported as an odds ratio (OR) with the associated 95% credibility interval (CrI). The secondary outcome was the incidence of clinical respiratory illness (CRI) reported as an OR with the associated 95% CrI. Surface under the cumulative ranking curve analysis (SUCRA) provided a ranking of each rPPE according to the primary outcome and the secondary outcome as data supplement. RESULTS: Six studies encompassing 12,265 HCWs were included. In terms of the incidence of laboratory-confirmed viral respiratory infection, the continuous wearing of N95 respirators (network OR, 0.48; 95% CrI: 0.27 to 0.86; SUCRA score, 85.4) showed more effective than the control group. However, in terms of reducing the incidence of CRI, there was no rPPE showing superior protective effectiveness. CONCLUSIONS: There are significant differences in preventive efficacy among current rPPE. Our result suggests that continuous wearing of N95 respirators on the whole shift can serve as the best preventive rPPE for HCWs from the VRID.

[Effect of pancreatic stent combined with somatostatin on the prevention of acute pancreatitis after endoscopic retrograde cholangiopancreatography].

Objective: To explore whether the use of pancreatic stent combined with somatostatin can produce the synergistic effect of preventing acute pancreatitis (AP) and hyperamylasemia (HP) after endoscopic retrograde cholangiopancreatography (ERCP). Methods: From January 2019 to December 2019, the clinical data of 325 patients with ERCP were analyzed retrospectively in cholelithic center of Shanghai East Hospital Affiliated to Tongji University. According to the different methods of AP prevention, the patients were divided into the observation group (pancreatic stent and somatostatin) and the control group (pancreatic stent) and the incidence of AP and HP were compared. Results: In the observation group, there were 5 cases of AP (3.65%) and 10 cases of HP (7.30%). In the control group, there were 7 cases of AP (3.72%) and 19 cases of HP (10.11%). The incidence of AP and HP in the observation group was lower than that in the control group, but the differences were not statistically significant (χ²=0.001, P=0.972; χ²=0.768, P=0.381). Conclusion: The use of pancreatic stent combined with somatostatin will not produce the synergistic effect of preventing AP and HP after ERCP.