Elevated MIF identified by multiple cytokine analyses facilitates macrophage M2 polarization contributing to postoperative recurrence in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by tissue heterogeneity and high postoperative recurrence risk. This study aims to employ cytokine analyses to identify serum biomarkers associated with postoperative CRSwNP recurrence and elucidate underlying recurrent mechanisms. METHODS: A prospective cohort study was conducted on CRSwNP patients undergoing functional endoscopic sinus surgery. Serum and tissue samples were collected and analyzed for multiple cytokines. Participants were followed for 3 years and categorized into recurrent and non-recurrent groups. Cytokine profiles were compared, and potential markers for recurrence were further assessed. Macrophage migration inhibitory factor (MIF) expression in macrophages was modulated, and their polarization and cytokine secretion were assessed. RESULTS: In the discovery cohort (21 recurrent and 40 non-recurrent patients), circulating cytokine profiles differed significantly, with 8 cytokines showing differential expression between the two groups. Among them, serum eotaxin, MIF, RANTES, and TRAIL exhibited promise in predicting recurrence. In the validation cohort (24 recurrent and 44 non-recurrent patients), serum eotaxin, MIF, and TRAIL levels were higher in recurrent cases. Tissue MIF was elevated in recurrent cases and had a strong predictive value for recurrence. Moreover, tissue MIF was co-expressed with CD206 in recurrent cases. Mechanistically, MIF overexpression promoted macrophage M2 polarization and TGF-ß, CCL-24, and MIF secretion, and MIF recombinant protein facilitated M2 polarization, and TGF-ß1 and CCL-24 production, contributing to CRSwNP recurrence. CONCLUSIONS: Serum-specific cytokine signatures were associated with postoperative recurrence risk in CRSwNP. Elevated MIF enhanced macrophage M2 polarization and cytokine secretion, contributing to the recurrent mechanisms of CRSwNP.

[Gemcitabine long-term maintenance chemotherapy benefits patients with survival: a multicenter, real-world study of advanced breast cancer treatment in China].

Objective: This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer. Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients. Methods: Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals). The clinicopathological data, the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed. To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy. Results: A total of 224 patients with advanced breast cancer were enrolled in this study, with a median age of 52 years (26-77 years), 55.4%(124/224) was postmenopausal. Luminal type were 83 cases, TNBC were 97 cases, and human epidermal growth factor receptor 2 (HER's-2) overexpression were 44. At the analysis, 224 patients who received the gemcitabine-based regimens were evaluated, included 5 complete reponse (CR), 77 partial response (PR), 112 stable disease (SD) and 27 progressive disease (PD). The objective response rate (ORR) was 36.6%(82/224). Seventy patients had serious adverse diseases, including leukopenia (9), neutrophilia (49), thrombocytopenia (15), and elevated transaminase (2). The median follow-up time was 41 months (26~61 months), and the median PFS was 5.6 months. The reasons of termination treatment were listed: disease progression were 90 patients; personal reasons were 51 patients; adverse drug reactions were 18 patients; completed treatment were 65 patients. It was found that progression-free survival (PFS) was significantly longer in patients receiving >6 cycles than that in patients with ≤6 cycles (8.2 months vs 5.4 months, HR=2.474, 95% CI: 1.730-3.538, P＜0.001). Conclusions: Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world. The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.

[Annual progress in pulmonary rehabilitation 2023].

Pulmonary rehabilitation is a key component of long-term management strategies for chronic respiratory diseases (CRD). This comprehensive intervention, carefully tailored to individual patients based on thorough assessments, has undergone significant expansion and refinement toward personalization and precision in recent years. This review consolidates findings from studies published between October 2022 and September 2023, covering advances in CRD rehabilitation, assessment criteria, mechanisms, and innovative equipments. The primary objective is to enhance the knowledge base of healthcare professionals and pave the way for future research efforts in this important area.

Mechanistic Investigation of Ni-Catalyzed Reductive Cross-Coupling of Alkenyl and Benzyl Electrophiles.

Mechanistic investigations of the Ni-catalyzed asymmetric reductive alkenylation of N-hydroxyphthalimide (NHP) esters and benzylic chlorides are reported. Investigations of the redox properties of the Ni-bis(oxazoline) catalyst, the reaction kinetics, and mode of electrophile activation show divergent mechanisms for these two related transformations. Notably, the mechanism of C(sp3) activation changes from a Ni-mediated process when benzyl chlorides and Mn0 are used to a reductant-mediated process that is gated by a Lewis acid when NHP esters and tetrakis(dimethylamino)ethylene is used. Kinetic experiments show that changing the identity of the Lewis acid can be used to tune the rate of NHP ester reduction. Spectroscopic studies support a NiII-alkenyl oxidative addition complex as the catalyst resting state. DFT calculations suggest an enantiodetermining radical capture step and elucidate the origin of enantioinduction for this Ni-BOX catalyst.

Electronic Structures of Nickel(II)-Bis(indanyloxazoline)-dihalide Catalysts: Understanding Ligand Field Contributions That Promote C(sp2)-C(sp3) Cross-Coupling.

NiII(IB) dihalide [IB = (3aR,3a'R,8aS,8a'S)-2,2'-(cyclopropane-1,1-diyl)bis(3a,8a-dihydro-8H-indeno[1,2-d]-oxazole)] complexes are representative of a growing class of first-row transition-metal catalysts for the enantioselective reductive cross-coupling of C(sp2) and C(sp3) electrophiles. Recent mechanistic studies highlight the complexity of these ground-state cross-couplings but also illuminate new reactivity pathways stemming from one-electron redox and their significant sensitivities to reaction conditions. For the first time, a diverse array of spectroscopic methods coupled to electrochemistry have been applied to NiII-based precatalysts to evaluate specific ligand field effects governing key Ni-based redox potentials. We also experimentally demonstrate DMA solvent coordination to catalytically relevant Ni complexes. Coordination is shown to favorably influence key redox-based reaction steps and prevent other deleterious Ni-based equilibria. Combined with electronic structure calculations, we further provide a direct correlation between reaction intermediate frontier molecular orbital energies and cross-coupling yields. Considerations developed herein demonstrate the use of synergic spectroscopic and electrochemical methods to provide concepts for catalyst ligand design and rationalization of reaction condition optimization.

[Effect of diurnal temperature range on the number of elderly inpatients with ischemic stroke in Hunan Province].

Objective: To study the effect of diurnal temperature range on the number of elderly inpatients with ischemic stroke in Hunan Province. Method: Demographic and disease data, meteorological data, air quality data, population, economic and health resource data of elderly inpatients with ischemic stroke were collected in 122 districts/counties of Hunan Province from January to December 2019. The relationships between the diurnal temperature range and the number of elderly inpatients with ischemic stroke were analyzed by using the distributed lag non-linear model, including the cumulative lag effect of the diurnal temperature range in different seasons, extremely high diurnal temperature range and extremely low diurnal temperature range. Results: In 2019, 152 875 person-times were admitted to the hospital for ischemic stroke in the elderly in Hunan Province. There was a non-linear relationship between the diurnal temperature range and the number of elderly patients with ischemic stroke, with different lag periods. In spring and winter, with the decrease in diurnal temperature range, the risk of admission of elderly patients with ischemic stroke increased (Ptrend<0.001, Ptrend=0.002);in summer, with the increase in diurnal temperature range, the risk of admission of elderly patients with ischemic stroke increased (Ptrend=0.024);in autumn, the change in the diurnal temperature range would not cause a change in admission risk (Ptrend=0.089). Except that the lag effect of the extremely low diurnal temperature range in autumn was not obvious, the lag effect occurred in other seasons under extremely low and extremely high diurnal temperature ranges. Conclusion: The high diurnal temperature range in summer and the low diurnal temperature range in spring and winter will increase the risk of admission of elderly patients with ischemic stroke, and the risk of admission of elderly patients with ischemic stroke will lag under the extremely low and extremely high diurnal temperature ranges in the above three seasons.

[Annual progress in pulmonary rehabilitation 2022].

Pulmonary rehabilitation can relieve dyspnea in patients, improve their healthy status and exercise tolerance. It is the most cost-effective comprehensive intervention. Although the role of pulmonary rehabilitation has been recognized and recommended in clinical guidelines, it is still underutilized worldwide. Therefore, how to improve the knowledge and awareness of pulmonary rehabilitation and to increase accessibility, thus promoting its application and completion, is the key point of clinical research. Related research has also made a series of important progress. This review summarized the latest research findings from September 2021 to October 2022, with the goal of increasing healthcare professionals' knowledge and awareness in order to improve patient referral to pulmonary rehabilitation.

[Application of veno-arterio-venous extracorporeal membrane oxygenation in patients with critical respiratory failure combined with refractory shock].

Objective: To preliminarily analyze the application experience of veno-arterio-venous extracorporeal membrane oxygenation (VAV-ECMO).The VAV-ECMO is a rescue strategy for patients with extremely critical respiratory failure combined with refractory shock. Methods: From February 2016 to February 2022, the characteristics and outcomes of patients who were started on either veno-venous or veno-arterial ECMO due to respiratory or hemodynamic failure, and then converted to VAV-ECMO in respiratory intensive care unit (ICU) of Beijing Chaoyang Hospital were analyzed. Results: A total of 15 patients underwent VAV-ECMO, aged 53 (40, 65) years, and 11 of whom were male. Within the group, VV-ECMO was initially used in 12 patients due to respiratory failure, but then VAV-ECMO was used due to cardiogenic shock (7/12) and septic shock (4/12), while VAV-ECMO was established in two patients due to lung transplantation. One patient was diagnosed with pneumonia complicated by septic shock, which was initially determined to be VA-ECMO, but then switched to VAV-ECMO because it was difficult to maintain oxygenation. The time from the establishment of VV or VA-ECMO to the switch to VAV-ECMO was 3 (1, 5) days and the VAV-ECMO support time was 5 (2, 8) days. ECMO-related complications were bleeding, mostly in the digestive tract (n=4) and airway hemorrhage (n=4), without intracranial hemorrhage, and poor arterial perfusion of the lower limbs (n=2). Among these 15 patients, the overall ICU mortality was 53.3%. The mortality of patients who received VAV-ECMO due to septic shock and cardiogenic shock was 100% (4/4) and 42.8% (3/7), respectively. Two patients who received VAV-ECMO due to lung transplantation all survived. Conclusion: VAV-ECMO may be a safe and effective treatment for carefully selected patients with critical respiratory failure associated with cardiogenic shock or end-stage lung disease lung transplantation transition, however, patients with septic shock may benefit the least.

Aetiology of tinea capitis in China: a multicentre prospective study.

BACKGROUND: Tinea capitis is still common in developing countries, such as China. Its pathogen spectrum varies across regions and changes over time. OBJECTIVES: This study aimed to clarify the current epidemiological characteristics and pathogen spectrum of tinea capitis in China. METHODS: A multicentre, prospective descriptive study involving 29 tertiary hospitals in China was conducted. From August 2019 to July 2020, 611 patients with tinea capitis were enrolled. Data concerning demography, risk factors and fungal tests were collected. When necessary, the pathogens were further identified by morphology or molecular sequencing in the central laboratory. RESULTS: Among all enrolled patients, 74·1% of the cases were in patients aged 2-8 years. The children with tinea capitis were mainly boys (56·2%) and were more likely than adults to have a history of animal contact (57·4% vs. 35·3%, P = 0·012) and zoophilic dermatophyte infection (73·5% vs. 47%). The adults were mainly female (83%) and were more likely than children to have anthropophilic agent infection (53% vs. 23·9%). The most common pathogen was zoophilic Microsporum canis (354, 65·2%), followed by anthropophilic Trichophyton violaceum (74, 13·6%). In contrast to the eastern, western and northeastern regions, where zoophilic M. canis predominated, anthropophilic T. violaceum predominated in central China (69%, P < 0·001), where the patients had the most tinea at other sites (20%) and dermatophytosis contact (26%) but the least animal contact (39%). Microsporum ferrugineum was the most common anthropophilic agent in the western area, especially in Xinjiang province. CONCLUSIONS: Boys aged approximately 5 years were the most commonly affected group. Dermatologists are advised to pay more attention to the different transmission routes and pathogen spectra in different age groups from different regions.

[A survey on clinical practice of tracheostomy decannulation in medical institutions at all levels across the country].

Objective: A questionnaire survey was conducted on the clinical practice of tracheostomy decannulation among medical staff in medical institutions at all levels across the country. Methods: The questionnaire was determined by literature review and expert consultation to investigate the clinical practice of tracheostomy decannulation among medical staff in comprehensive and rehabilitation hospitals of different levels across the country and the factors considered when deciding to decannulate. Statistical methods used χ² test and one-way ANOVA. Results: A total of 570 questionnaires were collected from all over the country, with 463 valid questionnaires. The survey results showed that the most important factors in clinical practice to determine the decannulation of the tracheostomy tube were upper airway patency, cough effectiveness, level of consciousness and oxygenation. Before decannulation, 220 (47.50%) would choose to change to metal cannula, and 384 (82.90%) would routinely occlude the tube. 294 (63.50%) thought that re-intubation within 24 hours after decannulation of the tracheostomy tube was failure of decannulation. The decannulation failure rate was mostly 2%-5%. Conclusions: Upper airway patency, cough effectiveness, level of consciousness and oxygenation were important factors when considering decannulation. Reintubation within 24 hours of decannulation was defined as failure by the majority of respondents.

[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.

Efficacy of utidelone plus capecitabine versus capecitabine for heavily pretreated, anthracycline- and taxane-refractory metastatic breast cancer: final analysis of overall survival in a phase III randomised controlled trial.

BACKGROUND: Primary analysis of the phase III trial BG01-1323L demonstrated that utidelone plus capecitabine significantly improved progression-free survival (PFS) and overall response rate (ORR) versus capecitabine alone in heavily-pretreated patients with metastatic breast cancer (MBC). Here, we report the final overall survival (OS) analysis and updates of other endpoints. PATIENTS AND METHODS: In total, 405 patients were randomised 2:1 to receive utidelone (30 mg/m2 IV daily, days 1-5, over 90 min) plus capecitabine (1000 mg/m2 orally b.i.d., days 1-14) or capecitabine alone (1250 mg/m2 orally b.i.d., days 1-14) every 21 days. The secondary endpoint, OS, was estimated using the Kaplan-Meier product-limit approach at a two-sided alpha level of 0.05 after the prespecified 310 death events had been reached. Exploratory analyses of the primary endpoint, PFS, and the secondary endpoint, ORR, were also done. Safety was analysed in patients who had at least one dose of study drug. RESULTS: At the final OS analysis, the median duration of follow-up was 19.6 months in the utidelone plus capecitabine group and 15.4 months in the capecitabine alone group. In the intention-to-treat population, 313 deaths had occurred at data cut-off, 203 of 270 patients in the combination group and 110 of 135 in the monotherapy group. Median OS in the combination group was 19.8 months compared with 16.0 months in the monotherapy group [hazard ratio (HR) = 0.75, 95% confidence intervals (CI) 0.59-0.94, P = 0.0142]. The updated analysis of PFS and ORR showed that the combination therapy remained superior to monotherapy. Safety results were similar to those previously reported with respect to incidence, severity and specificity. No late-emerging toxicities or new safety concerns occurred. CONCLUSIONS: For heavily-pretreated, anthracycline- and taxane-resistant MBC patients, utidelone plus capecitabine significantly improved OS versus capecitabine alone. These results support the use of utidelone plus capecitabine as a novel therapeutic regimen for patients with MBC.

The effect of immunonutrition in patients with acute pancreatitis: a systematic review and meta-analysis.

BACKGROUND: The effect of immunonutrition is controversial compared to standard supplementation with respect to the management of patients with acute pancreatitis. METHODS: An online literature search on four databases (PubMed, Cochrane, Embase and Web of Science) was performed to identify all of the randomised controlled trials assessing the effects of enteral or parenteral immunonutrition in acute pancreatitis. A fixed or random effects model was chosen using revman, version 5.3 (https://revman.cochrane.org). The count data were analysed using the risk ratio (RR) and 95% confidence interval (CI). RESULTS: Five hundred and sixty-eight patients were included via our search in which 14 articles matched our criteria for enrolling the meta-analysis. Immunonutrition significantly reduced the risk of organ failure (RR = 0.42; 95% CI = 0.26-0.70, P = 0.0008), infectious complications (RR = 0.78; 95% CI = 0.62-0.99; P = 0.04) and mortality (RR = 0.37; 95% CI = 0.21-0.66; P = 0.006). Length of hospital stay was also shorter in patients who received immunonutrition (mean difference = -1.73 days; 95% CI = -2.36 to -1.10; P < 0.00001). Total interventions of patients were decreased (RR = 0.73; 95% CI = 0.55-0.97; P = 0.03). Body mass index in patients with immunonutrition was reduced more than standard nutrition (mean difference = -2.00; 95% CI = -3.96 to -0.04; P = 0.05). CONCLUSIONS: Immunonutrition support such as glutamine and ω-3 fatty acids is potentially beneficial with respect to improving clinical outcomes in patients with acute pancreatitis.

[A prospective multi-center clinical investigation of HIV-negative pulmonary cryptococcosis in China].

Objective: To investigate the current status of the diagnosis and treatment of pulmonary cryptococcosis in respiratory medicine and improve the understanding of the clinical characteristics of HIV-negative pulmonary cryptococcosis in China. Methods: A prospective multi-center open cohort study was designed to screen for pulmonary cryptococcosis in the general wards and intensive care units of the Department of Respiratory Diseases in 22 hospitals. The HIV-negative patients with positive cryptococcal etiological diagnosis based on smear culture, antigen detection and histopathology were enrolled in the study. The clinical data of enrolled patients were collected and analyzed. Results: A total of 457 cases of pulmonary cryptococcosis were enrolled, among which 3.28% (15/457) were disseminated infections. The case fatality rate was 0.88% (4/457). The majority of the cases were diagnosed by histopathological examinations (74.40%, 340/457) and cryptococcus antigen detection (37.64%, 172/457). Patients with pulmonary cryptococcosis accounted for 2.04‰ (457/223 748) of the total hospitalized patients in the Department of Respiratory Diseases during the same period, and the ratio was the highest in south and east China. Meanwhile, 70.24% (321/457) of the patients had no underlying diseases, while 87.75% (401/457) were found to have immunocompetent status. Cough and expectoration were the most common clinical symptoms in patients with pulmonary cryptococcosis. However, 25.16% (115/457) of the patients had no clinical symptom or physical signs. In terms of imaging features on pulmonary CT, multiple pulmonary lesions were more common than isolated lesions, and there were more subpleural lesions than perihilar or medial lesions. Morphologically, most of the lesions were middle-sized nodules (1-5 cm) or small-sized nodules (3 mm to 1 cm). The sensitivity of serum cryptococcus antigen test was 71.99% (203/282). Moreover, antigen-positive patients differed from antigen-negative patients in terms of basic immune status, clinical symptoms, imaging features and infection types. Meanwhile, immunocompromised patients differed from immunocompetent patients in terms of clinical symptoms, physical signs, infection-related inflammation indicator levels, imaging features, serum cryptococcus antigen positive rate and prognosis. Conclusions: The majority of cases of HIV-negative pulmonary cryptococcosis in China had no underlying disease or immunocompromised status, and the overrall prognosis was favorable. However, early diagnosis of HIV-negative pulmonary cryptococcosis remains challenging due to the complicated manifestations of the disease.

Watermelon-like TiO2 nanoparticle (P25)@microporous amorphous carbon sphere with excellent rate capability and cycling performance for lithium-ion batteries.

To overcome the inferior rate capability and cycling performance of TiO2 nanomaterials as an anode material of lithium-ion batteries, we encapsulate TiO2 nanoparticles (P25) in carbon spheres through a facile pyrrole polymerization and carbonization. Material characterization demonstrates TiO2 nanoparticles are uniformly embedded in microporous amorphous carbon spheres, forming a watermelon-like structure. P25@C exhibits excellent high rate capability with average discharge capacity of 496, 416, 297, 240, 180, 99, 49 and 25 mAh g-1 at current rate of 0.5C, 1C, 5C, 10C, 20C, 50C, 100C and 200C, which shows superior long-term cycling performance with discharge capacity of 106.9 mAh g-1 at 20C after 5000 cycles. The capacity loss rate is only 0.008% per cycle. The outstanding lithium storage performance is ascribed to the watermelon-like composite structure, which remarkably improves electronic conductivity and structure stability of TiO2 nanoparticles. More importantly, the agglomeration of TiO2 nanoparticles is eliminated, and the entire surface of every TiO2 nanoparticle participates in the electrochemical reaction, which brings about an intense capacitive Li storage effect and leads to the high specific capacity and excellent rate capability of P25@C. This is confirmed through qualitative and quantitative analysis of the contributions from surface capacitive storage and bulk intercalation storage to the total capacity of the composite.

3D porous framework of ZnO nanoparticles assembled from double carbon shells consisting of hard and soft carbon networks for high performance lithium ion batteries.

Low electronic conductivity and large volume variation result in inferior lithium storage performance of ZnO. To overcome these shortcomings of ZnO, herein ZnO nanoparticles are encapsulated in resorcinol-formaldehyde resin-derived hard carbon and then further assembled into a 3-dimensional mesoporous framework structure using a polyvinyl pyrrolidone-derived soft carbon network. The synthesis methods include the polymerization of resorcinol-formaldehyde resin and a polyvinyl pyrrolidone-boiling method. ZnO@dual carbon has af large specific surface area (153.7 m2 g-1) and high porosity. It exhibits excellent cycling performance and high rate capability. After 350 cycles at 500 mA g-1, the ZnO@dual carbon still delivers a discharge capacity of 701 mAh g-1 while the actual discharge capacity of ZnO reaches 950.9 mAh g-1. At 2 A g-1, ZnO@dual carbon delivers the average discharge capacity of 469.6 mAh g-1. The electrochemical performance of ZnO@dual carbon is remarkably superior to those of ZnO@single carbon, pure carbon and pure ZnO nanoparticles, demonstrating the superiority of the dual carbon-assembly structure. This composite structure greatly improves the structural stability of ZnO, enhances its electron conductivity and overall electron transport capacity; which facilitates electrolyte penetration and Li ion diffusion, leading to improved cycling stability and good rate capability.

[Level and trend of respiratory diseases mortality in China from 2002 to 2016].

Objective: To analyze the level and trend of respiratory disease mortality in China from 2002 to 2016. Methods: The standardized mortality rates were calculated based on the China health statistics yearbook (2003-2012) and China statistical yearbook of health and family planning (2013-2017) data released by the statistical information center of National health Commission of the People's Republic of China. Joinpoint model was used to calculate the standardized mortality rates (SMR), Annual percentage change (APC) and the average annual percentage change (AAPC) for standardized mortality rates. Results: The SMR of respiratory diseases and chronic lower respiratory diseases were decreased significantly in 2002 to 2016 (AAPC=-3.6%, AAPC=-6.4%, P<0.001, respectively). The SMR of lung cancer showed a significant increase trend (AAPC=1.6%, P=0.001). There were no significant differences in the SMR of pneumonia and pneumonoconiosis (APCC=1.0%, P=0.242; APCC=-0.2%, P=0.905). Both urban and rural SMR of respiratory diseases were declining significantly (AAPC=-2.9%, P=0.001; AAPC=-4.2%, P<0.001). Both urban and rural SMR of lung cancer showed an increasing trend (AAPC=0.6%, P=0.022; AAPC=2.1%, P=0.003, respectively). The SMR of pneumonia in urban areas showed an upward trend (AAPC=2.7%, P=0.017). The SMR of respiratory disease of all age groups (<35 years old, 35-65 years old and ≥65 years old) showed a downward trend (AAPC=-3.8%, P=0.001; AAPC=-2.6%, P<0.001; AAPC=-3.9%, P<0.001). The SMR of pneumonia between 35 and 65 years old and SMR of lung cancer over 65 years old showed an increasing trend (AAPC=2.8%, P=0.001; AAPC=2.4%, P<0.001). The SMR of respiratory diseases among males and females showed a downtrend (AAPC=-3.1%, P<0.001; AAPC=-4.3%, P<0.001). However, the SMR of lung cancer in males and females increased significantly (AAPC=1.2%, P<0.001; AAPC=2.5%, P<0.001, respectively). There were no significant trends in the SMR of pneumonia and pneumoconiosis in males (AAPC=1.5%, P=0.096; AAPC=-1.6%, P=0.218). There was no obvious trend in the SMR of pneumonia in females (AAPC=-0.1%, P=0.872). Conclusions: The SMR of respiratory diseases in China generally shows a downward trend. The overall SMR and SMR of major respiratory diseases varies among different regions, genders and age groups.

[Phase â ¢ randomized controlled, multicenter, prospective study of recombinant anti-HER2 humanized monoclonal antibody (Cipterbin) combined with vinorelbine in patients with HER2 positive metastatic breast cancer: the HOPES Study].

Objective: To evaluate the clinical efficacy and safety of recombinant anti-HER2 humanized monoclonal antibody (Cipterbin) combined with vinorelbine in patients with HER2 positive metastatic breast cancer. Methods: Patients were randomized 2∶1 to test group and control group. Patients in test group received Cipterbin (4 mg/kg loading dose and 2 mg/kg maintenance dose each week, IV) combined with vinorelbine (25 mg/m(2) on days 1,8 and 15 of each 28 days, IV). Patients in control group received vinorelbine (25 mg/m(2) on days 1,8 and 15 of each 28 days, IV).The primary end point was progression free survival (PFS). Results: A total of 315 patients were enrolled from Jan 2009 to Jan 2013 (212 in test group and 103 in control group). The median PFS of test group was significantly longer than that of control group, 39.1 weeks vs 14.0 weeks (HR=0.24; 95%CI, 0.16-0.36; P<0.000 1). The objective response rate (ORR) and disease control rate (DCR) in test group were significantly higher than those in control group, ORR was 46.7% vs 18.45% (P<0.000 1) and DCR was 79.72% vs 45.63% (P<0.000 1). The incidence of neutropenia, leucopenia and erythrocytopenia were higher in both groups, but there was no significant difference between two groups.The most common adverse events associated with Cipterbin were infusion reactions. Left ventricular ejection fraction reduced to less than 50% in 5 patients, which were recovered. No serious cardiotoxicity. Conclusion: The recombinant anti-HER2 humanized monoclonal antibody (Cipterbin) combined with vinorelbine has significant efficacy and good safety. It is the optimized therapy regime for patients with taxane-pretreated HER2 positive metastatic breast cancer, which provides more targeted therapy opportunities for HER2 positive breast cancer patients in China.

[Postinflammatroy pulmonary fibrosis of COVID-19: the current status and perspective].

The novel coronavirus pneumonia (COVID-19) has been well controlled in China. Most of the COVID-19 patients were having postinflammatory pulmonary fibrosis (PPF) on the follow-up CT scan when discharged, and complaining about exertional dyspnea of different levels, presenting with an UIP (usual interstitial pneumonia) pattern or NSIP (non-specific interstitial pneumonia) pattern on the CT scans. Will the PPF get improved or stay stable, or progress? Such questions could only be answered by follow-up and monitoring of the pulmonary function. At the same time, we should learn from the lessons on pulmonary function loss of the SARS patients and MERS patients, some of whom had persistent impaired lung function after discharge. Pirfenidone and Nintedanib had been approved for the treatment of idiopathic pulmonary fibrosis(IPF), showing effectiveness on non-IPF pulmonary fibrosis as well. However, there are no studies about the application on PPF resulting from viral pneumonia. Given the follow-up status of SARS patients and MERS patients, and the PPF of COVID-19 patients, we should be careful about the discharged patients with a close follow-up, and further studies on PPF of COVID-19 are needed.

[Severe community-acquired pneumonia caused by Legionella pneumophila with acute respiratory failure: clinical characteristics and prognosis of 34 cases].

Objective: To describe the clinical characteristics and treatment of severe community-acquired pneumonia(SCAP) caused by Legionella pneumophila with acute respiratory failure and to analyze the risk factors for mortality. Methods: From October 2011 to October 2019, 34 patients were diagnosed with SCAP caused by Legionella pneumophila with acute respiratory failure.There were 25 males and 9 females, aged from 17 to 82 years, with a median age of 61 (48, 69) years. According to the prognosis, the patients were divided into a survival group and a death group for comparative analysis.The survival group included 24 patients, 17 males and 7 females, with a median age of 65 (55, 70) years. There were 10 cases in the death group, 8 males and 2 females, with a median age of 53 (50, 58) years. Multivariable logistic regression analysis was used for risk factors of ICU mortality. Results: The median time of admission to ICU was 7 (5, 11) days, the median time of stay in RICU was 12 (7, 22) days, and the PaO(2)/FiO(2) was 134 (91, 216) mmHg(1 mmHg=0.133 kPa). Ten patients died during ICU hospitalization, with a mortality of 29%. Sequential organ failure assessment (SOFA) of death group was 9 (7, 12), which was significantly higher than that of the survival group [4 (3, 8)], P=0.018. The time from onset of pneumonia symptoms to initiation of targeted treatment of the death group was 10 (7, 14) d, which was significantly longer than that of the survival group of [4 (3, 7) d], P=0.019. Multivariable logistic regression analysis showed that SOFA score (OR=1.461, 95%CI 1.041-2.051, P=0.028) and the time from onset of pneumonia symptoms to initiation of targeted treatment (OR=1.293, 95%CI 1.029-1.625, P=0.027) were independent risk factors for hospital mortality. Conclusions: The ICU mortality of severe legionella pneumonia was high. Critical organ dysfunctions and delayed initial targeted treatment were related with the increase of ICU mortality.