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Since early December 2019, the 2019 novel coronavirus disease (COVID-19) has caused pneumonia epidemic in Wuhan, Hubei province of China. This study aimed to investigate the factors affecting the progression of pneumonia in COVID-19 patients. Associated results will be used to evaluate the prognosis and to find the optimal treatment regimens for COVID-19 pneumonia. Patients tested positive for the COVID-19 based on nucleic acid detection were included in this study. Patients were admitted to 3 tertiary hospitals in Wuhan between December 30, 2019, and January 15, 2020. Individual data, laboratory indices, imaging characteristics, and clinical data were collected, and statistical analysis was performed. Based on clinical typing results, the patients were divided into a progression group or an improvement/stabilization group. Continuous variables were analyzed using independent samples t-test or Mann-Whitney U test. Categorical variables were analyzed using Chi-squared test or Fisher's exact test. Logistic regression analysis was performed to explore the risk factors for disease progression. Seventy-eight patients with COVID-19-induced pneumonia met the inclusion criteria and were included in this study. Efficacy evaluation at 2 weeks after hospitalization indicated that 11 patients (14.1%) had deteriorated, and 67 patients (85.9%) had improved/stabilized. The patients in the progression group were significantly older than those in the disease improvement/stabilization group (66 [51, 70] vs. 37 [32, 41] years, U = 4.932, P = 0.001). The progression group had a significantly higher proportion of patients with a history of smoking than the improvement/stabilization group (27.3% vs. 3.0%, χ = 9.291, P = 0.018). For all the 78 patients, fever was the most common initial symptom, and the maximum body temperature at admission was significantly higher in the progression group than in the improvement/stabilization group (38.2 [37.8, 38.6] vs. 37.5 [37.0, 38.4]°C, U = 2.057, P = 0.027). Moreover, the proportion of patients with respiratory failure (54.5% vs. 20.9%, χ = 5.611, P = 0.028) and respiratory rate (34 [18, 48] vs. 24 [16, 60] breaths/min, U = 4.030, P = 0.004) were significantly higher in the progression group than in the improvement/stabilization group. C-reactive protein was significantly elevated in the progression group compared to the improvement/stabilization group (38.9 [14.3, 64.8] vs. 10.6 [1.9, 33.1] mg/L, U = 1.315, P = 0.024). Albumin was significantly lower in the progression group than in the improvement/stabilization group (36.62 ± 6.60 vs. 41.27 ± 4.55 g/L, U = 2.843, P = 0.006). Patients in the progression group were more likely to receive high-level respiratory support than in the improvement/stabilization group (χ = 16.01, P = 0.001). Multivariate logistic analysis indicated that age (odds ratio [OR], 8.546; 95% confidence interval [CI]: 1.628-44.864; P = 0.011), history of smoking (OR, 14.285; 95% CI: 1.577-25.000; P = 0.018), maximum body temperature at admission (OR, 8.999; 95% CI: 1.036-78.147, P = 0.046), respiratory failure (OR, 8.772, 95% CI: 1.942-40.000; P = 0.016), albumin (OR, 7.353, 95% CI: 1.098-50.000; P = 0.003), and C-reactive protein (OR, 10.530; 95% CI: 1.224-34.701, P = 0.028) were risk factors for disease progression. Several factors that led to the progression of COVID-19 pneumonia were identified, including age, history of smoking, maximum body temperature at admission, respiratory failure, albumin, and C-reactive protein. These results can be used to further enhance the ability of management of COVID-19 pneumonia.

Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health 1 – 3 . Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing 4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae , which is designated here ‘WH-Human 1’ coronavirus (and has also been referred to as ‘2019-nCoV’). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China 5 . This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans. Phylogenetic and metagenomic analyses of the complete viral genome of a new coronavirus from the family Coronaviridae reveal that the virus is closely related to a group of SARS-like coronaviruses found in bats in China.

Background Minimally invasive thermal therapies show great prospect in non-small cell lung cancer (NSCLC) treatment. However, changes in immune cell populations following microwave ablation (MWA) in NSCLC microenvironment are not fully revealed. Objective The present study was conducted to identify changes in immune cell populations and analyse dysregulated genes in immune cells after MWA in NSCLC microenvironment. Methods The patients received fractionated MWA in two treatments separated by 3 weeks. Tumor biopsy samples were obtained through core-needle biopsy before each fractionated MWA procedure at the same site and used for single-cell RNA sequencing with the 10x Genomics pipeline. Results A total of 9 major cell types were identified after MWA, which include neutrophils, T cells, B cells, monocytes, epithelial cells, chondrocytes, macrophages, tissue stem cells, and endothelial cells. After MWA, the tumor tissue exhibited an increased proportion of T cells. MWA altered gene expression in each cell cluster at the single-cell level. Cell trajectory analysis revealed that the cells at the starting point were most like T helper cells, naïve T cells, and regulatory T cells; they then developed into anergic T cells, T follicular cells, natural killer T cells, T memory cells, and exhausted T cells, and finally ended as γδ T cells and cytotoxic T cells. Moreover, after MWA, more interaction between monocytes and T cells (or B cells) were identified. Conclusions MWA increases local T-cell abundance and alters monocyte interactions, thereby reshaping the tumor microenvironment. This study lays a foundation for investigating dysregulated genes that may contribute to the MWA-induced immune response in NSCLC. What is already known on this topic Thermal ablation may change the immune profiles of patients by activating various steps in the cancer immunity cycle. However, changes in immune cell populations following MWA of NSCLC have not been fully reported. What this study adds After MWA, an increase in interactions between monocytes and T cells intratumorally was observed, which promoted antitumor immunity. How this study might affect research, practice or policy The current study illuminates the MWA-caused systemic immune response in NSCLC, which may help to identify the dysregulated genes involved in the MWA-caused immune response.

Background Patient-derived xenografts and organoids were the most common patient-derived tumor models in vitro that were utilized in personalized drug screening, and the establishment rate and duration required to be improved. Patient-derived tumor-like cell clusters (PTCs) could be established within ten days for drug screening, with high establishment rate and accuracy in predicting clinical outcomes. This study aims to explore the accuracy of PTCs based on specimens obtained from percutaneous transthoracic needle biopsy (PTNB) in lung malignancy (LM) patients, and to investigate the predictors for the success of PTC culture. Materials and methods This retrospective cohort study included LM patients who underwent image-guided PTNB, and the specimens were used for PTC culture, which was followed by personalized drug screening of chemotherapy and molecular targeted therapy, and the accuracy was validated by previous or further treatments. The predictors of the success of PTC culture were identified by univariable and multivariable analyses. Results A total of 68 LM patients were enrolled, consisting of 57, 7, and 4 patients with non-small cell lung cancer, small cell lung cancer, and lung metastases, respectively. Pneumothorax was the predominant adverse event for PTNB, with an incidence rate of 20.6% (14/68). PTC models based on PTNB specimens were established successfully for 56 patients in 3.8 ± 2.3 days, with an 82.4% success rate. Five patients had not received treatments before or after PTC culture. PTC drug screening reveals 88.2% (45/51) overall consistency in predicting clinical outcomes. Necrotic area over half of the tumor (hazard ratio, 0.121; 95% confidence interval, 0.025–0.598; P  = 0.010) was identified as the negative predictor for the success of PTC culture. Conclusions PTC culture based on PTNB specimens could be established in 82.4% of LM patients, with a high accuracy in predicting clinical outcomes. Excessive necrosis in the tumor may predict the failure of PTC culture. Image-guided PTNB targeting enhanced or fluorodeoxyglucose‌ avid regions on images might contribute to improving the success rate of PTC culture.

Cryoablation (CA), high-intensity focused ultrasound (HIFU), irreversible electroporation (IRE), and vascular-targeted photodynamic therapy (VTP) have been evaluated as novel strategies for selected patients with prostate cancer (PCa). We aim to determine the current status of literature regarding the clinical outcomes among these minimally invasive therapies. A systematic search of PubMed, EMBASE, and the Cochrane Library for all English literature published from January 2001 to December 2019 was conducted to identify studies evaluating outcomes of CA, HIFU, IRE or VTP on PCa. Proportionality with 95% confidence intervals (CIs) was performed using STATA version 14.0. 56 studies consisting of 7383 participants were found to report data of interest and fulfilled the inclusion criteria in the final meta-analysis. The pooled proportions of positive biopsy after procedure were 20.0%, 24.3%, 24.2%, and 36.2% in CA, HIFU, IRE and VTP, respectively. The pooled proportions of BRFS were 75.7% for CA and 74.4% for HIFU. The pooled proportions of CSS were 96.1%, 98.2%, and 97.9% for CA, HIFU, and IRE, respectively. The pooled proportions of OS were 92.8% for CA and 85.2% for HIFU. The pooled proportions of FFS were 64.7%, 90.4%, and 76.7% for CA, IRE and VTP, respectively. The pooled proportions of MFS were 92.8% for HIFU and 99.1% for IRE. This meta-analysis shows that CA, HIFU, IRE, and VTP are promising therapies for PCa patients with similar clinical outcomes. However, further larger, well-designed randomized controlled trials are required to confirm this assertion.

The fascinating framework structures and unique properties of chiral covalent organic frameworks (COFs) make them promising candidates as novel separation medium for high-performance liquid chromatography (HPLC). However, the irregular morphology, inhomogeneous particle size, and low density of conventional COF particles will lead to a low column efficiency, undesirable chromatographic peak shape, and high column backpressure of such COF-packed columns. In this work, a chiral COF CTpBD was synthesized by the Schiff base reaction between benzidine (BD) and chiral organic monomer CTp obtained through the reaction of 1,3,5-triformylphoroglucinol (Tp) and (+)-diacetyl-L-tartaric anhydride ((+)-Ac-L-Ta). The chiral COF CTpBD was immobilized on the surface of amino functionalized silica (SiO 2 -NH 2 ) by an in situ growth approach to prepare the chiral COF core-shell microsphere composite CTpBD@SiO 2 , which was used as a novel chiral stationary phase (CSP) for HPLC enantioseparation. Various kinds of racemates were separated on the CTpBD@SiO 2 -packed column with a low column backpressure (8–11 bar). Some effects such as the analyte mass and column temperature on the HPLC enantioseparation have been studied in detail. The fabricated CTpBD@SiO 2 -packed column exhibited high column efficiency (e.g., 16,800 plates m −1 for atenolol), high enantioselectivity, and good reproducibility toward various racemates. The highest resolution value, retention factor, and separation factor reach to 2.11, 2.85, and 3.73, respectively. The relative standard deviations (RSD) of peak area, peak height, half-peak width, and retention time of atenolol were all below 3.0%. Graphical abstract

Medicinal plants are invaluable resources for mankind and play a crucial role in combating diseases. Arbuscular mycorrhizal fungi (AMF) are widely recognized for enhancing the production of medicinal active ingredients in medicinal plants. However, there is still a lack of comprehensive understanding regarding the quantitative effects of AMF on the accumulation of medicinal active ingredients. Here we conducted a comprehensive global analysis using 233 paired observations to investigate the impact of AMF inoculation on the accumulation of medicinal active ingredients. This study revealed that AMF inoculation significantly increased the contents of medicinal active ingredients by 27%, with a particularly notable enhancement observed in flavonoids (68%) and terpenoids (53%). Furthermore, the response of medicinal active ingredients in belowground organs (32%) to AMF was more pronounced than that in aboveground organs (18%). Notably, the AMF genus Rhizophagus exhibited the strongest effect in improving the contents of medicinal active ingredients, resulting in an increase of over 50% in both aboveground and belowground organs. Additionally, the promotion of medicinal active ingredients by AMF was attributed to improvements in physiological factors, such as chlorophyll, stomatal conductance and net photosynthetic rate. Collectively, this research substantially advanced our comprehension of the pivotal role of AMF in improving the medicinal active ingredients of plants and provided valuable insights into the potential mechanisms driving these enhancements.

Endoplasmic reticulum (ER) stress has been implicated in the pathophysiology of various pulmonary diseases via the activation of the unfolded protein response. However, the role of ER stress in pulmonary arterial hypertension (PAH) remains unclear. The well-known chemical chaperone 4-phenylbutyric acid (4-PBA) inhibits ER stress signaling. We hypothesized that known chemical chaperones, including 4-PBA, would inhibit the activation of ER stress and prevent and/or reverse PAH. Male Wistar rats were randomly divided into four groups: a normal control group (NORMAL group), a PAH group, and two PAH model plus 4-PBA treatment groups. The latter two groups included rats receiving 4-PBA by gavage each day as a preventive measure (the PRE group, with PBA starting on the day of PAH induction and continuing for 4 weeks) or as a reversal measure (the REV group, with PBA starting on the third week of PAH induction and continuing for 2 weeks). The PAH model was induced by intraperitoneally administering monocrotaline. The mean pulmonary artery pressure and mean right ventricular pressure were lower in the REV and PRE groups than in the NORMAL group. Furthermore, 4-PBA improved pulmonary arterial remodeling and suppressed the expression of ER stress indicators. Our findings indicate that PAH induces ER stress and provokes pulmonary arterial and right ventricular remodeling. Additionally, we show that attenuation of ER stress has the potential to be an effective therapeutic strategy for protecting pulmonary arteries.

Porous organic cages (POCs) are a new subclass of porous materials, which are constructed from discrete cage molecules with permanent cavities via weak intermolecular forces. In this study, a novel chiral stationary phase (CSP) has been prepared by chemically binding a [4 + 6]-type chiral POC (C120H96N12O4) with thiol-functionalized silica gel using a thiol-ene click reaction and applied to HPLC separations. The column packed with this CSP presented good separation capability for chiral compounds and positional isomers. Thirteen racemates have been enantioseparated on this column, including alcohols, diols, ketones, amines, epoxides, and organic acids. Upon comparison with a previously reported chiral POC NC1-R-based column, commercial Chiralpak AD-H, and Chiralcel OD-H columns, this column is complementary to these three columns in terms of its enantiomeric separation; and can also separate some racemic compounds that cannot be separated by the three columns. In addition, eight positional isomers (iodoaniline, bromoaniline, chloroaniline, dibromobenzene, dichlorobenzene, toluidine, nitrobromobenzene, and nitroaniline) have also been separated. The influences of the injection weight and column temperature on separation have been explored. After the column has undergone multiple injections, the relative standard deviations (RSDs) for the retention time and selectivity were below 1.0 and 1.5%, respectively, indicating the good reproducibility and stability of the column for separation. This work demonstrates that POCs are promising materials for HPLC separation.

To investigate the feasibility and efficacy of combining ultrasound-guided sharp needle technique with percutaneous transluminal angioplasty (PTA) for treating outflow stenosis or dysfunction in arteriovenous fistula (AVF) among hemodialysis patients. From October 2021 to March 2023, patients with occluded or malfunctional fistula veins not amenable to regularly angioplasty were retrospectively enrolled in the study. They underwent ultrasound-guided sharp needle intervention followed by PTA. Data on the location and length between the two veins, technical success, clinical outcomes, and complications were collected. Patency rates post-angioplasty were calculated through Kaplan-Meier analysis. A total of 23 patients were included. The mean length of the reconstructed extraluminal segment was 3.18 cm. The sharp needle opening was performed on the basilic vein (60.9%), brachial vein (26.1%), or upper arm cephalic vein (13%) to create outflow channels. Postoperatively, all cases presented with mild subcutaneous hematomas around the tunneling site and minor diffuse bleeding. The immediate patency rate for the internal fistulas was 100%, with 3-month, 6-month, and 12-month patency rates at 91.3%, 78.3%, and 43.5%, respectively. Sharp needle technology merged with PTA presents an effective and secure minimally invasive method for reconstructing the outflow tract, offering a new solution for recanalizing high-pressure or occluded fistulas.