Recognition of Mycobacterium tuberculosis by macrophage Toll-like receptor and its role in autophagy.

BACKGROUND: The pathogen responsible for tuberculosis is called Mycobacterium tuberculosis. Its interaction with macrophages has a significant impact on the onset and progression of the disease. METHODS: The respiratory pathway allows Mycobacterium tuberculosis to enter the body's lungs where it battles immune cells before being infected latently or actively. In the progress of tuberculosis, Mycobacterium tuberculosis activates the body's immune system and creates inflammatory factors, which cause tissue inflammation to infiltrate and the creation of granulomas, which seriously harms the body. Toll-like receptors of macrophage can mediate host recognition of Mycobacterium tuberculosis, initiate immune responses, and participate in macrophage autophagy. New host-directed therapeutic approaches targeting autophagy for drug-resistant Mycobacterium tuberculosis have emerged, providing new ideas for the effective treatment of tuberculosis. CONCLUSIONS: In-depth understanding of the mechanisms by which macrophage autophagy interacts with intracellular Mycobacterium tuberculosis, as well as the study of potent and specific autophagy-regulating molecules, will lead to much-needed advances in drug discovery and vaccine design, which will improve the prevention and treatment of human tuberculosis.

Defensins: A novel weapon against Mycobacterium tuberculosis?

Tuberculosis (TB) is a serious airborne communicable disease caused by organisms of the Mycobacterium tuberculosis (Mtb) complex. Although the standard treatment antimicrobials, including isoniazid, rifampicin, pyrazinamide, and ethambutol, have made great progress in the treatment of TB, problems including the rising incidence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), the severe toxicity and side effects of antimicrobials, and the low immunity of TB patients have become the bottlenecks of the current TB treatments. Therefore, both safe and effective new strategies to prevent and treat TB have become a top priority. As a subfamily of cationic antimicrobial peptides, defensins are rich in cysteine and play a vital role in resisting the invasion of microorganisms and regulating the immune response. Inspired by studies on the roles of defensins in host defence, we describe their research history and then review their structural features and antimicrobial mechanisms, specifically for fighting Mtb in detail. Finally, we discuss the clinical relevance, therapeutic potential, and potential challenges of defensins in anti-TB therapy. We further debate the possible solutions of the current application of defensins to provide new insights for eliminating Mtb.

Identification of a new risk score model based on hypoxia and EMT-related genes for predicting lung squamous cell carcinoma prognosis.

A complicated analysis of the prognostic characteristics of lung squamous cell carcinoma (LUSC) is needed. The aim of this study was to develop a risk score model to predict immunotherapeutic response and prognosis for patients with LUSC. A hypoxia and epithelial-mesenchymal transition-related risk score model was developed for prediction of LUSC. The correlation between risk score and clinical characteristics was determined. The single sample gene set enrichment analysis algorithm was utilized to determine the abundance of cell infiltration in tumor immune microenvironment in LUSC. The predictive value of risk score model in response to immunotherapy was evaluated. A hypoxia and epithelial-mesenchymal transition-related risk score model was constructed. This risk score model was correlated with the overall survival of LUSC. Patients with low-risk presented a high survival possibility. The high-risk group was involved in ECM receptor interaction, complement and coagulation cascades, intestinal immune network for IgA production. Finally, patients with low-risk score had significant clinical benefit. The risk score model was constructed to predict immunotherapeutic response and prognosis for patients with LUSC. In addition to identifying LUSC patients with poor survival, the results provide more information for the immune immunotherapy and microenvironment for LUSC.

Bu-Fei Yi-Shen Granules Reduce Acute Exacerbations in Patients with GOLD 3-4 COPD: A Randomized Controlled Trial.

Purpose: Chronic obstructive pulmonary disease (COPD) is a disease characterized by frequent acute exacerbations (AEs), especially in severe and very severe cases. We aimed to evaluate the efficacy and safety of Bu-fei Yi-shen granules (BYGs) for COPD. Patients and Methods: We conducted a multicenter, randomized, double-blinded, placebo-controlled trial of 348 COPD patients with GOLD 3-4 COPD. The patients were randomly assigned into experimental or control groups in a 1:1 ratio. Patients in the experimental group were prescribed BYG, while those in the control group were administered a placebo, orally, twice daily, with 5 days on and 2 days off per week for 52 weeks. The outcomes included AEs, pulmonary function, clinical signs and symptoms, dyspnea scores (mMRC), quality of life scores, and a 6-minute walk test (6MWT). Results: A total of 280 patients completed the trial, including 135 patients in the experimental group and 145 in the control group. Compared to the control group, significant differences were observed in frequencies of AEs (mean difference: -0.35; 95% CI: -0.61, -0.10; P = 0.006) and AE-related hospitalizations (-0.18; 95% CI: -0.36, -0.01; P = 0.04), 6MWD (40.93 m; 95% CI: 32.03, 49.83; P < 0.001), mMRC (-0.57; 95% CI: -0.76, -0.37; P < 0.001), total symptoms (-2.18; 95% CI: -2.84, -1.53; P < 0.001), SF-36 (11.60; 95% CI: 8.23, 14.97; P < 0.001), and mCOPD-PRO (-0.45; 95% CI: -0.57, -0.33; P < 0.001) after treatment. However, there were no significant differences in mortality, pulmonary function, and mESQ-PRO scores (P > 0.05). No obvious adverse events were observed. Conclusion: BYG, as compared to a placebo, could significantly reduce the frequencies of AEs and AE-related hospitalizations for GOLD 3-4 COPD patients. Clinical symptoms, treatment satisfaction, quality of life, and exercise capacity improved. There was no significant improvement in mortality and pulmonary function.

A novel polyhedral oligomeric silsesquioxane nanohybrid fluorescent sensor designed based on an osmotic mechanism for specific detection and intelligent scavenging of magnesium ions.

BACKGROUND: Mg2+ has long been recognized as one of the most vital cations due to its diverse physiological and pathological roles, making it indispensable in both biomedical and biological research. Organic fluorescent sensors are commonly employed for Mg2+ detection, but they often lack high selectivity and exhibit poor hydrophilicity, limiting their biomedical applications. RESULTS: Herein, we introduced a novel organic-inorganic hybrid fluorescence sensor, PFHBS, constructed on the POSS nanoplatforms. The efficient connection between PEGylated POSS and the small molecule sensor FHBS through Click chemistry enhances the selectivity and reduces interference, making this chemical sensor ideal for the accurate detection of Mg2+. Furthermore, the incorporation of POSS amplifies the ligand field effect of FHBS, making it more conducive to Mg2+ capture. The modification of PEG chains enhances the sensor's amphiphilicity, facilitating efficient cell penetration and effective Mg2+ detection at the biological level. SIGNIFICANCE: Finally, relying on spontaneous permeation, coupled with its strong ligand field effect and excellent cell permeability, the chemosensor demonstrates the capability to intelligently remove excess Mg2+ from the body. It has been successfully applied to mitigate renal overload resulting from acute Mg2+ poisoning.

Qualitative identification and quantitative comparison of Physochlainae Radix from different regions based on chemometric methods.

Physochlainae Radix (PR) is an essential herbal medicine that has been generally applied for treating cough and asthma. In this study, a comprehensive strategy for quality evaluation of PR from different origins was established by integrating qualitative identification, quantitative analysis, and chemometric methods. A total of 58 chemical components were identified by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS), and a sensitive and rapid UHPLC-QqQ-MS/MS method was established for the simultaneous determination of 12 compounds. In addition, multivariate statistical analysis was applied for discriminant analysis to compare the differences among 30 batches of PR samples. The results showed that the 30 batches of PR collected from four provinces could be clustered into three categories, in which scoparone, protocatechuic acid, tropic acid, and scopolin were important components to distinguish the primary and non-primary producing areas, as well as superior and inferior products of PR. Chemometric results were consistent and validated each other, and systematically explained the intrinsic quality characteristics of PR. This study first demonstrated that LC-MS combined with multivariate statistical analysis, provided a comprehensive and effective means for quality evaluation of PR.

The evidence framework of traditional Chinese medicine injection (Aidi injection) in controlling malignant pleural effusion: A clustered systematic review and meta-analysis.

INTRODUCTION: Aidi injection (Aidi), a traditional Chinese medicine injection, is often practiced to control malignant pleural effusion (MPE). OBJECTIVES: We performed a registered systematic review and meta-analysis (PROSPERO: CRD42022337611) to clarify the clinical role of Aidi in MPE, reveal optimal combinations of Aidi and chemical agents, their indications, therapeutic route and usage, and demonstrate their clinical effectiveness and safety. METHODOLOGY: All randomized controlled trials (RCTs) about Aidi in controlling MPE were collected from Chinese and English databases (up to October 2022). We clustered them into multiple homogenous regimens, evaluated the risk-of-bias at outcome level using a RoB 2, extracted and pooled the data using meta-analysis or descriptive analysis, and finally summarized their evidence quality. RESULTS: All 56 studies were clustered into intrapleural administration with Aidi alone or plus chemical agents, and intravenous administration with Aidi for MPE. Intrapleural administration with Aidi alone displayed similar clinical responses on Cisplatin (DDP) alone. Only administration with Aidi plus DDP significantly improved complete response and quality of life, and displayed a low pleurodesis failure, disease progression, hematotoxicity, gastrointestinal and hepatorenal toxicity. For patients with moderate to massive effusion, Karnofsky Performance Status score ≥ 50 or anticipated survival time ≥3 months, Aidi (50 ml to 80 ml each time, one time each week and three to eight times) plus DDP (20 to 30 mg, 40 to 50 mg, or 60 to 80 mg each time) significantly improved clinical responses. Most results had moderate to low quality. CONCLUSIONS: Current evidences indicate that Aidi, a pleurodesis agent, plays an interesting clinical role in controlling MPE. Aidi plus DDP perfusion is a most commonly used regimen, which shows a significant improvement in clinical responses. These findings also provide an indication and possible optimal usage for rational drug use.

MiR-24-1-5p Hinders Malignant Phenotypes of Clear Cell Renal Cell Carcinoma by Targeting SHOX2.

MiRNAs are essential epigenetic modulators that can regulate protein expression. According to the principle of base complementary pairing, miRNA is partially or completely complementary to the 3'-UTR region of its target gene, by which it inhibits the translation of the targeted gene. This study investigated the role of miR-24-1-5p in clear cell renal cell carcinoma (ccRCC). Data in TCGA-KIRC denoted that miR-24-1-5p was under-expressed in ccRCC. Bioinformatics analysis predicted that its target gene was SHOX2, which was significantly expressed in cancer tissues. Dual luciferase assay verified the targeting relationship between miR-24-1-5p and SHOX2. Cell function experiments demonstrated that overexpression of miR-24-1-5p significantly inhibited SHOX2 level and the malignant phenotypes of ccRCC cells. The above results illustrated that miR-24-1-5p/SHOX2 axis was critical for the oncogenesis and development of ccRCC, which might be helpful for us to understand the mechanism and novel therapeutic methods of ccRCC.

Automatic Multilabel Classification of Multiple Fundus Diseases Based on Convolutional Neural Network With Squeeze-and-Excitation Attention.

Purpose: Automatic multilabel classification of multiple fundus diseases is of importance for ophthalmologists. This study aims to design an effective multilabel classification model that can automatically classify multiple fundus diseases based on color fundus images. Methods: We proposed a multilabel fundus disease classification model based on a convolutional neural network to classify normal and seven categories of common fundus diseases. Specifically, an attention mechanism was introduced into the network to further extract information features from color fundus images. The fundus images with eight categories of labels were applied to train, validate, and test our model. We employed the validation accuracy, area under the receiver operating characteristic curve (AUC), and F1-score as performance metrics to evaluate our model. Results: Our proposed model achieved better performance with a validation accuracy of 94.27%, an AUC of 85.80%, and an F1-score of 86.08%, compared to two state-of-the-art models. Most important, the number of training parameters has dramatically dropped by three and eight times compared to the two state-of-the-art models. Conclusions: This model can automatically classify multiple fundus diseases with not only excellent accuracy, AUC, and F1-score but also significantly fewer training parameters and lower computational cost, providing a reliable assistant in clinical screening. Translational Relevance: The proposed model can be widely applied in large-scale multiple fundus disease screening, helping to create more efficient diagnostics in primary care settings.

Automatic generation of retinal optical coherence tomography images based on generative adversarial networks.

SIGNIFICANCE: The automatic generation algorithm of optical coherence tomography (OCT) images based on generative adversarial networks (GAN) can generate a large number of simulation images by a relatively small number of real images, which can effectively improve the classification performance. AIM: We proposed an automatic generation algorithm for retinal OCT images based on GAN to alleviate the problem of insufficient images with high quality in deep learning, and put the diagnosis algorithm toward clinical application. APPROACH: We designed a generation network based on GAN and trained the network with a data set constructed by 2014_BOE_Srinivasan and OCT2017 to acquire three models. Then, we generated a large number of images by the three models to augment age-related macular degeneration (AMD), diabetic macular edema (DME), and normal images. We evaluated the generated images by subjective visual observation, Fréchet inception distance (FID) scores, and a classification experiment. RESULTS: Visual observation shows that the generated images have clear and similar features compared with the real images. Also, the lesion regions containing similar features in the real image and the generated image are randomly distributed in the image field of view. When the FID scores of the three types of generated images are lowest, three local optimal models are obtained for AMD, DME, and normal images, indicating the generated images have high quality and diversity. Moreover, the classification experiment results show that the model performance trained with the mixed images is better than that of the model trained with real images, in which the accuracy, sensitivity, and specificity are improved by 5.56%, 8.89%, and 2.22%. In addition, compared with the generation method based on variational auto-encoder (VAE), the method improved the accuracy, sensitivity, and specificity by 1.97%, 2.97%, and 0.99%, for the same test set. CONCLUSIONS: The results show that our method can augment the three kinds of OCT images, not only effectively alleviating the problem of insufficient images with high quality but also improving the diagnosis performance.

Efficacy and safety of Jin-shui Huan-xian granule for idiopathic pulmonary fibrosis: study protocol for a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND AND RATIONALE: Idiopathic pulmonary fibrosis is a critical disease with a poor prognosis. Although different studies have been conducted for the treatment of idiopathic pulmonary fibrosis, limited treatments are available. Jin-shui Huan-xian granule (JHG), which is a Chinese medicine herbal compound, has shown promising efficacy in reducing frequencies of acute exacerbations, improving exercise capacity the quality of life of patients with idiopathic pulmonary fibrosis. This study is to evaluate the efficacy and safety of JHG for IPF. SUBJECTS AND METHODS: This is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 312 idiopathic pulmonary fibrosis patients will be enrolled and randomly allocated to one of the two groups with 1:1. After a 2-week washout period, 52-week treatment will also be performed for all the patients. Patients in the experimental group and the control group will be given JHG and JHG placebo, respectively. Outcome measures including acute exacerbations, pulmonary function, dyspnea, exercise capacity, and quality of life will be evaluated in this study. DISCUSSION: Based on our previous study, it is hypothesized that JHG will reduce acute exacerbations; improve exercise capacity, pulmonary function, and quality of life; and delay the disease progression-free. High-level evidence-based support for TCM in IPF will also be obtained in this study. TRIAL REGISTRATION: ClinicalTrials.gov NCT04187690. Register on December 11, 2019.

Autonomous Bionanorobots via a Cage-Shaped Silsesquioxane Vehicle for In Vivo Heavy Metal Detoxification.

Nanorobots hold great promise for integrated drug delivery systems that are responsive to molecular triggers. Herein, we successfully developed an automatic smart bionanorobot that has transport capability and recognizes and removes zinc ions from poisoned cells based on nanoscale polyhedral oligomeric silsesquioxane molecules. This intelligent bionanorobot can easily move inside and outside the cell and find zinc ions owing to its highly selective recognition to zinc ions and high cell permeability, especially the well-combined high penetration and strong binding energy. More importantly, it was also found that this intelligent bionanorobot can restore round HeLa cells to a normal fusiform cell morphology following high-concentration zinc treatment and does not interfere with cell proliferation and division. It was also shown by in vivo experiments that the bionanorobot can inhibit persistent enlargement of the liver caused by zinc ion poisoning.

Intrapleural Perfusion With Staphylococcal Enterotoxin C for Malignant Pleural Effusion: A Clustered Systematic Review and Meta-Analysis.

Introduction: The staphylococcal enterotoxin C (SEC), a commercially available bio-product from Staphylococcus aureus (S. aureus), has been widely used to control MPE. Objectives: We designed and performed a new systematic review (SR) and meta-analysis to clarify the perfusion protocols with SEC, determine their clinical effectiveness and safety, and reveal the indication and optimum usage for achieving the desired responses. Methodology: All randomized controlled trials (RCTs) about SEC for MPE were collected from electronic databases (from inception until July 2021), and clustered into multiple logical topics. After evaluating their methodological quality, we pooled the data from each topic using the meta-analysis or descriptive analysis, and summarized the evidence quality using the grading of recommendation assessment, development, and evaluation (GRADE) approach. Results: All 114 studies were clustered into SEC perfusion alone or plus chemical agents. The SEC alone showed a better complete response (CR), a lower pleurodesis failure, and adverse drug reactions (ADRs), and a higher fever than cisplatin (DDP) alone. The SEC and chemical agents developed 10 perfusion protocols. Among them, only SEC and DDP perfusion showed a better CR, a lower failure, disease progression and ADRs, and a higher fever than DDP alone. The SEC (100-200 ng per time, one time a week for one to four times) with DDP (30-40 mg, or 50-60 mg each time) significantly improved clinical responses for patients with moderate to large volume, Karnofsky performance status (KPS) scores ≥40, ≥50, or ≥60, and anticipated survival time (AST) ≥2 or 3 months. Most results were moderate to low quality. Conclusion: Current pieces of evidence indicate that super-antigen SEC is a pleurodesis agent, which provides an attractive alternative to existing palliative modalities for patients with MPE. Among 10 protocols, the SEC and DDP perfusion is a most commonly used, which shows a significant improvement in clinical responses with low ADRs. These findings also provide a possible indication and optimal usage for SEC and DDP perfusion.

Qingjin Yiqi granules for post-COVID-19 condition: A randomized clinical trial.

OBJECTIVE: To evaluate the effectiveness and safety of Qingjin Yiqi granules (QJYQ) on post-COVID-19 condition (PCC). METHOD: Patients who met the inclusion criteria were randomly assigned to two groups, the QJYQ group received QJYQ combined with standard rehabilitation treatments (SRTs) and the control group only received SRTs. The treatment course was 14 days. The primary outcomes were modified Medical Research Council (mMRC) scale and Borg scale, while the secondary outcomes included symptoms score and 6-minute walking distance (6MWD). The safety outcome was the incidence of adverse events. RESULTS: A total of 388 patients with PCC were enrolled and randomly assigned to the QJYQ group (n = 194) and the control group (n = 194). Compared to the controls, the mMRC scale was improved in the QJYQ group, which was better than that of the control group [ß (95%CI): -0.626 (-1.101, -0.151), p = 0.010]. A significant improvement in Borg scale was also observed in the QJYQ group compared to the control group [ß (95%CI): -0.395(-0.744, -0.046), p = 0.026]. There was no statistically significant difference in symptoms score and 6MWD between the two groups (p = 0.293, p = 0.724). No treatment-related adverse events were observed in either group. CONCLUSIONS: QJYQ can bring benefits to patients with PCC, mainly in the improvement of breathlessness and fatigue.

The intrapleural administration with thymic peptides in malignant pleural effusion: A clusteredsystematicreview and meta-analysis.

BACKGROUND: Thymic peptides (TPs) are often used to control malignant pleural effusion (MPE). So, we performed a clustered systematic review and meta-analysis to clarify the treatment regimens of TPs for MPE, demonstrate their clinical effectiveness and safety, and reveal the indications and optimal usage for a desired effectiveness. MATERIALS AND METHODS: We collected all trials of TPs for MPE from Chinese and English databases (from inception until May 2021). After evaluating their bias risk, we pooled the data from each regimen using the meta-analysis or descriptive analysis, and summarized the evidence quality using the Grading of Recommendation Assessment, Development and Evaluation approach (GRADE). RESULTS: Thirty-four trials were clustered into TPs for MPE from lung cancer or miscellaneous tumors. The TPs combined with chemical agents were mainly used in MPE from lung cancer. All five regimens, only thymosin with oxaliplatin (L-OHP) significantly improved the complete response (CR) [2.40 (1.84 to 3.13)], quality of life [2.04 (1.20 to 3.48)], 0.5- and 1-year overall survival (OS) rate [5.75 (3.02 to 10.92) and 5.29, (1.71 to 16.36)]. It also up-regulated the T lymphocyte levels, and reduced the pleurodesis failure, disease progression and adverse events. In patients with moderate to large volume, Karnofsky Performance Status score ≥ 50 or anticipated survival time ≥ 3 months, the thymosin (300 mg/time, one time/week and lasting two to eight times) with oxaliplatin (100 mg/m2) achieved a desired response. Most results were moderate quality. CONCLUSIONS: The current evidences indicate that the TPs are important pleurodesis agents, which combination with chemical agents are mainly used in MPE from lung cancer. The thymosin with L-OHP is a main regimen, which shows a significant improvement in clinical responses, antitumor immunity, and with a reasonable security. The evidence also provides indications and optimal usage for achieving a desired effectiveness.

Luteolin inhibits viability, migration, angiogenesis and invasion of non-small cell lung cancer vascular endothelial cells via miR-133a-3p/purine rich element binding protein B-mediated MAPK and PI3K/Akt signaling pathways.

Luteolin inhibits tumorigenesis of non-small cell lung cancer (NSCLC), but its mechanism still needs to be clarified. We hereby explored the effects of luteolin in vascular endothelial cells of NSCLC (NSCLC-VECs). After extraction and identification of NSCLC-VECs, cells were treated with luteolin and transfected. The viability, migration, angiogenesis and invasion of the cells were measured. The levels of miR-133a-3p, purine rich element binding protein B (PURB), vascular endothelial growth factor (VEGF), phosphatidylinositol 3-kinase (PI3K), Akt, mitogen-activated protein kinases (MAPK), matrix metalloproteinase (MMP)-2/-9 were determined. The interaction relationship of miR-133a-3p and PURB was identified. Luteolin inhibited the viability, migration, angiogenesis and invasion of NSCLC-VECs yet up-regulated miR-133a-3p level, while miR-133a-3p inhibitor counteracted the repressive effect of luteolin on the viability, migration, angiogenesis, and invasion in NSCLC-VECs. Luteolin inhibited the expressions of migration- and invasion-associated proteins (VEGF, MMP-2 and MMP-9), PI3K/Akt and MAPK signaling pathways-related factors, while miR-133a-3p inhibitor reversed the inhibitory effect of Luteolin on NSCLC-VECs. Luteolin decreased the level of PURB, which was targeted by miR-133a-3p. ShPURB promoted miR-133a-3p level in NSCLC-VECs, while reversing the promoting effects of miR-133a-3p inhibitor on the migration, invasion, and levels of migration- and invasion-associated proteins, PI3K/Akt and MAPK pathways-associated factors in NSCLC-VECs. Collectively speaking, luteolin inhibits the migration and invasion of NSCLC-VECs via miR-133a-3p/PURB- mediated MAPK and PI3K/Akt pathways.

Integrating Chinese and western medicine for COVID-19: A living evidence-based guideline (version 1).

BACKGROUND: The coronavirus disease 2019 (COVID-19) has turned into a pandemic and resulted in huge death tolls and burdens. Integrating Chinese and western medicine has played an important role in the fight against the COVID-19 pandemic. PURPOSE: We aimed to develop a living evidence-based guideline of integrating Chinese and western medicine for COVID-19. STUDY DESIGN: Living evidence-based guideline. METHODS: This living guideline was developed using internationally recognized and accepted guideline standards, dynamically monitoring the release of new clinical evidence, and quickly updating the linked living systematic review, evidence summary tables, and recommendations. Modified Delphi method was used to reach consensus for all recommendations. The certainty of the evidence, resources, and other factors were fully considered, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the certainty of evidence and the strength of recommendations. RESULTS: The first version of this living guidance focuses on patients who are mild or moderate COVID-19. A multidisciplinary guideline development panel was established. Ten clinical questions were identified based on the status of evidence and a face-to-face experts' consensus. Finally, nine recommendations were reached consensus, and were formulated from systematic reviews of the benefits and harms, certainty of evidence, public accessibility, policy supports, feedback on proposed recommendations from multidisciplinary experts, and consensus meetings. CONCLUSION: This guideline panel made nine recommendations, which covered five traditional Chinese medicine (TCM) prescription granules/decoction (MXXFJD, QFPD, XFBD, TJQW, and JWDY), three Chinese patent medicines (LHQW granules/capsule, JHQG granules, and LHQK granules), and one Chinese herbal injection (XBJ injection). Of them, two were strongly recommended (LHQW granules/capsule and QFPD decoction), and five were weakly recommended (MXXFJD decoction, XFBD decoction, JHQG granules, TJQW granules, and JWDY decoction) for the treatment of mild and moderate COVID-19; two were weakly recommended against (XBJ injection and LHQK granules) the treatment of mild and moderate COVID-19. The users of this living guideline are most likely to be clinicians, patients, governments, ministries, and health administrators.

Intrapleural Administration With Rh-Endostatin and Chemical Irritants in the Control of Malignant Pleural Effusion: A Systematic Review and Meta-Analysis.

INTRODUCTION: A modified and recombinant human endostatin (Rh-endostatin) is often used in the control of malignant pleural effusion (MPE) through intrapleural infusion. OBJECTIVES: To demonstrate the clinical response, survival, and safety of Rh-endostatin plus chemical irritants, their optimal combinations, treatment threshold, and optimal usage, we performed a new systematic review and meta-analysis. METHODOLOGY: All randomized controlled trials (RCTs) were collected from Chinese and English electronic databases (from inception until August 2020). We pooled the data using a series of meta-analyses and summarized the evidence quality following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: We included 75 RCTs recruiting 4,678 patients, which reported six combinations for Rh-endostatin plus chemical irritants. Among the six combinations, only Rh-endostatin plus cisplatin (DDP) with enough trials might improve the complete response [2.29 (1.93, 2.71)] and quality of life [3.01 (2.49, 3.63)] and reduce treatment failure [0.29 (0.25, 0.33)] and progressive disease [0.27 (0.22, 0.34)]. It might not increase the risk of adverse drug reactions. For patients with lung cancer, moderate to massive effusion, initial treatment, Karnofsky Performance Status (KPS) score ≥60, or anticipated survival time ≥3 months, Rh-endostatin (30-45 mg each time, once or twice a week 3-4 times) plus DDP (30-60 mg/m2) obtained a significant improvement in clinical response and a reduction of failure and progressive disease. Most results had good robustness and moderate quality. CONCLUSIONS: Current evidence suggests that Rh-endostatin with DDP may be an optimal combination, which may improve clinical response and reduce failure and progressive disease with good safety. Rh-endostatin (30-40 mg each time, once or twice a week 3-4 times) with DDP (30-40 mg/m2) may be an optimal usage for achieving an ideal response.

The Optimal Adjuvant Strategy of Aidi Injection With Gemcitabine and Cisplatin in Advanced Non-small Cell Lung Cancer: A Meta-analysis of 70 Randomized Controlled Trials.

Introduction: Aidi injection (Aidi) is composed of cantharidin, astragaloside, ginsenoside, and elentheroside E. As an important adjuvant therapy, Aidi in combination with gemcitabine and cisplatin (GP) is often used in the treatment of non-small cell lung cancer (NSCLC). Objectives: We performed a new evaluation to demonstrate the clinical efficacy and safety of the Aidi and GP combination and further explored an optimal strategy for achieving an ideal response and safety level in advanced NSCLC. Methodology: We collected all the related trials from Chinese and English-language databases, analyzed their methodological bias risk using the Cochrane evaluation Handbook for Systematic Reviews of Interventions Version 5.1.0, extracted all the data using a predefined data extraction form, pooled the data using a series of meta-analyses, and finally summarized the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: We included 70 trials with 5,509 patients. Compared with GP alone, the Aidi and GP combination showed a significant improvement in the objective response rate (ORR) [1.82 (1.62-2.04)], disease control rate (DCR) [2.29 (1.97-2.67)], and quality of life (QOL) [3.03 (2.55-3.60)] and a low incidence of hematotoxicity and gastrointestinal and hepatorenal toxicity. Aidi might be more suitable for patients who are first-treated, elderly, or patients with a Karnofsky Performance Status (KPS) score ≥ 60 or anticipated survival time (AST) ≥3 months. An Aidi (50 ml/day, 7-14 days/cycle for one to two cycles), gemcitabine (1000 mg/m2), and cisplatin (20-30 mg/m2, 40-50 mg/m2, or 60-80 mg/m2) might be an optimal regimen for realizing an ideal response and safety level. Most results were robust and of moderate quality. Conclusion: Current evidence indicates that Aidi's value in adjuvant chemotherapy may be broad-spectrum, not just for some regimens. The Aidi and GP combination may show a good short-term response, antitumor immunity, and safety level in patients with NSCLC. Aidi (50 ml/day, 7-14 days/cycle for one and two cycles) with GEM (1000 mg/m2) and DDP (20-30 mg/m2 or 40-50 mg/m2) may be an optimal regimen for realizing an ideal goal in patients who are first-treatment, elderly, or have a KPS score ≥ 60 or AST≥3 months.

Novel multifunctional nano-hybrid polyhedral oligomeric silsesquioxane-based molecules with high cell permeability: molecular design and application for diagnosis and treatment of tumors.

Chemotherapy mostly functions as a carrier for direct drug delivery to the tumor, which may induce secondary damage to healthy tissue cells around the tumor. To avoid this side effect, using multifunctional drugs with high cell permeability during chemotherapy is crucial to achieve significant antitumor efficacy. In this study, polyhedral oligomeric silsesquioxane-based multifunctional organic-inorganic hybrid molecules with potential for recognition, imaging, and treatment were designed and successfully synthesized through a facile and efficient one-pot reaction process. The structure and properties of the synthesized multifunctional molecules were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, mass spectrometry, fluorescence spectroscopy, cytotoxicity assay, surface tension testing, cell compatibility testing, hematoxylin and eosin staining, as well as in vivo and in vitro studies. The results demonstrated that these multifunctional molecules can be effectively used for delivering precisely-targeted imaging and therapeutic agents and exhibited considerable cell permeability. The excellent synergy between high permeability and precise targeting results in multifunctional molecules with superior diagnostic performance.