Aqueous extract of Descuraniae Semen attenuates lipopolysaccharide-induced inflammation by inhibiting ER stress and WNK4-SPAK-NKCC1 pathway.

Sepsis causes systemic inflammatory responses and acute lung injury (ALI). Despite modern treatments, sepsis-related ALI mortality remains high. Aqueous extract of Descuraniae Semen (AEDS) exerts anti-endoplasmic reticulum (ER) stress, antioxidant and anti-inflammatory effects. AEDS alleviates inflammation and oedema in ALI. Sodium-potassium-chloride co-transporter isoform 1 (NKCC1) is essential for regulating alveolar fluid and is important in ALI. The NKCC1 activity is regulated by upstream with-no-lysine kinase-4 (WNK4) and STE20/SPS1-related proline/alanine-rich kinase (SPAK). This study aimed to investigate the effects of AEDS on lipopolysaccharide (LPS)-induced ALI model in A549 cells, considering the regulation of ER stress, WNK4-SPAK-NKCC1 cascades, inflammation and apoptosis. Cell viability was investigated by the CCK-8 assay. The expressions of the proteins were assessed by immunoblotting analysis assays. The levels of pro-inflammatory cytokines were determined by ELISA. The expression of cytoplasmic Ca2+ in A549 cells was determined using Fluo-4 AM. AEDS attenuates LPS-induced inflammation, which is associated with increased pro-inflammatory cytokine expression and activation of the WNK4-SPAK-NKCC1 pathway. AEDS inhibits the WNK4-SPAK-NKCC1 pathway by regulating of Bcl-2, IP3R and intracellular Ca2+. WNK4 expression levels are significantly higher in the WNK4-overexpressed transfected A549 cells and significantly decrease after AEDS treatment. AEDS attenuates LPS-induced inflammation by inhibiting the WNK4-SPAK-NKCC1 cascade. Therefore, AEDS is regarded as a potential therapeutic agent for ALI.

Clinical effects of traditional Chinese herbal medicine management in patients with COVID-19 sequelae: A hospital-based retrospective cohort study in Taiwan.

Introduction: An estimated 43% of COVID-19 patients showed sequelae, including fatigue, neurocognitive impairment, respiratory symptoms, and smell or taste disorders. These sequelae significantly affect an individual's health, work capacity, healthcare systems, and socioeconomic aspects. Traditional Chinese herbal medicine (TCHM) management showed clinical benefits in treating patients with COVID-19 sequelae. This study aimed to analyze the effects of personalized TCHM management in patients with COVID-19 sequelae. Methods: After the COVID-19 outbreak in Taiwan, we recorded Chronic Obstructive Pulmonary Disease Assessment Tool (CAT), Chalder Fatigue Questionnaire (CFQ-11), and Brief Symptom Rating Scale (BSRS-5) to assess post-COVID respiratory, fatigue, and emotional distress symptoms, respectively. In this study, we retrospectively reviewed the medical records between July 2022 and March 2023. We analyzed the effects of TCHM administration after 14- and 28-days of treatment. Results: 47 patients were included in this study. The results demonstrated that personalized TCHM treatment significantly improved the CAT, CFQ-11, and BSRS-5 scores after 14 and 28 days. TCHM alleviated physical and psychological fatigue. In logistic regression analysis, there was no statistically significant differences in the severity of the baseline symptoms and TCHM administration effects concerning the duration since the initial confirmation of COVID-19, sex, age, or dietary preference (non-vegetarian or vegetarian). Conclusions: Our study suggested that personalized TCHM treatment notably reduced fatigue, respiratory and emotional distress symptoms after 14- and 28-days of treatment in patients with COVID-19 sequelae. We propose that TCHM should be considered as an effective intervention for patients with COVID-19 sequelae.

Pulmonary rehabilitation improves exercise capacity, health-related quality of life, and cardiopulmonary function in patients with non-small cell lung cancer.

BACKGROUND: Lung cancer significantly impairs exercise capacity and health-related quality of life (HRQL). Pulmonary rehabilitation (PR) has demonstrated positive effects on exercise capacity and HRQL in lung cancer patients. However, its impact on cardiopulmonary function needs further exploration. The aim of this study was to explore the effects of PR on cardiopulmonary function, exercise capacity and HRQL in patients with lung cancer. METHODS: Patients with lung cancer were enrolled in a 12-week PR program. Each participant underwent a thorough evaluation, which included spirometry, cardiopulmonary exercise testing, respiratory muscle strength test, and evaluation of HRQL using the Chronic Obstructive Pulmonary Disease Assessment Test (CAT). RESULTS: Fifty-six patients completed the PR program. Following PR, exercise capacity significantly improved, as evidenced by increased peak oxygen uptake and work rate (both p < 0.05). Exertional symptoms were notably reduced, including leg soreness and dyspnea at peak exercise, accompanied by a decrease in the CAT score (all p < 0.05). Furthermore, improvements in cardiopulmonary function were observed, encompassing respiratory muscle strength, ventilatory equivalent, tidal volume, stroke volume index, and cardiac index at peak exercise (all p < 0.05). CONCLUSIONS: PR demonstrated notable enhancements in cardiopulmonary function, exertional symptoms, exercise capacity, and HRQL in patients with lung cancer.

High-intensity aerobic exercise training improves exercise capacity, dyspnea, and fatigue in patients with severe asthma using triple inhaler.

Objectives: Asthma is a chronic respiratory disease that affects millions of people worldwide and causes severe symptoms such as wheezing, coughing, and breathing difficulty. Despite modern treatments, 3%-10% of patients develop severe asthma, which requires high-dose medications, and they may still experience frequent and severe symptoms, exacerbations, and psychological impacts. This study aimed to investigate the effects of high-intensity aerobic exercise training (HIAET) in patients with severe asthma. Materials and Methods: Patients with severe asthma were recruited, and cardiopulmonary exercise tests, dyspnea, and leg fatigue scores were performed before HIAET. Participants underwent a 12-week hospital-based HIAET, which involved exercising twice weekly to reach 80% of their peak oxygen uptake (VO2). Results: Eighteen patients with severe asthma underwent HIAET, which resulted in significant improvement in peak VO2 (1214.0 ± 297.9-1349.4 ± 311.2 mL/min, P = 0.004) and work rate (80.6 ± 21.2-96.2 ± 24.8 watt, P < 0.001) and decrease in dyspnea (5.1 ± 1.8-4.1 ± 1.2, P = 0.017) and fatigue scores (5.2 ± 2.3-4.0 ± 1.2, P = 0.020) at peak exercise. No significant changes were observed in spirometry results, respiratory muscle strength, or circulatory parameters. Conclusion: HIAET can lead to improved exercise capacity and reduced dyspnea and fatigue scores at peak exercise without changes in spirometry, respiratory muscle strength, and circulatory parameters.

The differences in the adrenergic receptors of proximal urethra between sexes.

Objectives: The bladder and urethra work as a physiologically functional unit to facilitate continence in the storage and voiding phase. Sex differences have been found in the urethral contraction in response to α-adrenergic receptor activation. This study aimed to investigate the role of adrenergic receptors in the proximal urethra of male and female mice. Materials and Methods: Urinary bladder and proximal urethral smooth muscle (USM) samples from male and female C57BL/6 mice were isolated and mounted in an organ bath. Results: Acetylcholine-induced contraction of the urinary bladder was compared in male and female mice. Phenylephrine and norepinephrine (NE) induced little contraction at a lower concentration, but a relaxing phase of female proximal USM was observed at a higher concentration. This contraction profile was inhibited by NG-nitro-L-arginine, lidocaine, and capsaicin. In addition, the NE-induced contraction was greater in the incubation of propranolol than that of L-NNA or lidocaine. These results suggested that the ß-adrenoceptor may be the dominant receptor of female proximal USM, and the activity of calcitonin gene-related peptide sensory nerves and nitrergic nerves may pose an anti-contraction effect on the proximal urethra in female mice. Conclusion: ß-adrenoceptor may be the dominant receptor of female proximal USM. The use of ß-adrenergic receptor blocker agents might have the potential for the treatment of female voiding dysfunction.

Evaluation of the relationship of tricuspid regurgitation peak gradient/tricuspid annulus plane systolic excursion to exercise capacity, cardiac index, and ventilatory function during exercise in patients with COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) often causes cardiopulmonary dysfunction, which deteriorates exercise capacity. Cardiopulmonary exercise testing (CPET) and echocardiography are common tools for evaluating cardiovascular function. No studies have analyzed the correlation between echocardiography-derived parameters and cardiopulmonary response during exercise. OBJECTIVES: We analyzed the correlation between echocardiographic parameters such as tricuspid regurgitation peak gradient (TRPG), tricuspid annular plane systolic excursion (TAPSE), TRPG/TAPSE and CPET-derived parameters. METHODS: Seventy-seven patients with COPD were evaluated. We analyzed the correlation between parameters derived from echocardiography, exercise capacity, cardiovascular and ventilatory parameters derived from CPET. RESULTS: The correlation between TRPG/TAPSE and work rate (WR) was moderate and negative (-0.4423, p = 0.0003), while TRPG had a weak negative correlation with WR (r= -0.3099, p = 0.0127). Oxygen uptake at peak exercise was weakly negatively correlated with TRPG/TAPSE (-0.3404, p = 0.0059), TRPG (r= -0.3123, p = 0.0120), and the ratio of early mitral inflow velocity to early mitral annular diastolic velocity (E/E'). The correlation between TRPG/TAPSE and exercise capacity was higher than that of TPRG, TAPSE, and E/E'. TRPG/TAPSE exhibited a moderate negative correlation with cardiac index, whereas TRPG and TAPSE showed a weak correlation. The correlation between TRPG/TAPSE and cardiac function during exercise was higher than that of TPRG, TAPSE, and E/E'. TRPG/TAPSE, TRPG, TAPSE, and E/E' were weakly negatively correlated with lung function. CONCLUSIONS: In assessing exercise capacity, cardiac function, and gas exchange, TRPG/TAPSE proves to be superior to other cardiac parameters. Higher TRPG/TAPSE levels corresponded to lower exercise capacity, cardiovascular and ventilatory function.

Early pulmonary rehabilitation of COVID-19 patients in an isolation ward and intensive care unit.

When patient with coronavirus disease 2019 (COVID-19) are hospitalized, the limited space for activity, disease itself causes fever, muscle aches, fatigue, respiratory failure with mechanical ventilation, or medications such as steroids or neuromuscular blocking can cause muscle dysfunction. Pulmonary rehabilitation (PR) should be arranged for these patients with COVID-19. However, the literature on early PR within 1 week of admission on patients with COVID-19 are limited. This review focuses on early PR in COVID-19 patients admitted to isolation wards or intensive care units. The essential components of early PR programs include education, breathing exercise, airway clearance, and physical activity training. Breathing exercises, including diaphragmatic and pursed-lip breathing, are known to improve lung function in chronic obstructive pulmonary disease and are also recommended for COVID-19 patients. Poor airway clearance can further aggravate pneumonia. Airway clearance techniques help patients to clear sputum and prevent the aggravation of pneumonia. Early physical activity training allows patients to maintain limb muscle function during hospitalization. It is recommended to design appropriate indoor exercise training for patients with frequency 1-2 times a day, and intensity should not be too high (dyspnea Borg Scale ≤3) in the acute stage. In order to achieve safe training, criteria for selecting stable patients and training termination are important. Early PR may help reduce the length of hospital stay, maintain functional status, improve symptoms of dyspnea, relieve anxiety, and maintain health-related quality of life in these patients after discharge.

Impact of bisoprolol and amlodipine on cardiopulmonary responses and symptoms during exercise in patients with chronic obstructive pulmonary disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often have exercise intolerance. The prevalence of hypertension in COPD patients ranges from 39-51%, and ß-blockers and amlodipine are commonly used drugs for these patients. OBJECTIVES: We aimed to study the impact of ß-blockers and amlodipine on cardiopulmonary responses during exercise. METHODS: A total 81 patients with COPD were included and the patients underwent spirometry, cardiopulmonary exercise tests, and symptoms questionnaires. RESULTS: There were 14 patients who took bisoprolol and 67 patients who did not. Patients with COPD taking ß-blockers had lower blood oxygen concentration (SpO2) and more leg fatigue at peak exercise but similar exercise capacity as compared with patients not taking bisoprolol. There were 18 patients treated with amlodipine and 63 patients without amlodipine. Patients taking amlodipine had higher body weight, lower blood pressure at rest, and lower respiratory rates during peak exercise than those not taking amlodipine. Other cardiopulmonary parameters, such as workload, oxygen consumption at peak exercise, tidal volume at rest or exercise, cardiac index at rest or exercise were not significantly different between patients with or without bisoprolol or amlodipine. Smoking status did not differ between patients with or without bisoprolol or amlodipine. CONCLUSIONS: COPD is often accompanied by hypertension, and ß-blockers and amlodipine are commonly used antihypertensive drugs for these patients. Patients with COPD taking bisoprolol had lower SpO2 and more leg fatigue during peak exercise. Patients taking amlodipine had lower respiratory rates during exercise than those not taking amlodipine. Exercise capacity, tidal volume, and cardiac index during exercise were similar between patients with and without bisoprolol or amlodipine.

Artificial Intelligence-Assisted Chest X-ray for the Diagnosis of COVID-19: A Systematic Review and Meta-Analysis.

Because it is an accessible and routine image test, medical personnel commonly use a chest X-ray for COVID-19 infections. Artificial intelligence (AI) is now widely applied to improve the precision of routine image tests. Hence, we investigated the clinical merit of the chest X-ray to detect COVID-19 when assisted by AI. We used PubMed, Cochrane Library, MedRxiv, ArXiv, and Embase to search for relevant research published between 1 January 2020 and 30 May 2022. We collected essays that dissected AI-based measures used for patients diagnosed with COVID-19 and excluded research lacking measurements using relevant parameters (i.e., sensitivity, specificity, and area under curve). Two independent researchers summarized the information, and discords were eliminated by consensus. A random effects model was used to calculate the pooled sensitivities and specificities. The sensitivity of the included research studies was enhanced by eliminating research with possible heterogeneity. A summary receiver operating characteristic curve (SROC) was generated to investigate the diagnostic value for detecting COVID-19 patients. Nine studies were recruited in this analysis, including 39,603 subjects. The pooled sensitivity and specificity were estimated as 0.9472 (p = 0.0338, 95% CI 0.9009-0.9959) and 0.9610 (p < 0.0001, 95% CI 0.9428-0.9795), respectively. The area under the SROC was 0.98 (95% CI 0.94-1.00). The heterogeneity of diagnostic odds ratio was presented in the recruited studies (I2 = 36.212, p = 0.129). The AI-assisted chest X-ray scan for COVID-19 detection offered excellent diagnostic potential and broader application.

The von Hippel-Lindau Tumor Suppressor Gene Mutations Modulate Lipocalin-2 Expression in Ferroptotic-Inflammatory Pathways.

A previous study of an animal model with tumor suppressor gene von Hippel-Lindau (VHL) conditional knockdown suggested that tissue inflammation and fibrosis play important roles in the development of clear-cell renal cell carcinoma (ccRCC), which is consistent with the epidemiological evidence linking inflammatory kidney disease and renal cancer. Ferroptosis and inflammation have been linked in a recent study, but the exact mechanism remains unclear. This study is aimed at investigating the mechanism of lipocalin-2- (LCN-2-) mediated ferroptosis and inflammation in vhl-mutated HK-2 cells and mouse primary proximal tubule cells (mRTCs) and the polarization of macrophage RAW 264.7 cells. Based on the levels of lipid reactive oxygen species (ROS) and the expression of glutathione peroxidase 4 (GPX4) in HK-2 cells, we observed that a VHL mutation increased ROS production and depressed GPX4 expression, whereas LCN-2 knockdown reversed these effects. Accordingly, VHL appears to affect ferroptosis in an LCN-2-dependent manner. We also revealed that LCN-2 sensitizes HK-2 cells to inflammation and macrophage RAW 264.7 cells to M1-like polarization. This study provides novel insights into the potential therapeutic target and strategy for attenuating the progression of ccRCC by revealing the role of VHL in regulating chronic inflammation within the LCN-2-ferroptosis pathway.

Transcriptome analysis in patients with asthma after inhaled combination therapy with long-acting ß2-agonists and corticosteroids.

Introduction: Asthma is one of the major public health problems that imposes a great burden on societal, financial, and healthcare around the world. Asthma poorly affects the health-related quality of life and daily activities of patients. Treatment of asthma, including inhaled corticosteroids (ICS) and long-acting beta-agonists (LABAs), mainly aims to improve the lung function and reduce symptoms and exacerbations. Current treatment regimens are symptom-based strategies, and the status of airway inflammation after treatment is yet unknown. We conducted this study to understand the comprehensive inflammation or airway remodeling status of patients after ICS-LABA treatment through RNA transcriptome analysis. Materials and methods: Eight newly diagnosed asthmatic patients and two healthy subjects were recruited in this study. Asthmatic patients underwent blood tests, lung function test, and RNA transcriptome analysis before and after ICS-LABA treatment. Results: In comparison with healthy subjects, pretreatment asthmatic patients had higher expression of protein tyrosine kinase and related signaling pathways. After ICS-LABA treatment, the expression of nuclear receptor transcription coactivator, N-acetyltransferase, protein tyrosine kinase, nuclear receptor, and RNA polymerase II-activating transcription factor were downregulated. However, the post-treatment asthmatic patients still had higher expression of cysteine-type endopeptidase, endodeoxyribonuclease, apolipoprotein, and unfolded protein was still upregulated than healthy subjects. Conclusions: The combination of ICS/LABAs decreased airway inflammatory and remodeling pathways. However, allergen stimulation-related pathways were still upregulated in patients after ICS/LABA treatment. The combination of medication and allergen removal is a complete strategy for asthma.

Combinations of scalp acupuncture location for the treatment of post-stroke hemiparesis: A systematic review and Apriori algorithm-based association rule analysis.

Background: Post-stroke hemiparesis strongly affects stroke patients' activities of daily living and health-related quality of life. Scalp acupuncture (SA) is reportedly beneficial for post-stroke hemiparesis. However, there is still no standard of SA for the treatment of post-stroke hemiparesis. Apriori algorithm-based association rule analysis is a kind of "if-then" rule-based machine learning method suitable for investigating the underlying rules of acupuncture point/location selections. This study aimed to investigate the core SA combinations for the treatment of post-stroke hemiparesis by using a systematic review and Apriori algorithm-based association rule analysis. Methods: We conducted a systematic review to include relevant randomized controlled trial (RCT) studies investigating the effects of SA treatment in treating patients with post-stroke hemiparesis, assessed by the Fugl-Meyer Assessment (FMA) score. We excluded studies using herbal medicine or manual acupuncture. Results: We extracted 33 SA locations from the 35 included RCT studies. The following SA styles were noted: International Standard Scalp Acupuncture (ISSA), WHO Standard Acupuncture Point Locations (SAPL), Zhu's style SA, Jiao's style SA, and Lin's style SA. Sixty-one association rules were investigated based on the integrated SA location data. Conclusions: SAPL_GV20 (Baihui), SAPL_GV24 (Shenting), ISSA_MS6_i (ISSA Anterior Oblique Line of Vertex-Temporal, lesion-ipsilateral), ISSA_MS7_i (ISSA Posterior Oblique Line of Vertex-Temporal, lesion-ipsilateral), ISSA_PR (ISSA Parietal region, comprised of ISSA_MS5, ISSA_MS6, ISSA_MS7, ISSA_MS8, and ISSA_MS9), and SAPL_Ex.HN3 (Yintang) can be considered the core SA location combination for the treatment of post-stroke hemiparesis. We recommend a core SA combination for further animal studies, clinical trials, and treatment strategies.

Review of epidermal growth factor receptor-tyrosine kinase inhibitors administration to non-small-cell lung cancer patients undergoing hemodialysis.

Non-small-cell lung cancer (NSCLC) causes significant mortality worldwide. Patients with chronic renal failure have an increased risk of developing lung cancer. NSCLC Patients with chronic renal failure undergoing hemodialysis (HD) often exhibit poor performance, and chemotherapy is generally contraindicated. Oral epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are effective treatment agents for NSCLC patients. However, the benefits and adverse effects of EGFR-TKIs in NSCLC undergoing HD are known. There are no clinical studies on the effects of EGFR-TKIs on NSCLC patients undergoing HD. We reviewed all previous case reports about EGFR-TKIs in NSCLC patients undergoing HD. It is difficult to design studies about the effects of EGFR-TKIs in patients undergoing HD, and this review is quite important. EGFR-TKIs are well tolerated in patients undergoing HD. The main routes of elimination of EGFR-TKIs are metabolism via the liver, and renal elimination is minor. The recommended doses and pharmacokinetics of these EGFR-TKIs for patients undergoing HD are similar to those for patients with normal renal function. The plasma protein binding of EGFR-TKIs is very high, and it is not necessary to adjust the dose after HD. In conclusion, EGFR-TKIs are effective and well tolerated in patients undergoing HD.

Aqueous Extract of Descuraniae Semen Attenuates Lipopolysaccharide-Induced Inflammation and Apoptosis by Regulating the Proteasomal Degradation and IRE1α-Dependent Unfolded Protein Response in A549 Cells.

Background: Lipopolysaccharide (LPS)-induced acute lung injury (ALI) induces endoplasmic reticulum stress, unfolded protein response (UPR), apoptosis, and inflammation. Inositol-requiring enzyme 1 (IRE1)-α is important for adaptive and apoptotic UPR determination during ER stress. The aqueous extract of Descuraniae Semen (AEDS) is reported to be a safe and effective herb for the treatment of pulmonary edema as it shows anti-inflammatory activities. Methods: We investigated the effects of AEDS on LPS-induced ALI in A549 cells with respect to the regulation of IRE1α-dependent UPR, proteasomal degradation, mitochondrial membrane potential (MtMP), inflammation, and apoptosis. Results: AEDS attenuated ER stress by regulating the proteasomal degradation. LPS induced ER stress [binding immunoglobulin protein (BiP), phosphorylated IRE1α, sliced X-box binding protein 1 [XBP1s], phosphorylated cJUN NH2-terminal kinase (pJNK), B-cell lymphoma (Bcl)-2-associated X (Bax), Bcl-2], inflammation (nucleus factor-kappa B (NF-κB) p65 nuclear translocation, nucleus NF-κB, pro-inflammatory cytokines] and apoptosis [C/EBP homologous protein (CHOP), cytochrome c, caspase-8, and caspase-6, and TUNEL] were significantly attenuated by AEDS treatment in A549 cells. AEDS prevents LPS-induced decreased expression of MtMP in A549 cells. Conclusions: AEDS attenuated LPS-induced inflammation and apoptosis by regulating proteasomal degradation, promoting IRE1α-dependent adaptive UPR, and inhibiting IRE1α-dependent apoptotic UPR. Moreover, IRE1α-dependent UPR plays a pivotal role in the mechanisms of LPS-induced ALI. Based on these findings, AEDS is suggested as a potential therapeutic option for treating patients with ALI.

Comparison of T790M Acquisition After Treatment With First- and Second-Generation Tyrosine-Kinase Inhibitors: A Systematic Review and Network Meta-Analysis.

Background: Lung adenocarcinoma is a common disease with a high mortality rate. Epidermal growth factor receptor (EGFR) mutations are found in adenocarcinomas, and oral EGFR-tyrosine kinase inhibitors (EGFR-TKIs) show good responses. EGFR-TKI therapy eventually results in resistance, with the most common being T790M. T790M is also a biomarker for predicting resistance to first- and second-generation EGFR-TKIs and is sensitive to osimertinib. The prognosis was better for patients with acquired T790M who were treated with osimertinib than for those treated with chemotherapy. Therefore, T790M mutation is important for deciding further treatment and prognosis. Previous studies based on small sample sizes have reported very different T790 mutation rates. We conducted a meta-analysis to evaluate the T790M mutation rate after EGFR-TKI treatment. Methods: We systematic reviewed the electronic databases to evaluate the T790M mutation rate after treatment with first-generation (gefitinib, erlotinib, and icotinib) and second-generation (afatinib and dacomitinib) EGFR-TKIs. Random-effects network meta-analysis and single-arm meta-analysis were conducted to estimate the T790M mutation rate of the target EGFR-TKIs. Results: A total of 518 studies were identified, of which 29 were included. Compared with afatinib, a higher odds ratio (OR) of the T790M mutation rate was observed after erlotinib [OR = 1.48; 95% confidence interval (CI):1.09-2.00] and gefitinib (OR = 1.45; 95% CI: 1.11-1.90) treatments. An even OR of the T790M mutation rate was noted after icotinib treatment (OR = 0.91, 95% CI: 0.46-1.79) compared with that after afatinib. The T790M mutation rate was significantly lower with afatinib (33%) than that with gefitinib (49%) and erlotinib treatments (47%) (p < 0.001). The acquired T790M mutation rate in all participants was slightly lower in Asians (43%) than that in Caucasians (47%). Conclusions: Erlotinib and gefitinib had a higher OR for the T790M mutation than afatinib. The T790M mutation rate was significantly lower in afatinib than in gefitinib and erlotinib. T790M is of great significance because osimertinib shows a good prognosis in patients with T790M mutation. Systematic Review Registration: PROSPERO, identifier CRD42021257824.

Deciphering the role of damage-associated molecular patterns and inflammatory responses in acute lung injury.

Acute lung injury (ALI) is characterized by diffuse pulmonary infiltrates and causes great mortality. ALI presents with overproduction of proinflammatory cytokines, cell death, destruction of alveoli-endothelial barriers, and neutrophil infiltration in lung tissues. Damage-associated molecular patterns (DAMPs) are molecules released from damaged cells due to infection, trauma, etc. DAMPs activate innate and adaptive immunity, trigger inflammatory responses, and are important in the initiation and development of ALI. We reviewed the literatures on DAMPs in ALI. Alveolar macrophages (AMs), neutrophils, and epithelial cells (AECs) are important in the pathogenesis of ALI. We comprehensively analyzed the interaction between DAMPs and AMs, alveolar neutrophils, and AECs. During the initial stage of ALI, ruptured cell membranes or destroyed mitochondria release DAMPs. DAMPs activate the inflammasome in nearby sentinel immune cells, such as AMs. AMs produce IL-1ß and other cytokines. These mediators upregulate adhesion molecules of the capillary endothelium that facilitate neutrophil recruitment. The recruited neutrophils detect DAMPs using formyl peptide receptors on the membrane, guiding their migration to the injured site. The accumulation of immune cells, cytokines, chemokines, proteases, etc., results in diffuse alveolar damage and pulmonary hyperpermeability with protein-rich fluid retention. Some clinical studies have shown that patients with ALI with higher circulating DAMPs have higher mortality rates. In conclusion, DAMPs are important in the initiation and progression of ALI. The interactions between DAMPs and AMs, neutrophils, and AECs are important in ALI. This review comprehensively addresses the mechanisms of DAMPs and their interactions in ALI.

Combination of Acupoints for Alzheimer's Disease: An Association Rule Analysis.

Background: Alzheimer's disease (AD) is an ongoing neurological degeneration characterized by amnesia and a decline in cognitive abilities. Hippocampal neurogenesis is the leading cause of AD. Mild cognitive impairment (MCI), a prodromal state of AD, is mainly due to the degradation of neuropsychiatric manifestations. Previous systematic reviews demonstrated that treatment with acupuncture with Chinese herbs is tolerable and effective in improving cognitive function in patients with AD. Our investigation aimed to discover the main acupoint combination for AD management based on a preceding systematic review and meta-analysis of randomized control trials (RCTs). Materials and Methods: Our investigation was executed using association rule analysis, which is a common data mining technique accessible within R. Our study elucidated acupoint locations as binary data from 15 of the included studies using the Apriori algorithm. Results: Thirty-two acupoints were selected from 15 RCTs. The 10 most frequent acupoints were selected. We inspected 503 association rules using the interpreted acupuncture data. The obtained results showed that {SP6, BI10} ≥ {HT7} and {HT7, BI10} ≥ {SP6} were the most associated rules in 15 RCTs. Conclusion: The combination of acupoints ({SP6, BI10} ≥ {HT7} and {HT7, BI10} ≥ {SP6}) can be acknowledged as a core combination for future acupuncture regimens of AD.

Different Responses to Pulmonary Rehabilitation in COPD Patients with Different Work Efficiencies.

Background: Chronic obstructive pulmonary disease (COPD) often involves the cardiopulmonary dysfunction that deteriorates health-related quality of life (HRQL) and exercise capacity. Work efficiency (WE) indicates the efficiency of overall oxygen consumption (VO2) during exercise. This study investigated whether different WEs have different effects on pulmonary rehabilitation (PR). Methods: Forty-five patients with stable COPD were scheduled for PR. The PR programs consisted of twice-weekly sessions for three months. These patients were comprehensively evaluated by cardiopulmonary exercise testing and COPD assessment test (CAT) before and after PR. We compared these parameters between patients with a normal versus poor WE. Results: Twenty-one patients had a normal WE and twenty-four patients had a poor WE (<8.6 mL/min/watt). Patients with a poor WE had earlier anaerobic metabolism, a poorer oxygen pulse, lower exercise capacity, more exertional dyspnea, and a poorer HRQL than those with a normal WE. PR improved exercise capacity, HRQL, anaerobic threshold, exertional dyspnea and leg fatigue in patients with either normal or poor WE. However, significant improvement of WE, oxygen pulse, respiratory frequency (Rf) during exercise, chest tightness, activity and sleepiness by CAT were noted only in patients with a poor WE. Among the patients with a poor WE, 29% patients had WE returned to normal after PR. Conclusion: Patients with different WE had different responses to PR. PR improved exercise capacity and HRQL regardless of a normal or poor WE. However, WE, oxygen pulse, Rf during exercise, chest tightness, activity and sleepiness were only improved in patients with a poor WE.

Efficacy and Safety of Complementary Therapy With Jing Si Herbal Tea in Patients With Mild-To-Moderate COVID-19: A Prospective Cohort Study.

Background: Since late 2019, there has been a global COVID-19 pandemic. To preserve medical capacity and decrease adverse health effects, preventing the progression of COVID-19 to severe status is essential. Jing-Si Herbal Tea (JSHT), a novel traditional Chinese medicine formula was developed to treat COVID-19. This study examined the clinical efficacy and safety of JSHT in patients with mild-to-moderate COVID-19. Methods: In this prospective cohort study, we enrolled 260 patients with mild-to-moderate COVID-19. The enrolled patients were divided into the JSHT (n = 117) and control (n = 143) groups. Both groups received standard management. The JSHT group was treated with JSHT as a complementary therapy. Results: Compared with standard management alone, JSHT combined with standard management more effectively improved the reverse transcription-polymerase chain reaction cycle threshold value, C-reactive protein level, and Brixia score in the adult patients with mild-to-moderate COVID-19, especially in the male and older patients (those aged ≥60 years). The results revealed that the patients treated with JSHT combined with standard management had 51, 70, and 100% lower risks of intubation, Medisave Care Unit admission, and mortality compared with those receiving standard management only. Conclusions: JSHT combined with standard management more effectively reduced the SARS-CoV-2 viral load and systemic inflammation and alleviated lung infiltrates in the patients with mild-to-moderate COVID-19, especially in the male and older patients (those aged ≥60 years). JSHT combined with standard management may prevent critical status and mortality in patients with mild-to-moderate COVID-19. JSHT is a promising complementary therapy for patients with mild-to-moderate COVID-19.

Wild Bitter Melon Extract Abrogates Hypoxia-Induced Cell Death via the Regulation of Ferroptosis, ER Stress, and Apoptosis in Microglial BV2 Cells.

Microglial cells are well-known phagocytic cells that are resistant to the central nervous system (CNS) and play an important role in the maintenance of CNS homeostasis. Activated microglial cells induce neuroinflammation under hypoxia and typically cause neuronal damage in CNS diseases. In this study, we propose that wild bitter melon extract (WBM) has a protective effect on hypoxia-induced cell death via regulation of ferroptosis, ER stress, and apoptosis. The results demonstrated that hypoxia caused microglial BV-2 the accumulation of lipid ROS, ferroptosis, ER stress, and apoptosis. In this study, we investigated the pharmacological effects of WBM on BV-2 cells following hypoxia-induced cell death. The results indicated that WBM reversed hypoxia-downregulated antiferroptotic molecules Gpx4 and SLC7A11, as well as upregulated the ER stress markers CHOP and Bip. Moreover, WBM alleviated hypoxia-induced apoptosis via the regulation of cleaved-caspase 3, Bax, and Bcl-2. Our results suggest that WBM may be a good candidate for preventing CNS disorders in the future.