Work-family conflict among primary health workers during the COVID-19 pandemic: Its mediating role in the relationship between workload and job burnout.

AIMS AND OBJECTIVES: This study explores the situation of workload, work-family conflict and job burnout among primary health workers in China in the context of COVID-19 and identifies the mediating effect of work-family conflict between workload and job burnout. BACKGROUND: Since the breakout of the COVID-19 pandemic, primary health workers have been working on the frontline of the epidemic and may experience increasing workload, work-family conflict and job burnout. It is important to focus on the issue of how to alleviate job burnout of primary health workers. DESIGN: A cross-sectional study (STROBE) was used. METHODS: Data were collected from 785 primary health workers in China. Multiple regression analysis was used to examine the mediating effect of work-family conflict between workload and job burnout. RESULTS: 18.7%, 10.4% and 39.5% of respondents had high job burnout in the dimensions of emotional exhaustion, depersonalization and personal accomplishment, respectively. 34.6% of the respondents had high or very high workload, and 12.8% of the respondents had high or very high work-family conflict. Results of multiple regression analysis indicated that work-family conflict mediated the relationship between workload and job burnout. Workload (ß = .163, CI = .207-.549) and work-family conflict (ß = .211, CI = .311-.640) positively influenced job burnout, and workload (ß = .428, CI = .375-.508) positively influenced work-family conflict. CONCLUSION: The study indicated that primary health workers experienced a high level of job burnout, especially in the personal accomplishment dimension. Furthermore, this study verified the mediating effect of work-family conflict between workload and job burnout. RELEVANCE TO CLINICAL PRACTICE: Some interventions for alleviating workload, work-family conflict and job burnout should be taken, including workplace assistance programmes, family-friendly policies and a well-integrated healthcare system. NO PATIENT OR PUBLIC CONTRIBUTION: This study does not involve patient or public contribution in any part. IMPACT STATEMENT: Nurses and other primary health workers are health gatekeepers of residents and play a vital role in the healthcare system. Due to the breakout of COVID-19, they have taken more work and are more vulnerable to work overload, work-family conflict and the consequent job burnout. Some interventions should be taken to effectively alleviate their job burnout and improve their health and performance.

Suhuang antitussive capsule ameliorates post-infectious cough in mice through AhR-Nrf2 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Suhuang antitussive capsule (SH capsule), a typical traditional Chinese medicines (TCMs) compound, is widely used for the treatment of post-infectious cough (PIC) in the clinic. Our previous studies have demonstrated that SH capsule possesses significant ameliorative effects on cough variant asthma (CVA), sputum obstruction and airway remodeling. AIM OF THE STUDY: This study is designed to investigate the ameliorative effects and potential mechanisms of SH capsule on PIC in mice. MATERIALS AND METHODS: To establish the PIC model, ICR mice were induced by lipopolysaccharide (LPS) (3 mg/kg) once, followed by cigarettes smoke (CS) exposure for 30 min per day for 30 days. Mice were intragastrically (i.g.) administrated with SH capsule at the doses of 3.5, 7, 14 g/kg each day for 2 weeks since the 24th day. The number of coughs, coughs latencies, enzyme-linked immunosorbent assay (ELISA) and histological analysis were used to investigate the effects of SH capsule on PIC mice. Quantitative-polymerase chain reaction (Q-PCR) and western blotting were conducted to evaluate the levels of mRNA and proteins associated with Aryl hydrocarbon receptor (AhR)-NF-E2-related factor 2 (Nrf2) pathway. Superoxide dismutase (SOD), glutathione (GSH) and total antioxidant capacity (T-AOC) assays were performed to evaluate the oxidative stress. A549 cells were used to investigate the ameliorative effects of SH capsule in vitro. RESULTS: SH capsule effectively diminished the number of coughs and extended coughs latencies in PIC mice. The airway inflammation was alleviated by decreasing the expression levels of inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6). Moreover, SH capsule dose-dependently activated AhR-Nrf2 pathway and induced the nuclear translocation in vitro and in vivo. Besides, SH capsule significantly increased the levels of SOD, GSH and T-AOC in mice. CONCLUSION: Our study demonstrates that SH capsule ameliorates airway inflammation-associated PIC in mice through activating AhR-Nrf2 pathway and consequently alleviating inflammatory responses and oxidative stress.

Preservation of mitochondrial homeostasis is responsible for the ameliorative effects of Suhuang antitussive capsule on non-resolving inflammation via inhibition of NF-κB signaling and NLRP3 inflammasome activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Suhuang antitussive capsule (Suhuang), one of traditional antitussive Chinese patent medicines, has been used for the treatment of post-infectious cough and cough variant asthma in clinical practice. It has been demonstrated to show numerous biological actions including antitussive and anti-inflammatory effects. AIM OF THE STUDY: This study aims to investigate the effects of Suhuang on non-resolving inflammation and its underlying molecular mechanism. MATERIAL AND METHODS: In vitro, mitochondrial membrane potential and ROS were detected by flow cytometry analysis. mtDNA release and mPTP fluorescence were determined by Q-PCR and fluorescence microplate reader analysis. Cytochrome C release and 8-OHdG levels were evaluated by ELISA. Additionally, the effects of Suhuang on Drp1, MMP9, IκBα/NF-κB and NLRP3/ASC/Caspase-1 expression were determined by Q-PCR, gelatin zymography or immunoblot analysis. In vivo, C57/BL6 mice were orally administrated for 2 weeks with Suhuang, then lung injury was induced by LPS. Inflammatory mediators mRNA, histological assessment and NF-κB/Caspase-1/IL-1ß levels were evaluated by Q-PCR, H&E staining and immunoblot analysis. Two sepsis models of mice were further used to evaluate its anti-inflammatory effects. RESULTS: Suhuang restored mitochondrial homeostasis by inhibiting Drp1 activation and mitochondrial fission. Besides, Suhuang reduced mPTP opening, mitochondrial membrane potential collapse, ROS overproduction and mtDNA release. Moreover, Suhuang down-regulated MMP9 expression. As a consequence of preserved mitochondrial homeostasis, Suhuang inhibited NF-κB pathway activation by prevention of NF-κB-p65 phosphorylation and IκBα degradation. Suhuang also limited NLRP3 inflammasome activation by blocking NLRP3-ASC interaction and promoting NLRP3 ubiquitination degradation. Drp1 knockdown in vitro diminished the inhibitory effects of Suhuang on inflammatory responses, indicating the essential role of Drp1 in the Suhuang's activity. Consistently, the therapeutic effects of Suhuang were confirmed in LPS-inhaled mice, which recapitulated the protective actions of Suhuang in mitochondrial homeostasis in vitro. Additionally, two sepsis models of mice confirmed the inhibitory effects of Suhuang on uncontrolled inflammation. CONCLUSIONS: Altogether, our work reveals that Suhuang inhibits non-resolving inflammation through inhibition of NF-κB signaling and NLRP3 inflammasome activation by preserving mitochondrial homeostasis, providing new pharmacological data for the clinical use of Suhuang. Our study also suggests mitochondrial homeostasis as a potential intrinsic regulatory strategy for treating inflammatory diseases.

Suhuang antitussive capsule inhibits NLRP3 inflammasome activation and ameliorates pulmonary dysfunction via suppression of endoplasmic reticulum stress in cough variant asthma.

Pulmonary dysfunction is tightly associated with cough variant asthma (CVA), a respiratory damage disease. Suhuang antitussive capsule (Suhuang), one of traditional Chinese patent medicines, plays a crucial role in the treatment and complication of CVA in the long clinical application. In this study, we aimed to investigate the protective effects and underlying antitussive mechanisms of Suhuang on pulmonary function in ovalbumin (OVA)-induced CVA rats. Administration (i.g.) of Suhuang significantly alleviated pulmonary damage and dysfunction. Suhuang improved ER stress and PKCε translocation via regulation of Ca2+ trafficking. Suhuang also inhibited NLRP3 inflammasome activation, as evidenced by disrupting the assembly of NLRP3 inflammasome and reducing the expression of cleaved caspase-1, and decreased IL-1ß secretion. Besides, it's identified that TXNIP induction and RIP1-RIP3-Drp1 pathway were required for the inhibitory routes of Suhuang from ER stress to NLRP3 inflammasome activation. Consistent with the in vivo findings, Suhuang also attenuated ER stress/NLRP3 inflammasome activation, and thereby restored pulmonary homeostasis in vitro. Meantime, these functions were diminished by blocking ER stress, indicating that ER stress is essential for the effects of Suhuang on pulmonary function. A further in vivo analysis showed that Suhuang-driven pharmacological inactivation of NLRP3 inflammasome and amelioration of pulmonary dysfunction were reversed by an ER stress inducer tunicamycin, well confirming the beneficial effects of Suhuang on pulmonary function by regulation of ER stress. Collectively, these results indicated that Suhuang contributed to impairing NLRP3 inflammasome activation via inhibition of ER stress, which was responsible for the protection of pulmonary homeostasis. These findings may provide a pharmacological groundwork and important new experimental data regarding the clinical treatment of Suhuang in CVA patients.

Suhuang Antitussive Capsules-Ameliorative Effects on LPS-Induced Sputum Obstruction in Mice Through Promoting HGF Secretion.

Sputum obstruction is one of common cough complications, which is tightly associated with airway inflammation. Suhuang antitussive capsule (SH Capsule), a classic traditional Chinese medicine prescription, has been used for the treatment of post-cold cough and cough variant asthma in the long clinical application. This study aims to investigate the effects and underlying mechanisms of SH Capsule on LPS-induced sputum obstruction in mice. The results showed that SH Capsule effectively promoted the tracheal phenol red output and mucociliary clearance. SH Capsule also alleviated airway inflammation-mediated mucin 5AC (MUC5AC) level through EGFR-ERK signaling. A further in vivo analysis showed that HGF inhibitor SU11274 abrogated the effects of SH Capsule on MUC5AC, well demonstrating that HGF was required for the beneficial effects of SH Capsule on expectoration in vivo. Moreover, SH Capsule promoted HGF secretion in a colon-dependent manner, which reached lung tissues via blood circulation. Collectively, this study provided new pharmacological data for clinical use of SH Capsule, and proposed a novel mechanism by which SH Capsule was pharmacologically promising for treating sputum obstruction.