Yingxiang Acupoint Embedding Improves Mucosal Barrier Function in Rats with Local Allergic Rhinitis.

INTRODUCTION: Epithelial barrier disruption is the initial cause of various diseases. We previously reported that acupoint catgut embedding (AE) improves tight junction proteins (TJs) in rats with allergic rhinitis. However, whether AE improves the epithelial barrier in local allergic rhinitis (LAR) remains unknown. METHODS: A total of 36 Sprague Dawley (SD) male rats aged 5-7 weeks were divided into 6 groups with 6 rats each: control group, LAR model group, false acupoint embedding + LAR group, acupoint embedding + LAR group, capsaicin + LAR group, and tunicamycin + acupoint embedding + LAR group. Behavioral observation, ELISA to detect inflammatory factors in nasal lavage fluid and serum IgE, nasal mucosal permeability test, hematoxylin-eosin staining, PCR to detect Substance P (SP), Western blot, and immunofluorescence to detect endoplasmic reticulum stress (ERS) index and TJs were used to investigate the mechanism of AE in LAR. RESULTS: AE improved the symptoms and pathological features of nasal mucosa of LAR rats, reduced the inflammatory factors (IL4, IL5, IL13) of nasal lavage fluid, and showed no significant change in serum IgE levels in all groups. In addition, AE decreased the expression of SP in nasal mucosa of LAR rats, inhibited ERS, increased the expression of tight junction protein, reduced the permeability of nasal mucosa, and improved the function of nasal mucosal barrier. CONCLUSION: This study confirms that AE can improve the nasal mucosal barrier function of LAR by reducing the expression of SP, inhibiting ERS and increasing the expression of TJs, thus enhancing the nasal mucosal barrier function.

Clinical efficacy of acupoint catgut embedding in the treatment of allergic rhinitis: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy of acupoint catgut embedding in the treatment of allergic rhinitis by Meta-analysis. METHODS: Pubmed, Web of Science, Embase, Elsevier, CNKI, and VIP databases were searched for clinical randomized controlled trials (RCTS) on acupoint catgut embedding for allergic rhinitis from the establishment of the database to December 30, 2022. RevMan5.4 and Stata12 software were used for Meta-analysis. RESULTS: A total of 17 articles were included, involving 1231 patients. Meta-analysis showed that the total effective rate of acupoint catgut embedding for allergic rhinitis was higher than that of the control group [Pooled Odds Ratio = 5.19, 95%CI (3.14, 8.58), P < 0.00001]. Sensitivity analysis indicated that the total effective rate of acupoint catgut embedding in the treatment of allergic rhinitis was stable. The efficacy of the acupoint embedding group was better than that of the western medicine group [OR = 5.78, 95%CI (3.25, 10.27), P < 0.00001]. Acupoint embedding decreased serum IL-33 levels [MD = -70.79, 95%CI (-102.60, -38.98), P < 0.0001] and improved TNNSS score [MD = -0.25, 95%CI (-0.40, -0.11), P = 0.0005] was statistically different from the control group. CONCLUSION: Acupoint catgut embedding in the treatment of allergic rhinitis has a certain effect, but the accuracy of this conclusion still needs to be verified by higher-quality RCT in the later stage.

Association between air pollution and the prevalence of allergic rhinitis in Chinese children: A systematic review and meta-analysis.

Background: Allergic rhinitis (AR) is a common chronic inflammatory disease with bothersome symptoms. However, the effect of air pollution on the prevalence of AR in children is controversial. Objective: This study aimed to investigate the association between air pollution and the prevalence of AR in Chinese children. Methods: This study, in China, included 160,356 students ages 0-18 years who completed a questionnaire about the accuracy of the International Study of Asthma and Allergies in Childhood (ISAAC). The effect of different air pollutants on the prevalence rate were evaluated by meta-analysis. Also, it evaluated the effect of different air pollutants on the prevalence rate. Results: The differences in the effects of sulfur dioxide (SO2) exposure (combined odds ratio [ORcombined] 1.03 [95% confidence interval {CI}, 1.01-1.05]; p = 0.010) and nitrogen dioxide (NO2) exposure (ORcombined 1.11 [95% CI, 1.05-1.18]; p = 0.0006) on the risk of childhood AR was statistically significant. The effect of particulate matter with aerodynamic diameter of <10 µm (PM10) exposure on the risk of childhood AR was statistically significant (ORcombined 1.02 [95% CI, 1.01-1.03]; p < 0.001), the effect of particulate matter with aerodynamic diameter of <2.5 µm (PM2.5) exposure on the risk of childhood AR was statistically significant (ORcombined 1.15 [95% CI, 1.03-1.29]; p = 0.02), and the effect of ozone exposure on the risk of childhood AR was not statistically significant (ORcombined 0.98 [95% CI, 0.67-1.41]; p = 0.13). Conclusion: NO2, SO2, PM2.5, and PM10 were associated with the prevalence of AR in Chinese children. PM2.5 had the highest correlation with AR prevalence.

S-Allylmercapto-N-acetylcysteine ameliorates elastase-induced chronic obstructive pulmonary disease in mice via regulating autophagy.

Autophagy-impairment is involved in the pathological process of chronic obstructive pulmonary disease (COPD), and relates to inflammation and emphysema in lung injury. This study aimed to elucidate the protective effect of S-Allylmercapto-N-acetylcysteine (ASSNAC) against COPD via regulating the autophagy. Firstly, porcine pancreatic elastase (PPE)-induced COPD model in A549 cells was established, and ASSNAC was verified to alleviate the autophagy-impairment from the results of western blotting analysis of LC3BⅡ/Ⅰ and monodansylcadaverine (MDC) staining of autophagosome. Secondly, Balb/c mice were stimulated by PPE to induce the COPD model in vivo. The histological analysis of lung tissues presented that ASSNAC could alleviate the lung injury induced by PPE. Thirdly, the secretions of NO, TNF-α and IL-1ß in serum and BALF were reduced by ASSNAC compared with the PPE group. Finally, the mechanism of therapeutic effects of ASSNAC against COPD through regulating the autophagy-impairment was clarified. That is, ASSNAC inhibits the phosphorylation of PI3K/Akt/mTOR signaling pathways. In a word, this research provides a reference for ASSNAC to be an effective drug for pulmonary diseases.

Attenuation of Human Lysozyme Amyloid Fibrillation by ACE Inhibitor Captopril: A Combined Spectroscopy, Microscopy, Cytotoxicity, and Docking Study.

Misfolding proteins could form oligomers or amyloid fibers, which can cause a variety of amyloid-associated diseases. Thus, the inhibition of protein misfolding and fibrillation is a promising way to prevent and treat these diseases. Captopril (CAP) is an angiotensin-converting enzyme inhibitor (ACEI) that is widely used to treat diseases such as hypertension and heart failure. In this study, we found that CAP inhibits human lysozyme (HL) fibrillation through the combination techniques of biophysics and biochemistry. The data obtained by thioflavin-T (ThT) and Congo red (CR) assays showed that CAP hindered the aggregation of HL amyloid fibrils by reducing the ß-sheet structure of HL amyloid, with an IC50 value of 34.75 ± 1.23 µM. Meanwhile, the particle size of HL amyloid decreased sharply in a concentration-dependent approach after CAP treatment. According to the visualization of atomic force microscopy (AFM) and transmission electron microscopy (TEM), we verified that in the presence of CAP, the needle-like fibers of HL amyloid were significantly reduced. In addition, CAP incubation dramatically improved the cell survival rate exposed to HL fibers. Our studies also revealed that CAP could form hydrogen bonds with amino acid residues of Glu 35 and Ala 108 in the binding pocket of HL, which help in maintaining the α-helical structure of HL and then prevent the formation of amyloid fibrillation. It can be concluded that CAP has antiamyloidogenic activity and a protective effect on HL amyloid cytotoxicity.

LncRNA as a multifunctional regulator in cancer multi-drug resistance.

BACKGROUND: Malignant tumors have become the most dangerous disease in recent years. Chemotherapy is the most effective treatment for this disease; however, the problem of drug resistance has become even more common, which leads to the poor prognosis of patients suffering from cancers. Thus, necessary measures should be taken to address these problems at the earliest. Many studies have demonstrated that drug resistance is closely related to the abnormal expressions of long non-coding RNAs (lncRNAs). METHODS AND RESULTS: This review aimed to summarize the molecular mechanisms underlying the association of lncRNAs and the development of drug resistance and to find potential strategies for the clinical diagnosis and treatment of cancer drug resistance. Studies showed that lncRNAs can regulate the expression of genes through chromatin remodeling, transcriptional regulation, and post-transcriptional processing. Furthermore, lncRNAs have been reported to be closely related to the occurrence of malignant tumors. In summary, lncRNAs have gained attention in related fields during recent years. According to previous studies, lncRNAs have a vital role in several different types of cancers owing to their multiple mechanisms of action. Different mechanisms have different functions that could result in different consequences in the same disease. CONCLUSIONS: LncRNAs closely participated in cancer drug resistance by regulating miRNA, signaling pathways, proteins, cancer stem cells, pro- and ant-apoptosis, and autophagy. lncRNAs can be used as biomarkers of the possible treatment target in chemotherapy, which could provide solutions to the problem of drug resistance in chemotherapy in the future.

Icariin-induced inhibition of SIRT6/NF-κB triggers redox mediated apoptosis and enhances anti-tumor immunity in triple-negative breast cancer.

Abnormal activation of the nuclear factor-kappa B (NF-κB) signaling pathway is closely implicated in triple-negative breast cancer growth, metastasis, and tumor immune escape. In this study, the anti-cancer effects of icariin, a natural flavonol glycoside, toward breast cancer cells and the underlying mechanisms were investigated. This investigation showed that icariin selectively inhibited proliferation and triggered apoptosis in breast cancer cells in a concentration- and time-dependent manner, but exhibited little cytotoxicity in normal breast cells. Moreover, icariin induced cell apoptosis via a mitochondria-mediated pathway, as indicated by the upregulated ratio of Bax/Bcl-2 and reactive oxygen species induction. Importantly, icariin impaired the activation of the NF-κB/EMT pathway, as evidenced by upregulation of SIRT6, resulting in inhibition of migration and invasion of breast cancer cells. Additionally, oss-128167, an inhibitor of SIRT6, dramatically attenuated anti-migration and anti-invasion effects of icariin. Transcriptomic analysis verified that impairment of NF-κB led to the selective function of icariin in breast cancer cells. Notably, icariin exhibited a significant tumor growth inhibition and anti-pulmonary metastasis effect in a tumor mouse model of MDA-MB-231 and 4T1 cells by regulating the tumor immunosuppressive microenvironment. Together, these results showed that icariin could effectively trigger apoptosis and inhibit the migration of breast cancer cells via the SIRT6/NF-κB signaling pathway, suggesting that icariin might serve as a potential candidate drug for the treatment of breast cancer.

Traditional Chinese medicine foot bath combined with acupoint massage for the treatment of diabetic peripheral neuropathy: A systematic review and meta-analysis of 31 RCTs.

In this study, we aim to evaluate the efficiency and safety of traditional Chinese medicine foot bath combined with acupoint massage for the treatment of diabetic peripheral neuropathy. A total of eight online databases were searched to collect studies published up to February 2019. Study quality of each included article was evaluated by the Cochrane Collaboration risk of bias tool. Systematic reviews and meta-analyses were conducted based on the Cochrane systematic review method by using the RevMan 5.3 software. Traditional Chinese medicine foot bath combined with acupoint massage was the main therapy in experimental group. Interventions in control groups include western medicine, oral traditional Chinese medicine, other symptomatic treatment of western medicine, and blank control. Primary outcomes in this study include sensory nerve conduction velocity (SNCV), motor nerve conduction velocity (MNCV), total effective rate, and neuropathic syndrome score. Finally, 31 trials involving 3284 participants were included. The results of systematic reviews and meta-analyses showed that traditional Chinese medicine foot bath combined with acupoint massage was significantly better compared with the control groups in terms of the total effective rate, SNCV, MNCV, and neuropathic syndrome score. No case of adverse effect was reported. These findings show that traditional Chinese medicine foot bath combined with acupoint massage may be safer and more effective for the treatment of DPN. However, due to the low methodological quality, further research with randomized controlled trials (RCTs) of higher quality is required to prove its efficacy and better evidence for clinical treatment.

Effect of catgut implantation at acupoints for the treatment of allergic rhinitis: a randomized, sham-controlled trial.

BACKGROUND: The effect and safety of catgut implantation at acupoints o treat allergic rhinitis (ICD-10 code J30.4) remain controversial. Here, we used a sham catgut implantation group to determine whether catgut implantation at acupoints is an effective and safe treatment for allergic rhinitis. METHODS: A randomized double-blind clinical trial, with parallel groups was conducted. Skin prick and puncture test (SPT) was performed to confirm the diagnosis before enrollment. The participants received two sessions of treatments of active or sham catgut implantation at acupoints (once every two weeks) with a follow-up phase of 8 weeks. The visual analogue scale (VAS) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) were used to determine the severity of allergic rhinitis. The use of anti-allergic medication was used as a secondary indicator. The incidence of adverse events was also recorded and analyzed. RESULTS: An improvement of the VAS and RQLQ scores was observed in both the active and sham-controlled group sat four and eight weeks after the treatment in the self-control analysis. Comparison revealed no significant difference between the treatment and sham-controlled groups until 8 weeks after the 2-week treatment regimen (t = -2.424, P = 0.017). However, the RQLQ scores significantly differed between the two groups after 4 weeks of treatment completion (t = -2.045, P = 0.05) and this difference lasted until the end of 8-week follow-up (t = -2.246, P = 0.033). Throughout the treatment regimen, none of the participants took any relief medication, and no severe adverse events occurred. CONCLUSION: Our findings suggest that catgut implantation at acupoints is an effective and safe method for symptomatic treatment of allergic rhinitis. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TRC- 12002191 (Date of Registration: 2012-05-09).

Getting to Know the Effect Theory of Traditional Pediatric Tuina in the View of Modern Medicine in Three Minor Perspectives.

Pediatric tuina is a traditional Chinese medicine (TCM) modality that is well-accepted and applied in China currently. As a traditional medicine, it is based on TCM theories and clinical experience. In the TCM area, the "self-healing" system of the human body includes two aspects: self-regulation and adaptation, through which pediatric tuina could rectify dysfunctional states and guide the transition back to homeostasis. Pediatric tuina manipulations sufficiently, specifically, and accurately simulate certain sensory receptors in the skin, which in turn activates the internal self-healing function of the human body. We summarized the main opinions on pediatric tuina mechanism in ancient literature into three minor perspectives and demonstrated them by combining them with modern medical knowledge. First, children at a young age are more responsive to stimulations on the skin surface; second, the sensory receptors and pediatric tuina acupoints on the skin surface have a similar distribution pattern; third, the specific manipulations of pediatric tuina provide multiple stimuli that are detected by a variety of surface sensory receptors for information collection. Each point could be tested via clinical trials with appropriate-designed comparisons.

Inflammatory bowel disease and risk for hemorrhoids: a Mendelian randomization analysis.

Observational studies have reported an association between inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), and hemorrhoids (HEM). However, the presence of a causal relationship within this observed association remains to be confirmed. Consequently, we utilized the Mendelian randomization (MR) method to assess the causal effects of IBD on hemorrhoids. We validated the association between IBD and hemorrhoids in humans based on genome-wide association studies (GWAS) data. To investigate the causal relationship between IBD and hemorrhoids, we performed a two-sample Mendelian randomization study using training and validation sets. The genetic variation data for IBD, CD, UC, and hemorrhoids were derived from published genome-wide association studies (GWAS) of individuals of European. Two-sample Mendelian randomization and Multivariable Mendelian randomization (MVMR) were employed to determine the causal relationship between IBD (CD or UC) and hemorrhoids. Genetically predicted overall IBD was positively associated with hemorrhoids risk, with ORs of 1.02 (95% CIs 1.01-1.03, P = 4.39 × 10-4) and 1.02 (95% CIs 1.01-1.03, P = 4.99 × 10-5) in the training and validation sets, respectively. Furthermore, we found that CD was positively associated with hemorrhoids risk, with ORs of 1.02 (95% CIs 1.01-1.03, P = 4.12 × 10-6) and 1.02 (95% CIs 1.01-1.02, P = 3.78 × 10-5) for CD in the training and validation sets, respectively. In addition, we found that UC in the training set was positively associated with hemorrhoids risk (ORs 1.02, 95% CIs 1.01-1.03, P = 4.65 × 10-3), while no significant causal relationship between UC and hemorrhoids was shown in the validation set (P > 0.05). However, after MVMR adjustment, UC in the training set was not associated with an increased risk of hemorrhoids. Our study showed that there is a causal relationship between CD and hemorrhoids, which may suggest that clinicians need to prevent the occurrence of hemorrhoids in CD patients.

Preparation and evaluation of inhalable S-allylmercapto-N-acetylcysteine and nintedanib co-loaded liposomes for pulmonary fibrosis.

Orally marketed products nintedanib (NDNB) and pirfenidone (PFD) for pulmonary fibrosis (PF) are administered in high doses and have been shown to have serious toxic and side effects. NDNB can cause the elevation of galectin-3, which activates the NF-κB signaling pathway and causes the inflammatory response. S-allylmercapto-N-acetylcysteine (ASSNAC) can alleviate the inflammation response by inhibiting the TLR-4/NF-κB signaling pathway. Therefore, we designed and prepared inhalable ASSNAC and NDNB co-loaded liposomes for the treatment of pulmonary fibrosis. The yellow, spheroidal co-loaded liposomes with a particle size of 98.32±1.98 nm and zeta potential of -22.5 ± 1.58 mV were produced. The aerodynamic fine particle fraction (FPF) and mass median aerodynamic diameter (MMAD) of NDNB were >50 % (81.14 %±0.22 %) and <5 µm (1.79 µm±0.06 µm) in the nebulized liposome solution, respectively. The results showed that inhalation improved the lung deposition and retention times of both drugs. DSPE-PEG 2000 in the liposome formulation enhanced the mucus permeability and reduced phagocytic efflux mediated by macrophages. ASSNAC reduced the mRNA over-expressions of TLR-4, MyD88 and NF-κB caused by NDNB, which could reduce the NDNB's side effects. The Masson's trichrome staining of lung tissues and the levels of CAT, TGF-ß1, HYP, collagen III and mRNA expressions of Collagen I, Collagen III and α-SMA in lung tissues revealed that NDNB/Lip inhalation was more beneficial to alleviate fibrosis than oral NDNB. Although the dose of NDNB/Lip was 30 times lower than that in the oral group, the inhaled NDNB/Lip group had better or comparable anti-fibrotic effects to those in the oral group. According to the expressions of Collagen I, Collagen III and α-SMA in vivo and in vitro, the combination of ASSNAC and NDNB was more effective than the single drugs for pulmonary fibrosis. Therefore, this study provided a new scheme for the treatment of pulmonary fibrosis.

Optogenetics Neuromodulation of the Nose.

Recently developed optogenetic technology, which allows high-fidelity control of neuronal activity, has been applied to investigate the neural circuits underlying sensory processing and behavior. The nasal cavity is innervated by the olfactory nerve and trigeminal nerve, which are closely related to common symptoms of rhinitis, such as impairment of smell, itching, and sneezing. The olfactory system has an amazing ability to distinguish thousands of odorant molecules at trace levels. However, there are many issues in olfactory sensing mechanisms that need to be addressed. Optogenetics offers a novel technical approach to solve this dilemma. Therefore, we review the recent advances in olfactory optogenetics to clarify the mechanisms of chemical sensing, which may help identify the mechanism of dysfunction and suggest possible treatments for impaired smell. Additionally, in rhinitis patients, alterations in the other nerve (trigeminal nerve) that innervates the nasal cavity can lead to hyperresponsiveness to various nociceptive stimuli and central sensitization, causing frequent and persistent itching and sneezing. In the last several years, the application of optogenetics in regulating nociceptive receptors, which are distributed in sensory nerve endings, and amino acid receptors, which are distributed in vital brain regions, to alleviate overreaction to nociceptive stimuli, has gained significant attention. Therefore, we focus on the progress in optogenetics and its application in neuromodulation of nociceptive stimuli and discuss the potential clinical translation for treating rhinitis in the future.

Association of sugar consumption with risk of depression and anxiety: a systematic review and meta-analysis.

Background: Sugar consumption has increased dramatically around the world, and at the same time, the prevalence of mental illnesses such as depression and anxiety continues to increase. While previous research has explored the impact of various dietary factors on mental health, the specific impact of dietary sugar consumption on the risk of depression and anxiety disorders remains elusive. This study aimed to comprehensively assess this relationship through a systematic review and meta-analysis. Methods: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Network (CNKI), and WangFang were systematically searched for studies of the association between total dietary sugar intake and risk of depression and/or anxiety. The articles that meet the criteria are screened and included in the systematic review, and the data are extracted after assessing their quality. Stata 18.0 software was used for the meta-analysis. Results: Forty studies with 1,212,107 participants were included in the analysis. Results showed that sugar intake increased the risk of depression by 21% (OR = 1.21, 95% CI: 1.14, 1.27), while the overall association between sugar intake and anxiety risk was not statistically significant (OR = 1.11, 95% CI: 0.93, 1.28). Despite high heterogeneity (I 2 = 99.7%), the results were statistically significant (p < 0.000). Subgroup analyses showed that the association between sugar consumption and depression risk remains consistent across different study designs (cross-sectional, cohort, and case-control studies) and different sample sizes (<5,000, 5,000-10,000, >10,000). Women have a higher risk of depression than men (OR = 1.19, 95% CI: 1.04, 1.35). Among the different exposure measures, the Food Frequency Questionnaire (FFQ) showed the most significant effect (OR = 1.32, 95% CI: 1.08, 1.67, I 2 = 99.7%, p < 0.000). The measuring tool of subgroup analysis showed that there was a significant correlation between sugar intake and risk of depression, PHQ-9 (OR = 1.29, 95% CI: 1.17, 1.42, I2 = 86.5%, p < 0.000), and CES-D (OR = 1.28, 95% CI: 1.14, 1.44, I 2 = 71.3%, p < 0.000). High-quality cross-sectional and cohort studies showed a significant association between sugar intake and depression risk, with most results being robust. While the overall analysis of sugar intake and anxiety risk was not significant, some subgroups approached significance, particularly in studies with a sample size of <5,000 (OR = 1.14, 95% CI: 0.89, 1.46) and studies using the FFQ questionnaire (OR = 1.31, 95% CI: 0.90, 1.89). Conclusion: Total dietary sugar consumption was significantly associated with increased risk of depression in the general population, whereas the association with risk of anxiety was not significant. Further high-quality studies are needed to verify these associations and ensure their reliability. This study highlights the impact of dietary sugar intake on mental health, identifies potentially high-risk groups through subgroup analysis, and provides new insights into the prevention of depression and anxiety. Systematic review registration: CRD42024540548.

Physical activity and risk of Parkinson's disease: an updated systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Although recent meta-analyses have shown that the association between physical activity (PA) and the risk of developing Parkinson's disease (PD) is influenced by gender differences, a growing number of studies are revealing the general applicability of this association across genders. This study aimed to reassess the association and dose-response relationship between PA and PD risk in populations. METHODS: A systematic search of PubMed, Embase, Cochrane Library, and Web of Science databases was conducted in this study from inception to February 1, 2024, without language restrictions. Stratified analyses were conducted to explore the association between PA and PD risk, combining multivariate-adjusted effect estimates via random-effects models, and to validate the dose-response relationship between the two. RESULTS: This study included 21 observational studies, comprising 13 cohort studies and 8 case-control studies. The pooled analysis revealed that PA significantly reduced the risk of developing PD [relative risk (RR) = 0.77, 95% CI 0.70-0.85]. In addition, the dose-response analysis revealed both linear and nonlinear associations, with linear results indicating a 9% reduction in PD risk for every 10 MET-h/wk increase in PA. The study also demonstrated that the protective effect of PA against PD was significant for both sexes. Moreover, no statistically significant effects of PA on preventing PD were observed in individuals with a BMI > 26 (RR = 0.35, 95% CI 0.12-1.02) or in Asian populations (RR = 0.78, 95% CI 0.60-1.01); however, the trends suggest potential protective effects, warranting further investigation. Sensitivity analyses confirmed the robustness of these findings. CONCLUSION: This meta-analysis produced substantial evidence to reaffirm the protective effect of high PA on PD across various population groups and the inverse dose-response relationship with PD risk, and to validate the protective effect of PA among different demographic groups.

A cisplatin and disulphiram co-loaded inclusion complex overcomes drug resistance by inhibiting cancer cell stemness in non-small cell lung cancer.

Introduction: Non-small cell lung cancer (NSCLC) accounting for about 80-85% of all lung cancer cases is one of the fastest-growing malignancies in terms of incidence and mortality worldwide and is commonly treated with cisplatin (DDP). Although treatment may initially be effective, the DDP therapy often leads to the development of chemoresistance and treatment failure. Disulphiram (DSF), an old alcohol-aversion drug, has been revealed to help reverse drug resistance in several cancers. In addition, several studies have shown a close relationship between drug resistance and cancer cell stemness.Methods: In this study, DDP and DSF were embedded in hydroxypropyl-ß-cyclodextrin (CD) to prepare a co-loaded inclusion complex of DDP and DSF (DDP-DSF/CD) with enhanced solubility and therapeutic effects. The effects and mechanism of DSF on the DDP resistance from the perspective of cancer cell stemness were determined.Results: Our data show that DDP-DSF/CD increased cytotoxicity and apoptosis of DDP-resistant A549 (A549/DDP) cells, inhibited stem cell transcriptional regulatory genes and drug resistance-associated proteins and reversed the DDP resistance in vitro and in vivo.Discussion: Overall, DDP-DSF/CD could be a promising formulation for the reversal of DDP resistance in NSCLC by inhibiting cancer cell stemness.

Extending the Grading of Recommendations Assessment, Development and Evaluation (GRADE) in Traditional Chinese Medicine (TCM): The GRADE-TCM.

AIM: To extend and form the "Grading of Recommendations Assessment, Development and Evaluation in Traditional Chinese Medicine" (GRADE-TCM). METHODS: Methodologies were systematically reviewed and analyzed concerning evidence-based TCM guidelines worldwide. A survey questionnaire was developed based on the literature review and open-end expert interviews. Then, we performed expert consensus, discussion meeting, opinion collection, external examination, and the GRADE-TCM was formed eventually. RESULTS: 265 Chinese and English TCM guidelines were included and analyzed. Five experts completed the open-end interviews. Ten methodological entries were summarized, screened and selected. One round of consensus was conducted, including a total of 22 experts and 220 valid questionnaire entries, concerning 1) selection of the GRADE, 2) GRADE-TCM upgrading criteria, 3) GRADE-TCM evaluation standard, 4) principles of consensus and recommendation, and 5) presentation of the GRADE-TCM and recommendation. Finally, consensus was reached on the above 10 entries, and the results were of high importance (with voting percentages ranging from 50 % to 81.82 % for "very important" rating) and strong reliability (with the Cr ranging from 0.93 to 0.99). Expert discussion meeting (with 40 experts), opinion collection (in two online platforms) and external examination (with 14 third-party experts) were conducted, and the GRADE-TCM was established eventually. CONCLUSION: GRADE-TCM provides a new extended evidence-based evaluation standard for TCM guidelines. In GRADE-TCM, international evidence-based norms, characteristics of TCM intervention, and inheritance of TCM culture were combined organically and followed. This is helpful for localization of the GRADE in TCM and internationalization of TCM guidelines.

[Effects of Baidanhuang lavage fluid nasal irrigation on the postoperative patients with chronic rhinosinusitis with nasal polyps].

OBJECTIVE: To observe the clinical efficacy of Baidanhuang lavage fluid nasal irrigation (BLFNI) on postoperative patients with chronic sinusitis with nasal polyps (CRwNP). METHODS: Ninety postoperative patients with CRwNP were randomly assigned to two groups, the treatment group (60 cases) and the control group (30 cases). After nasal endoscopic surgery, all patients received routine therapies, while the nasal cavity perfusion device was used to irrigate. Patients in the treatment group were treated with BLFNI, while those in the control group were irrigated with physiologic saline with dexamethasone and gentamycin. The physic liquor was maintained in the nasal cavity for 15 min, 14 days as one therapeutic course: once per 3 days in first treatment course; once per 5 days in the second treatment course; once per 7 days in the third treatment course. The irrigation times gradually reduced as time went by. The VAS scoring was performed in four clinical symptoms, such as nasal obstruction, rhinorrhea, olfaction disorders, discomforts or pain in the face or head. The Lund-Kenenedy quantification scoring method was used for nasal endoscopy to assess the polyps size, mucous membrane, scar, surface scab, and quality of life (QOL). The SNOT-20 rating scales were filled to investigate the QOL. All the assessments were carried out before surgery, 1.5, 3, and 6 months, respectively. The comprehensive efficacy assessment was conducted 1 year later. RESULTS: The 1-year cure rate was 79.25% in the treatment group and 76.92% in the control group, and the total effective rate was 90.57% in the treatment group and 84.62% in the control group. There was no statistical difference between the two groups (P > 0.05). The nasal cavity cleaning time and the epithelization time was (2.15 +/- 0.13) weeks and (9.17 +/- 1.67) weeks respectively in the treatment group, earlier than those in the control group [(2.65 +/- 0.15) weeks and (10.71 +/- 3.12) weeks, P < 0.05]. At week eight 22 patients in the treatment group ended the lavage due to recovery, while 5 patients in the control group ended the lavage, showing statistical difference (P < 0.05). Compared with the control group, better results were obtained in the treatment group in relieving the total VAS score at postoperative 6 weeks and 3 months, in the single score of symptoms at 3 months after operation, the rhinorrhea at postoperative 6 months and 1 year (P < 0.05). The total endoscopic score, and the single score for nasal mucous membrane edema, and nasal secretion at postoperative 1.5 month were lower in the treatment group than in the control group (P < 0.05). The total score of SNOT-20 questionnaire, and the integrals for five major indicators at postoperative 1.5 and 3 months were lower in the treatment group than in the control group (P < 0.05). CONCLUSIONS: The perioperative application of BLFNI could alleviate postoperative mucosal inflammation, shorten the cavity cleaning time, speed up the process of epithelization, improve the QOL, and elevate the operative efficacy. Its therapeutic roles were more prominent within perioperative 1.5-3 months.

Prevalence of hearing loss in COVID-19 patients: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: 'Hearing loss' has been reported as a clinical atypical symptom in some COVID-19 patients. We searched and collated the existing literature for a systematic review and meta-analysis to assess the prevalence of hearing loss during the COVID-19 epidemic. METHODS: An exhaustive search of the PubMed, Embase, Web of Science, China National Knowledge Infrastructure and other sources from the inception of the database until 31st December 2022. The Search terms were set to: 'COVID-19', 'SARS-CoV-2', '2019-nCoV', 'hearing impairment', 'hearing loss', 'auditory dysfunction'. The literature data meeting the inclusion criteria were extracted and analyzed. Prevalence was pooled from individual studies using a randomized effects meta-analysis. RESULTS: A total of 22 studies were included in the final analysis, involving 14281 patients with COVID-19 infection, of which 482 patients had varying degrees of hearing loss. Our final meta-analysis demonstrated that the prevalence of hearing loss in COVID-19-positive patients was 8.2% (95%CI 5.0-12.1). Subgroup analysis of age showed that the prevalence of middle-aged and older patients aged 50-60 and over 60 years was 20.6% and 14.8%, respectively, which was significantly higher than that of patients aged 30-40 (4.9%) and 40-50 years (6.0%). CONCLUSION: Hearing loss is one of the clinical symptoms of COVID-19 infection, compared with other diseases, it is less likely to attract the attention of clinical experts or researchers. Raising awareness of this disease can not only enable early diagnosis and treatment of hearing loss, and improve the quality of life of patients, but also enhance our vigilance against virus transmission, which has important clinical and practical significance.

Role of lncRNAs in the pathogenic mechanism of human decreased ovarian reserve.

Decreased ovarian reserve (DOR) is defined as a decrease in the quality and quantity of oocytes, which reduces ovarian endocrine function and female fertility. The impaired follicular development and accelerated follicle atresia lead to a decrease in the number of follicles, while the decline of oocyte quality is related to the disorder of DNA damage-repair, oxidative stress, and the dysfunction of mitochondria. Although the mechanism of DOR is still unclear, recent studies have found that long non-coding RNA (lncRNA) as a group of functional RNA molecules participate in the regulation of ovarian function, especially in the differentiation, proliferation and apoptosis of granulosa cells in the ovary. LncRNAs participate in the occurrence of DOR by affecting follicular development and atresia, the synthesis and secretion of ovarian hormones. This review summarizes current research on lncRNAs associated with DOR and reveals the potential underlying mechanisms. The present study suggests that lncRNAs could be considered as prognostic markers and treatment targets for DOR.