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Su Yuan,1,2 Biao Zuo,2,3 Si-Cong Zhou,1,2 Meng Wang,2,3 Kai-Yue Tan,2,3 Zhi-Wei Chen,2,3 Wen-Fu Cao1– 3 1Department of Combination of Chinese and Western Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing, People’s Republic of China; 3College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Wen-Fu Cao, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, People’s Republic of China, Email caowenfu20220401@163.comPurpose: Our study aims to reveal the pharmacological mechanism of Astragaloside IV in the treatment of pulmonary fibrosis(PF) through network pharmacology and experimental validation.Methods: We first determined the in vivo anti-pulmonary fibrosis effect of Astragaloside IV by HE, MASSON staining, and lung coefficients, then used network pharmacology to predict the signaling pathways and molecularly docked key pathway proteins, and finally validated the results by in vivo and in vitro experiments.Results: In in vivo experiments, we found that Astragaloside IV improved body weight (P < 0.05), increased lung coefficients (P < 0.05), and reduced lung inflammation and collagen deposition in mice with pulmonary fibrosis. The network pharmacology results showed that Astragaloside IV had 104 cross-targets with idiopathic pulmonary fibrosis, and the results of KEGG enrichment analysis indicated that cellular senescence could be an important pathway for Astragaloside IV in the treatment of pulmonary fibrosis. Astragaloside IV also bound well to senescence-associated proteins, according to molecular docking results. The results of both in vivo and in vitro experiments showed that Astragaloside IV significantly inhibited senescence protein markers such as P53, P21, and P16 and delayed cellular senescence (P < 0.05). In in vivo experiments, we also found that Astragaloside IV reduced the production of SASPs (P < 0.05), and in in vitro experiments, Astragaloside IV also reduced the production of ROS. In addition, by detecting epithelial-mesenchymal transition(EMT)-related marker protein expression, we also found that Astragaloside IV significantly inhibited the development of EMT in both in vivo and in vitro experiments (P < 0.05).Conclusion: Our research found that Astragaloside IV could alleviate bleomycin-induced PF by preventing cellular senescence and EMT.Keywords: astragaloside IV, pulmonary fibrosis, network pharmacology, cellular senescence, epithelial-mesenchymal transition

An Wen,1,2 Er-Ling Leng,3 Wen-Feng Cao,1,2 Zheng-bing Xiang,1,2 Wei Rao,1,2 Wen Cai,1,2 Yong-Liang Zhou,1,2 Fan Hu,1,2 Ling-feng Wu,1,2 Ping Zhang,1,2 Shi-Min Liu1,2 1Department of Neurology, Jiangxi Provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), Nanchang, People’s Republic of China; 2Institution of Neurology, Jiangxi Provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), Nanchang, People’s Republic of China; 3Department of Pediatrics, Jiangxi provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), Nanchang, People’s Republic of ChinaCorrespondence: Shi-Min Liu, Department of Neurology, Jiangxi provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), No. 92 Aiguo Road, Nanchang, 330006, People’s Republic of China, Tel +791-8772-1401, Email aifeng420@163.comObjective: Central nervous system (CNS) infection has a high incidence and mortality worldwide. Tuberculous meningitis (TBM) accounts for approximately 5– 6% of all extrapulmonary tuberculosis (TB), and is considered an extremely lethal form of CNS TB, which has become an important threat to human health. Anemia is a common symptom of TB, and its prevalence is generally higher in patients with TBM than in other meningitis patients and healthy individuals. Anemia can increase a person’s susceptibility to common infectious diseases, including TB, by compromising the immune system. Information regarding anemia during the hospitalization of TBM is still scarce in China. This study aimed to describe in detail the prevalence of anemia in patients with TBM in Southern China and its association with the clinical forms of TB, as well as other characteristics of these patients.Methods: We conducted a retrospective analysis of patients diagnosed with TBM at two tertiary hospitals in southern China. The demographic characteristics, clinical characteristics, and laboratory results of 114 patients with TBM were collected. Multivariate logistic regression analysis was performed to explore the risk factors for anemia in patients with TBM.Results: Electronic medical record data of adult patients diagnosed with TBM from January 2004 to December 2019 were reviewed. Among 134 patients with TBM, 20 were excluded and 114 were analyzed, of whom 33 had anemic, the prevalence rate of anemia was 28.9%. Among patients with anemia, 51.5% had hypochromic microcytic anemia, 33.3% had normochromic normocytic anemia, and 15.2% had macrocytic anemia. Fever duration, TBM grade III and ESR were found to be independent predictors of anemia.Conclusion: Anemia was highly prevalent in patients with TBM, mainly hypochromic microcytic anemia. Besides, Fever duration, TBM grade III and ESR are predictors of anemia in patients with TBM.Keywords: tuberculosis, tuberculous meningitis, anemia, risk factors, prediction

An Wen,1,2 Wen-Feng Cao,1,2 Shi-Min Liu,1,2 Yong-Liang Zhou,1,2 Zheng-Bing Xiang,1,2 Fan Hu,1,2 Ling-Feng Wu,1,2 Wen Cai,1,2 Er-Ling Leng3 1Department of Neurology, Jiangxi Provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), Nanchang, People’s Republic of China; 2Institution of Neurology, Jiangxi Provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), Nanchang, People’s Republic of China; 3Department of Pediatrics, Jiangxi Provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), Nanchang, People’s Republic of ChinaCorrespondence: Er-Ling Leng, Department of Pediatrics, Jiangxi Provincial People’s Hospital (The First Affiliated Hospital of Nanchang Medical College), No.92 Aiguo Road, Nanchang, 330006, People’s Republic of China, Tel +86791-8772-1401, Email wenan666@sina.comObjective: Tuberculous meningitis (TBM) is a common form of central nervous system (CNS) tuberculosis (TB). Cranial nerve palsy is a serious complication of TBM. Literature regarding this subject is still limited in China. This study evaluated the incidence of cranial nerve palsy in patients with TBM in South China, its association with the clinical forms of TB, and other patient characteristics.Methods: A retrospective chart review of patients with a diagnosis of TBM between January 2004 and December 2019 was conducted, and the demographic characteristics, clinical characteristics, and laboratory results of 114 patients were collected and followed up for 3 months. A multivariate logistic regression analysis model was used to explore the risk factors of cranial nerve palsy in patients with TBM.Results: A total of 114 patients were enrolled in this study. Cranial nerve palsy was observed in approximately 38 (33.3%) of TBM patients. Among them, 13 (28.3%) had optic nerve palsy, 24 (52.2%) had oculomotor nerve palsy, 5 (10.9%) had abducens nerve palsy, 2 (4.3%) had auditory nerve palsy, 1 (2.2%) had glossopharyngeal nerve palsy, and 1 (2.2%) had vagus nerve palsy. Using logistic regression analysis, focal neurological deficit, extracranial TB and cerebrospinal fluid (CSF) total white cell count (WCC) were shown to be risk factors for cranial nerve palsy.Conclusion: The prevalence rate of cranial nerve palsy was 33.3% in patients with TBM. Focal neurological deficits, extracranial TB and CSF total WCC are important predictors of cranial nerve palsy in patients with TBM.Keywords: tuberculous meningitis, tuberculosis, cranial nerve palsy, risk factors, prediction

Rationale: Cerebral infarction is a common ischemic cerebrovascular disease, associated with high rates of morbidity, disability, and recurrence, that can seriously affect patient physical and mental health, as well as quality of life. Carotid artery stenosis is an independent risk factor of cerebral infarction. Following rapid developments in interventional technology and materials science, carotid artery stenting has arisen an important treatment option for carotid artery stenosis. However, surgery is associated with complications, such as postoperative hyperperfusion syndrome, which poses a serious threat to the life and health of patients. Staged angioplasty (SAP), that is, one-time revascularization of the carotid artery stenting, is divided into 2 stages. This method reduces the occurrence of hyperperfusion syndrome after stenting by increasing the ipsilateral cerebral blood flow in stages and gradually increasing the cerebral perfusion pressure., Patient Concerns: Herein, we present 2 cases of elderly patients with severe carotid artery stenosis who underwent SAP to prevent hyperperfusion syndrome., Diagnoses: The final diagnosis was based on cervical vascular color Doppler ultrasonography, cervical vascular magnetic resonance angiography, and cerebral vascular digital subtraction angiography., Intervention: Both patients with severe carotid artery stenosis underwent a staged intravascular intervention., Outcomes: Both patients were followed up for 1 year, with neither developing any new cerebral infarction or recurrent stent restenosis., Lessons: When treating SAP, it is crucial to consider that patients with unstable carotid plaques may not be suitable for staging. Additionally, during phase II carotid stenting, it is important to assess any changes in the arterial morphology and select the appropriate device accordingly., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: To assess the clinical and safety outcomes of endovascular treatment (EVT) administered more than 24 h after the onset of symptoms in patients with acute ischemic stroke resulting from anterior circulation large-vessel occlusion or stenosis (AIS-ACLVO/S)., Methods: We enrolled consecutive AIS-ACLVO/S patients who received EVT in our hospital between January 2019 and February 2022 and divided them into two groups based on the time from AIS onset to EVT: EVT < 24 h group and EVT >24 h group. The successful reperfusion (modified thrombolysis in cerebral infarction, [mTICI] ≥2b), 90-day modified Rankin Scale score (mRS), intracranial hemorrhage (ICH), and symptomatic ICH (sICH), as well as mortality, were analyzed in the two groups of patients., Results: A total of 239 patients were included in the study, with 214 patients in the EVT < 24 h group (67.8 ± 0.8 years, 126 males) and 25 patients in the EVT > 24 h group (62.80 ± 2.0 years, 22 males). Both groups were similar in terms of hypertension, diabetes history, responsible vessels, and Alberta stroke program early computed tomography scores ( p  > 0.05). However, the EVT < 24 h group had significantly higher age, history of atrial fibrillation, proportion of patients receiving intravenous thrombolysis, and NIHSS scores before EVT than the EVT > 24 h group. AIS etiology differed between the groups, with more cases of large artery atherosclerosis in the EVT > 24-h group and more cases of cardioembolism in the EVT < 24-h group. Successful reperfusion (mTICI ≥2b), ICH, and sICH were similar between the groups. The 90-day functional independence rate (mRS ≤ 2) was significantly higher in the EVT > 24-h than in the EVT < 24-h group (80% vs. 39.7%, p  < 0.001), while the 90-day mortality rate was lower in the EVT > 24-h group (0% vs. 24.8%, p  < 0.001)., Conclusion: In our study, we found that EVT beyond 24 h of symptom onset in patients selected with multimodal MR screening, was associated with high functional independence rates and low mortality. Larger or randomized studies are needed to confirm these findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wen, Cao, Zhao, Wu, Zhou, Xiang, Rao and Liu.)

Objective: The utility of metagenomic next-generation sequencing (mNGS) in the diagnosis of tuberculous meningitis (TBM) remains uncertain. We performed a meta-analysis to comprehensively evaluate its diagnostic accuracy for the early diagnosis of TBM., Methods: English (PubMed, Medline, Web of Science, Cochrane Library, and Embase) and Chinese (CNKI, Wanfang, and CBM) databases were searched for relevant studies assessing the diagnostic accuracy of mNGS for TBM. Review Manager was used to evaluate the quality of the included studies, and Stata was used to perform the statistical analysis., Results: Of 495 relevant articles retrieved, eight studies involving 693 participants (348 with and 345 without TBM) met the inclusion criteria and were included in the meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver-operating characteristic curve of mNGS for diagnosing TBM were 62% (95% confidence interval [CI]: 0.46-0.76), 99% (95% CI: 0.94-1.00), 139.08 (95% CI: 8.54-2266), 0.38 (95% CI: 0.25-0.58), 364.89 (95% CI: 18.39-7239), and 0.97 (95% CI: 0.95-0.98), respectively., Conclusions: mNGS showed good specificity but moderate sensitivity; therefore, a more sensitive test should be developed to assist in the diagnosis of TBM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xiang, Leng, Cao, Liu, Zhou, Luo, Hu and Wen.)

Tuberculous meningitis (TBM) is the most common type of central nervous system tuberculosis (TB) and has the highest mortality and disability rate. Early diagnosis is key to improving the prognosis and survival rate of patients. However, laboratory diagnosis of TBM is often difficult due to its paucibacillary nature and sub optimal sensitivity of conventional microbiology and molecular tools which often fails to detect the pathogen. The gold standard for TBM diagnosis is the presence of MTB in the CSF. The recognised methods for the identification of MTB are acid-fast bacilli (AFB) detected under CSF smear microscopy, MTB cultured in CSF, and MTB detected by polymerase chain reaction (PCR). Currently, many studies consider that all diagnostic techniques for TBM are not perfect, and no single technique is considered simple, fast, cheap, and efficient. A definite diagnosis of TBM is still difficult in current clinical practice. In this review, we summarise the current state of microbiological and molecular biological diagnostics for TBM, the latest advances in research, and discuss the advantages of these techniques, as well as the issues and challenges faced in terms of diagnostic effectiveness, laboratory infrastructure, testing costs, and clinical expertise, for clinicians to select appropriate testing methods., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cao, Leng, Liu, Zhou, Luo, Xiang, Cai, Rao, Hu, Zhang and Wen.)

Background: For clear cell renal cell carcinoma (ccRCC) with cystic component similar to multilocular cystic renal neoplasm of low malignant potential (MCRN-LMP) and solid low-grade component simultaneously, we propose the designation "ccRCC with cystic component similar to MCRN-LMP" and to study the relationship between MCRN-LMP and it., Methods: Twelve cases of MCRN-LMP and 33 cases of ccRCC with cystic component similar to MCRN-LMP were collected from 3,265 consecutive RCCs to compare them in clinicopathological features, immunohistochemical findings (PAX8, CA-IX, CK7, Vimentin, CD10, P504s, TFE3, 34βE12) and prognosis., Results: There was no significant difference in age, sex ratio, tumor size, treatment, grade and stage between them (P > 0.05). All ccRCCs with cystic component similar to MCRN-LMP coexisted with MCRN-LMP and solid low-grade ccRCCs, and MCRN-LMP component ranged from 20 to 90% (median, 59%). The positive ratio of CK7 and 34βE12 in MCRN-LMPs and ccRCCs' cystic parts was significantly higher than that in ccRCCs' solid parts, but the positive ratio of CD10 in MCRN-LMPs and ccRCCs' cystic parts was significantly lower than that in ccRCCs' solid parts (P < 0.05). There was no significant difference of all immunohistochemistry profiles between MCRN-LMPs and ccRCCs' cystic parts (P > 0.05). No patient developed recurrence or metastasis., Conclusions: MCRN-LMP and ccRCC with cystic component similar to MCRN-LMP have similarity and homology in clinicopathological features, immunohistochemical findings and prognosis, and form a low-grade spectrum with indolent or low malignant potential behavior. The ccRCC with cystic component similar to MCRN-LMP may be a rare pattern of cyst-dependent progression from MCRN-LMP., (© 2023. The Author(s).)

Overview: In treating pulmonary fibrosis (PF), traditional Chinese medicine (TCM) has received much attention, but its mechanism is unclear. The pharmacological mechanisms of TCM can be explored through network pharmacology. However, due to its virtual screening properties, it still needs to be verified by in vitro or in vivo experiments. Therefore, we investigated the anti-PF mechanism of Yiqi Huayu Decoction (YHD) by combining network pharmacology with in vivo experiments. Methods: Firstly, we used classical bleomycin (BLM)-induced rat model of PF and administrated fibrotic rats with YHD (low-, medium-, and high-dose). We comprehensively assessed the treatment effect of YHD according to body weight, lung coefficient, lung function, and histopathologic examination. Second, we predict the potential targets by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) combined with network pharmacology. In brief, we obtained the chemical ingredients of YHD based on the UHPLC-MS/MS and TCMSP database. We collected drug targets from TCMSP, HERB, and Swiss target prediction databases based on active ingredients. Disease targets were acquired from drug libraries, Genecards, HERB, and TTD databases. The intersecting targets of drugs and disease were screened out. The STRING database can obtain protein-protein interaction (PPI) networks and hub target proteins. Molecular Complex Detection (MCODE) clustering analysis combined with enrichment analysis can explore the possible biological mechanisms of YHD. Enrichment analyses were conducted through the R package and the David database, including the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Reactome. Then, we further validated the target genes and target proteins predicted by network pharmacology. Protein and gene expression detection by immunohistochemistry, Western blot (WB), and real-time quantitative PCR (rt-qPCR). Results: The results showed that high-dose YHD effectively attenuated BLM-induced lung injury and fibrosis in rats, as evidenced by improved lung function, relief of inflammatory response, and reduced collagen deposition. We screened nine core targets and cellular senescence pathways by UHPLC-MS/MS analysis and network pharmacology. We subsequently validated key targets of cellular senescence signaling pathways. WB and rt-qPCR indicated that high-dose YHD decreased protein and gene expression of senescence-related markers, including p53 (TP53), p21 (CDKN1A), and p16 (CDKN2A). Increased reactive oxygen species (ROS) are upstream triggers of the senescence program. The senescence-associated secretory phenotypes (SASPs), containing interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-β1 (TGF-β1), can further exacerbate the progression of senescence. High-dose YHD inhibited ROS production in lung tissue and consistently reduced the SASPs expression in serum. Conclusion: Our study suggests that YHD improves lung pathological injury and lung function in PF rats. This protective effect may be related to the ability of YHD to inhibit cellular senescence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zuo, Zuo, Du, Yuan, Xuan, Zhang, Chen and Cao.)

Aim: Gut microbiota is of crucial importance to cardiac health. Astragaloside IV (AS-IV) is a main active ingredient of Huangqi, a traditional edible and medicinal herb that has been shown to have beneficial effects on cardiac fibrosis (CF). However, it is still uncertain whether the consumption of AS-IV alleviates cardiac fibrosis through the gut microbiota and its metabolites. Therefore, we assessed whether the anti-fibrosis effect of AS-IV is associated with changes in intestinal microbiota and fecal metabolites and if so, whether some specific gut microbes are conducive to the benefits of AS-IV., Methods: Male C57BL-6J mice were subcutaneously injected with isoprenaline (ISO) to induce cardiac fibrosis. AS-IV was administered to mice by gavage for 14 days. The effects of AS-IV on cardiac function, myocardial enzyme, cardiac weight index (CWI), and histopathology of ISO-induced CF mice were investigated. Moreover, 16S rRNA sequencing was used to establish gut-microbiota profiles. Fecal-metabolites profiles were established using the liquid chromatograph-mass spectrometry (LC-MS)., Results: AS-IV treatment prevented cardiac dysfunction, ameliorated myocardial damage, histopathological changes, and cardiac fibrosis induced by ISO. AS-IV consumption increased the richness of Akkermansia, Defluviitaleaceae&#95;UCG-011, and Rikenella. AS-IV also modulated gut metabolites in their feces. Among 141 altered gut metabolites, amino acid production was sharply changed. Furthermore, noticeable correlations were found between several specific gut microbes and altered fecal metabolites., Conclusions: An increase of Akkermansia, Defluviitaleaceae&#95;UCG-011, and Rikenella abundance, and modulation of amino acid metabolism, may contribute to the anti-fibrosis and cardiac protective effects of Astragaloside IV., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Du, Shi, Chen, Hu, Zuo, Xiong and Cao.)

Background: In this study, we evaluated and compared the accuracy of blood and cerebrospinal fluid (CSF) interferon release tests [interferon-gamma release assays (IGRAs)] in the diagnosis of tuberculous meningitis (TBM) by a meta-analysis of the relevant literature., Methods: We searched for studies published before 2021 in Medline, Embase, the Cochrane database, and Chinese databases. All studies used the QuantiFERON-TB Gold In-Tube and/or T-SPOT.TB method. Blood and/or CSF tests that met the guidelines for the quality assessment of studies with diagnostic accuracy were included. We used the revised diagnostic accuracy study quality assessment to assess the quality of the included studies. Begg's funnel plots were used to assess publication bias in the meta-analysis of the diagnostic studies, and statistical analyses were performed by using Stata (Version 12) software., Results: A total of 12 blood and/or CSF IGRA studies were included in this meta-analysis, with 376 patients and 493 controls. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curve (SROC) of the blood IGRAs in the pooled data from 12 studies were 74% (95% CI: 0.65-0.82), 78% (95% CI: 0.68-0.86), 3.38 (95% CI 2.26-5.06), 0.33 (95% CI: 0.23-0.46), 10.25 (95% CI: 5.46-19.25), and 0.83 (95% CI: 0.79-0.86), respectively. For CSF IGRAs, these values for the pooled data from the 10 studies included were 79% (95% CI: 0.71-0.85), 95% (95% CI: 0.88-0.98), 16.30 (95% CI 6.5-40.83), 0.22 (95% CI: 0.16-0.31), 57.93 (95% CI: 22.56-148.78), and 0.91 (95% CI: 0.88-0.93), respectively., Conclusion: CSF IGRAs exhibited a better diagnostic accuracy than blood IGRAs in diagnosing TBM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wen, Leng, Liu, Zhou, Cao, Yao and Hu.)

Background: Tuberculous meningitis (TBM) is the most serious form of extrapulmonary tuberculosis caused by Mycobacterium tuberculosis , and is characterized by high morbidity and mortality. Unfortunately, it is difficult to distinguish TBM from bacterial meningitis (BM) based on clinical features alone. The latest diagnostic tests and neuroimaging methods are still not available in many developing countries. This study aimed to develop a simple diagnostic algorithm based on clinical and laboratory test results as an early predictor of TBM in South China., Methods: A retrospective study was conducted to compare the clinical and laboratory characteristics of 114 patients with TBM and 47 with BM. Multivariate logistic regression analysis was performed on the characteristics of independently predicted TBM to develop a new diagnostic rule., Results: Five characteristics were predictive of a diagnosis of TBM: duration of symptoms before admission; tuberculous symptoms; white blood cell (WBC) count, total cerebrospinal fluid WBC count, and cerebrospinal fluid chloride concentration. The sensitivity and specificity of the new scoring system developed in this study were 81.6 and 93.6%, respectively., Conclusion: The new scoring system proposed in this study can help physicians empirically diagnose TBM and can be used in countries and regions with limited microbial and radiological resources., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wen, Liu, Cao, Zhou, Luo, Xiang, Hu, Zhang and Leng.)

Background: The outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread to become a global emergency since December 2019. Chinese herbal medicine plays an important role in the treatment of COVID-19. Chinese herbal medicine honeysuckle is an extremely used traditional edible and medicinal herb. Many trials suggest that honeysuckle has obtained a good curative effect for COVID-19; however, no systematic evaluation on the clinical efficacy of honeysuckle in the treatment of COVID-19 is reported. This study aimed to evaluate the efficacy and safety of Chinese herbal medicine honeysuckle in the treatment of COVID-19. Methods: Seven electronic databases (PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and China Biology Medicine) were searched to identify randomized controlled trials (RCTs) of honeysuckle for adult patients (aged ≥ 18 years) with COVID-19. The Cochrane Risk of Bias Tool was applied to assess the methodological quality of trials. Review Manager 5.3 software was used for data analysis. Results: Overall, nine RCTs involving 1,286 patients were enrolled. Our meta-analyses found that combination therapy of honeysuckle and conventional therapy was more effective than conventional therapy alone in lung computed tomography (CT) [relative risk (RR) = 1.24, 95% confidence interval (95%CI) (1.12, 1.37), P < 0.0001], clinical cure rate [RR = 1.21, 95%CI (1.12, 1.31), P < 0.00001], and rate of conversion to severe cases [RR = 0.50, 95%CI (0.33, 0.76), P = 0.001]. Besides, combination therapy can improve the symptom score of fever, cough reduction rate, symptom score of cough, and inflammatory biomarkers (white blood cell (WBC) count; C-reactive protein (CRP)) ( P < 0.05). Conclusion: Honeysuckle combined with conventional therapy may be beneficial for the treatment of COVID-19 in improving lung CT, clinical cure rate, clinical symptoms, and laboratory indicators and reducing the rate of conversion to severe cases. Besides, combination therapy did not increase adverse drug events. More high-quality RCTs are needed in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Du, Shi, Cao, Chen, Zuo and Hu.)

Diabetic nephropathy (DN), a common microvascular complication of diabetes, is one of the main causes of end-stage renal failure (ESRD) and imposes a heavy medical burden on the world. Yiqi Jiedu Huayu decoction (YJHD) is a traditional Chinese medicine formula, which has been widely used in the treatment of DN and has achieved stable and reliable therapeutic effects. However, the mechanism of YJHD in the treatment of DN remains unclear. This study aimed to investigate the mechanism of YJHD in the treatment of DN. Sprague-Dawley rats were randomly divided into a normal control group, a diabetic group, an irbesartan group, and three groups receiving different doses of YJHD. Animal models were constructed using streptozotocin and then treated with YJHD for 12 consecutive weeks. Blood and urine samples were collected during this period, and metabolic and renal function was assessed. Pathological kidney injury was evaluated according to the kidney appearance, hematoxylin-eosin staining, Masson staining, periodic-acid Schiff staining, periodic-acid Schiff methenamine staining, and transmission electron microscopy. The expression levels of proteins and genes were detected by immunohistochemistry, western blotting, and real-time qPCR. Our results indicate that YJHD can effectively improve renal function and alleviate renal pathological injury, including mesangial matrix hyperplasia, basement membrane thickening, and fibrosis. In addition, YJHD exhibited podocyte protection by alleviating podocyte depletion and morphological damage, which may be key in improving renal function and reducing renal fibrosis. Further study revealed that YJHD upregulated the expression of the autophagy-related proteins LC3II and Beclin-1 while downregulating p62 expression, suggesting that YJHD can promote autophagy. In addition, we evaluated the activity of the mTOR pathway, the major signaling pathway regulating the level of autophagy, and the upstream PI3K/Akt and AMPK pathways. YJHD activated the AMPK pathway while inhibiting the PI3K/Akt and mTOR pathways, which may be crucial to its promotion of autophagy. In conclusion, our study shows that YJHD further inhibits the mTOR pathway and promotes autophagy by regulating the activity of the PI3K/Akt and AMPK pathways, thereby improving podocyte injury, protecting renal function, and reducing renal fibrosis. This study provides support for the application of and further research into YJHD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xuan, Xi, Zhang, Tao, Zhang and Cao.)

Quantum key distribution (QKD) networks hold promise for sharing secure randomness over multi-partities. Most existing QKD network schemes and demonstrations are based on trusted relays or limited to point-to-point scenario. Here, we propose a flexible and extensible scheme named as open-destination measurement-device-independent QKD network. The scheme enjoys security against untrusted relays and all detector side-channel attacks. Particularly, any users can accomplish key distribution under assistance of others in the network. As an illustration, we show in detail a four-user network where two users establish secure communication and present realistic simulations by taking into account imperfections of both sources and detectors.

The root of Gentiana straminea Maxim. (Gentianaceae), is officially listed as "Qin-Jiao" in the Chinese Pharmacopoeia for the treatment of rheumatic arthritis, icteric hepatitis, constipation, pain, and hypertension. To establish the geographical origin traceability in G. straminea , its chemical profiles were determined by a UPLC-Q exactive mass spectrometer, from which 43 compounds were identified by comparing retention times and mass spectrometry. Meanwhile, a pair of isomers (loganin and secologanol) was identified by mass spectrometry based on their fragmentation pathway. A total of 42 samples from difference habitats were determined by an UPLC-Q exactive mass spectrometer and the data were assayed with multivariate statistical analysis. Eight characteristic compounds were identified to determine the geographical origin of the herb. To estimate the key characteristic markers associated with pharmacological function, the inhibiting activities of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced macrophages were examined. This finding is crucial in realizing the determination of botanical origin and evaluating the quality of G. straminea .

Background: Lots of previous reports have suggested a potential association of atopic dermatitis (AD) with stroke and myocardial infarction (MI). However, the result is still controversial, Consequently, we conducted this meta-analysis to estimate the relationship of AD with Stroke and MI., Methods: PubMed, Embase, and Web of Science databases were searched from inception to June 2018. Stroke and MI were considered as a composite endpoint. We calculated pooled hazard ratios (HRs) with 95% confidence intervals (CIs). Subgroup and sensitivity analysis were performed to assess the potential sources of heterogeneity of the pooled estimation., Results: A total of 12 articles with 15 studies involving 3,701,199 participants were included in this meta-analysis. Of these, 14 studies on stroke and 12 on MI. Pooled analysis showed participants with AD experienced a significant increased risk of stroke (combined HR, 1.15; 95% CI, 1.08-1.22; P = .000) and MI (combined HR, 1.13; 95% CI, 1.02-1.24; P = .014), compared with participants without AD. The risk of stroke and MI was significant both in male subjects (stroke: HR: 1.33, 95% CI: 1.14-1.56; MI: HR: 2.01, 95% CI: 1.31-3.08), but not in female subjects (HR: 1.02, 95% CI: 0.77-1.35; MI: HR: 0.98, 95% CI: 0.72-1.32). The results were more pronounced for ischemic stroke (HR: 1.16, 95% CI: 1.13-1.19) in the stratified with stroke type. Stratifying by AD type, the risk of stroke was significant in severe AD (HR: 1.29, 95% CI: 1.08-1.54) and moderate AD (HR: 1.11, 95% CI: 1.01-1.22) for MI., Conclusions: AD is independently associated with an increased risk of stroke and MI, especially in male subjects and ischemic stroke and the risk is associated with the severity of AD.

To determine whether glycated hemoglobin and mean arterial pressure (MAP) during thrombolysis are prognostic factors of intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) for acute ischemic stroke (AIS).A total of 125 AIS patients, who received rt-PA intravenous thrombolysis in our hospital, were included into the present study, and divided into good prognosis group and poor prognosis group. Univariate and multivariate logistic regression analyses were used to determine the prognostic factors of AIS treated by rt-PA thrombolysis, Spearman correlation analysis was used to analyze the correlation of the accumulated cigarette consumption in the smoking subgroup and glycated hemoglobin in the diabetic subgroup with the prognosis after intravenous thrombolysis and the symptomatic intracranial hemorrhage (sICH).Univariate analysis revealed that the interval from onset to thrombolysis, baseline National Institutes of Health Stroke Scale (NIHSS) score, MAP during thrombolysis and DRAGON score were prognostic factors. Multivariate logistic regression analysis revealed that baseline NIHSS score and MAP during thrombolysis were independent prognostic factors for rt-PA thrombolysis. Furthermore, the glycated hemoglobin index was positively correlated with the incidence of sICH.The NIHSS score before thrombolysis and MAP during thrombolysis were independent factors for the prognosis of AIS treated by thrombolysis. The higher the glycated hemoglobin index of diabetic patients, the more likely they are to develop sICH, the glycated hemoglobin index was negatively correlated with the prognosis after intravenous thrombolysis. The accumulated cigarette consumption was negatively correlated with the prognosis after intravenous thrombolysis.

Purpose: The aquaporin (AQP) family consists of a number of small integral membrane proteins that transport water and glycerol. AQPs are critical for trans-epithelial fluid transport. Recent reports demonstrated that AQPs, particularly AQP1 and AQP5, are expressed in high grade tumor cells of a variety of tissue origins, and that AQPs are involved in cell migration and metastasis. Based on this background, we examined whether AQP3, another important member of the AQP family, could facilitate cell migration in human breast cancers., Methods: Potential role of AQP3 was examined using two representative breast cancer cell lines (MDA-MB-231 and Bcap-37). Briefly, AQP3 expression was inhibited with a lentivirus construct that stably expressed shRNA against the AQP3 mRNA. AQP3 expression inhibition was verified with Western blot. Cell migration was examined using a wound scratch assay in the presence of fibroblast growth factor-2 (FGF-2). In additional experiments, AQP3 was inhibited by CuSO4. Fibroblast growth factor receptor (FGFR) kinase inhibitor PD173074, PI3K inhibitor LY294002, and MEK1/2 inhibitor PD98059 were used to dissect the molecular mechanism of FGF-2 induced AQP3 expression., Results: FGF-2 treatment increased AQP3 expression and induced cell migration in a dose dependent manner. Silencing AQP3 expression by a lentiviral shRNA inhibited FGF-2 induced cell migration. CuSO4, a water transport inhibitor selective for AQP3, also suppressed FGF-2-induced cell migration. The FGFR kinase inhibitor PD173074, significantly inhibited FGF-2-induced AQP3 expression and cell migration. The PI3K inhibitor LY294002 and MEK1/2 inhibitor PD98059 inhibited, but not fully blocked, FGF-2-induced AQP3 expression and cell migration., Conclusions: AQP3 is required for FGF-2-induced cell migration in cultured human breast cancer cells. Our findings also suggest the importance of FGFR-PI3K and FGFR-ERK signaling in FGF-2-induced AQP3 expression. In summary, our findings suggest a novel function of AQP3 in cell migration and metastasis of breast cancers.

Aim: To study the expression pattern of Ets-like protein 1 (Elk-1) in human esophageal squamous cell carcinoma (ESCC) and to analyze its relationship with clinicopathologic parameters., Methods: The expression of Elk-1 in fresh esophageal cancer tissues and their corresponding normal mucosae was detected immunohistochemically (IHC) by means of tissue microarray (TMA). Its correlation with clinical characteristics was evaluated and analyzed by univariate analysis. All statistical analyses were performed by SPSS version 13.0., Results: Expression level of transcription factor Elk-1 increased in 78.5% (84/107) ESCC tissues compared with their matched normal esophageal epithelium. However, the expression of Elk-1 did not show any obvious correlation with degree of differentiation of esophageal carcinoma (in well-differentiated, moderately-differentiated and poorly-differentiated tumors, the increased expression was 7/8, 60/74, and 19/25, respectively, P > 0.05). Moreover, no obvious correlation was found with lymph node metastasis and depth of invasion., Conclusion: Increased expression of transcription factor Elk-1 may play an important role in esophageal carcinogenesis.

Aim: To investigate the role of transglutaminase 3 (TGM3) gene in human esophageal squamous cell carcinoma (ESCC), and analyze its relationship with clinicopathological parameters., Methods: Gene expression of TGM3 in fresh esophageal cancer tissues and their corresponding normal mucosas was detected immunohistochemically (IHC) by means of tissue microarray (TMA). Its correlation with clinical characteristics was evaluated and analyzed by univariate analysis. All statistical analyses were performed by SPSS version 10.0., Results: Expression rate of TGM3 was reduced to 81.8% in ESCC. Expression of TGM3 was significantly inversely correlated with histological grade of esophageal carcinoma (in grade I, II and III tumors, the reduced expression was 4/7, 57/71, and 20/21, respectively, P < 0.05), whereas it had no obvious correlations with lymph node metastasis and depth of invasion., Conclusion: Reduced expression of TGM3 may play an important role in esophageal carcinogenesis.

Previously we have identified the presence of two different phosphatidate phosphohydrolase (PPH) activities in rat adipose tissue, based on Mg(2+)-dependency. In the present investigation, we have further characterized these isoenzymes, using both aqueous dispersed and membrane-bound phosphatidate as substrates and differentiated these activities on the basis of both Mg(2+)-dependency and N-ethylmaleimide (NEM)-sensitivity. These two distinguishing criteria gave identical estimates of PPH activities present in the different subcellular fractions. The microsomal and cytosol fractions contained mainly the Mg(2+)-dependent (NEM-sensitive) form, which was inhibited by various thiol reagents, was inactivated by heating at 55 degrees C for 20 min, and was decreased significantly within 2 h after intraperitoneal administration of cystamine (200 mg/kg). Such treatments had no effects on the Mg(2+)-independent (NEM-insensitive) form of PPH, which was mainly located in the plasma membranes, mitochondrial and microsomal fractions. Addition of Lipid A and guanosine 5'-[gamma-thio]triphosphate to the assay mixture had no effect on the PPH activities. The Mg(2+)-independent PPH form, which was thermostable in the intact subcellular fractions, became thermolabile when these fractions were disrupted in the presence of Triton X-100. The present studies demonstrate that: (1) the thermostability is not a satisfactory index to differentiate these isoenzymes; (2) the thiol/disulphide exchange may be involved in the regulation of Mg(2+)-dependent PPH activity; and (3) the PPH isoenzymes do not seem to be under G-protein control in adipose tissue, as reported previously in the mesangial cell line.