The coinfection of respiratory viruses and bacteria is a major cause of morbidity and mortality worldwide, despite the development of vaccines and powerful antibiotics. As a macromolecule that is difficult to absorb in the gastrointestinal tract, a homogeneous polysaccharide from Houttuynia cordata (HCPM) has been reported to exhibit anti-complement properties and alleviate influenza A virus (H1N1)-induced lung injury; however, the effects of HCPM without in vitro antiviral and antibacterial activities on more complicated pulmonary diseases resulting from viral-bacterial coinfection remains unclear. This study established a representative coinfection murine pneumonia model infected with H1N1 (0.2 LD₅₀) and methicillin-resistant Staphylococcus aureus (MRSA, 10⁷ CFU). HCPM significantly improved survival rate and weight loss, and ameliorated gut-lung damage and inflammatory cytokine production. Interestingly, the therapeutic effect of HCPM on intestinal damage preceded that in the lungs. Mechanistically, HCPM inhibited the overactivation of the intestinal complement (C3a and C5a) and suppressed the activation of the NLR family pyrin domain-containing 3 (NLRP3) pathway, which contributes to the regulation of the Treg/Th17 cell balance in the gut-lung axis. The results indicate the beneficial effects of an anti-complement polysaccharide against viral-bacterial coinfection pneumonia by modulating crosstalk between multiple immune regulatory networks.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Tumor volume increases continuously in the advanced stage, and aside from the self-renewal of tumor cells, whether the oncogenic transformation of surrounding normal cells is involved in this process is currently unclear. Here, we show that oral squamous cell carcinoma (OSCC)-derived small extracellular vesicles (sEVs) promote the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of normal epithelial cells but delay their apoptosis. In addition, nuclear-cytoplasmic invaginations and multiple nucleoli are observed in sEV-treated normal cells, both of which are typical characteristics of premalignant lesions of OSCC. Mechanistically, miR-let-7c in OSCC-derived sEVs is transferred to normal epithelial cells, leading to the transcriptional inhibition of p53 and inactivation of the p53/PTEN pathway. In summary, we demonstrate that OSCC-derived sEVs promote the precancerous transformation of normal epithelial cells, in which the miR-let-7c/p53/PTEN pathway plays an important role. Our findings reveal that cancer cells can corrupt normal epithelial cells through sEVs, which provides new insight into the progression of OSCC.
Carcinoma, Squamous Cell/pathology* ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cell Transformation, Neoplastic ; Down-Regulation ; Epithelial Cells/metabolism* ; Extracellular Vesicles/pathology* ; Humans ; MicroRNAs/metabolism* ; Mouth Neoplasms/pathology* ; PTEN Phosphohydrolase/metabolism* ; Tumor Suppressor Protein p53/metabolism*

Objective:To study the regulatory effect of Wumen-Yiji powder on 5-hydroxytryptamine (5-HT) signal transduction system in intestine and hypothalamus of diarrhea irritable bowel syndrome (IBS-D) model rats. Methods:Sixty male SD rats were randomly divided into blank group (10 rats) and diarrhea irritable bowel syndrome group (50 rats). The diarrhea irritable bowel syndrome group formed the diarrhea irritable bowel syndrome model after 2 weeks of senna leaf gavage and restraint stress. They were randomly divided into model group, deshute group (1.5 mg/kg), low, medium and high dose group of Wumen-Yiji San (6, 12, 24 g/kg), with 10 rats in each group. After continuous administration for 2 weeks, the contents of 5-HT in serum, colon and hypothalamus were detected by ELISA; HE staining was used to observe the pathological changes of colon in each group. The protein and mRNA levels of tryptophan hydroxylase 1 (TPH-1), serotonin receptor 3 (5-HT3R), serotonin receptor 4 (5-HT4R), serotonin transporter (SERT) in colon and hypothalamus were detected by Western blot and RT-PCR, respectively. Results:Compared with the model group, the pathological morphology of colon in each treatment group was improved. Compared with the model group, the level of 5-HT in serum and colon significantly decreased ( P<0.05), and the level of 5-HT in hypothalamus of rats in the low, medium, high dose group of Wumen-Yiji San significantly increased ( P<0.05). The expression of TPH-1, 5-HT3R and 5-HT4R protein significantly decreased ( P<0.05), and the expression of SERT protein in the medium, high dose group of Wumen-Yiji San significantly increased ( P<0.05). The expression of TPH-1, 5-HT3R and 5-HT4R protein in hypothalamus increased ( P<0.05), and the expression of SERT protein in the high dose group of Wumen-Yiji San significantly decreased ( P<0.05). The mRNA levels of TPH-1 (4.778 ± 0.604, 3.278 ± 0.668, 1.670 ± 0.361 vs. 6.877 ± 0.148), 5-HT3R (3.807 ± 0.463, 2.697 ± 0.455, 1.132 ± 0.136 vs. 6.322 ± 0.778), 5-HT4R (4.521 ± 0.234, 2.801 ± 0.351, 1.331 ± 0.142 vs. 6.741 ± 0.293) in colon tissue of low, medium and high dose groups of Wumen-Yiji San decreased ( P<0.05). The level of 5-HT4R mRNA (0.616 ± 0.208, 0.726 ± 0.226 vs. 0.521 ± 0.062) increased ( P<0.05), and the level of SERT mRNA (1.563 ± 1.023 vs. 2.612 ± 1.035) in medium, high dose group of Wumen-Yiji San decreased ( P<0.05). Conclusion:The result showed that Wumen-Yiji San could regulate the expression of 5-HT signaling system relating proteins and mRNA in the colon and hypothalamus of IBS-D rats within a certain dose range, so as to improve the symptoms of IBS-D.

Pediatric cough is a heterogeneous condition in terms of symptoms and the underlying disease mechanisms. Symptom phenotypes hold complicated interactions between each other to form an intricate network structure. This study aims to investigate whether the network structure of pediatric cough symptoms is associated with the prognosis and outcome of patients. A total of 384 cases were derived from the electronic medical records of a highly experienced traditional Chinese medicine (TCM) physician. The data were divided into two groups according to the therapeutic effect, namely, an invalid group (group A with 40 cases of poor efficacy) and a valid group (group B with 344 cases of good efficacy). Several well-established analysis methods, namely, statistical test, correlation analysis, and complex network analysis, were used to analyze the data. This study reports that symptom networks of patients with pediatric cough are related to the effectiveness of treatment: a dense network of symptoms is associated with great difficulty in treatment. Interventions with the most different symptoms in the symptom network may have improved therapeutic effects.

How to discover the valuable knowledge from the large amount of prescription data accumulated in the long-term medical practice of traditional Chinese medicine (TCM) is one of the important contents of TCM modernization.Based on the prescription data of Xue' s clinical practice of many years,this paper explored the method of combining TCM network and prescription network to find out Xue' s common core drug combination.Based on 9,584 prescriptions in the Hospital Information System of Guang'anmen Hospital of China Academy of Chinese Medical Sciences,prescription network and drug network were constructed according to the similarity of prescription composition and drug co-occurrence relationship.Using the complex network analysis methods,such as community analysis method,to analyze the prescription and drug compatibility,the results were evaluated and analyzed by Xue and his successors.As a result,through complex network analysis,126 modular prescriptions and 4 TCM modules were obtained.One of the core components of the prescription module included Xiao Chai Hu decoction,Yin Qiao powder,and Sheng Jiang powder compound addition and subtraction.It was in consistent with the drug composition of exogenous febrile prescriptions excavated earlier.In conclusion,using the complex network methods,we can get some core drug combinations prescribed by Prof.Xue,and achieve the common compound core drug combination for treating diseases with certain vantages,laying a foundation for further inheriting and excavating Xue' s effective experience.

To assess relationships between xanthine oxidase (XOD) and nephropathogenic infectious bronchitis virus (NIBV) infection, 240 growing layers (35 days old) were randomly divided into two groups (infected and control) of 120 chickens each. Each chicken in the control and infected group was intranasally inoculated with 0.2 mL sterile physiological saline and virus, respectively, after which serum antioxidant parameters and renal XOD mRNA expression in growing layers were evaluated at 8, 15 and 22 days post-inoculation (dpi). The results showed that serum glutathione peroxidase and superoxide dismutase activities in the infected group were significantly lower than in the control group at 8 and 15 dpi (p < 0.01), while serum malondialdehyde concentrations were significantly higher (p < 0.01). The serum uric acid was significantly higher than that of the control group at 15 dpi (p < 0.01). In addition, the kidney mRNA transcript level and serum activity of XOD in the infected group was significantly higher than that of the control group at 8, 15 and 22 dpi (p < 0.05). The results indicated that NIBV infection could cause the increases of renal XOD gene transcription and serum XOD activity, leading to hyperuricemia and reduction of antioxidants in the body.
Antioxidants ; Chickens ; Glutathione Peroxidase ; Hyperuricemia ; Infectious bronchitis virus* ; Kidney ; Malondialdehyde ; RNA, Messenger* ; Superoxide Dismutase ; Uric Acid ; Xanthine Oxidase* ; Xanthine*

Objective:To observe the changes of glyeemia, urine protein, serum creatinine, blood urea nitrogen and glycosylated hemoglobin in diabetic nephropathy rats and treating effects of Xiaokekang. Methods: Streptozotocin (STZ) was abdominally administered and was feeded by high lipid diet to establish diabetic nephropathy model in rats. Animals were divided into three groups: model group, Xiaokekang treatment group and normal group. Changes in glycemia, serum lipids, serum creatinine, blood urea nitrogen were measured at the 8th, 12th and 16th week after STZ injection. Glycosylated hemoglobin was measured at the 16th weeks after STZ injection. Results: Glycemia, serum lipids, serum creatinine were higher at the 8th, 12th and 16th week compared with normal group. Serum creatinine was higher at the 12th and 16th week, and glycosylated hemoglobin was also highter than that of the normal group. Xiaokekang reduced these changes. Conclusion: Xiaokekang can reduce glycemia, serum lipids and protect renal function.

Heart sounds are highly valuable to the clinical diagnoses of most cardiovascular diseases, so the analysis of phonocardiographic signals is helpful to diagnosing cardiovascular diseases clinically. Phonocardiographic signals are non-stable, so it is necessary to choose appropriate method in time-frequency analysis. The traditional method such as Fourier Transform is dissatisfactory. Continuous Wavelet Transform (CWT) and Matching (MPM) Pursuit Method are both effective methods. They can be used to extract and cluster the characteristics of the signals. By analysis and comparison, the two methods showed the advantages over traditional methods. Additionally, their respective merits and demerits are indicated.
Algorithms ; Fourier Analysis ; Heart Sounds ; Humans ; Phonocardiography ; Signal Processing, Computer-Assisted

BACKGROUNDEndostar™ (rh-endostatin, YH-16) is a new recombinant human endostatin developed by Medgenn Bioengineering Co. Ltd., Yantai, Shandong, P.R.China. Pre-clinical study indicated that YH-16 could inhibit tumor endothelial cell proliferation, angiogenesis and tumor growth. Phase I and phase II studies revealed that YH-16 was effective as single agent with good tolerance in clinical use.The current study was to compare the response rate , median ti me to progression (TTP) ,clinical benefit andsafety in patients with advanced non-small cell lung cancer ( NSCLC) , who were treated with YH-16 plus vi-norelbine and cisplatin (NP) or placebo plus NP.

METHODSFour hundred and ninety-three histologically or cy-tologically confirmed stage IIIB and IV NSCLC patients , withlife expectancy > 3 months and ECOG perform-ance status 0-2 , were enrolledin a randomized ,double-blind ,placebo-controlled , multicenter trial ,either trialgroup : NP plus YH-16 (vinorelbine 25 mg/m² on day 1 and day 5 ,cisplatin 30mg/m² on days 2 to 4 , YH-167.5mg/m² on days 1 to 14) or control group : NP plus placebo (vinorelbine 25 mg/m² on day 1 and day 5 ,cis-platin 30 mg/m² on days 2 to 4 ,0.9% sodium-chloride 3 .75 ml on days 1 to 14) every 3 weeks for 2-6 cycles .The trial endpoints included response rate ,clinical benefit rate ,time to progression,quality of life and safety .

RESULTSOf 486 assessable patients , overall response rate was 35.4% in trial group and 19.5% in controlgroup (P=0 .0003) . The median TTP was 6 .3 months and 3 .6 months for trial group and control group respectively (P < 0 .001) . The clinical benefit rate was 73 .3 %in trial group and 64.0% in control group (P=0 .035) .In untreated patients of trial group and control group ,the response rate was 40 .0% and 23.9%(P=0 .003) ,the clinical benefit rate was 76 .5 % and 65 .0 % (P=0 .023) ,the median TTP was 6 .6 and 3 .7months (P=0 .0000) ,respectively .In pretreated patients of trial group and control group ,the response ratewas 23.9% and 8.5%(P=0 .034) ,the clinical benefit rate was 65.2% and 61.7%(P=0 .68) ,the median TTP was 5 .7 and 3 .2 months (P=0 .0002) ,respectively . The relief rate of clinical symptoms in trial groupwas higher than that of those in control group ,but no significance existed (P > 0 .05) . The score of quality oflife in trial group was significantly higher than that in control group (P=0 .0155) after treatment . There were no significant differences in incidence of hematologic and non-hematologic toxicity , moderate and severe sideeffects betweentrial group and control group .

CONCLUSIONSThe addition of YH-16 to NP regimen results in significantly and clinically meaningful improvement in response rate , median time to tumor progression,and clinical benefit rate compared with NP alone in advanced NSCLC patients . YH-16 in combination with chemotherapy shows a synergic activity and a favorable toxic profile in advanced cancer patients .