Objective To elucidate the changes in the gut microbiota and molecular mechanism of huaier in enhancing the efficacy of oxaliplatin (OXA) chemotherapy in gastric cancer (GC). Methods The effects of huaier on the gut microbiota structure and intestinal barrier function in MKN45-bearing mice were analyzed by using 16S rRNA sequencing, RT-qPCR, and IHC. UPLC-MS and network pharmacology, as well as in vivo experimental approaches, were employed to investigate the key bioactive constituents of huaier systematically and elucidate the underlying mechanisms by which huaier exerts therapeutic effects against GC. The expression of the PI3K/AKT/SREBP pathway was detected in cancer cells and tissues via Western blot analysis. The safety profile of huaier combined with OXA was verified through serum biochemistry and HE-stained tissue section analyses. Results Huaier inhibited the PI3K/AKT/SREBP pathway by increasing the abundance of Akkermansia muciniphila, reduced lipid droplet deposition, and ultimately enhanced the sensitivity to OXA in the treatment of GC. Conclusion This study demonstrates the value of huaier in gastric cancer treatment by enhancing chemosensitivity and provides novel insights into its systemic therapeutic effects through molecular mechanisms and gut microbiota modulation.

BACKGROUND:Minipigs are often used in research fields such as skin injury,vascular trauma and cosmetic medicine because they are highly similar to human beings in terms of skin tissue structure and cardiovascular system.Hydrogel as a wound repair drug possesses a variety of excellent physicochemical properties such as strong water retention and adhesion,which can provide isolation moisturization and drug release for wounds. OBJECTIVE:To summarize and conclude the progress of the application of trauma models for different experimental purposes of hydrogel therapy for minipigs,to reveal the development status of various types of minipig trauma models,to analyze the deficiencies of minipig trauma models at the present stage. METHODS:The relevant articles published in Web of Science database and CNKI database from the establishment of each database to 2023 were checked,using"piglet,miniature pig,minipig,miniature pig;gel,hydrogel;trauma,injury,wound,lesion,incision"as Chinese search terms and"Miniature Swine,Miniature pig,minipig;gel,hydrogel;injury,wound,lesion,incision"as English search terms.A total of 438 Chinese and English documents were retrieved,and 59 documents were included in the study through the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)At present,the main models used clinically for trauma repair are large animal species(dogs and pigs),rabbits,and rodents(rats and mice).Because the skin structure of the minipig is more like that of humans,the minipig is the most ideal animal model for trauma repair.(2)In the in-vitro skin injury model,skin defect model is the basic wound model,which can be divided into full skin defect model and medium-thickness skin defect model according to the depth of the wound defect.Burn wound model and infected wound model are multidimensional models with hot metal scald and bacterial culture imposed on the basis of the skin defect model,which have the advantages of high safety coefficient and low operation difficulty.(3)In the in-vivo trauma repair model,mini-pigs are used as esophageal cricothyrotomy model which is more in line with the pathological state of clinical diseases.Mini-pigs are used in the gastric perforation and vascular hemostasis model,which can visually demonstrate the stronger organ adhesion,hemostatic properties and tissue regeneration-promoting effects of the hydrogel.(4)The specific parts of the pig also has the corresponding mode of use:pig ear is usually used to evaluate the hydrogel drug delayed-release effect.Porcine cellular proteins and pig skin collagen are mostly used to prepare composite hydrogels of tissue origin.

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

【Objective】 To clarify the hematological characteristics and current situation of chronic mountain sickness among Tibetan residents in extreme high altitude area (more than 5 000 m above the sea level) of Ali district based on the analysis of physical examination and blood test results. 【Methods】 Totally 250 Tibetan residents were selected by convenient sampling for blood oxygen saturation (SpO2), heart rate, and blood routine examination. Chronic mountain sickness was determined according to the hemoglobin (Hb) level and SpO2. 【Results】 The red blood cell (RBC), Hb and hematocrit (HCT) of the Tibetan residents at 5 200-meter altitude were all higher than the normal physiological reference range of China. Mean red blood cell volume (MCV), mean red blood cell hemoglobin content (MCH), mean red blood cell hemoglobin concentration (MCHC), white blood cell (WBC) and platelet (PLT) were in the upper limit of the reference value. The RBC, Hb, HCT and MCHC of male Tibetan residents were higher than those of females, while PLT was lower than that of females, with significant differences. There were no statistical differences in MCV, MCH or WBC among different genders of Tibetan residents. The SpO2 of the Tibetan residents was about 85% of the normal value, and the males had higher SpO2 than the females in the same age group, and the difference was statistically significant, but the heart rate did not differ significantly. The prevalence rate of chronic mountain sickness in this area was as high as 16.4%, and the prevalence rate of heavy manual workers was significantly higher than that of light manual workers, with significant differences. 【Conclusion】 The high-altitude anoxic environment causes the changes in red blood cells, hemoglobin, and oxygen saturation of local residents, and the prevalence of chronic mountain sickness increases significantly. Labor intensity is one of the risk factors for chronic mountain sickness in high-altitude areas.

The existing retinal vessels segmentation algorithms have various problems that the end of main vessels are easy to break, and the central macula and the optic disc boundary are likely to be mistakenly segmented. To solve the above problems, a novel retinal vessels segmentation algorithm is proposed in this paper. The algorithm merged together vessels contour information and conditional generative adversarial nets. Firstly, non-uniform light removal and principal component analysis were used to process the fundus images. Therefore, it enhanced the contrast between the blood vessels and the background, and obtained the single-scale gray images with rich feature information. Secondly, the dense blocks integrated with the deep separable convolution with offset and squeeze-and-exception (SE) block were applied to the encoder and decoder to alleviate the gradient disappearance or explosion. Simultaneously, the network focused on the feature information of the learning target. Thirdly, the contour loss function was added to improve the identification ability of the blood vessels information and contour information of the network. Finally, experiments were carried out on the DRIVE and STARE datasets respectively. The value of area under the receiver operating characteristic reached 0.982 5 and 0.987 4, respectively, and the accuracy reached 0.967 7 and 0.975 6, respectively. Experimental results show that the algorithm can accurately distinguish contours and blood vessels, and reduce blood vessel rupture. The algorithm has certain application value in the diagnosis of clinical ophthalmic diseases.
Algorithms ; Fundus Oculi ; Optic Disk ; ROC Curve ; Retinal Vessels/diagnostic imaging*

To investigate the material basis and mechanism of Liupao tea on preventing COVID-19 by network pharmacology and molecular docking.The active ingredients and targets of Liupao tea were searched through the literature and the TCMSP databases and the network between the two was built by Cytoscape 3.7.1.Then using GenCards platform to predict the disease targets,mapping the common targets between Liupao tea and disease.The common targets were imported into the STRING database for exploring the protein-protein interaction.Core targets were enriched by gene ontology (GO) enrichment analysis and KEGG (kyoto encyclopedia of genes and genomes) pathway enrichment analysis using DAVID database etc..Finally,the screened active components were docked with the receptor protein SARS-CoV-2 3CL hydrolase (Mpro).Six active ingredients of Liupao tea were screened,such as (-)-epigallocatechin gallate (EGCG),(+)-catechin,(-)-catechin gallate,α-spinasterol,pelargonidin chloride and squalene,and 156 targets were identified.Among them,there were 112 common targets and 38 core targets with COVID-19.GO enrichment analysis (P<0.01) involved lipopolysaccharide,cell response to hypoxia,etc..And the KEGG pathway enrichment analysis (P<0.01)was conducted to obtain the HIF-1,IL-17,T cell receptor and other signaling pathways associated with COVID-19.The results of molecular docking showed that the active ingredients of Liupao tea were well bound to the receptor protein Mpro.The active ingredients of Liupao tea may control HIF-1,IL-17,T cell receptors signaling pathways by binding Mpro hydrolase and acting on inflammation and immune related targets such as MAPK1,TNF to prevent COVID-19.The EGCG of Mpro activity was determined ,and the IC50 was 3.4 μmol/L,which confirmed that EGCG was a certain inhibition effect on Mpro.

Objective: To investigate the clinical, immunological and virological characteristics of HIV-1 infected patients in the acute phase, for the sake of improving the diagnosis of acute infection with HIV-1. Methods: We retrospectively analyzed the clinical manifestation and laboratory data of patients with acute HIV-1 infection who were admitted to the Center of Infectious Diseases, Guangzhou Eighth People’s Hospital from January 2012 to June 2017. Results: Forty-four patients were enrolled into the study, 86.4% of them were male. 59.1% patients were homosexually transmitted. Clinical symptoms and signs mostly consisted of fever (84.1%), lymphadenopathy (56.8%) and so on, while 15.9% patients had central nervous system symptoms. Most common opportunistic infection included lung infection (50.0%) and oropharyngeal candidiasis (22.7%). Leucopenia (10 patients, 22.7%), and decreased CD4⁺ T cell count (267.5 cells/μl), inverted CD4⁺ /CD8⁺ ratio (86.4%) was mostly seen. Compared to patients who had HIV RNA load less than 6 lg copies/ml, the group of patients who had HIV RNA load more than 6 lg copies/ml had lower levels of CD4⁺ T cells (t=-3.724, P=0.001). Conclusions Patients with acute HIV infection have many different kinds of clinical symptoms and can be accompanied by opportunistic infection, and with high viremia.

Muhidrug resistance (MDR) is one of the important reasons for the failure of clinical anticancer drugs,involving multiple mechanisms.Among them,the classical MDR mechanism mediated by P-glycoprotein (P-gp) is closely related to the formation of MDR,which can excrete intracellular chemotherapeutic drugs through the "drug pump" effect and significantly reduce the therapeutic effect.Curcumin is mainly extracted from the underground rhizome of Chinese medicine turmeric,with a wide range of pharmacological activity.Recent studies have found that curcumin also has a role in reversing the MDR of the tumor,by inhibiting both P-gp function and expression,and this process involves a variety of signal paths.

Objective To explore skeletal‐related events (SREs) clinical factors and analysis prognosis factors on patients with non‐small cell lung cancer(NSCLC) with bone metastases .Methods We collected clinical data of pathology confirmed 383 patients with non‐small cell lung cancer between April 2007 and January 2007 in the third affiliated hospital of the third military medical uni‐versity .It was used to screening for Emission Computed Tomography (ECT ) for bone metastases .And then it was need to con‐firmed for CT ,MRI or PET‐CT or pathology .Statistics in patients between clinical features and the SREs prediction factor with Univariate and Multivariate .And Kaplan‐Meier method analysis of survival in the non‐small cell lung cancer patients with bone me‐tastases .Results Out of 383 patients with bone metastases ,178 patients with SREs .The incidence was 46 .5% .Univariate analysis showed that women ,adenocarcinoma ,never smoking history ,single bone metastases ,bisphosphonate therapy ,targeted therapy in patients with bone metastases are less likely to have SREs ,it was considered statistically significant (P<0 .05) .Multivariate analy‐sis showed multiple bone metastases and no bisphosphonate therapy is independent risk factors for SREs .Median survival time was 14 .5 months in non‐small cell lung cancer patients with bone metastases ,1 year survival rate was 46 .5% ,2 years survival rate was 15 .9% .The survival analysis shows that more bisphosphonate treatment and bisphosphonate with EGFR‐TKI therapy on the prog‐nosis of patients with statistically significance (P<0 .05) .Conclusion It was likely to occur SREs in NSCLC patients with bone metastases .No bisphosphonate and multiple bone metastases are independent risk factors for SREs .Bisphosphonate treatment may prevent or reduce occur SREs for NSCLC patients with bone metastases ,and it may prolong survival ,it speculated that bisphospho‐nate may have resistant NSCLC cell activity .

Objective To study the postpartum pelvic floor rehabilitation on the improvement of pelvic floor electrical physiological indexes and the prevention of female pelvic floor dysfunction in China. Methods A multicenter prospective randomized controlled study was carried out. From October 2011, postpartum women in five provinces were randomly assigned into treatment group and control group. The women in treatment group received electrical stimulation and biofeedback treatment. The women in control group performed pelvic floor muscle exercise at home. When 6 months and 12 months after delivery, comparing two groups of patients with pelvic floor electrical physiological indexes and pelvic organ prolapse quantitation measurements (POP-Q), to evaluate the effect of postpartum pelvic floor rehabilitation on the prevention of pelvic floor dysfunction. Pelvic floor impact questionnaire short form (PFIQ-7) and pelvic organ prolapse/incontinence sexual questionnaire-12 (PISQ-12) were used to evaluate the influence on quality of life and sexual life. Results Until June 2013, 324 women were participated, 124 in control group, 200 in treatment group. According to the baseline results, there was statistical significance in the results of pelvic floor electrical physiological indexes between the treatment and control groups in postpartum 6 months and 12 months; the proportion above level Ⅲ of type Ⅰ and type Ⅱ muscle fibers strength in the treatment group, it was from 41.5% (83/200) and 40.5% (81/200) to 76.3% (145/190) and 79.5% (151/190) in postpartum 6 weeks and postpartum 6 months, increased to 80.6%(58/72) and 80.6%(58/72) in postpartum 12 months, improved significantly comparing with the control group (P<0.01). According to Point Aa, treatment group and control group in the postpartum 6 weeks was (-2.2 ± 0.7) versus (-2.4 ± 0.6) cm, in postpartum 12 months (-2.5 ± 1.1) versus (-2.7 ± 0.6) cm, the improvement in treatment group was statistically significant (P<0.01). And the other points were not significantly different (P>0.05). There was no significant difference in the questionnaires in quality of life and quality of sexual life (P>0.05). Conclusion Neuromuscular electrical stimulation and biofeedback therapy in the early postpartum period could obviously improve pelvic floor electrical physiological indexes, and is beneficial to prevent the pelvic floor dysfunction.