Objective To establish a three-dimensional visualization model of complex anal fistula based on high-resolution mag-netic resonance imaging(HR-MRI),and to explore its feasibility and clinical application value.Methods The clinical and imaging data of 26 patients with complex anal fistula were analyzed retrospectively,and a three-dimensional visualization model based on HR-MRI images was established.The Parks typing,internal orifice,external orifice,branch fistula and abscess were evaluated by radiolo-gists and anorectal surgeons in HR-MRI images and the three-dimensional visualization model,and the SPSS 22.0 software was used to analyze the assessment results against the clinical surgery one by one.Results A total of 26 patients had 17 trans sphincteric fis-tulas,7 inter sphincteric fistulas,and 2 suprasphincteric fistulas,and the accuracy of Parks typing based on HR-MRI images and three-dimensional visualization model was 100％;26 patients had a total of 33 internal orifices,and the evaluation of internal orifices based on HR-MRI images was better than that of three-dimensional visualization model(P=0.180 vs P=0.022);15 patients had a total of 32 external orifices,and the evaluation of external orifices based on three-dimensional visualization model was better than that of HR-MRI images(P=0.791 vs P=0.049);20 patients had perianal abscesses,and the evaluations based on HR-MRI images and three-dimensional visualization model were both highly accurate(P=0.549 vs P=0.625);18 patients with branch fistula,the evaluation of branch fistula based on three-dimensional visualization model was significantly better than that of HR-MRI images(P=1.000 vs P＜0.001).Conclusion Based on three-dimensional visualization model of HR-MRI,the evaluation of complex anal fistula Parks typing,external orifice,branch fistula and abscess is more accurate,which is worthy of further research and promotion.

The development, progression, and curative efficacy of head and neck squamous cell carcinoma (HNSCC) are influenced by complex interactions between epithelial and immune cells. Nevertheless, the specific changes in the nature of these interactions and their underlying molecular mechanisms in HNSCC are not yet fully understood. Cuproptosis, a form of programmed cell death that is dependent on copper, has been implicated in cancer pathogenesis. However, the understanding of cuproptosis in the context of HNSCC remains limited. In this study, we have discovered that cuproptosis-related long non-coding RNAs (CRLs) known as JPX play a role in promoting the expression of the oncogene urokinase-type plasminogen activator (PLAU) by competitively binding to miR-193b-3p in HNSCC. The increased activity of the JPX/miR-193b-3p/PLAU axis in malignant epithelial cells leads to enhanced cell proliferation, migration, and invasion in HNSCC. Moreover, the overexpression of PLAU in tumor epithelial cells facilitates its interaction with the receptor PLAUR, predominantly expressed on macrophages, thereby influencing the abnormal epithelial-immune interactome in HNSCC. Notably, the JPX inhibitor Axitinib and the PLAU inhibitor Palbociclib may not only exert their effects on the JPX/miR-193b-3p/PLAU axis that impacts the malignant tumor behaviors and the epithelial-immune cell interactions but also exhibit synergistic effects in terms of suppressing tumor cell growth and arresting cell cycle by targeting epidermal growth factor receptor (EGFR) and cyclin-dependent kinase (CDK4/6) for the treatment of HNSCC.
Humans ; MicroRNAs/metabolism* ; RNA, Long Noncoding/metabolism* ; Head and Neck Neoplasms/metabolism* ; Cell Proliferation ; Squamous Cell Carcinoma of Head and Neck/genetics* ; Urokinase-Type Plasminogen Activator/genetics* ; Cell Movement ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Carcinoma, Squamous Cell/genetics* ; Neoplasm Invasiveness

OBJECTIVE: To investigate the involvement of endothelial cells (ECs)-derived exosomes in the anti-apoptotic effect of Danhong Injection (DHI) and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis. METHODS: A mouse permanent myocardial infarction (MI) model was established, followed by a 14-day daily treatment with DHI, DHI plus GW4869 (an exosomal inhibitor), or saline. Phosphate-buffered saline (PBS)-induced ECs-derived exosomes were isolated, analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction (ddPCR). The exosomes induced by DHI (DHI-exo), PBS (PBS-exo), or DHI+GW4869 (GW-exo) were isolated and injected into the peri-infarct zone following MI. The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography, Masson's trichrome staining, and TUNEL apoptosis assay. The Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to evaluate the expression levels of miR-125b/p53-mediated pathway components, including miR-125b, p53, Bak, Bax, and caspase-3 activities. RESULTS: DHI significantly improved cardiac function and reduced infarct size in MI mice (P<0.01), which was abolished by the GW4869 intervention. DHI promoted the exosomal secretion in ECs (P<0.01). According to the results of exosomal miRNA microarray assay, 30 differentially expressed miRNAs in the DHI-exo were identified (28 up-regulated miRNAs and 2 down-regulated miRNAs). Among them, DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs, a recognized apoptotic inhibitor impeding p53 signaling (P<0.05). Remarkably, treatment with DHI and DHI-exo attenuated apoptosis, elevated miR-125b expression level, inhibited capsase-3 activity, and down-regulated the expression levels of proapoptotic effectors (p53, Bak, and Bax) in post-MI hearts, whereas these effects were blocked by GW4869 (P<0.05 or P<0.01). CONCLUSION DHI and DHI-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in post-infarction myocardium.
Mice ; Animals ; Tumor Suppressor Protein p53/metabolism* ; Endothelial Cells/metabolism* ; Exosomes/metabolism* ; bcl-2-Associated X Protein/metabolism* ; Myocardium/metabolism* ; Myocardial Infarction/drug therapy* ; Apoptosis ; MicroRNAs/metabolism*

OBJECTIVE To investigate the effects of pharmacological inhibition of STING by C-176,a STING selective inhibitor,in experimental model of Parkinson's disease.METHODS The acute and sub-acute mice mod-els of Parkinson's disease(PD)were established by in-traperitoneal injection of 1-methyl-4-(2′-methylphenyl)-1,2,3,6-tetrahydrophine(MPTP).The selective STING inhibitor C-176 was administered by intraperitoneal injec-tion.The potential neuroprotective effects of C-176 were evaluated by behavioral test,tyrosine hydroxylase(TH)immunostaining,Nissl staining,Western blotting,qPCR and immunofluorescence.For in vitro study,the effects of C-176 on LPS/MPP+-induced inflammatory responses in BV2 microglial cells were determined by real time RT-PCR and Western blotting analysis.RESULTS Our study revealed that C-176 significantly inhibited STING signaling activation,ameliorated MPTP-induced dopami-nergic neurotoxicity,motor deficit and associated neuroin-flammation.Furthermore,pharmacological inhibition of STING in BV2 microglia treated with LPS/MPP+ exhibited decreased inflammatory responses.More importantly,C176 also reduced NLRP3 inflammasome activation both in vitro and in vivo.CONCLUSION The results of our study suggest that pharmacologic inhibition of STING protects against neuroinflammation that may act at least in part through suppressing NLRP3 inflammasome acti-vation and thus ameliorated dopaminergic neurodegener-ation.STING signaling may holds great promise for the development of new treatment strategy for PD as an effective therapeutic target.

Objective: To analyze the drug resistance and genomic characteristics of Salmonella enterica serovar London isolated from clinical and food sources in Hangzhou City from 2017 to 2021. Methods: A total of 91 Salmonella enterica serovar London strains isolated from Hangzhou City from 2017 to 2021 were analyzed for drug susceptibility, pulsed field gel electrophoresis (PFGE) typing and whole genome sequencing. Multilocus sequence typing (MLST), core genome multilocus sequence typing (cgMLST) and detection of drug resistance genes were performed by using the sequencing data. Phylogenetic analysis was conducted to compare the 91 genomes from Hangzhou City with 347 genomes from public databases. Results: No significant difference in the drug resistance rate was observed between clinical strains and food strains to 18 drugs in Hangzhou City(all P>0.05), and the multidrug resistance (MDR) rate was 75.8% (69/91). Most strains were resistant to 7 drug classes simultaneously. One strain was resistant to Polymyxin E as well as positive for mcr-1.1, and 50.5% (46/91) of the strains were resistant to Azithromycin and were positive for mph(A). All 91 Salmonella enterica serovar London strains were ST155, which were subdivided into 44 molecular types by PFGE and 82 types by cgMLST. Phylogenetic analysis showed that most strains from Hangzhou City (83/91) were clustered together, and a small number of human isolates from Europe, North America and pork isolates from Hubei and Shenzhen were mixed in the cluster. Other strains from Hangzhou City (8/91) were closely related to strains from Europe, America and Southeast Asia. Strains isolated from pork were the most closely related to clinical strains. Conclusion: The epidemic of Salmonella enterica serovar London in Hangzhou City is mainly caused by the spread of ST155 strains, which is mainly transmitted locally. At the same time, cross-region transmission to Europe, North America, Southeast Asia, and other provinces and cities in China may also occur. There is no significant difference in the drug resistance rate between clinical strains and food strains, and a high level of MDR is found in the strains. Clinical infection of Salmonella enterica serovar London may be closely related to pork consumption in Hangzhou City.
Humans ; Salmonella enterica/genetics* ; Serogroup ; Anti-Bacterial Agents/pharmacology* ; Multilocus Sequence Typing ; Cities ; London ; Clonidine ; Phylogeny ; Genomics ; Drug Resistance ; Electrophoresis, Gel, Pulsed-Field ; Microbial Sensitivity Tests

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

OBJECTIVE: To compare the clinical efficacy and its effect on serum levels of tumor necrosis factor α(TNF-α), interleukin 1β(IL-1β), interleukin 6 (IL-6) and prostaglandin E₂ (PGE₂) between short needling (close-to-bone needling) and conventional acupuncture for knee osteoarthritis (KOA) with blood stasis obstruction. METHODS: A total of 68 KOA patients with blood stasis obstruction were randomized into a short needling group (34 cases, 3 cases dropped off) and a conventional acupuncture group (34 cases, 3 cases dropped off). The same acupoints (Dubi [ST 35], Neixiyan [EX-LE 4], Binzhong [Extra], Liangqiu [ST 34], etc. on the affected side) were selected in the two groups. In the short needling group, short needling technique was adopted, the needles were slowly inserted and the needle bodies were shaken, thus gradually penetrated to the bone. In the conventional acupuncture group, conventional acupuncture was adopted, the needles were penetrated to the muscle. After qi-arrival, Dubi (ST 35) and Neixiyan (EX-LE 4), Zusanli (ST 36) and Liangqiu (ST 34) were connected with CMNS6-1 electronic acupuncture instrument, with disperse-dense wave, 2 Hz/10 Hz in frequency, the current intensity was based on patients' feeling, the needles were retained for 30 min, at the same time, the knee joint was irradiated for 30 min with a special electromagnetic wave apparatus in the two groups. Once every other day, 3 times a week for 4 weeks. Before and after treatment, the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) score, knee joint pain visual analogue scale (VAS) score, inflammatory response related indexes (serum TNF-a, IL-1β, IL-6 and PGE₂) and knee joint ultrasound were observed，and the clinical effect was evaluated in the two groups. RESULTS: After treatment，the pain, stiffness, function scores and total scores of WOMAC were decreased as compared with those before treatment in the two groups (P<0.05), except for the pain score, the changes of above scores in the short needling group were greater than the conventional acupuncture group (P<0.05). After treatment, the VAS scores, serum levels of TNF-a, IL-1β, IL-6, PGE₂ and knee joint synovium thickness, intra-articular effusion were decreased as compared with those before treatment in the two groups (P<0.05), the levels of TNF-a, IL-1β, IL-6 in the short needling group were lower than the conventional acupuncture group (P<0.05). The total effective rate in the short needling group was 87.1% (27/31), which was superior to 83.9% (26/31) in the conventional acupuncture group (P<0.05). CONCLUSION Short needling could improve the knee joint function, relieve the pain and inflammatory response, improve the knee joint synovium inflammatory response, reduce the knee joint intra-articular effusion for KOA patients, its effect is better than conventional acupuncture.
Acupuncture Points ; Humans ; Inflammation ; Interleukin-6 ; Osteoarthritis, Knee/therapy* ; Pain ; Prostaglandins E

This article aims to investigate the ameliorative effect of Linderae Radix ethanol extract on hyperlipidemia rats induced by high-fat diet and to explore its possible mechanism from the perspective of reverse cholesterol transport(RCT). SD rats were divided into normal group, model group, atorvastatin group, Linderae Radix ethanol extract(LREE) of high, medium, low dose groups. Except for the normal group, the other groups were fed with a high-fat diet to establish hyperlipidemia rat models; the normal group and the model group were given pure water, while each administration group was given corresponding drugs by gavage once a day for five weeks. Serum total cholesterol(TC), triglyceride(TG), high density lipoprotein-cholesterol(HDL-c), low density lipoprotein-cholesterol(LDL-c), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) levels were measured by automatic blood biochemistry analyzer; the contents of TC, TG, total bile acid(TBA) in liver and TC and TBA in feces of rats were detected by enzyme colorimetry. HE staining was used to observe the liver tissue lesions; immunohistochemistry was used to detect the expression of ATP-binding cassette G8(ABCG8) in small intestine; Western blot and immunohistochemistry were used to detect the expression of peroxisome proliferator-activated receptor gamma/aerfa(PPARγ/α), liver X receptor-α(LXRα), ATP-binding cassette A1(ABCA1) pathway protein and scavenger receptor class B type Ⅰ(SR-BⅠ) in liver. The results showed that LREE could effectively reduce serum and liver TC, TG levels, serum LDL-c levels and AST activity, and increase HDL-c levels, but did not significant improve ALT activity and liver index; HE staining results showed that LREE could reduce liver lipid deposition and inflammatory cell infiltration. In addition, LREE also increased the contents of fecal TC and TBA, and up-regulated the protein expressions of ABCG8 in small intestine and PPARγ/α, SR-BⅠ, LXRα, and ABCA1 in liver. LREE served as a positive role on hyperlipidemia model rats induced by high-fat diet, which might be related to the regulation of RCT, the promotion of the conversion of cholesterol to the liver and bile acids, and the intestinal excretion of cholesterol and bile acids. RCT regulation might be a potential mechanism of LREE against hyperlipidemia.
Animals ; Biological Transport ; Cholesterol/metabolism* ; Diet, High-Fat/adverse effects* ; Hyperlipidemias/metabolism* ; Liver/metabolism* ; Rats ; Rats, Sprague-Dawley ; Triglycerides/metabolism*

Objective: To understand the health literacy and relevant factors of cancer prevention consciousness in Chinese urban residents from 2015 to 2017. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. The self-designed questionnaire was used to collect the information of demographic characteristics and cancer prevention consciousness focusing on nine common risk factors, including smoking, alcohol, fiber food, food in hot temperature or pickled food, chewing betel nut, helicobacter pylori, moldy food, hepatitis B infection, estrogen, and exercise. The logistic regression model was adopted to identify the influencing factors. Results: The overall health literacy of the cancer prevention consciousness was 77.4% (24 980 participants), with 77.4% (12 018 participants), 79.9% (6 406 participants), 77.2% (1 766 participants) and 74.5% (4 709 participants) in each group (P<0.001). The correct response rates for nine risk factors ranged from 55.2% to 93.0%. The multivariate logistic regression analysis showed that compared with community residents, people with primary school level education or below, and the number of people living together in the family <3, the cancer risk assessment/screening intervention population, cancer patients, those with junior high school level educationor above and the number of people living in the family ≥3 had better health literacy of the cancer prevention consciousness (all P values <0.05). Compared with females, 39 years old and below, government-affiliated institutions or civil servants, from the eastern region, males, older than 40 years, company or enterprise employees, and from the middle or western region had worse health literacy of the cancer prevention consciousness (all P values <0.05). Conclusion The health literacy of the cancer prevention consciousness in Chinese urban residents should be improved. The cancer screening intervention, gender, age, education, occupation, the number of people co-living in the family, and residential region were associated with the health literacy of the cancer prevention consciousness.

Objective: To understand the consciousness of the cancer early detection among urban residents and identify the influencing factors from 2015 to 2017. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. Self-designed questionnaires were used to collect population, socioeconomic indicators, self-cancer risk assessment, regular participation in physical examination and other information. The multivariate logistic regression model was used to identify the factors of people who had not regularly participated in the regular physical examination in the past five years. Results: The self-assessment results of 32 357 residents showed that there were 27.54% (8 882) of total study population with self-reported cancer risk, 45.48% (14 671) without cancer risk and 26.98% (8 704) with unclear judgement on their own cancer risk. Among population with cancer risk, 79.84% (7 091) considered physical examination accounted. In the past five years, there were 21 105 (65.43%) residents participated in regular physical examination and 11 148 (34.56%) participated in non-scheduled one, respectively. The multivariate logistic regression analysis showed that compared with unmarried and western region residents, divorced, middle and eastern region residents had a stronger consciousness to participate in the regular physical examination (P<0.05). Compare with residents with annual household income less than 20 000 CNY in 2014, cancer risk assessment/screening intervention population, and self-assessment with cancer risk, residents with annual household income between 20 000 CNY and 59 000 CNY in 2014, occupational population, community residents, cancer patients, self-reported cancer-free risk, and self-assessment with unclear judgement of cancer risk were less likely to participate in the regular physical examination (all P values <0.05). Conclusion From 2015 to 2017, the Chinese urban residents had a acceptable consciousness of the cancer early detection. The marital status, annual household income, population group and self-assessment of cancer risk were related to the consciousness of the cancer early detection of people who had not participated in the regular physical examination in the past five years.