To understand the pathogenicity and drug resistance of swine-derived E.coli and its bio-logical characteristics in some areas in Hebei,E.coli was isolated and identified from diarrheal fe-ces of piglets collected from swine farms,and the isolated strains were subjected to drug sensitivity test,detection of the ability to form biofilm,pathogenicity test,virulence gene test,drug resistance gene test,and identification of phylogenetic subgroups.The results showed that a total of 35 patho-genic E.coli strains were isolated from the feces of diarrheic piglets,and most of the isolates were multidrug-resistant,and were resistant to at least three antibiotics,including amoxicillin(88.57％),ampicillin(88.57％),doxycycline(88.75％),sulfisoxazole(77.17％),lincomycin(100％),and chloramphenicol(100％);the isolates were severely resistant.The isolates all carried virulence genes,with a total of five virulence genes detected,namely,EAST1(77.14％),eaeA(17.14％),stx2e(5.71％),LT(2.86％),and STb(2.86％),and the isolates also carried multi-re-sistance genes,with a total of five virulence genes detected,namely,bla TEM-1(65.71％),bla CTX-M(20.00％),tetA(82.86％),tetB(14.29％),aadA2(17.14％),aac(6')-Ib(14.29％),qnrS(17.14％),sul 1(40.00％),sul2(34.29％),and floR(60.00％);the phylogenetic grouping showed that the isolates had a high proportion of group B1 and group A;and all 35 isolates showed differ-ent pathogenicity after infection of mice.This study provides a reference for the selection of effec-tive therapeutic drugs and the development of prevention and control programs for swine-origin pathogenic E.coli in Hebei Province.

Objective We explored the anti-depressant activity and mechanism of arecoline in vivo in a mouse model of depression induced by chronic unpredictable mild stress.The aim was to explore the possible mechanisms of action,providing experimental evidence for further research into the health benefits of arecoline and theoretical support for the scientific development and utilization of this resource.Methods Sixty quarantine-qualified SPF C57BL/6J mice were divided randomly into a control group,model group,fluoxetine group(20 mg/kg),and arecoline low-,medium-,and high-dose groups(10,20,and 40 mg/kg,respectively)according to body mass(n=10 mice per group).The effects of arecoline on the behavior of the mice were evaluated by open-field,tail-suspension,and forced-swimming tests.Serum corticosterone and serum and brain levels of superoxide dismutase(SOD)were detected by enzyme-linked immunoassay.Malondialdehyde(MDA),catalase(CAT),5-hydroxytryptamine(5-HT),and norepinephrine(NE)levels in brain tissue,and dopamine(DA),gamma-aminobutyric acid(GABA),tumor necrosis factor(TNF-α),interleukin(IL)-10,IL-1β,brain-derived neurotrophic factor(BDNF),tropomyosin receptor kinase B(TrkB),and cAMP-response element binding protein(CREB)were detected by Western Blot.Results Arecoline significantly reduced the total distance and average speed of the model mice in open field tests and increased activities,and significantly reduced the immobility time in the tail suspension and forced swimming tests.Arecoline also significantly decreased serum corticosterone levels,increased SOD and CAT,and decreased MDA levels.5-HT,DA,NE,and GABA levels were significantly increased,and the cytokines TNF-α,IL-6,and IL-1β were significantly decreased.Expression levels of BDNF,TrkB,and CREB in the brain tissue were significantly increased.Conclusions Research has found that arecoline has a significant antidepressant ability,and its mechanism may be achieved by reducing oxidative stress damage,inhibiting neuroinflammation,regulating neurotransmitter balance,and regulating the BDNF/TrkB/CREB signaling pathway..This study explored the antidepressant efficacy of arecoline and preliminarily revealed its possible regulatory mechanism,which can provide data support for the neuroactivity of arecoline and lay a theoretical foundation for the development of arecoline as medicine.

This case report highlights the successful treatment of moderate-to-severe thyroid-associated ophthalmopathy(TAO) with teprotumumab in a patient who had previously failed multiple therapies, including intravenous steroid pulse therapy, local thyroid injections of cyclophosphamide, octreotide and dexamethasone, tocilizumab treatment, total thyroidectomy, and orbital radiation. Despite these interventions, there was no improvement in TAO. Following treatment with teprotumumab, the patient experienced a reduction of 5 mm in left eye proptosis and 4 mm in right eye proptosis, a 6-point decrease in the clinical activity score(CAS), a 2-point reduction in the diplopia score, and a significant improvement in quality of life, with sustained effects lasting 72 weeks. The treatment was well tolerated, with mild side effects including muscle spasm, fatigue, and dryness of the skin and nasal mucosa. This case report aims to raise clinical awareness regarding efficacy and safety of teprotumumab.

This case report highlights the successful treatment of moderate-to-severe thyroid-associated ophthalmopathy(TAO) with teprotumumab in a patient who had previously failed multiple therapies, including intravenous steroid pulse therapy, local thyroid injections of cyclophosphamide, octreotide and dexamethasone, tocilizumab treatment, total thyroidectomy, and orbital radiation. Despite these interventions, there was no improvement in TAO. Following treatment with teprotumumab, the patient experienced a reduction of 5 mm in left eye proptosis and 4 mm in right eye proptosis, a 6-point decrease in the clinical activity score(CAS), a 2-point reduction in the diplopia score, and a significant improvement in quality of life, with sustained effects lasting 72 weeks. The treatment was well tolerated, with mild side effects including muscle spasm, fatigue, and dryness of the skin and nasal mucosa. This case report aims to raise clinical awareness regarding efficacy and safety of teprotumumab.

OBJECTIVE: To propose a machine learning-based method for predicting the trajectories during manual acupuncture manipulation (MAM), aiming to improve the precision and consistency of acupuncture practitioner' operation and provide the real-time suggestions on MAM error correction. METHODS: Computer vision technology was used to analyze the hand micromotion when holding needle during acupuncture, and provide a three-dimensional coordinate description method of the index finger joints of the holding hand. Focusing on the 4 typical motions of MAM, a machine learning-based MAM trajectory predictive model was designed. By integrating the changes of phalangeal joint angle and hand skeletal information of acupuncture practitioner, the motion trajectory of the index finger joint was predicted accurately. Besides, the roles of machine learning-based MAM trajectory predictive model in the skill transmission of acupuncture manipulation were verified by stratified randomized controlled trial. RESULTS: The performance of MAM trajectory predictive model, based on the long short-term memory network (LSTM), obtained the highest stability and precision, up to 98%. The learning effect was improved when the model applied to the skill transmission of acupuncture manipulation. CONCLUSION The machine learning-based MAM predictive model provides acupuncture practitioner with precise action prediction and feedback. It is valuable and significant for the inheritance and error correction of manual operation of acupuncture.
Humans ; Acupuncture Therapy/instrumentation* ; Machine Learning ; Adult ; Male ; Female

To understand the pathogenicity and drug resistance of swine-derived E.coli and its bio-logical characteristics in some areas in Hebei,E.coli was isolated and identified from diarrheal fe-ces of piglets collected from swine farms,and the isolated strains were subjected to drug sensitivity test,detection of the ability to form biofilm,pathogenicity test,virulence gene test,drug resistance gene test,and identification of phylogenetic subgroups.The results showed that a total of 35 patho-genic E.coli strains were isolated from the feces of diarrheic piglets,and most of the isolates were multidrug-resistant,and were resistant to at least three antibiotics,including amoxicillin(88.57％),ampicillin(88.57％),doxycycline(88.75％),sulfisoxazole(77.17％),lincomycin(100％),and chloramphenicol(100％);the isolates were severely resistant.The isolates all carried virulence genes,with a total of five virulence genes detected,namely,EAST1(77.14％),eaeA(17.14％),stx2e(5.71％),LT(2.86％),and STb(2.86％),and the isolates also carried multi-re-sistance genes,with a total of five virulence genes detected,namely,bla TEM-1(65.71％),bla CTX-M(20.00％),tetA(82.86％),tetB(14.29％),aadA2(17.14％),aac(6')-Ib(14.29％),qnrS(17.14％),sul 1(40.00％),sul2(34.29％),and floR(60.00％);the phylogenetic grouping showed that the isolates had a high proportion of group B1 and group A;and all 35 isolates showed differ-ent pathogenicity after infection of mice.This study provides a reference for the selection of effec-tive therapeutic drugs and the development of prevention and control programs for swine-origin pathogenic E.coli in Hebei Province.

Objective We explored the anti-depressant activity and mechanism of arecoline in vivo in a mouse model of depression induced by chronic unpredictable mild stress.The aim was to explore the possible mechanisms of action,providing experimental evidence for further research into the health benefits of arecoline and theoretical support for the scientific development and utilization of this resource.Methods Sixty quarantine-qualified SPF C57BL/6J mice were divided randomly into a control group,model group,fluoxetine group(20 mg/kg),and arecoline low-,medium-,and high-dose groups(10,20,and 40 mg/kg,respectively)according to body mass(n=10 mice per group).The effects of arecoline on the behavior of the mice were evaluated by open-field,tail-suspension,and forced-swimming tests.Serum corticosterone and serum and brain levels of superoxide dismutase(SOD)were detected by enzyme-linked immunoassay.Malondialdehyde(MDA),catalase(CAT),5-hydroxytryptamine(5-HT),and norepinephrine(NE)levels in brain tissue,and dopamine(DA),gamma-aminobutyric acid(GABA),tumor necrosis factor(TNF-α),interleukin(IL)-10,IL-1β,brain-derived neurotrophic factor(BDNF),tropomyosin receptor kinase B(TrkB),and cAMP-response element binding protein(CREB)were detected by Western Blot.Results Arecoline significantly reduced the total distance and average speed of the model mice in open field tests and increased activities,and significantly reduced the immobility time in the tail suspension and forced swimming tests.Arecoline also significantly decreased serum corticosterone levels,increased SOD and CAT,and decreased MDA levels.5-HT,DA,NE,and GABA levels were significantly increased,and the cytokines TNF-α,IL-6,and IL-1β were significantly decreased.Expression levels of BDNF,TrkB,and CREB in the brain tissue were significantly increased.Conclusions Research has found that arecoline has a significant antidepressant ability,and its mechanism may be achieved by reducing oxidative stress damage,inhibiting neuroinflammation,regulating neurotransmitter balance,and regulating the BDNF/TrkB/CREB signaling pathway..This study explored the antidepressant efficacy of arecoline and preliminarily revealed its possible regulatory mechanism,which can provide data support for the neuroactivity of arecoline and lay a theoretical foundation for the development of arecoline as medicine.

Objective:To observe the effects of Zhulian stimulant type Ⅰ acupuncture on the expression of brain-derived neurotrophic factor (BDNF) and its receptor TrkB and tissue homogenate cyclic adenosine phosphate (cAMP) in rats with diabetic bladder (DCP); To explore the mechanism of Zhulian stimulant type Ⅰacupuncture on DCP.Methods:Totally 50 SD rats were divided into control group, model group, Western medicine group, ordinary acupuncture group, Zhulian stimulant type Ⅰ acupuncture treatment group (acupuncture treatment group) according to random number table method, with 10 rats in each group. DCP rat model was prepared by intraperitoneal injection of streptozotocin (STZ), except for the control group. The Western medicine group was given mecobalamine for gavage; acupoints of "Zhongji", "Sanyinjiao", "Liechou" and "Taichong" were selected. The ordinary acupuncture group was treated with ordinary acupuncture technique, and the acupuncture treatment group was treated with Zhulian stimulant type Ⅰ acupuncture, 1 time/d, 30 minutes/time. Samples were taken after 4 weeks of treatment. The maximum bladder volume, residual urine volume and wet weight of the bladder were detected. The morphology of rat bladder was observed by HE staining. The expression level of BDNF was detected by immunohistochemistry. The expression of cAMP was detected by Western blot. The level of TrkB was determined by ELISA. Real-time fluorescence quantitative PCR (RT-PCR) was used to detect the mRNA expressions of BDNF and cAMP.Results:Compared with model group, maximum bladder volume, residual urine volume and wet weight of bladder in Western medicine group, ordinary acupuncture group and acupuncture treatment group decreased ( P<0.01), and those in Western medicine group and acupuncture treatment group were lower than those in ordinary acupuncture group ( P<0.01). The expressions of BDNF mRNA and protein, cAMP mRNA and protein in Western medicine group, ordinary acupuncture group and acupuncture treatment group increased ( P<0.05), and the level of TrkB increased, and the Western medicine group and acupuncture treatment group were higher than that in ordinary acupuncture group ( P<0.05). Conclusions:Zhuliping stimulant type Ⅰ acupuncture has a protective effect on the bladder function of diabetic rats. The mechanism may be related to the up-regulation of BDNF and mRNA, TrkB, cAMP and mRNA expressions.

Objective:To investigate the molecular mechanisms of chronic rhinosinusitis (CRS), to identify key cell subgroups and genes, to construct effective diagnostic models, and to screen for potential therapeutic drugs.Methods:Key cell subgroups in CRS were identified through single-cell transcriptomic sequencing data. Essential genes associated with CRS were selected and diagnostic models were constructed by hdWGCNA (high dimensional weighted gene co-expression network analysis) and various machine learning algorithms. Causal inference analysis was performed using Mendelian randomization and colocalization analysis. Potential therapeutic drugs were identified using molecular docking technology, and the results of bioinformatics analysis were validated by immunofluorescence staining. Graphpad Prism, R, Python, and Adobe Illustrator software were used for data and image processing.Results:An increased proportion of basal and suprabasal cells was observed in CRS, especially in eosinophilic CRS with nasal polyps (ECRSwNP), with P=0.001. hdWGCNA revealed that the "yellow module" was closely related to basal and suprabasal cells in CRS. Univariate logistic regression and LASSO algorithm selected 13 key genes ( CTSC, LAMB3, CYP2S1, TRPV4, ARHGAP21, PTHLH, CDH26, MRPS6, TENM4, FAM110C, NCKAP5, SAMD3, and PTCHD4). Based on these 13 genes, an effective CRS diagnostic model was developed using various machine learning algorithms (AUC=0.958). Mendelian randomization analysis indicated a causal relationship between CTSC and CRS (inverse variance weighted: OR=1.06, P=0.006), and colocalization analysis confirmed shared genetic variants between CTSC and CRS (PPH4/PPH3>2). Molecular docking results showed that acetaminophen binded well with CTSC (binding energy:-5.638 kcal/mol). Immunofluorescence staining experiments indicated an increase in CTSC +cells in CRS. Conclusion:This study integrates various bioinformatics methods to identify key cell types and genes in CRS, constructs an effective diagnostic model, underscores the critical role of the CTSC gene in CRS pathogenesis, and provides new targets for the treatment of CRS.

Objective:This report presents the initial outcomes of endoscopic intermuscular dissection (EID), a novel technique introduced by our team for the diagnostic resection of early rectal cancer, focusing on the postoperative status of the vertical margins.Methods:On January 26, 2024, a patient with early rectal cancer (cT1-2N0M0) underwent Endoscopic Intermuscular Dissection. The EID procedure consists of six steps: (1) mucosal incision; (2) submucosal dissection; (3) superficial muscular layer incision; (4) intermuscular dissection; (5) complete tumor removal; (6) wound management.Results:The patient was a 70-year-old male with rectal cancer (cT1-2N0M0). The tumor was located on the left anterior wall of the rectum, approximately 9 cm from the anal margin, and measured 20mm in size. The dissection rate was 2.68 mm2/minute, and the total duration of the surgery was 109 minutes. The patient was successfully discharged on the fifth day after surgery. Pathological examination of the post-endoscopic surgery specimen revealed pT1b, with negative vertical margins. Follow-up after more than one month showed good recovery with no complications such as bleeding, perforation, infection, or stricture occurring. Colonoscopy indicated the presence of a granulation tissue suggestive of inflammation.Conclusion:Endoscopic Intermuscular Dissection for the diagnostic resection of early rectal cancer is potentially safe and may achieve negative vertical margins.