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

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.

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.

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.

Objective:To observe the inhibiting effects of manual acupuncture(MA)on bladder cell apoptosis in rats with diabetic neurogenic bladder(DNB)based on the protein and mRNA expression of B-cell lymphoma-leukemia(Bcl)-2,Bcl-2-associated X(Bax)protein,caspase-3,and the protein expression of α-smooth muscle actin(α-SMA),transforming growth factor(TGF)-β in the bladder tissue. Methods:A DNB rat model was established via intraperitoneal injection of streptozotocin(STZ).The rats were randomly divided into a control group,a model group,and an MA group,with 10 rats in each group.For the MA group,MA was applied after modeling.The body mass,fasting blood glucose(FBG),bladder wet weight,and bladder histomorphology were observed.Protein and mRNA expression levels of Bcl-2,Bax,and caspase-3 and the protein expression of α-SMA and TGF-β in the bladder tissue were determined.The apoptotic index of bladder cells was also evaluated. Results:After STZ injection,compared with the control group,the model group and the MA group both showed higher FBG from week 3 and lower body mass from week 9(P<0.05),and had a larger bladder wet weight(P<0.05).Compared with the model group,the MA group showed a smaller bladder wet weight(P<0.05).The histopathological evaluation indicated that MA improved muscle fiber alignment and detrusor cell compensatory hypertrophy in the bladder tissue.In addition,compared with the control group,the apoptotic index increased significantly in the model group and the MA group(P<0.05);the protein and mRNA expression levels of Bax and caspase-3 and the protein expression level of TGF-β in the bladder tissue in the model group and the MA group increased significantly(P<0.05),while the protein and mRNA expression levels of Bcl-2 and the protein expression level of α-SMA in the bladder tissue decreased significantly(P<0.05).Compared with the model group,the apoptotic index of the MA group decreased significantly(P<0.05);the protein and mRNA expression levels of Bax and caspase-3 and the protein expression level of TGF-β in the bladder tissue decreased significantly(P<0.05),while the protein and mRNA expression levels of Bcl-2 and the protein expression level of α-SMA in the bladder tissue increased significantly(P<0.05). Conclusion:MA can protect the bladder by inhibiting the excessive apoptosis of bladder cells,which may be related to the down-regulation of Bax and caspase-3 proteins and mRNAs and TGF-β protein expression,and the up-regulation of Bcl-2 protein and mRNA and α-SMA protein expression.

AIM:To investigate of the effect of Shenqifuzheng injection(SFI)combined with PD-L1 antibody on tumor immune microenvironment and its efficacy.METHODS:A subcutaneous transplanta-tion tumor model for B16F10-LUC melanoma was created.The expression of Ki67,CD31,CD8,CD16,CD163,FOXP3,LY6C,LY6G with labeling antibodies was used to detect CD8+T cells,Treg cells,NK cells,MDSCs cells,centrocytes,and granulocytes in the tumor tissues via immunohistochemistry.Flow cy-tometry was used to measure the ratios of CD11c+,IA/IE+,and CD80+cells in splenic tissue,as well as the ratios of CD8+T,CD4+T,and Treg cells in tumor tissue.Additionally,granulocyte count and NK cell expression were analyzed.RESULTS:The immuno-histochemistry results indicate that the drug admin-istration group effectively suppressed tumor angio-genesis and cell proliferation,while decreasing the expression level of immunosuppressive cytokines CD4+T cells,Treg cells,MDSCs and centroblasts.Ad-ditionally,CD8 and NK cell infiltration was promot-ed compared to the control group.The results of the flow analysis demonstrated a significant in-crease in the expression level of CD8+T cells within tumor tissues,as well as inhibition of CD4+T,Treg,and DC cell infiltration within the spleen in the drug administration group.Additionally,the tumor volume analysis indicated that the drug administra-tion group effectively inhibited tumor growth.The flow results illustrate that the group administering treatment exhibited significant increases in CD8+T cell expression levels in tumor tissue and DC cells in the spleen.Furthermore,the treatment effec-tively inhibited the infiltration of CD4+T and Treg cells.The results also indicate that the treatment significantly reduced tumor growth,with the tumor inhibition rate being better with PD-L1 antibody alone than with the SFI group.Additionally,combin-ing drugs resulted in superior results compared to the PD-L1 antibody group alone.CONCLUSION:SFI combined with a PD-L1 antibody can have synergis-tic anti-tumor effects,potentially enhancing DC cell infiltration and promoting T cell activation.Immu-nohistochemistry results indicate a positive impact on the tumor immune microenvironment.

OBJECTIVE To evaluate the mechanisms underlying the antidepressant effect of ZBH2012001,a novel serotonin and norepinephrine reuptake inhibitor(SNRI),in general and its ability to enhance monoaminergic transmission and suppress neuroinflammation in particular.METHODS① Male ICR mice were divided into vehicle(distilled water),duloxetine(DLX,10 or 20 mg·kg-1)and ZBH2012001(5,10 and 20 mg·kg-1)groups.One hour following ig administration,the antidepressant effect of ZBH2012001 was evaluated using the tail suspension test(TST)and forced swimming test(FST).② Radioligand binding assay was conducted to evaluate the affinity of ZBH2012001 for human serotonin transporters(hSERTs)and human norepinephrine transporters(hNETs).③ Mice were divided into vehicle(distilled water),DLX(10 or 20 mg·kg-1)and ZBH2012001(5,10 and 20 mg·kg-1)groups.One hour following drug administration,the 5-hydroxytryptophan(5-HTP)-induced head-twitch test or yohimbine-induced lethality test were performed to evaluate the effect of ZBH2012001 on the function of the 5-hydroxytryptamine(5-HT)and norepinephrine(NE)systems.④ Mice were divided into vehicle(distilled water+0.1%acetic acid),reserpine model(distilled water+reserpine 5 mg·kg-1),DLX(DLX 20 mg·kg-1+reserpine 5 mg·kg-1)and ZBH2012001(ZBH2012001 5,10 and 20 mg·kg-1+reserpine 5 mg·kg-1)groups.One hour following drug administration,reserpine was injected intraperitoneally to establish a monoamine-depletion model.The ptosis,akinesia,and hypothermia assays were performed to evaluate the effect of ZBH2012001 on the down-regulation of the reserpine-induced monoamine system.The TST in mice was used to evaluate the effect of ZBH2012001 on reserpine-induced depressive-like behavior while high-performance liquid chromatography with electrochemical detection(HPLC-ECD)was used to measure the levels of monoamines and their metabolites in the hippocampal tissue of reserpine-induced monoamine-depletion mice.ELISA was employed to detect the contents of tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)in the hippocampal tissue of reserpine-induced monoamine-depletion mice.Western blotting was used to assess the expressions of ionized calcium-binding adapter molecule-1(Iba-1)and nuclear factor-kappa B(NF-κB)in the hippocampal tissue of reserpine-induced monoamine-depletion mice.RESULTS ① Compared with the vehicle group,ZBH2012001(5,10 and 20 mg·kg-1)significantly reduced the immobility time both in the TST in mice(P<0.01,respectively),and ZBH2012001(20 mg·kg-1)and in the FST in mice(P<0.05).② ZBH2012001 competitively inhibited the binding of[3H]-imipramine to hSERTs and[3H]-nisoxetine to hNETs,with the half maximal inhibitory concentration(IC50)values of 84.95 and 712.90 nmol·L-1,respectively.③Com-pared with the vehicle group,ZBH2012001(10 and 20 mg·kg-1)significantly increased the head twitches induced by 5-HTP in mice(P<0.01,respectively)and increased the mortality rate in mice induced by yohimbine(P<0.05,P<0.01).④ In the reserpine-induced monoamine-depletion model in mice,compared with the vehicle group,mice in the reserpine model group exhibited ptosis,akinesia and hypothermia feature(P<0.01,respectively),significantly prolonged immobility time in the TST(P<0.01),significantly decreased the levels of NE,5-HT and dopamine(DA)(P<0.05,P<0.01),significantly increased the metabolic conversion rate of 5-HT and DA(P<0.01,respectively),significantly elevated levels of TNF-α and IL-6(P<0.05,respectively),and significantly increased expressions of Iba-1 and NF-κB(P<0.05,respectively)in the hippocampus.Compared with the model group,ZBH2012001(5,10 and 20 mg·kg-1)significantly antagonized ptosis and hypothermia behaviors induced by reserpine(P<0.01,respectively),ZBH2012001(10 and 20 mg·kg-1)significantly shortened the immobility time in reserpine-treated mice(P<0.05,P<0.01),ZBH2012001(20 mg·kg-1)significantly increased the levels of NE and 5-HT in the hippocampus of reserpine-treated mice(P<0.05,respectively),decreased the metabolic conversion rate of 5-HT(P<0.05),significantly reduced the contents of TNF-α and IL-6 in the hippocampus of reserpine-treated mice(P<0.05,respectively),ZBH2012001(5,10 and 20 mg·kg-1)significantly reduced the expression of Iba-1 protein in the hippocampus of reserpine-treated mice(P<0.01,respec-tively),and ZBH2012001(20 mg·kg-1)significantly reduced the expression of NF-κB protein in the hippocampus of reserpine-treated mice(P<0.05).CONCLUSION ZBH2012001 exerts its antidepres-sant effect through a dual mechanism involving monoamine enhancement and inflammation suppres-sion.