ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.

ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.

ObjectiveTo evaluate the efficacy of Shexiang Baoxinwan in treating stable angina pectoris with Qi stagnation and blood stasis syndrome in patients with coronary artery disease （CAD） complicated with anxiety and depression and explore its underlying mechanisms. MethodsThis study employed a randomized， double-blind， and placebo-controlled clinical trial design. Patients admitted to the hospital were randomly assigned to the observation group and the control group， with 52 patients in each group. Patients in the observation and control groups received Shexiang Baoxinwan and placebo， respectively， both in combination with conventional Western medication. The dose was 45.0 mg， three times daily， for a total duration of eight weeks. The primary outcome was the Seattle Angina Questionnaire （SAQ） scores before and after treatment. Secondary outcomes included changes in traditional Chinese medicine （TCM） syndrome score， the patient health questionnaire-9 （PHQ-9）， generalized anxiety disorder-7 （GAD-7）， inflammatory markers ［interleukin-18 （IL-18）， interleukin-10 （IL-10）， tumor necrosis factor-alpha （TNF-α）， CD40， etc.］， monoamine neurotransmitters ［e.g.， dopamine （DA）］， vascular endothelial function markers ［e.g.， endothelin-1（ET-1）］， adipokines， and ischemia-modified albumin （IMA）. Adverse reactions were also recorded. ResultsA total of 92 patients completed the study， with 44 in the observation group and 48 in the control group. Compared with baseline， both groups showed significant decreases in PHQ-9， GAD-7， and TCM syndrome scores following treatment （P<0.05）， along with a significant increase in SAQ scores （P<0.05）. In the observation group， DA levels were significantly increased （P<0.05）， while levels of IL-18， TNF-α， CD40， ET-1， and IMA were decreased （P<0.05）. In contrast， the control group exhibited significantly increased CD40 levels （P<0.05）. Compared with the control group after treatment， the observation group showed significant improvements in the SAQ dimensions of physical limitation， angina stability， treatment satisfaction， and disease perception， as well as in TCM syndrome score， PHQ-9 score， IL-18， CD40， ET-1， and IMA （P<0.05）. No adverse reactions were observed in either group during treatment. ConclusionShexiang Baoxinwan can improve anxiety and depression， alleviate angina symptoms， and reduce TCM symptoms of Qi stagnation and blood stasis in CAD patients. The mechanism may involve anti-inflammation， improvement of vascular endothelial function， reduction of IMA， and increase of monoamine neurotransmitter levels.

ObjectiveTo evaluate the efficacy of Shexiang Baoxinwan in treating stable angina pectoris with Qi stagnation and blood stasis syndrome in patients with coronary artery disease （CAD） complicated with anxiety and depression and explore its underlying mechanisms. MethodsThis study employed a randomized， double-blind， and placebo-controlled clinical trial design. Patients admitted to the hospital were randomly assigned to the observation group and the control group， with 52 patients in each group. Patients in the observation and control groups received Shexiang Baoxinwan and placebo， respectively， both in combination with conventional Western medication. The dose was 45.0 mg， three times daily， for a total duration of eight weeks. The primary outcome was the Seattle Angina Questionnaire （SAQ） scores before and after treatment. Secondary outcomes included changes in traditional Chinese medicine （TCM） syndrome score， the patient health questionnaire-9 （PHQ-9）， generalized anxiety disorder-7 （GAD-7）， inflammatory markers ［interleukin-18 （IL-18）， interleukin-10 （IL-10）， tumor necrosis factor-alpha （TNF-α）， CD40， etc.］， monoamine neurotransmitters ［e.g.， dopamine （DA）］， vascular endothelial function markers ［e.g.， endothelin-1（ET-1）］， adipokines， and ischemia-modified albumin （IMA）. Adverse reactions were also recorded. ResultsA total of 92 patients completed the study， with 44 in the observation group and 48 in the control group. Compared with baseline， both groups showed significant decreases in PHQ-9， GAD-7， and TCM syndrome scores following treatment （P<0.05）， along with a significant increase in SAQ scores （P<0.05）. In the observation group， DA levels were significantly increased （P<0.05）， while levels of IL-18， TNF-α， CD40， ET-1， and IMA were decreased （P<0.05）. In contrast， the control group exhibited significantly increased CD40 levels （P<0.05）. Compared with the control group after treatment， the observation group showed significant improvements in the SAQ dimensions of physical limitation， angina stability， treatment satisfaction， and disease perception， as well as in TCM syndrome score， PHQ-9 score， IL-18， CD40， ET-1， and IMA （P<0.05）. No adverse reactions were observed in either group during treatment. ConclusionShexiang Baoxinwan can improve anxiety and depression， alleviate angina symptoms， and reduce TCM symptoms of Qi stagnation and blood stasis in CAD patients. The mechanism may involve anti-inflammation， improvement of vascular endothelial function， reduction of IMA， and increase of monoamine neurotransmitter levels.

Objective To discuss the effects of the"twelve needles for hands and feet"acupuncture on the brain response mechanism and acupoint specificity in hemiplegic patients after ischemic stroke using fMRI.Methods Totally 43 inpatients from Dongzhimen Hospital of Beijing University of Chinese Medicine from December 2018 to March 2023 were included.The included patients were randomly divided into a true acupoint group of 23 cases and a fake acupoint group of 20 cases using the random number table method for clinical scale evaluation and magnetic resonance scanning.The true acupoint group received"twelve needles for hands and feet"acupuncture;the fake acupoint group was treated with acupuncture by opening 1 inch next to the meridian point,once a day,for consecutive 10 d.Intervention completed,excluding subjects who fell out during the intervention process,had unsatisfactory MRI data quality and had incomplete clinical scales,and conducting data processing and analysis.Bilateral anterior central gyrus(PreCG),amygdala(AMYG),caudate nucleus(CAU),putamen lenticularis(PUT),pallidus lenticularis(PAL)and thalamus(THA)were selected as regions of interest(ROI),and the changes in Granger causality(GC)and differences in scale scores between the two groups before and after treatment were compared.Results After intervention in the true acupoint group,the GC of CAU.R → PreCG.R,AMYG.R → PAL.R was stronger than before intervention,and the GC of THA.L→PAL.L,AMYG.R→THA.R in the true acupoint group was weaker than before intervention(P<0.05);after intervention with fake acupoints,the GC of AMYG.R→PUT.L in the false acupoint group was stronger than before intervention,and the GC of THA.L→PreCG.R,AMYG.L→CAU.L was weaker than before intervention(P<0.05);the GC of THA.R→PAL.L before intervention was stronger than false acupoint group,the GC of CAU.L→PreCG.R,PUT.L→PreCG.R before intervention was weaker than fake acupoint group(P<0.05);the GC of CAU.R→PreCG.R,THA.L→PreCG.R,AMYG.R→CAU.L,THA.L→PAL.R,AMYG.L→THA.L after intervention in the true acupoint group was stronger than the false acupoint group,and the GC of AMYG.R→AMYG.L after intervention in the true acupoint group was weaker than the fake acupoint group(P<0.05).Conclusion"Twelve needles for hands and feet"acupuncture can stimulate preferential compensation of the right motor circuit,bilateral basal ganglia remodeling,and balance regulation of excitatory inhibitory effects on the thalamus in patients with radiation-induced coronary stroke,thereby improving the degree of motor dysfunction and neurological deficits;acupuncture at acupoints stimulates brain activity more than at non-acupoints,indicating acupoint specificity.

Objective:To explore the medication law of national TCM master Lu Fang in the treatment of primary trigeminal neuralgia (PTN) based on data mining.Methods:With the prescription of the outpatient patients of Harbin Traditional Chinese Medicine Hospital of Professor Lu Fang from September 2014 to September 2022 as the data source, the frequency, property and taste, and meridian tropism of the prescribed drugs were analyzed using Excel 2022 software. R 4.2.1 was used for mining analysis on Chinese materia medica, including correlation, relevance, and clustering,and the medication law in the treatment of PTN was discussed.Results:A total of 300 prescriptions were analyzed, involving 177 kinds of Chinese materia medica, with a frequency of 3 120 times, and 34 kinds of of high-frequency Chinese materia medica. The high frequently Chinese materia medica included Chuanxiong Rhizoma, Angelicae Dahuricae Radix, Puerariae Lobatae Radix, Ligustici Rhizoma et Radix, and Viticis Fructus. The main properties were warm, slightly cold, and neutral, while the main tastes were pungent, bitter, and sweet. The meridian tropism analysis ranked the liver, lung, spleen, and stomach meridians in descending order. Analysis yielded 21 strong association rules, and the association analysis formed a core prescription group based on Chuanxiong Rhizoma, Angelicae Dahuricae Radix, and Ligustici Rhizoma et Radix. The analysis obtained 5 types of clustering combinations.Conclusion:Professor Lu Fang's the medication law to treat primary trigeminal neuralgia is mainly dispelling wind and alleviating pain, which is often combined with the methods, such as searching and dredging collaterals, clearing and dispelling the stagnated heat, calming the liver and subduing yang, soothing the liver and invigorating the spleen.

Objective To discuss the effects of the"twelve needles for hands and feet"acupuncture on the brain response mechanism and acupoint specificity in hemiplegic patients after ischemic stroke using fMRI.Methods Totally 43 inpatients from Dongzhimen Hospital of Beijing University of Chinese Medicine from December 2018 to March 2023 were included.The included patients were randomly divided into a true acupoint group of 23 cases and a fake acupoint group of 20 cases using the random number table method for clinical scale evaluation and magnetic resonance scanning.The true acupoint group received"twelve needles for hands and feet"acupuncture;the fake acupoint group was treated with acupuncture by opening 1 inch next to the meridian point,once a day,for consecutive 10 d.Intervention completed,excluding subjects who fell out during the intervention process,had unsatisfactory MRI data quality and had incomplete clinical scales,and conducting data processing and analysis.Bilateral anterior central gyrus(PreCG),amygdala(AMYG),caudate nucleus(CAU),putamen lenticularis(PUT),pallidus lenticularis(PAL)and thalamus(THA)were selected as regions of interest(ROI),and the changes in Granger causality(GC)and differences in scale scores between the two groups before and after treatment were compared.Results After intervention in the true acupoint group,the GC of CAU.R → PreCG.R,AMYG.R → PAL.R was stronger than before intervention,and the GC of THA.L→PAL.L,AMYG.R→THA.R in the true acupoint group was weaker than before intervention(P<0.05);after intervention with fake acupoints,the GC of AMYG.R→PUT.L in the false acupoint group was stronger than before intervention,and the GC of THA.L→PreCG.R,AMYG.L→CAU.L was weaker than before intervention(P<0.05);the GC of THA.R→PAL.L before intervention was stronger than false acupoint group,the GC of CAU.L→PreCG.R,PUT.L→PreCG.R before intervention was weaker than fake acupoint group(P<0.05);the GC of CAU.R→PreCG.R,THA.L→PreCG.R,AMYG.R→CAU.L,THA.L→PAL.R,AMYG.L→THA.L after intervention in the true acupoint group was stronger than the false acupoint group,and the GC of AMYG.R→AMYG.L after intervention in the true acupoint group was weaker than the fake acupoint group(P<0.05).Conclusion"Twelve needles for hands and feet"acupuncture can stimulate preferential compensation of the right motor circuit,bilateral basal ganglia remodeling,and balance regulation of excitatory inhibitory effects on the thalamus in patients with radiation-induced coronary stroke,thereby improving the degree of motor dysfunction and neurological deficits;acupuncture at acupoints stimulates brain activity more than at non-acupoints,indicating acupoint specificity.

Background/Aims: Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking. Methods: Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth. Results: Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy. Conclusions UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.

Objective:To study the genomic sequence of Coxsackievirus A8 (CV-A8) associated with hand, foot and mouth disease (HFMD) from 2013 to 2018 in China and to analyze the genetic evolution of each coding region of the full-length genome.Methods:The genome sequences of 11 CV-A8 strains isolated from patients with HFMD in different regions of China from 2013 to 2018 were determined. Sequence alignment and genetic evolution analysis were performed by Sequencher 5.0 and MEGA 7.0 software, etc.Results:Sequence alignment showed that the genome length of 11 CV-A8 strains ranged from 7 393 bp to 7 400 bp. There was no base insertion or deletion in the coding region compared with the prototype strain, but there were individual base insertion or deletion in the non-coding region. The nucleotide and amino acid similarities in the VP1 region of 11 CV-A8 strains were 78.3%-98.6% and 92.6%-99.7%, respectively, and the nucleotide and amino acid sequences identities with the CV-A8 prototype strain were 78.3%-98.2% and 92.6%-99.7%, respectively. Based on the phylogenetic analysis of VP1 region sequences, the CV-A8 can be divided into five genotypes: A, B, C, D and E. The 11 CV-A8 strains in this study belonged to genotypes C (1 strain), D (2 strains) and E (8 strains). The nucleotide and amino acid similarities of 11 CV-A8 full-length genomes were 81.3%-98.8% and 95.9%-99.5%, respectively. The phylogenetic tree of the P2 region showed that the eight E genotypes CV-A8 had the closest evolutionary distance with CV-A4, CV-A14, and CV-A16. The phylogenetic tree of the P3 region showed that the eight E genotypes CV-A8 had a close evolutionary distance with CV-A5, CV-A16, CV-A14 and CV-A4.Conclusions:The 11 CV-A8 stains in this study showed significant intra-genotype diversity in capsid region and recombinant diversity in non-capsid region which indicated that CV-A8 quasispecies were still undergoing dynamics variation. CV-A8 may become an important pathogen of HFMD and the monitoring of CV-A8 needs to be further strengthened.

Objective To observe the clinical efficacy of abdominal electroacupuncture plus umbilicus application with Chinese medication in treating poststroke constipation.Method A total of 160 patients with poststroke constipation were randomized into a treatment group and a control group, 80 cases in each group. The treatment group was intervened by abdominal electroacupuncture plus umbilicus application with Chinese medication, while the control group was intervened by oral administration of Phenolphthalein tablets. The constipation symptoms scores were observed before and after the treatment, and the clinical efficacies were compared.Result In the treatment group, the constipation symptoms scores were significantly changed after the treatment (P<0.05). In the control group, the scores of defecation duration and abdominal bloating were significantly changed after the treatment (P<0.05). The constipation scores in the treatment group were significantly different from those in the control group after the treatment (P<0.05). The recovery rate and total effective rate were respectively 66.3% and 92.5% in the treatment group, versus 40.0% and 78.8% in the control group, and the between-group differences were statistically significant (P<0.05). Conclusion Abdominal electroacupuncture plus umbilicus application with Chinese medication is an effective method in treating poststroke constipation.