Attention deficit hyperactivity disorder （ADHD） is often accompanied by tic disorder. The core pathogenesis is considered to be ministerial fire scorching yin and internal stirring of deficient wind， which leads to disharmony between the body and spirit， resulting in clinical manifestations. The treatment principles emphasize nourishing yin fluids， calming ministerial fire， and extinguishing endogenous wind （内风）. The method of nourishing yin fluids is applied throughout the entire treatment process， commonly using ingredients such as Shudihuang （Rehmanniae Radix Praeparata）， Shanzhuyu （Corni Fructus）， Gouqizi （Lycii Fructus）， Wuweizi （Schisandrae Chinensis Fructus）， and Tusizi （Cuscutae Semen）. These are combined with approaches to harmonize the zang-fu organs， primarily including extinguishing liver wind， clearing heart fire， nourishing kidney water， and strengthening spleen earth， thereby stabilizing ministerial fire and extinguishing endogenous wind. Additionally， emotional regulation and smoothing emotional constraint are essential to improve clinical symptoms in children with ADHD comorbid with tic disorder.

Numerous c-mesenchymal-epithelial transition(c-MET)inhibitors have been reported as potential anticancer agents.However,most fail to enter clinical trials owing to poor efficacy or drug resistance.To date,the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed.In this study,we constructed the largest c-MET dataset,which included 2,278 molecules with different struc-tures,by inhibiting the half maximal inhibitory concentration(IC50)of kinase activity.No significant differences in drug-like properties were observed between active molecules(1,228)and inactive mol-ecules(1,050),including chemical space coverage,physicochemical properties,and absorption,distri-bution,metabolism,excretion,and toxicity(ADMET)profiles.The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding(t-SNE)high-dimensional data.Further clustering and chemical space networks(CSNs)analyses revealed commonly used scaffolds for c-MET inhibitors,such as M5,M7,and M8.Activity cliffs and structural alerts were used to reveal"dead ends"and"safe bets"for c-MET,as well as dominant structural fragments consisting of pyr-idazinones,triazoles,and pyrazines.Finally,the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules,including at least three aromatic het-erocycles,five aromatic nitrogen atoms,and eight nitrogen-oxygen atoms.Overall,our analyses revealed potential structure-activity relationship(SAR)patterns for c-MET inhibitors,which can inform the screening of new compounds and guide future optimization efforts.

The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis （GS/CACM 337-2023） was released by the China Association of Chinese Medicine on December 13^th， 2023. This expert consensus was developed by experts in methodology， pharmacy， and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine （CACM） and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine （pulmonary diseases） and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung， acute bronchitis， and acute attack of chronic bronchitis from the aspects of applicable populations， efficacy evaluation， usage， dosage， drug combination， and safety. It is expected to guide the rational drug use in medical and health institutions， give full play to the unique value of Qinbaohong Zhike oral liquid， and vigorously promote the inheritance and innovation of Chinese patent medicines.

BACKGROUND:Intervertebral disc degeneration is the main pathological factor causing low back pain,which is closely related to macrophage-mediated immune inflammation.Tongdu Huoxue Decoction is a proven prescription for the treatment of intervertebral disc degeneration,but it is still unclear whether it can treat intervertebral disc degeneration by regulating the polarization phenotype of macrophages to inhibit inflammation in intervertebral disc tissue.OBJECTIVE:To investigate the regulatory effects of Tongdu Huoxue Decoction on the expression of macrophage-related inflammatory factors in intervertebral disc tissues of rats,as well as its mechanisms for the treatment of intervertebral disc degeneration.METHODS:Twenty-four Sprague-Dawley rats were randomly divided into sham operation group,model group,and Tongdu Huoxue Decoction group,with eight rats in each group.An intervertebral disc degeneration model was established using the annulus fibrosus puncture method in the latter two groups.On the 1st postoperative day,10.8 g/kg Tongdu Huoxue Decoction was given by gavage in the Tongdu Huoxue Decoction group,and the same dose of saline was given by gavage in the sham operation group and the model group,once a day.After 4 weeks of intervention,histopathological changes in the intervertebral disc tissues were assessed using hematoxylin-eosin.Immunohistochemistry and quantitative real-time PCR were performed to detect the relative expression levels of CD68,CD206,interleukin 1β,interleukin 10,type II collagen,and matrix metalloproteinase 13 proteins or mRNA in the intervertebral disc tissues.RESULTS AND CONCLUSION:(1)Hematoxylin-eosin staining results revealed that the model group exhibited a significant decrease in intervertebral disc height,disorganized annulus fibrosus structure with fissures,and unclear demarcation between the nucleus pulposus and the annulus fibrosus.The Tongdu Huoxue Decoction group showed organized arrangement of the annulus fibrosus with pyknosis.(2)Immunohistochemical results demonstrated that,compared with the model group,the Tongdu Huoxue Decoction group had significantly lower expressions of CD68,interleukin 1β,and matrix metalloproteinase 13,and significantly higher expressions of CD206,type II collagen and interleukin 10(P<0.05 or P<0.01).(3)qPCR results showed that there were significant differences in the mRNA expression of CD68,CD206,interleukin 1β,matrix metalloproteinase 13,type II collagen,and interleukin 10 between the three groups(P<0.001).To conclude,Tongdu Huoxue Decoction can improve intervertebral disc degeneration in the rat model of intervertebral disc degeneration,and its mechanism is associated with the inhibition of macrophage-related inflammatory responses in the intervertebral discs.

Objective In this study,we investigated the correlation between the scores for different Liebowitz Social Anxiety Scale(LSAS)subscale models and the metabolic activity in specific regions of the brain using 18F-fluorodeoxyglucose(FDG)positron emission tomography/computed tomography(PET/CT)(18F-FDG PET),thereby improving the understanding of the neurobiological characteristics of social anxiety.Methods A total of 39 cognitively normal participants(29 men and 10 women,aged 30-63 years)were enrolled.All participants underwent LSAS assessment and brain 18F-FDG PET scanning.Correlations between metabolic activities in various brain regions and scores from the different LSAS subscales were analyzed accordingly.Results LSAS subscale scores were significantly correlated with metabolic activity in specific brain regions.In the Safren model,the score for the observation by others subscale was positively correlated with the left fusiform gyrus(P<0.001,false discovery rate[FDR]-corrected)and the left caudate tail(P<0.001,FDR-corrected),suggesting a close association between mood states related to observation by others and the metabolic activity in these regions.In the Baker model,the score for the eating and drinking subscale was negatively correlated with the right precuneus(P<0.001,FDR-corrected),while the score for the assertiveness subscale was positively correlated with the left caudate nucleus(P<0.001,FDR-corrected).These findings revealed the complex associative patterns between various mood and behavioral dimensions and metabolic activities in specific brain regions.Conclusion Social anxiety symptoms are closely associated with metabolic changes in specific brain regions,including the left insula,left caudate tail,and right precuneus.Moreover,different social situations activate distinct brain regions.Compared with individuals with social anxiety disorder,normal individuals exhibit involvement of fewer brain regions when experiencing social anxiety.These findings provide new experimental evidence for understanding the neural mechanisms underlying social anxiety.

Objective·To explore the value of combined diaphragm and intercostal muscle ultrasound assessment compared with conventional diaphragm ultrasound in predicting the weaning outcome in mechanically ventilated patients with sepsis.Methods·Mechanically ventilated patients with sepsis,consecutively admitted to the Department of Critical Care Medicine of Affiliated Hospital of Nantong University from October 2022 to December 2023,were selected.During the peri-weaning period,after the patient's sepsis condition improved and the patient passed the spontaneous breathing trial(SBT),ultrasound evaluation of respiratory muscles was performed by ultrasound qualified personnel with ultrasound qualification and experience in bedside ultrasound examination.Diaphragm excursion(DE),thickening fraction of diaphragm(TFD),and thickening fraction of intercostal muscle(TFic)were measured,respectively.The patients were divided into a successful weaning group(n=114)and a failed weaning group(n=24)according to the weaning results.Receiver operating characteristic(ROC)curves were used to analyze the value of diaphragm ultrasound and intercostal muscle ultrasound,alone and in combination,in predicting ventilator weaning outcome.Results·TFic and TFic/TFD were significantly higher in the failed weaning group during SBT than in the successful weaning group(all P<0.05).The areas under the ROC curve(AUROC)of DE,TFD,and TFic to predict weaning failure in mechanically ventilated patients with sepsis during the period of SBT were 0.689(0.591?0.776),0.657(0.557?0.747),and 0.769(0.676?0.846),respectively,whereas the combined indexes TFic/TFD and TFic&TFD_mix had AUROCs of 0.867(0.786?0.925)and 0.860(0.778?0.920),respectively.TFic/TFD with a cutoff value of>0.95 had a sensitivity of 86.7%and a specificity of 75.3%in predicting weaning failure,and TFic&TFD_mix with a cutoff value of>0.13 had a sensitivity of 86.6%and a specificity of 80.9%in predicting weaning failure.Moreover,the intercostal muscle ultrasonography method had an intra-observer intraclass correlation coefficient(ICC)of 0.890 and an extra-observer ICC of 0.876 for measurement reliability,which were both rated as good(P<0.001).Conclusion·Combined diaphragm and intercostal muscle ultrasonography provides a more comprehensive picture of the patient's overall respiratory muscles,and has a higher guiding value in predicting the weaning outcomes in mechanically ventilated patients with sepsis than diaphragm ultrasound alone.

Objective To explore the biomechanical safety of applying traditional Chinese orthopedic manipulation therapy after anterior cervical discectomy and fusion(ACDF)surgery,so as to provide a theoretical basis for clinical treatment in biomechanics.Methods Based on CT data,a three-dimensional finite element model of the normal C0-T1 cervical spine was established,and an ACDF postoperative finite element model of the C5-6 segment was constructed on this basis.Cervical spine rotation manipulation was simulated at the C4 and C7 segments of both models,and the von Mises stresses of the vertebral body,bilateral facet joints,intervertebral discs,and internal fixation system under manipulation loading of the C4 and C7 segments in both models were compared and analyzed.Results When the C4 segment was manipulated,the stress on the C5,C6,and C7 vertebral bodies in the ACDF postoperative model decreased by 12.3％,11.5％,and 26.4％,compared to the normal model.The stress on the left facet joints of the C4-5,C5-6,and C6-7 segments decreased by 12.3％,58.8％,and 15.4％,and the stress on the right facet joints decreased by 16.6％,92.1％,and 17.2％.The stress on the C4-5 and C6-7 segments decreased by 13.2％and 4.0％,while the maximum stress of the fusion cage,titanium plate,and screws in the C5-6 segment were 9.349,111.9,and 300.8 MPa.When the C7 segment was manipulated,the stress on the C4,C5,and C6 vertebral bodies in the ACDF postoperative model increased significantly compared to the normal model,especially the C5 vertebral body,with an increase of nearly 18 times.Except for the stress on the left facet joint of the C4-5 segment increased by 57.7％,the stress on the bilateral facet joints of other segments generally decreased,but the stress on the C4-5 and C6-7 segments increased by 43.2％and 21.7％and the stresses on the fusion cage,titanium plate,and screws in the C5-6 segment were 2.926,205.4,and 256.2 MPa.Conclusions The safety of performing manipulation on the upper vertebral body of the fusion segment after ACDF surgery is relatively high,but performing manipulation on the lower vertebral body of the fusion segment may lead to stress concentration and increase the risk of injury.When postoperative conservative treatment is implemented,the manipulation safety and indications should be considered to avoid operations in high-risk areas,and more precise and safe manipulation intervention treatment should be implemented based on the specific postoperative biomechanical state of the patient.

Objective The objective of this study was to investigate the effects of maytansine on proliferation,migration,in-vasion,apoptosis and autophagy of human thyroid cancer C643 cells.Methods C643 cells were treated with different concentrations(0.049,0.195,0.781,3.125,12.5,50 and 200 μmol/L)of maytansine,the effect of maytansine on the proliferation of C643 cells was detected by the sulforhodamine B(SRB)method,and the concentration of subsequent experiments was determined.C643 cells in the logarithmic growth stage period were divided into the control group,low-dose group,mid-dose group and high-dose group.The effects of maytansine on migration and invasion abilities of C643 cells were detected by cell scratch and Transwell chamber assay;The levels of reactive oxygen species(ROS)were detected by 2′,7′-dichlorofluorescein diacetate(DCFH-DA)fluorescent probe experi-ment;The apoptosis rate of C643 cells was detected by flow cytometry;The expression of proteins related to apoptosis or autophagy was detected by Western blot.Results Maytansine at concentrations of 0.049,0.195,0.781,3.125,12.5,50 and 200 μmol/L could in-hibit the proliferation of C643 cells(P<0.05),and exhibited a significant concentration time dependence.The half maximal inhibitory concentrations(IC50)at 24,48 and 72 h were 54.255,5.193 and 0.647 μmol/L,respectively;The cell scratch and Transwell chamber results showed that maytansine at concentrations of 0.1,1 and 10 μmol/L could reduce the migration and invasion abilities of C643 cells(P<0.05 and P<0.01).The fluorescence probe results showed that maytansine at concentrations of 0.1,1 and 10μmol/L could increase the intracellular ROS levels of C643 cells(P<0.01).The flow cytometry results showed that maytansine at concentrations of 0.1,1 and 10 μmol/L could concentration dependently increase the apoptosis rate of C643 cells(P<0.01).The Western blot results showed that with the increase of maytansine concentrations,the expression of Bax protein related to apoptosis in C643 cells increased(P<0.05),the expression of Bcl-2 decreased(P<0.05),the expression of LC3Ⅱ/Ⅰ(P<0.05)and Beclin-1(P<0.01)increased,while the expression of p62 decreased(P<0.001).Conclusion Maytansine can inhibit the proliferation,migration and invasion of human thyroid cancer C643 cells,and induce the synergistic effect on apoptosis and autophagy by increasing intracellular ROS levels.

Objective To explore the biomechanical characteristics of different types of lumbar disc herniation(LDH),and provide a theoretical basis for the clinical classification,diagnosis,and treatment of LDH.Methods A normal lumbar spine model with spinal nerves and four types of LDH models(central type,paracentral type/lateral recess type,intervertebral foramen type,extreme type)were constructed,and the biomechanical characteristics of the intervertebral discs and nerve roots in neutral posture and under six degrees of freedom conditions were analyzed.Results In neutral position,the stress of normal intervertebral disc was carger than that of the herniated intervertebral disc,and the stress ratio of annulus fibrosus and nucleus pulposus in normal model was greater than that of annulus fibrosus and nucleus pulposus in herniated models.In neutral position,the disc stress was mainly concentrated at the incisor between the protrusion and normal part,and recruitment occurred at outer edge of the disc.In flexion and extension position,the stress of the herniated intervertebral disc shifted to the right side.The maximum stress of herniated intervertebral disc appeared during right flexion,and the nerve root stress on the right side was carger than that on the left side.The stress of the herniated intervertebral disc during right rotation was slightly lower than that during right flexion,and the stress of nerve root on the right side was smaller than that on the left side.Conclusions The intervertebral disc is important in maintaining lumbar dynamic and static stability and flexibility.Different positions have an obvious effect the intervertebral disc stress.For patients with LDH,forward bending,flexion of the affected side and large extension should be avoided.Appropriate rotation of the affected side can help relieve the symptoms of nerve root compression.

Objective To investigate the effect of acupuncture at Hegu(LI4)on neural activity in the visual cortex of healthy volunteers using functional near-infrared spectroscopy(fNIRS).Methods Each healthy volunteer underwent three sets of trials in a resting state:the LI4 group received acupuncture stimulation at the right Hegu(LI4)acupoint;the negative control was the sham acupoint group(SHAM group);and the positive control was the visual stimulation group(VISUAL group).fNIRS was used to simultaneously monitor changes in oxygenated hemoglobin(Oxy-Hb)levels in the vis-ual cortex during various stages of acupuncture or visual tasks,thereby reflecting the activation level of the visual cortex.The entire acupuncture procedure was performed with the subjects' eyes closed.fNIRS recorded the raw optical density values of hemodynamics in the region of interest(ROI)of the visual cortex during each task phase.The relative coefficientβ value for oxygenated hemoglobin was obtained via Matlab analysis,and the coefficient difference Δβ value between the task period and the baseline period was calculated,representing the degree of change in oxygenated hemoglobin content in-duced by the stimulus,which reflected the change in activation level of the visual cortex after acupuncture or visual stimu-lation.A larger Δβ value indicates a higher degree of visual cortex activation.Generalized estimating equations(GEE)were applied to analyze the differences in visual cortex activation levels among the LI4,SHAM,and VISUAL groups.Results In channels 15 and 17 of the striate area and channels 10 and 13 of the extrastriate area,the Δβ values of sub-jects in the LI4 group during the needle manipulation and withdrawal phases were significantly higher than those in the SHAM group(all P＜0.01).When comparing the Δβ values of the LI4 group during the needle manipulation and withdrawal phases with those of the VISUAL group,under the current sample size,the differences were not statistically significant(all P＞0.05).The Δβ values in both the striate and extrastriate areas of the LI4 group peaked during the needle manipulation phase.Conclusion Acupuncture at Hegu(LI4)can effectively activate the visual cortex in healthy volunteers,with the most significant increase in activation observed during the needle manipulation phase.