With the rapid development of artificial intelligence technology,small molecule generation models have emerged as a significant research direction in the field of drug discovery.These models,including Generative Adversarial Networks(GANs),Variational Autoencoders(VAEs),and diffusion models,have proven to possess remarkable capabilities in optimizing drug properties and generating complex molecular structures.This article comprehensively analyzes the application of the aforementioned advanced technologies in the drug discovery process,demonstrating how they supplement and enhance traditional drug design methods.At the same time,it addresses the challenges facing current methods in terms of data quality,model complexity,computational cost,and generalization ability,with a prospect of future research directions.

Objective To investigate the patterns of gait and locomotion in three dimension space using OptiTrack motion capture system in 30 healthy people aged 20-70 years. Methods The 3D OptiTrack motion capture system was applied in young(aged 20-30 years,n=10),middle-aged(aged 40-50 years,n=10)and the elderly (aged 60-70 years,n=10)to capture the gait and the rhythmic oscillations of the trunk,head,hip and kneewhen subjects walked on the treadmill under three different conditions of normal walking,walking under visual interfering and walking under proprioceptive interfering.Several markers were placed on the subject.For each locomotor trial, the preferred walking speed,stride width,stride time,the absolute angular dispersions and the stander deviation of four segments around the roll,pitch and yaw axes,and gait instability(λ)were calculated to assess the equilibrium strategies of head,trunk,pelvis and knee under different experimental conditions. Results With increasing age, there were decreases in preferring walking speed(PWS)and increases in stride width(F=3.23,3.87;P=0.030, 0.020,respectively).The absolute angle of the segment of head in roll axis was significantly smaller in young group than in middle age and elderly group(F=4.01,3.72;P=0.035,0.028,respectively)under the condition of normal walking and proprioceptive interfering.The trunk sway in yaw was significantly decreased while significantly increased in roll plane either in normal walking or walking under proprioception interfering(F=3.19,P=0.015) .The standard deviation(SD)of movement of head,trunk and hip in yaw direction was higher in young group than in middle-age and elderly group(F=2.89,3.14,3.92;P=0.036,0.019,0.034,respectively),but was lower in young group in roll direction than in middle-age and elderly group(F= 3.90,2.56,3.28;P= 0.017,0.021,0.056, respectively),the difference existed only in hip and trunk under proprioception interfering.The SD value of movement of bilateral knee joints was increased in elderly subjects.Using mediolateral-λ(ML-λ)to predict the gait stability,the results showed a significantly increased λ value by our small circle,and the λ value was positively correlated with age(r=0.03,P<0.05). Conclusions With aging,the abnormal adjustment of body posture and the incongruity of gait may cause a high risk for falling,and gait instability begins to increase as early as age 40-50 years.This finding supports that local dynamic stability is likely to be an indicator of falling risk.OptiTrack motion capture system can be used to evaluate a balance for rehabilitation.

Objective:To investigate the status of the vestibular function of the patients with chronic positional symptoms after peripheral acute vestibular syndrome (AVS) and the curative effect of the vestibular rehabilitation therapy (VRT). Method:Using caloric test (CT), head shaking nystagmus test (HST), cervical vestibular evoked myogenic potentials as well as ocular vestibular evoked myogenic potentials to estimate the function of semicircular canal and otolith organs. The patients with normal VEMPs are divided as Group A. Otherwise are as Group B. Both groups are treated with VRT. The curative effect is estimated by vestibular symptom index (VSI) and Berg balance scale (BBS). Result:Thirty-three of 37 patients (86.5%) had an abnormal result of CT and HST, with 23 of these patients (65.7%) had an abnormal of both test. Twenty-two patients (59.5%) were in Group A and 15 (40.5%) in Group B. Before the therapy, Group B had a higher score of the balance and dizziness symptoms of VSI (P<0.05), and Group A had a higher score of the BBS (P<0.05). After the therapy, the VSI scores of both groups dropped and scores of the BBS raised. Conclusion:Patients with chronic positional symptoms after peripheral AVS have dynamic vestibular lesions to different extents. Those with otolith organs lesions tend to have a worse function of balance. Nevertheless, patients have a better off after VRT.

ObjectiveTo investigate the surgical procedure, characteristics and clinical efficacy of anatomical hepatectomy with Glissonian approach for hepatolithiasis.MethodsClinical data of 37 patients with hepatolithiasis who underwent anatomical hepatectomy with Glissonian approach in the First People's Hospital of Shunde Affiliated to Southern Medical University between May 2009 and July 2014 were retrospectively analyzed. Among the patients, 9 were males and 28 were females with the age ranging from 27 to 83 years old and the median of 53 years old. According to the hepatolithiasis classification of Biliary Tract Surgery Group of Surgery Branch of Chinese Medical Association (2007), 27 cases were with typeⅠhepatolithiasis and 10 cases were with typeⅡ hepatolithiasis. The informed consents of all patients were obtained and the local ethical committee approval was received. Anatomical hepatectomy with Glissonian approach and intraoperative cholangioscopic lithotomy were performed on the patients. The conditions during operation, postoperative complications of bile leakage, liver failure, abdominal infection, and stone clearance rate were observed.ResultsAll patients completed the operations successfully. Four cases underwent resection of single segment, 1 of segmentⅢ and part of segmentⅧ, 10 of left lateral lobe, 13 of left lobe, 1 of segmentⅣ andⅤ, 1 of right anterior lobe, 4 of right posterior lobe, 2 of right lobe, and 1 of left lateral lobe and right posterior lobe. The median length of operation was 300(140-450) min and the intraoperative blood loss was 350(10-800) ml. No death was observed during perioperative period. And no bile leakage, liver failure or abdominal infection was observed after operation. The stone clearance rate of patients with typeⅠand typeⅡ hepatolithiasis was respectively 93%(25/27) and 6/10, and the overall stone clearance rate was 84% (31/37).ConclusionsAnatomical hepatectomy with Glissonian approach has the advantages of relatively easy dissection of intrahepatic ducts, low possibility of accidental injury to biliary ducts, easy discrimination of liver resection border, easy protection of normal caudate lobe and clear intraoperative dissection. Thus, it is a safe and practical liver resection method for hepatolithiasis.

Objective:To investigate the neuroprotective effects of simvastatin on lipopolysaccharide (LPS)-induced rat model ofParkinson's disease(PD) and the mechanisms involved.Methods:Hemiparkinsonian rat models were induced by stereotaxieal injection ofLPS in the right substantia nigra compacta.After2 weeks of simvastatin treatment, rotational behavior test was performed after the intraperitoneal injection of apomorphine.Expression of tyroxine hydroxylase (TH) and glial fibrillary acidic protein were analyzed through immunohistochemical staining of substantia nigra and striatum, and the level ofTNF-α was evaluated using enzyme-linked immunosorbent assay.Results:Comparing with untreated group, behavioral symptoms of the rats were significantly less in the rats that received simvastatin treatment.TheTH positive cell count in substantia nigra and striatum were significantly increased(P<0.05) andTNF-α expression was significantly decreased(P<0.05) in simvastatin group compared to untreated group.Conclusions:Simvastatin could effectively inhibit the activation of astrocytes, reduceTNF-α expression, and exert anti-inflammatory effects, and thus protect the dopaminergic neurons in substantia nigra and striatum of the rat model ofPD.

Objective To examine the effect of simvastatin treatment on Parkinson's disease rats induced by lipopolysaccharide (LPS) and its mechanism.Methods The LPS-PD model was established by injection of LPS (5 mg/mL) into the right substantia nigra compacta (SNC),and rats were randomly divided into control group,LPS-model group and simvastatin treatment group with 15 rats in each group.Rats in the simvastatin treatment group was intraperitoneally administered simvastatin (5 mg/kg) before,and daily for 14 days after surgery,while the control group and LPS-model group received same volume normal saline and LPS respectively.Ionized calcium binding adaptor molecule 1 (Iba-1)-positive cells and the expression of tyrosine hydroxylase (TH),tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the SNC were detected by immunohistochemistry,Western blotting and enzyme-linked immunosorbent assay,respectively.The effect of simvastatin in the PD model was also examined in behavioral tests.Results The LPS-model group exhibited typical animal PD behaviors.Compared with the control group,the LPS-model group exhibited a decreased number of DA neurons,and comparison of the intact side to reduce 81.13％ (P＜0.01) in the SNC,as well as increases in the Iba-1-positive cell number,iNOS,IL-1β and TNF-α expression (P＜0.05).These effects were inhibited by simvastatin treatment (P＜0.05).Conclusion Simvastatin mediates a protective effect on dopaminergic neurons in the SNC in the LPS-PD model,possibly by inhibiting glial cells (astrocytes and microglia) activation,and playing an anti-inflammatory role,thus improving substantia nigra function.

OBJECTIVE: To investigate the risk factor,type and characteristic nystagmus of the otolith abnormal migration during diagnosis and treatment for posterior semicircular canal benign paroxysmal positional vertigo (PSC-BPPV). The therapy and prevention is also discussed. METHOD: Four hundred and seventy-nine patients with PSC-BPPV were treated by Epley's canalith repositioning procedures(CRP) from March 2009 to March 2012. We observed otolith abnormal migration complicating during diagnosis and treatment. According the type of otolith abnormal migration, the additional repositioning maneuver was performed. RESULT: The rate of complication was 8. 1%(39/479), with canal conversion in 5.4%(26/479) and primarily canal reentry in 2.7%(13/479). The rate of incidence of conversion to horizontal canal conversion and anterior canal were 4. 8%(23/479)and 0. 6%(3/479) respectively. All the patient was cured in follow up. The risk factors were unappropriated head movement during or after CRP, including another Dix-Hallpike were performed immediately. CONCLUSION To prevent the complications,the pathognostic positioning sequence and angle of head rotation are commenced during CRP. Appropriate short time postural restrictions post-treatment is necessary. Careful observation of nystagrnus variation is crucial to determine the otolith abnormal migration.
Benign Paroxysmal Positional Vertigo ; therapy ; Head ; Humans ; Incidence ; Nystagmus, Pathologic ; etiology ; Otolithic Membrane ; Patient Positioning ; adverse effects ; Semicircular Canals ; Vertigo

ObjectiveTo analyze the changes of imaging and the efficacy of sympathetic cervical spondylosis before and after treatment and discuss the correlation of them.Methods Seventy-one sympathetic cervical spondylosis inpatients who examined by X-ray,CT,transcranial Doppler (TCD) or color Doppler flow imaging(CDFI) were collected.After comprehensive treatment,the efficacy was evaluated according to the recovery of patients' symptoms,and the cases with imaging abnormalities were examined again.Then the correlation between the changes of imaging and the efficacy was analyzed.ResultsAfter treatment,all 71 cases,including 45 cases with excellent efficacy,18 cases with good effect and 8 cases turned effective,showed a fine rate 88.7％ (63/71) and an effective rate 100.0％ (71/71).The rechecked imaging results showed:in 36 lantoaxial subluxation cases by CT scanning,26 cases turned to be normal,6 cases were improved and 4 cases had finally no change; in 68 cases with abnormal X-ray imaging,67 cases were improved and 1 case had finally no change; in 38 cases with abnormal TCD results,24 cases turned to be normal,2 cases were improved,10 cases showed changes and 2 cases had finally no change;in 36 cases with abnormal cervical CDFI results,9 cases turned to be normal,10 cases were improved,15 cases showed changes and 2 cases had finally no change.The analysis of correlation between the changes of imaging and the efficacy showed:changes count by the value 0,r =0.388,t =3.500,P＜ 0.01 ; changes count by the value 0.5,t =0.361,t =3.211,P ＜0.01.ConclusionsThe efficacy of sympathetic cervicalspondylosis has positive correlation with the changes of imaging and the causes of this disease are complex.So complete and well inspection can help the syndrome differentiation treatment and confirm the efficacy.

Objective To explore applied characteristics of the prolene hernia system(PHS) in inguinal hernioplasty, and management during and after operation, and long-term effect of this kind of hemioplasty in aged patients. Methods 69 aged patients using PHS were followed and analyzed retrospectively. Results Tension-free inguinal hernioplasty with the PHS were performed in 69 aged patients of groin hernia. Operative time ranged from 45min to 160min. Post-operatively, 3 patients developed gentle scrotal swelling, and 20 patients had been adminis- tered anodyne for pain of incision, and 12 cases experienced retention of urine, 1 case developed pneumonia, and 2 cases oeeurred incisional infection and gore. 68 cases of them recovered daily life about 2 to 3 weeks after operation. During follow-up period from 6 months to 77 months,there was no recurrence of inguinal hernia and no pain in in-guinal region, but 2 patients feel discomfort sporadically. Conclusion The PHS strengthens the myopectineal orifice and seals up-area of it,so the system is especially preferred in treating aged patients of groin hernias who have some defectsof anatomic structure in inguinal region. The local anaesthesia is also suitable for this kind of hernioplasty in aged patients.

To examine the ability of intrastriatal gene transfer of vascular endothelial growth factor 165 mediated by adenoviral vector to rescue dopaminergic neurons in a rat model of Parkinson's disease (PD), we constructed recombinant replication-deficent adenoviral vectors carrying the gene of VEGF165 (Ad-VEGF), and injected Ad-VEGF (or Ad-LacZ and PBS as controls) into the striatum of rats 7 days after the lesion by 6-hydroxydopamine. The rat rotational behavior analysis and tyrosine hydroxylase (TH) immunohistochemistry were performed to assess the change of dopaminergic neurons. Our results showed that the rats receiving Ad-VEGF injection displayed a significant improvement in apomorphine-induced rotational behavior and a significant preservation of TH-positive neurons and fibers compared with control animals. It is concluded that intrastriatal gene transfer by Ad-VEGF may rescue the dopaminergic neurons from degeneration in a rat model of PD.