Allostery, or allosteric regulation, is the phenomenon in which protein functional activity is altered by the binding of an effector at an allosteric site that is topographically distinct from the orthosteric, active site. As one of the most direct and efficient ways to regulate protein function, allostery has played a fundamental role in innumerable biological processes of all living organisms, including enzyme catalysis, signal transduction, cell metabolism, and gene transcription. It is thus considered as "the second secret of life". The abnormality of allosteric communication networks between allosteric and orthosteric sites is associated with the pathogenesis of human diseases. Allosteric modulators, by attaching to structurally diverse allosteric sites, offer the potential for differential selectivity and improved safety compared with orthosteric drugs that bind to conserved orthosteric sites. Harnessing allostery has thus been regarded as a novel strategy for drug discovery. Despite much progress having been made in the repertoire of allostery since the turn of the millennium, the identification of allosteric drugs for therapeutic targets and the elucidation of allosteric mechanisms still present substantial challenges. These challenges are derived from the difficulties in the identification of allosteric sites and mutations, the assessment of allosteric protein-modulator interactions, the screening of allosteric modulators, and the elucidation of allosteric mechanisms in biological systems. To address these issues, we have developed a panel of allosteric services for specific allosteric applications over the past decade, including (i) the creation of the Allosteric Database, with the aim of providing comprehensive allosteric information such as allosteric proteins, modulators, sites, pathways, etc., (ii) the construction of the ASBench benchmark of high-quality allosteric sites for the development of computational methods for predicting allosteric sites, (iii) the development of Allosite and AllositePro for the prediction of the location of allosteric sites in proteins, (iv) the development of the Alloscore scoring function for the evaluation of allosteric protein-modulator interactions, (v) the development of Allosterome for evolutionary analysis of query allosteric sites/modulators within the human proteome, (vi) the development of AlloDriver for the prediction of allosteric mutagenesis, and (vii) the development of AlloFinder for the virtual screening of allosteric modulators and the investigation of allosteric mechanisms. Importantly, we have validated computationally predicted allosteric sites, mutations, and modulators in the real cases of sirtuin 6, casein kinase 2α, phosphodiesterase 10A, and signal transduction and activation of transcription 3. Furthermore, our developed allosteric methods have been widely exploited by other users around the world for allosteric research. Therefore, these allosteric services are expected to expedite the discovery of allosteric drugs and the investigation of allosteric mechanisms.

ObjectiveTo observe the effect of routine rehabilitation combined with digital acupoint pressure on motor function of stroke patients with hemiplegia.Methods58 stroke patients with hemiplegia were randomly divided into the therapy group (n=30) and control group (n=28). The patients of the therapy group were treated with routine rehabilitation combined with digital acupoint pressure, and those of the control group were treated only with routine rehabilitation. The limbs motor function was evaluated with Fugl-Meyer Assessment (FMA) and activities of daily living (ADL) was evaluated with Modified Barthel Index (MBI) before and after 12-week treatment.ResultsBefore treatment, there were no significant differences in scores of FMA and MBI between two groups ( P>0.05). After treatment, FMA scores of the patients in the therapy group increased ( P<0.05) and significantly superior to that of the control group ( P<0.01), MBI scores also significantly higher than that of the control group ( P<0.01).ConclusionThe routine rehabilitation combined with digital acupoint pressure can improve the motor function of stroke patients and the effect is better than routine rehabilitation alone.

Objective To investigate the efficacy of emergency endoscopy for the treatment of patients with acute obstructive suppurative cholangitis(AOSC)and the difference compared with therapy of routine operation.Methods After ERCP were performed on 36 patients with AOSC,EST and/or ENBD were executed subsequently.To those asthenic patients complicated with diseases or tumors,ENBD was used to alleviate symptoms and then decided whether to take stones secondly or drain by ERBD.Biochemical indicators,physical sysmtoms and signs were monitored so as to compare with those of 32 patients with AOSC treated by routine operation.Results The clinical effect was satisfactory,and the relief of pain,incidence of complicated diseases,hospital stay,level of serum TBIL after treatment had significant difference between those in study group and in control group(all P＜0.05).Conclusion Endoscopic therapy is safe,easy and minimally invasive,which is suitable for the patients with AOSC.

Objective To study the effect of operation after neoadjuvant chemotherapy on gastric cancer patients with Ⅲ,Ⅳ grade.Methods 120 gastric cancer patients with Ⅲ,Ⅳ grade were selected.52 cases in the control group were given routine operation,68 cases in the observation group received neoadjuvant chemotherapy plus operation treatment.The operation resection rate,solid tumor progress assessment and postoperative recurrence rate in three months,six months and one year were observed.Results The radical resection of the observation group was 62.24％ (43/68),which was significantly higher than that of the control group 46.15％ (24/52) (x2 =5.81,P ＜0.05).The palliative resection and laparotomy of observation group were 20.59％ (14/68) and 16.18％ (11/68),which were significantly lower than those of the control group (x2 =4.04,4.92,all P ＜ 0.05).Tumor remission of the observation group was 61.76％ (43/68),which was significantly higher than that of the control group 50％ (26/52)(P ＜ 0.05).The tumor progress of the observation group was 17.65％ (12/68),which was significantly lower than that of the control group 28.85％ (15/52) (x2 =4.17,P ＜ 0.05).The tumor recurrence rates in 3 months and 6 months of the observation group were 10.29％ (7/68) and 17.65％ (12/68),which were significantly lower than those of the control group (x2 =4.61,P ＜ 0.05).Conclusion Neoadjuvant chemotherapy before operation can improve the operation resection rate,reduce the relapse rate,delay the recurrence and metastasis of gastric cancer,improve the prognosis of the patients.

Objective:To compare the clinical effect of high tibial osteotomy (HTO) with Giebel blade plate or straddle nail internal fixation for the treatment of osteoarthritis of knee with varum.Methods:Twenty-three cases of knee OA with genu varum were performed with HTO,in which 8 case by using Giebel blade plate and 15 cases by using straddle nail.Results:All patients were followed up.The genu varum defection were corrected obviously.Six months after operation,comparison between the two groups showed no significant differences in scoring on HSS standard.One case of nail rupture and two cases of loss of anticipant angle occurred in the group of straddle nail.Conclusion:HTO with either Giebel blade plate or straddle nail both apparently shows many advantages in the treatment of osteoarthritis of knee.HTO with Giebel blade plate can exercise more early and have much less complications than HTO with straddle nail internal fixation.

Objective: To evaluate the compatibility of the nHA/PA composite implant. Methods: The component was implanted into the proximal humeral metaphysis of rabbits. The prosthetic humeral head replacement was performed in 20 rabbits. The rabbits were killed at the 3rd, 6th, 12th, 24th week after operation. Specimens were observed by histology and immunohistochemitry. Results; Immuno-histochemistry results showed that there were some CD4+ , CD8+ lymphocytes infiltrated into the interface at the 3rd week, without other inflammatory cells being observed. While at 6th, 12th, 24th week, neither lymphocytes nor inflammatory cells were seen. Conclusion; The nHA/PA prostheses show good biocompatibility.

Objective To observe the effects of hyperbaric oxygen on metabolic syndrome risk factors in the elderly. Methods Sixty-one patients were randomly divided into a hyperbaric oxygen (HBO) group which inhaled pure oxygen at 0.2 MPa,a normal pressure oxygen (NPO) group which inhaled oxygen at 0.1 MPa, and a normal pressure air (NPA) group which inhaled air in 0.1 MPa. Metabolic syndrome risk factors were then assessed before and after treatment. Results Before treatment, the incidence of metabolic syndrome risk factors did not differ between the various groups. After treatment, blood sugar, blood pressure,blood fluidity and insulin resis-tance had declined significantly in the hyperbaric oxygen group, and the difference as compared to the NPO and NPA groups was significant. Conclusion The results indicate that HBO can help control metabolic syndrome risk factors in the elderly, controlling blood sugar, adjusting blood pressure, reducing blood viscosity, and improving dyslipidemia.

Objective:To compare the clinical effect of lateral and posterior approaches during the total hip replacement(THA) with Minimal-Incision Surgery(MIS).Methods:Twenty-three cases were performed with lateral approach,All were performed by the same surgeon.23 cases who had undergone a MIS THA with lateral approach were compared with 36 cases who had undergone MIS THA with the posterior approaches.The average follow-up period was 12 weeks.The patients were compared with respect to the length of the incision,surgical time,intra-operative blood loss,Harris hip score,component malpositioning,complications.Results:There were no differences between the two approaches with regard to the length of the skin incision,operating time,Harris hip score,component malpositioning and major complications.Statistically significant differences were found in two groups in terms of blood sedimentation and C-reaction protein.Conclusion:Both approaches can be effectively performed without increased risk of complications.Significant benefits of posterior approaches include less soft tissue damage.

Objective To investigate the vitamin D level among children aged 0-12 years old and its correlation with hemoglo‐bin (HGB) level .Methods 3 254 children aged 0-12 years old in the child healthcare department of our hospital during 2013 were selected .The basic development indicators were collected and the fasting blood was extracted for detecting the related clinical indi‐cators of 25‐hydroxyl vitamin D level ,HGB ,etc .The situation of vitamin D overall distribution and distribution among different age stages were performed the preliminary statistical analysis ;the correlation between vitamin D level among different age stages with HGB was investigated .Results The vitamin D level among 78 .9% of children in Chenzhou city was in the normal level .The pe‐ripheral blood vitamin D level showed the significantly decreasing trend with the age increase (r= -0 .510 ,P<0 .05) .Our study found that the HGB levels during 3 age stages of 0- <2 ,4- <6 and 7- <10 years old in the normal vitamin D level group were obviously higher than that in the low vitamin D level group .The vitamin D level in children was positively correlated with HGB(lev‐el P<0 .05) .The further research found that the vitamin D level in the age stages of 0- <2 ,4- <6 years old was positively corre‐lated with the HGB level(P<0 .05) ,while no correlation between them was found in the age stage of 7- <10 years old .Conclusion The vitamin D nutritional status in children of Chenzhou city is good in general now .The vitamin D level in children appears a ob‐viously downward trend with the age increase ,which conformed to the children′s growth and development characteristics ;in differ‐ent age stages ,the positive correlation exists between children′s vitamin D and HGB levels ,the vitamin D deficiency may affect chil‐dren′s hemoglobin generation ,thus could lead to anemia occurrence in children .

This article summarizes doctor LI Fu-ren’s academic thoughts on gerocony, such as coexistance with disease is an ordinary state for the old, protecting zhengqi is the essence of gerocomy, dealing correctly with the dialectical relationship between fuzheng and quxie is critical to clinical work, preventing possible disease is the key to anti-aging, etc., and gives an in- depth analysis from aspects of basic theory and concrete medication.