0.05).In1?g/kg dosage group,no neutralizing activity was detected at the end of convalescent period.CONCLUSION:The neutralizing antibodies can be detected in the serum of both hamsters and rhesus monkeys after repeating injection of recombinant consensus interferon?.The titers of antibody are in direct ratio with the duration and the injected dose.

Objective To determine the effects of histone deacetylase inhibitor suberoylanilide hydroxamic acid(SAHA) on the cell proliferation and apoptosis of the human hepatic stellate cell line LX-2.The possible underlying mechanisms were also investigated.Methods The LX-2 cells were treated with SAHA in vitro.The morphology of LX-2 cells in different concentrations groups was observed by inverted microscope;the proliferation of LX-2 cells was measured by MTT assay;the Annexin V-FITC and PI staining was used to detect the apoptosis of LX-2 cells by flow cytometry and fluorescence microscope;the expression of α-SMA,collagen Ⅰ,acH3K9,acH3K14 and acH3K18 were detected by Western blot.Results The morphology change of LX-2 cells showed that SAHA inhibited the proliferation rate of LX-2 cells and in a dose dependent manner(P<0.05).The LX-2 cells were sensitive to SAHA along with time increasing,and in a time-dependent manner(P<0.05).Western blot showed that the expression levels of α-SMA and collagen-Ⅰ were significantly lower(P<0.05),on the contrary,the acetylation levels of acH3K9,acH3K14 and acH3K18 were significantly higher (P<0.05).Conclusions The increased acetylation of the histone acH3K9,acH3K14,acH3K18 and the lower expressed α-SMA and collagen-Ⅰ in LX-2 cells may be one of the mechanisms of SAHA.

Objective To evaluate the effects of normovolemic hemodilution (NH) with hetastarch starch 130/0.4 and electrolyte solution on blood coagulation during resection for liver cancer in the elderly patients.Methods Forty patients,of ASA physical status Ⅱ,aged 65-74 yr,scheduled for elective resection for liver cancer under general anesthesia,were randomly divided into NH group (n =20) and control group (group C,n =20).NH group underwent NH with 6％ hematocrit starch 130/0.4 and electrolyte solution after induction of anesthesia,while group C underwent routine fluid management.Before induction of anesthesia (T1),at 30 min after NH (T2),at 1 h during operation (T3),and at the end of operation (T4),venous blood samples were collected for measurement of the routine parameters of blood coagulation,and levels of soluble fibrin monomer complex (SFMC),and platelet membrane glycoprotein (PAC-1,platelet activation marker).Results Compared with group C,no significant changes were found in intraoperative blood loss,PT,APTT,and levels of SFMC and PAC-1,the volume of allogeneic blood transfused was reduced,and Fib was decreased at T2-4 in NH group.Compared with the baseline value at T1,Fib was decreased significantly at T2-4 in NH group,and PT and APTT were prolonged but still within the normal range,and no significant changes were found in the other parameters in both groups.Conclusion NH with hetastarch starch 130/0.4 and electrolyte solution exerts no effect on blood coagulation during resection for liver cancer and provides blood-saving effect to some extent in the elderly patients.

Abstract: Objective （ ） To evaluate the internal exposure levels and risk in nuclear medicine workers NMWs engaged in Methods radionuclide therapy in Guangdong Province. A total of 61 NMWs from eight hospitals in Guangdong Province were selected as the study subjects using the convenient sampling method. The 0.364 MeV full energy peak efficiency was detected in （ ） in vitro ， - deltoid muscle of right upper arm as background and thyroid gland by direct measurement method and the iodine 131 （131 ） Results ，131 I activity in thyroid gland was calculated to evaluate the internal irradiation level. Among the 61 NMWs I was ， detected in the thyroid gland of four nuclear medical staffs in three hospitals and the detection rate was 6.6%. The median and - ［M（ P-P ）］ 131 （ - ） 0 100 percentile 0 100 of thyroid I activity were 42.9 35.1 47.1 Bq. When assuming that the monitoring period was ， M（ P-P ） （ - ） ， 30 days the 0 100 of single committed effective dose in thyroid gland was 0.014 0.011 0.015 mSv and the annual dose （ - ） Conclusion of internal irradiation was 0.162 0.132 0.180 mSv/a. The internal exposure of NMWs in the eight hospitals in （ ） ， Guangdong Province meets the annual effective dose limits ≤20.000 mSv/a . However it is necessary to pay attention to the internal radiation protection of NMWs and take reasonable protective measures to reduce the internal exposure risk of NMWs.

AIM:To study the effects of suberoylanilide hydroxamic acid (SAHA) on the apoptosis of hepatic stellate cells (HSCs) and expression of associated proteins, and to investigate the mechanisms of SAHA to induce apoptosis.METHODS:The rat HSCs were isolated by OptiPrep gradient centrifugation method.The effect of SAHA on HSC proliferation was detected by real-time cell analyzer.The morphological changes of HSCs treated with SAHA at different concentrations were observed under inverted microscope.The apoptotic rates of HSCs were analyzed by flow cytometry with Annexin V-FITC/PI staining and fluorescence microscopy.The protein expression of α-smooth muscle actin (α-SMA), collagen I, tissue inhibitor of metalloproteinase 1 (TIMP1), glucose-regulated protein 78 (GRP78) and histone deacetylase 6 (HDAC6) was detected by Western blotting.The interaction of GRP78 with HDAC6 in the HSCs was determined by co-immunoprecipitation.RESULTS:HSCs were successfully isolated and cultured for 14 d, during which the HSCs changed gradually from rest state to active state.SAHA significantly inhibited the proliferation of HSCs in a time-and dose-dependent manner (P<0.05).The results of Western blotting showed that the protein expression levels of α-SMA, TIMP1, collagen-I and HDAC6 were significantly decreased (P<0.05), while GRP78 was significantly increased (P<0.05).Compared with activated HSCs, GRP78 and total acetyl-lysine protein were significantly increased in the co-immunoprecipitated HSCs treated with SAHA, while HDAC6 protein was significantly decreased, indicting that GRP78 formed a complex with HDAC6.CONCLUSION:The anti-hepatic fibrosis effect of SAHA may be related to down-regulation of HDAC6 and up-regulation of acetylated GRP78, thus inducing endoplasmic reticulum stress of HSCs and promoting the apoptosis of HSCs.

Objective To investigate the effect of Panax notoginsenosides monomers ginsenoside Rg 1 in inhibiting hepatic fibro-sis .Methods The rat model of hepatic fibrosis was established by using 50% Ccl4 ,total 35 d .The different doses of Rg1was ad-ministered by hypodermical injection .At the end of the treatment ,the pathological changes of hepatic tissue were observed by light and transmission electron microscope .The stereological method was adopted to measure the volume density (Vvm) ,area density (Svm) ,specific surface(Qm) and surface number density (Nam) of liver cell mitochondria in various groups .Results The stereo-logical data of liver cell mitochondria showed that the statistical differences existed among various groups .Vvm in the Panax Notog-insenosides ,low dose Rg1 and isotonic saline groups were significantly increased compared with the normal control group with sta-tistical difference(P<0 .01);Vvm in the high dose Rg1 ,middle dose Rg1 and colchicine groups showed the increasing trend com-pared with the normal control group without statistical difference (P>0 .05);Vvm in the high ,middle and low dose Rg1 ,Panax No-toginsenosides and colchicine groups showed the decreasing trend compared with the isotonic saline group without statistical differ-ence(P>0 .05) .Svm in the low dose Rg1 ,Panax Notoginsenosides ,colchicine and isotonic saline groups were significantly increased compared with the normal group with statistical difference (P<0 .01);Svm in the high dose Rg1 ,middle dose Rg1 ,Panax Notogin-senosides and colchicine groups was significantly induced compared with the isotonic saline group with statistical difference (P<0 .01);Svm in the high dose Rg1 was reduced compared with the middle dose Rg1 group(P<0 .05) .Nam in the low dose Rg1 ,col-chicine and isotonic saline group was significantly increased compared with the normal group (P<0 .01);Nam in the high dose Rg1 , middle dose Rg1 and Panax Notoginsenosides groups were significantly reduced compared with the isotonic saline group with statis-tical difference(P<0 .01);Nam in the high dose Rg1 group was reduced compared with the middle dose Rg 1 group with statistical difference (P<0 .05) .Qm in all groups was reduced compared with normal group without statistical difference (P>0 .05) .Conclu-sion Rg1 has antifibrosis effects of Panax notoginsenosides ,even exceeds Panax notoginsenosides in some aspects ,and the above-mentioned effect is positively correlated with dose .Rg1 is an ideal drug for preventing and treating liver fibrosis .

COVID-19 epidemic continues to spread around the world till these days, and it is urgent to develop more safe and effective new drugs. Due to the limited P3 biosafety laboratories for directly screening inhibitors of virulent viruses with high infectivity, it is necessary to develop rapid and efficient screening methods for viral proteases and other related targets. The main protease (M^pro), which plays a key role in the replication cycle of SARS-CoV-2, is highly conserved and has no homologous proteases in humans, making it an ideal target for drug development. From two different levels, namely, molecular level and cellular level, this paper summarizes the reported screening methods of SARS-CoV-2 M^pro inhibitors through a variety of representative examples, expecting to provide references for further development of SARS-CoV-2 M^pro inhibitors.

As a common protease with high similarity among coronavirus species, the main protease (M^pro) of SARS-CoV-2 is responsible for the catalytic hydrolysis of viral precursor proteins into functional proteins, which is essential for coronavirus replication and is one of the ideal targets for the development of broad-spectrum antiviral drugs. This paper reviews the main protease inhibitors of SARS-CoV-2, including their molecular structures, potencies and drug-like profiles, binding modes and structure-activity relationships, etc.

Objective To investigate the methods ofmicrosurgical treatment of Arnold-Chiari Ⅰ malformation combined with syringomyelia and their curative effects.Methods The clinical data of 185 patients with Arnold-Chiari Ⅰ malformation combined with syringomyelia,admitted to our hospital from January 1997 to June 2010 and received different surgical treatments,were summarized.The relationship between curative effects and operative methods were analyzed.Results When these 185 patients were discharged from our hospital,the clinical signs and symptoms eliminated in 156 (84.3％)and not changed in 29; no symptomatic deterioration and death were noted.One hundred and forty-seven patients were followed up for 3 months-12 years; symptoms disappeared or alleviated in 110 (74.8％),not changed in 26 and deteriorated in 11.The MR findings in 95 patients demonstrated that the cisternals reconstructed and expanded in 82 and the cavities in spinal cords reduced in 79.Conclusion Both posterior fossa decompression + duraplasty and removal of cerebella tonsils + plastic operation of cistern magna are effective and advisable methods in the treatment of Arnold-Chiari Ⅰ malformation combined with syringomyelia.

OBJECTIVETo assess the efficacy and experience of gracilis muscle transposition for complex rectovaginal fistula (RVF) and rectourethral fistula (RUF).

METHODSNineteen patients underwent gracilis muscle transposition for complex RVF and RUF from May 2009 to November 2011 in the Beijing Shijitan Hospital and the clinical data were prospectively collected. The success rate and complications were recorded. SF-36 quality of life score, Wexner fecal incontinence score, and female sexual function score before surgery and 6 months after surgery were recorded.

RESULTSIn 19 patients, there were 8 males (RUF) and 11 females (RUF). The times of failed attempt repair preoperatively ranged from 0-3 (mean, 1.0). The diameter of the fistula ranged from 0.5-3.0 cm (mean, 1.6), and all fistulas located above the sphincter. The operative time ranged from 145-400 minutes (median, 240). The postoperative hospital stay ranged from 10-39 days (median 21). Early postoperative complications included thigh pain and numbness in 2 cases, leg numbness in 2 cases. No long-term complications were noticed. The follow-up period ranged from 6-35 months (median, 18). The gracilis muscle transposition had a healing rate of 94.7% (18/19). As compared with the preoperative level, Wexner score decreased from 10.0±8.8 to 2.9±5.8, and the continence function improved significantly (P=0.002). Sexual function score of 11 female patients increased from 1.0±1.8 to 4.0±4.0, and the sexual function had a significant improvement after surgery (P=0.022). SF-36 quality of life scores improved significantly (P<0.001).

CONCLUSIONSGracilis muscle transposition for complex rectovaginal fistula and rectourethral fistula has high success rate with mild and rare complications.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Muscle, Skeletal ; surgery ; Prospective Studies ; Rectal Fistula ; surgery ; Rectovaginal Fistula ; surgery ; Surgical Flaps ; Thigh ; surgery ; Treatment Outcome ; Urethra ; surgery ; Urinary Fistula ; surgery ; Young Adult