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The Omicron BA.2 variant has become a dominant infective strain worldwide. Receptor binding studies reveal that the Omicron BA.2 spike trimer have 11-fold and 2-fold higher potency to human ACE2 than the spike trimer from the wildtype (WT) and Omicron BA.1 strains. The structure of the BA.2 spike trimer complexed with human ACE2 reveals that all three receptor-binding domains (RBDs) in the spike trimer are in open conformation, ready for ACE2 binding, thus providing a basis for the increased infectivity of the BA.2 strain. JMB2002, a therapeutic antibody that was shown to have efficient inhibition of Omicron BA.1, also shows potent neutralization activities against Omicron BA.2. In addition, both BA.1 and BA.2 spike trimers are able to bind to mouse ACE2 with high potency. In contrast, the WT spike trimer binds well to cat ACE2 but not to mouse ACE2. The structures of both BA.1 and BA.2 spike trimer bound to mouse ACE2 reveal the basis for their high affinity interactions. Together, these results suggest a possible evolution pathway for Omicron BA.1 and BA.2 variants from human-cat-mouse-human circle, which could have important implications in establishing an effective strategy in combating viral infection.
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Objective:To investigate the change of the detection rate of colorectal cancer (CRC), colorectal adenoma and advanced adenoma in adults under colonoscopy in Shihezi in the past ten years.Methods:Data of patients who completed colonoscopy in the First Affiliated Hospital of Shihezi University School of Medicine from January 1, 2010 to December 31, 2019 were investigated. The medical records were collected by consulting the electronic medical record system, including the age and sex of patients and the location, quantity, size and pathological type of lesions. The detection rates, including the overall detection rate in the past 10 years, those in the first 5 years (from 2010 to 2014) and the second 5 years (from 2015 to 2019) of colorectal adenomas, advanced colorectal adenomas and CRC, were studied.Results:A total of 50 645 cases were included, 14 931 cases were excluded by the exclusion criteria, and finally a total of 35 714 cases were included in the data analysis. The 10-year overall detection rates of colorectal adenoma, advanced colorectal adenoma and CRC were 17.65% (6 302/35 714), 4.45% (1 589/35 714) and 3.71% (1 324/35 714), respectively. The overall detection rates of colorectal adenoma and advanced colorectal adenoma in the second 5 years were higher respectively than those in the first 5 years [20.33% (4 565/22 457) VS 13.10% (1 737/13 257), 4.69% (1 053/22 457) VS 4.04% (536/13 257)]. The overall detection rate of CRC in the second 5 years [3.30% (741/22 457)] was lower than that in the first 5 years [4.40% (583/13 257)].Conclusion:Compared with 2010 to 2014, the detection rate of colorectal adenoma in Shihezi area in 2015 to 2019 increased significantly, the detection rate of advanced colorectal adenoma increased slightly, and the detection rate of CRC decreased slightly. Therefore, the detection and resection of colorectal adenoma by colonoscopy may be important in reducing the incidence of CRC.
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The Omicron variant of SARS-CoV-2 has rapidly become the dominant infective strain and the focus efforts against the ongoing COVID-19 pandemic. Here we report an extensive set of structures of the Omicron spike trimer by its own or in complex with ACE2 and an anti-Omicron antibody. These structures reveal that most Omicron mutations are located on the surface of the spike protein, which confer stronger ACE2 binding by nearly 10 folds but become inactive epitopes resistant to many therapeutic antibodies. Importantly, both RBD and the closed conformation of the Omicron spike trimer are thermodynamically unstable, with the melting temperature of the Omicron RBD decreased by as much as 7{degrees}C, making the spiker trimer prone to random open conformations. An unusual RBD-RBD interaction in the ACE2-spike complex unique to Omicron is observed to support the open conformation and ACE2 binding, serving the basis for the higher infectivity of Omicron. A broad-spectrum therapeutic antibody JMB2002, which has completed Phase 1 clinical trial, is found to interact with the same two RBDs to inhibit ACE2 binding, in a mode that is distinguished from all previous antibodies, thus providing the structural basis for the potent inhibition of Omicron by this antibody. Together with biochemical data, our structures provide crucial insights into higher infectivity, antibody evasion and inhibition of Omicron.
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Objective:To compare the therapeutic effects of percutaneous nephrostomy and ureteral stent drainage in the treatment of infectious hydronephrosis.Methods:From June 2017 to June 2018, 92 patients with infectious hydronephrosis in the First Hospital of Jiaxing were selected.The patients' hospital number was entered into the computer and the patients were divided into group A(percutaneous nephrolithotomy and drainage treatment, 46 cases) and group B(transurethral ureteral stent drainage treatment, 46 cases) by lottery.The treatment effect and safety were compared between the two groups.Results:There were no statistically significant differences in age, male/female, duration of disease, site of renal disease, primary disease, and underlying disease between the two groups(all P>0.05). There was no statistically significant difference in the success rate of disposable catheter placement between group A and group B(97.73% vs.100.00%, χ 2=0.126, P>0.05). The efficacy of group A was significantly higher than that of group B(97.73% vs.81.40%, χ 2=4.617, P<0.05). There were no statistically significant differences in the incidence rates of bleeding, infection, drainage tube abscess and puncture abscess between the two groups(all P>0.05). Conclusion:Percutaneous nephrostomy in the treatment of infectious hydronephrosis is more effective than ureteral stent drainage.Both of two methods have high safety of treatment.Clinical treatment should be based on the specific circumstances of the patients to obtain a significant clinical effect.
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Objective:To provide reference for domestic colleagues by introducing the contents of the discipline construction of the National Clinical Research Center for mental disorders.Methods:By reviewing the original intention of the construction of the National Clinical Research Centers initiated by many ministries and departments, taking into account of the actual construction practice at hospital level in the field of mental disorders, this paper discusses the discipline construction of the National Clinical Research Center.Results:From the aspects of construction goals, purposes, overall operation modes, construction of collaborative innovation research network, the paper clarifies the concrete measures of the construction of the center.Conclusions:Through the evaluation of the current situation, the National Clinical Research Center for mental disorders has defined the focus of the construction: to build a management platform and two professional platforms, in order to provide support for the development of high-quality and high-level clinical research, and provide support for the transformation of clinical medicine.
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Objective To investigate the application of pedicled tunica vaginalis flap cover new urethra in redo and second-stage hypospadias repair.Methods Retrospective analysis was performed in 45 redo hypospadias repair cases,aged from 1 year 3 months to 9 years 4 months (median 5 years 3month).All patients were divided into urethral dehiscence after hypospadias repair (group A) and the second stage surgery of two-stage hypospadias repair (group B) based on medical history.According to the site of dehiscence,the group A were further divided into midshaft urethral dehiscence (A1) and glans and distal urethral dehiscence with urethral opening located on midshaft (A2).After new urethra was completed,the appropriate size of the pedicledtunica vaginalis flap was transferred to cover the new urethra.Results There was no scrotal hematoma occurred in all 45 cases,and somecomplications occurred,including scrotal swelling in 1 case,high-riding testicle in 2 cases,penile clockwise torsion in 1 case,urethrocutaneous fistula in 6 cases.All the 45 cases were followed up for 1 to 4 years,with mean of 1.8 years.One more urethrocutaneous fistula occurred in group A2 and 1 more urethrocutaneous fistula with urethral stricture occurred in group B.There was no penile curvature and urethral diverticulum occurred in all cases.Conclusions Pedicled tunica vaginalis flap could be used as waterproofing layer to cover new urethra in redo hypospadias repair and presented a low incidence rate of postoperative complications.
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Objective To establish a rapid and accurate method for quantitative determination of erlotinib hydrochloride by proton nuclear magnetic resonance(1H-NMR). Methods Maleic acid was used as an internal standard,and DMSO-d6 was employed as solvent.The pulse width was 9.54 μs,the delay time was 20 s,the scanning frequency was 64 and the testing temperature was set as 300℃.Under this condition,the 1H-NMR data of the mixture of erlotinib hydrochloride and maleic acid were obtained.The content of erlotinib hydrochloride was calculated by comparing the response signal area of sample (As) and internal standard (Ar). Results Proton signal peaked at δ 8.84 and δ 8.47 for erlotinib hydrochloride and at δ6.26 for maleic acid served as quantitation peaks.The content of erlotinib hydrochloride was obtained by calculating the average of the test results of the two quantitative peaks.The concentration of erlotinib hydrochloride (2.88~19.08 mg·mL-1) and the peak area of quantification peaks showed a good linear correlation.The precision RSD was 0.36% (n=6),the repeatability RSD was 0.83%(n=6) and the sample recovery was 100.91% (n=6).The content of 3 batches of erlotinib hydrochloride was 92.26%,91.94%and 92.09%,the average was 92.10% and its RSD was 0.17%.The obtained results were generally consistent with those obtained from mass balance method. Conclusion This established method is simple to handle as compared to traditional methods,and the analysis results are accurate.1H-NMR provides a novel method for the determination of erlotinib hydrochloride and can be used for the quality control of erlotinib hydrochloride.
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ABSTRACT:Objective To assess the effect of prolonged laparoscopic surgery on peritoneal mesothelial cells and fibrinolysis in humans.Methods We examined prospectively 1 6 consecutive patients who underwent laparoscopic surgery (LAP)and 2 1 patients who underwent conventional open surgery (OP)for high-medium rectal cancer with curative intent.During the procedure,biopsy of the parietal peritoneum was made before operation and at 45 min,90 min,and 120 min after operation.The tissue-type plasminogen activator (tPA)and plasminogen activator inhibitor-1 (PAI-1 )were determined by enzyme-linked immunosorbent assay in peritoneal tissues.The cellular injury was detected by LDH assay.The proliferation was quantified by MTT assay.Results PAI-1 activity in the peritoneal tissue was significantly lower in LAP group than in the OP group.tPA activity decreased after 45min of open surgery,but there was no significant change in the LAP group.With time extension,the LDH activity increased and the proliferation of the mesothelial cells decreased.Conclusion Preservation of a prolonged hypofibrinolytic state by inhibition of PAI-1 up-regulation during LAP may predispose patients to less postoperative peritoneal adhesion. The cellular injury becomes apparent and the proliferation is inhibited during prolonged laparoscopic surgery.
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Central poststroke pain (CPSP) is a neuropathic pain syndrome that can occur after stroke.This syndrome is characterized by pain and sensory abnormalities in the body parts that correspond to the stroke lesion.CPSP occurs ia 1％-12％ of stroke patients.A definite diagnosis of CPSP is difficult,mainly because of the variable clinical picture,the frequent concurrence of several pain types,and the lack of clear diagnostic criteria for CPSP.Management of the CPSP is challenging.This article reviews the diagnostic evaluation and treatment of CPSP.
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<p><b>OBJECTIVE</b>To investigate the function of repair gene LIG4 in radiosensitivity enhancement of rectal cancer cells by curcumin.</p><p><b>METHODS</b>Human rectal cancer cells HT-29 were cultured in normal. LIG4-overexpression HT-29 cells and blank control plasmid HT-29 cells were established by gene transfection. Both kind of HF-29 cells were further randomly divided into curcumin group, radiotherapy group, curcumin plus radiotherapy group (combined group) and control group. The growth inhibition and apoptosis of cells were detected by MTT and Annexin V/PI respectively. Change of tumor volume was observed in nude mouse xenograft model, and the apoptosis of tumor cells was analyzed by TUNEL.</p><p><b>RESULTS</b>Regarding blank control plasmid HT-29 cells, the growth inhibition rate and apoptosis rate in combined group were significantly higher than those in radiotherapy group(all P<0.05); tumor volume of nude mouse in combined group was significantly smaller than that in radiotherapy group, and the apoptotic index in combined group was significantly higher than that in radiotherapy group (all P<0.05). However, regarding LIG4-overexpression HT-29 cells, the growth inhibition rate and apoptosis rate were not significantly different between combined group and radiotherapy group(all P>0.05); the tumor volume of nude mouse and the apoptotic index were also not significantly different between combined group and radiotherapy group (all P>0.05).</p><p><b>CONCLUSION</b>Down-regulation of LIG4 is an important mechanism of radiosensitivity enhancement of rectal cancer cells by curcumin.</p>
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OBJECTIVE@#Aimed to analyse the clinical features of the patients with sphenoid sinus mucocele, achieve earlier diagnosis and more timely intervention and decrease the occurrence of misdiagnoses.@*METHOD@#A retrospective study was first conducted in patients with sphenoid sinus mucoele treated in Xiangya hospital from Jan 2000 to Jan 2015. Then literature reports on this disease were collected and analyzed from China National Knowledge Infrastructure (CNKI) and Wan Fang database.@*RESULT@#We collected 82 patients with sphenoid sinus mucocele treated in Xiangya hospital. There were 52 patients presented with headache, 31 patients presented with visual impairment, 10 patients presented with cranial nerve palsy, 2 patients presented with exophthalmos, 15 patients presented with nasal symptoms, and 5 patients with no obvious symptoms. There was no significant difference for symptoms distribution between male and female patients (P > 0.05). Among 45 patients with headache as first symptom and 10 patients with ethmoid sinus mucocele, there were 18 patients and 8 patients subsequently suffering from visual impairment, respectively. We also collected 161 patients in literature except for enrolling, the 82 patients treated in Xiangya hospital, and found that headache was the most common symptom, followed by visual impairment, in the two independent cohorts.@*CONCLUSION@#To the best of our knowledge, this is the study of maximum sample for sphenoid sinus mucocele in China. Headache and visual impairment are the most common symptoms for sphenoid sinus mucocele. Surgical treatment should be early performed when the desease accompanied with headache or ethmoid sinus mucocele, to avoid other complications such as visual impairment and even blindness.
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Female , Humans , Male , China , Cranial Nerve Diseases , Databases, Factual , Diagnostic Errors , Ethmoid Sinus , Exophthalmos , Headache , Mucocele , Diagnosis , Pathology , Paranasal Sinus Diseases , Retrospective Studies , Sphenoid Sinus , Pathology , Vision DisordersABSTRACT
Objective To investigate the feasibility, safety and efficiency of endovascular treatment for patients with aorto-bilateral-iliac artery total occlusive disease.Methods A total of 35 patients with aorto-bi-iliac artery total occlusive disease treated with endovascular therapy in Peking Union Medical College Hospital and the First Hospital of Shijiazhuang between Jan 2012 and Dec 2013 were retrospectively analyzed.Results There were 33 males and 2 females, mean age (67 ± 6) years treated during the study period.Technical success rate was 100％.129 bare stents and 4 covered stents were implanted.There were no peri-operative death.Postoperative leg ankle brachial index (ABI) improved significantly (0.86 vs.0.28, P ＜ 0.28).Postoperative complications occurred in 2 patients (5.7％), including brachial artery thrombosis and rupture of external iliac artery post-dilation.The mean follow-up period was 16.5 months (2-28 months).Two patients (5.7％) were lost to follow up.Re-intervention was performed in 3 patients (8.6％) due to reocclusion of the stents.Primary patency was 91％ (30/33) Conclusions Endovascular treatment is effective for aorto-bi-iliac artery total occlusive disease with low complications and acceptable mid-term patent rate.
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Objective To investigate the value of multi slice spiral computed tomography (MSCT) reconstruction technique for diagnosis and preoperative evaluation of pancreatic carcinoma.Methods The multi-phase enhanced CT images of thirty-five cases of pancreatic carcinoma proved histologically were analyzed retrospectively.The techniques of volume rendering (VR),multi-planar reconstruction (MPR) and curved planar reformation (CPR) were used to deal with the images,and the relation between the pancreatic tumor and its surrounding structures,vessels,bile duct were observed,then the evaluation of possible surgical resection was performed,then it was compared with operative results.Results Among the 35 patients,27 vessels invasion was showed in 9 patients,common bile duct invasion in 19 patients,pancreatic duct invasion in 12 patients,duodenum invasion in 7 patients,posterior wall of stomach in 2 patients was invaded; one patient had regional portal hypertension with splenomegaly,peri-pancreatic lymph nodes enlargement was detected in 14 patients,para-aortic lymph nodes enlargement was detected in 4 patients,and liver metastasis was found in 3 patients.According to CT evaluation,surgery could be performed in 21 cases,finally 19 patients underwent curative pancreatic cancer resection,and 2 patients underwent palliative surgery.According to CT evaluation,surgery could not be performed in 14 cases,and all of the patients underwent palliative surgery.The coincidence percentage of pre-operative evaluation and post-operative results of curative surgery,palliative surgery was 90％ and 88％.Conclusions MSCT reconstruction technique is useful for diagnosis of pancreatic carcinoma regional invasion and metastasis,and it can increase the accuracy of assessment of tumor resectability.
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Objective To investigate the relation between a set of single nucleotide polymorphisms (SNP) in core gene of HBV in chronic hepatitis B patients and HBV DNA levels. Methods PCR restriction fragment length polymorphism(PCR-RFLP) assay and restriction enzyme Tsp509I were adopted to determine HBV SNP in HBV core gene. Nucleotide sequences of core gene were determined using the dideoxy chain termination method. HBV DNA levels were quantitated with real-time PCR. Results Five typical RFLP patterns, RFLP-C, RFLP-D, RFLP-E, RFLP-G and RFLP-C/G mixture were found and the distribution of HBV RFLP patterns was as follows: C, 61. 5% ; D, 2. 6% ; E, 9.6%; G, 16.7%; C/G mixture, 9.6%. Five SNPs, A165T, A336C, A336T, T337C and T385C, were found to be associated with RFLP patterns change and only SNP A336C or A336T caused the substitution of Glu-83 with Asp in HBcAg. The serum HBV DNA levels in RFLP-C group were higher than that in RFLP-G (P =0. 02) and RFLP-C/G group(P = 0. 006) , respectively, furthermore, the positive rate of serum ALT in RFLP-C/G group was lower than that in RFLP-C, RFLP-E and RFLP-G group, respectively. Under the condition of HBeAg-positive, the serum HBV DNA levels in RFLP-C group were higher than that in RFLP-G (P = 0. 015) and RFLP-C/G group(P =0.008) , respectively. Conclusion PCR-RFLP used in this study can be adopted to determine HBV SNPs, not genotypes in Chinese patients with chronic hepatitis B. The serum HBV DNA level in RFLP-C group higher than that in RFLP-G or RFLP-C/G group maybe associated with amino acid mutation, Glu83 Asp.
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Objective To study the changes of T lymphocyte subtype levels and serum levels of leukotriene B4 ( LTB4 )in children with acute leukemia (AL). Methods The activity of T lymphocyte subsets:CD3+ T cells,CD4+ T cells,CD8 + T cell levels and NK cell were detected in 40 cases of AL and 40 control by Flow Cytometry(FCM). The serum level of LTB4 was measured by ELISA in all subjects. ResultsCompared with normal control , the percentages of CD3 + T cells ( [ 49.51 ± 6.53 ] ％ vs [ 67.63 ± 5.23 ] ％ ), CD4 + T cells ([22.15±4.87]％ vs [34.43 ±5.07]％),CD8+ T cell ([23.41 ±3.96]％ vs [28. 17 ±4.61]％),NK cell ( [5.41 ± 4.25 ] ％ vs [ 13.10 ± 4.91 ] ％ ) were significantly lower in children AL patients, ( Ps ＜0.01 ). However,the serum levels of LTB4 increased significantly in AL patients compared with normal control ( [ 25.23 ± 6.24 ] ng/L vs [ 8.28 ± 2.53 ] ng/L, P ＜ 0.01 ). ConclusionT lymphocyte subtype and serum level of LTB4 showed significant changes in children AL patients compared with normal control, which revealed an important theoretical basis to AL pathogenesis.
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Objective To evaluate the effect of pepliteal artery endovascular angioplasty for the treatment of diabetic foot. Methods 65 cases (69 limbs) of diabetic foot were treated by long bloon endovascular angioplasty. Results No death occured. 60 cases (64 limbs) were successfully treated and 5 cases (5 limbs) failed. The imme-diately success rate was 92.75%. The pain relieved, the temperature was improved and the ankle brachial index (ABI) was up to 0.84±0.11. Anterior tibial artery or posterior tibial artery of 39 limbs could be touched. 21 limbs were cured by debride and change dressings. 10 limbs were cured after the gangrene was ablated. 6 limbs were cured after the gangrene was debrided. 22 limbs were cured after toe amputation. Half of the foot was amputated. No limb was amputated. Every month was further consulted by Doppler and the rate of follow upwas 100%. 6 limbs of 6 cases were reobliterated (1,1,2,2 cases occurred after 1,6,12,18 month respectively.) and treated by endovascular an-gioplasty again. Conclusion Endovascular angioplasty below the knees for the treatment of diabetic foot is an effec-tive method for the limbs saving, with minimal invasive, safety, less complication and retreatment. It can be used as a first choice for the artery obliteration of diabetic foots.
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<p><b>BACKGROUND</b>To study etiology of clinically diagnosed non A-E hepatitis.</p><p><b>METHODS</b>HBV, TTV, human parvovirus B19, SENV DNA were detected by nested polymerase chain reactions (nPCR), while HGV, HCV RNA were tested by reverse transcription nested polymerase chain reactions (RT-nPCR).</p><p><b>RESULTS</b>Of 60 patients with clinically diagnosed non A-E hepatitis, 30 (50.0%) were HBV DNA positive alone, 10 (16.7%) HBV and TTV DNA positive, 6 (10.0%) HBV and B19 DNA positive; 1 (1.7%) HBV, SENV DNA and HCV RNA positive, 1 (1.7%) HCV RNA positive alone, 1 (1.7%) HCV RNA and B19 DNA positive, 2 (3.3%) B19 DNA positive alone, 1 (1.7%) TTV DNA positive alone, and the remaining 8 (13.3%) negative for all viruses. All the 60 patients were HGV RNA negative. There were no differences in serum biochemical markers of hepatitis B patients with or without TTV or B19 virus infection.</p><p><b>CONCLUSIONS</b>HBV is a major etiologic agent for the clinically diagnosed non A-E hepatitis. HGV, TTV, B19 and SEBV may not be associated with nonA-E hepatitis.</p>
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Adult , Aged , Female , Humans , Male , Middle Aged , DNA, Viral , Blood , Hepacivirus , Genetics , Hepatitis B , Diagnosis , Hepatitis B virus , Genetics , Hepatitis, Viral, Human , Diagnosis , Virology , RNA, Viral , Blood , Sequence Analysis, DNAABSTRACT
AIM: To observe the therapeutic action of Guizhifuling Capsule (Ramuluo Cinnamomi, Poria, Cortex moutan, Semen Persicae, etc.)on hyperplasia of mammary glands in rast, and to explore the new therapeutic effectiveness and its mechanism. METHODS: To inject extrinsic E2 and Pt into muscle to reproduce rats model of hyperplasia of mammary glands, to observe the morphologic changes of nipple in every group, determine extradiol and progesterone content on plasma in experimental rats by radio immunoassay, and study the changes of ER and PR by immunohistochemical method. RESULTS: Compared with the model group, Guizhi Fuling Capsule can markedly abate papilledema, proliferation of lobule, acinus and duct in mammary glands, reduce obviously changes of blood, estradiol on plasma, the ER and PR content of mammary glands and increase progesterone. CONCLUSION:Cuizhi Fuling Capsules have the good therapeutic action on hyperplasia of mammary glands in rats, its mechanism is related to correcting changes of blood, adjusting the blood concentration of sexual hormone in experimental rats and its expression of receptor.
