Effectiveness of HPV vaccines in real-world study / 中华微生物学和免疫学杂志

Human papillomavirus (HPV) is an epitheliotropic virus. High-risk HPV infections lead to precancerous lesions which may progress to cancer in the cervix, vagina and vulva, while low-risk HPV infections cause benign lesions such as genital warts and recurrent respiratory papillomas. HPV infection remains one of the major public health problems threatening human health. To date, six prophylactic preventive HPV vaccines have been licensed, and the effectiveness of HPV vaccination has gradually appeared in some countries with earlier vaccination. HPV vaccination has been proved to be effective in protecting against diseases related to HPV infection, which leads to significant reductions in the incidence of vaccine-type HPV-related infection, high cervical lesions, anogenital warts, recurrent respiratory papillomatosis and other relevant diseases. The herd protection effect of the vaccines is outstanding. Meanwhile, a bivalent HPV vaccine has been demonstrated for the cross-protection against HPV infections of non-vaccine types (HPV31/33/45) in real-world vaccination practice.

Genome charaterization based on the Spike-614 and NS8-84 loci of SARS-CoV-2 reveals two major onsets of the COVID-19 pandemic

The global COVID-19 pandemic has lasted for three years since its outbreak, however its origin is still unknown. Here, we analyzed the genotypes of 3.14 million SARS-CoV-2 genomes based on the amino acid 614 of the Spke (S) and the amino acid 48 of NS8 (nonstructural protein 8), and identified 16 linkage haplotypes. The GL haplotype (S_614G and NS8_48L) was the major haplotype driving the global pandemic and accounted for 99.2% of the sequenced genomes, while the DL haplotype (S_614D and NS8_48L) caused the pandemic in China in the spring of 2020 and accounted for approximately 60% of the genomes in China and 0.45% of the global genomes. The GS (S_614G and NS8_48S), DS (S_614D and NS8_48S) and NS (S_614N and NS8_48S) haplotypes accounted for 0.26%, 0.06%, and 0.0067% of the genomes, respectively. The main evolutionary trajectory of SARS-CoV-2 is DS[->]DL[->]GL, whereas the other haplotypes are minor byproducts in the evolution. Surprisingly, the newest haplotype GL had the oldest time of most recent common ancestor (tMRCA), which was May 1 2019 by mean, while the oldest haplotype had the newest tMRCA with a mean of October 17, indicating that the ancestral strains that gave birth to GL had been extinct and replaced by the more adapted newcomer at the place of its origin, just like the sequential rise and fall of the delta and omicron variants. However, they arrived and evolved into toxic strains and ignited a pandemic in China where the GL strains did not exist at the end of 2019. The GL strains had spread all over the world before they were discovered, and ignited the global pandemic, which had not been noticed until the pandemic was declared in China. However, the GL haplotype had little influence in China during the early phase of the pandemic due to its late arrival as well as the strict transmission controls in China. Therefore, we propose two major onsets of the COVID-19 pandemic, one was mainly driven by the haplotype DL in China, the other was driven by the haplotype GL globally.

Hetero-bivalent Nanobodies Provide Broad-spectrum Protection against SARS-CoV-2 Variants of Concern including Omicron

Following Delta, Omicron variant triggered a new wave of SARS-CoV-2 infection globally, adaptive evolution of the virus may not stop, the development of broad-spectrum antivirals is still urgent. We previously developed two hetero-bivalent nanobodies with potent neutralization against original WT SARS-CoV-2, termed aRBD-2-5 and aRBD-2-7, by fusing aRBD-2 with aRBD-5 or aRBD-7, respectively. Here, we resolved crystal structures of these nanobodies in complex with RBD, and found the epitope of aRBD-2 differs from that of aRBD-5, aRBD-7. aRBD-2 binds to a conserved epitope which renders its binding activity to all variants of concern (VOCs) including Omicron. Interestingly, although monovalent aRBD-5 and aRBD-7 lost binding to some variants, they effectively improved the overall affinity when transformed into the hetero-bivalent form after being fused with aRBD-2. Consistent with the high binding affinities, aRBD-2-5-Fc and aRBD-2-7-Fc exhibited ultra-potent neutralization to all five VOCs; particularly, aRBD-2-5-Fc neutralized authentic virus of Beta, Delta and Omicron with the IC50of 5.98[~]9.65 ng/mL or 54.3[~]87.6 pM. Importantly, aRBD-2-5-Fc provided in vivo prophylactic protection for mice against WT and mouse-adapted SARS-CoV-2, and provided full protection against Omicron in hamster model when administrated either prophylactically or therapeutically. Taken together, we found a conserved epitope on RBD, and hetero-bivalent nanobodies had increased affinity for VOCs over its monovalent form, and provided potent and broad-spectrum protection both in vitro and in vivo against all tested major variants, and potentially future emerging variants. Our strategy provides a new solution in the development of therapeutic antibodies for COVID-19 caused by newly emergent VOCs.

A comprehensive review on immuno-nanomedicine for breast cancer therapy: Technical challenges and troubleshooting measures.

Nanosized drug carriers have received a major attention in cancer therapeutics and theranostics. The immuno-nanomedicine is a combination of monoclonal antibody (mAb)/mAb-drug-nanoparticles. The immuno-nanomedicine offers a promising strategy to target cancer cells. However, the understating of nanotechnology, cancer biology, immunomedicine, and nanoparticle surface chemistry has provided a better clue to prepare the effective immuno-nanomedicine for cancer therapy. Moreover, the selection of nanoparticles type and its composition is essential for development of efficient drug delivery system (DDS) to target the cancer cell site. Immuno-nanomedicine works in the ligand-receptor binding mechanism through the interaction of mAb conjugated nanoparticles and specific antigen over expressed on target cancer cells. Therefore, the selection of specific receptors in the cancer cell and their ligand is important to prepare the active immuno-nanomedicines. Moreover, the factors such as drug loading, entrapment efficiency, size, shape, and ligand conjugation of a nanocarrier are considered as major factors for a better cancer cell, internalization, drug release, and cancer cell ablation. The target-based over-expression of antigen, mAb is engineered and conjugated with nanoparticles for successful targeting of the cancer cells without causing adverse effects to normal cells. Therefore, this review analyzed the fundamental factors in the immuno-nanomedicine for breast cancer and its technical challenges in the fabrication of the antibody alone/and drug conjugated nanoparticles.

Potent in vitro Neutralization of SARS-CoV-2 by Hetero-bivalent Alpaca Nanobodies Targeting the Spike Receptor-Binding Domain

Cell entry by SARS-CoV-2 requires the binding between the receptor-binding domain (RBD) of the viral Spike protein and the cellular angiotensin-converting enzyme 2 (ACE2). As such, RBD has become the major target for vaccine development, while RBD-specific antibodies are pursued as therapeutics. Here, we report the development and characterization of SARS-CoV-2 RBD-specific VHH/nanobody (Nb) from immunized alpacas. Seven RBD-specific Nbs with high stability were identified using phage display. They bind to SARS-CoV-2 RBD with affinity KD ranging from 2.6 to 113 nM, and six of them can block RBD-ACE2 interaction. The fusion of the Nbs with IgG1 Fc resulted in homodimers with greatly improved RBD-binding affinities (KD ranging from 72.7 pM to 4.5 nM) and nanomolar RBD-ACE2 blocking abilities. Furthermore, fusion of two Nbs with non-overlapping epitopes resulted in hetero-bivalent Nbs, namely aRBD-2-5 and aRBD-2-7, with significantly higher RBD binding affinities (KD of 59.2 pM and 0.25 nM) and greatly enhanced SARS-CoV-2 neutralizing potency. The 50% neutralization dose (ND50) of aRBD-2-5 and aRBD-2-7 was 1.22 ng/mL ([~]0.043 nM) and 3.18 ng/mL ([~]0.111 nM), respectively. These high-affinity SARS-CoV-2 blocking Nbs could be further developed into therapeutics as well as diagnosis reagents for COVID-19. ImportanceTo date, SARS-CoV-2 has caused tremendous loss of human life and economic output worldwide. Although a few COVID-19 vaccines have been approved in several countries, the development of effective therapeutics including SARS-CoV-2 targeting antibodies remains critical. Due to their small size (13-15 kDa), highly solubility and stability, Nbs are particularly well suited for pulmonary delivery and more amenable to engineer into multi-valent formats, compared to the conventional antibody. Here, we report a serial of new anti-SARS-CoV-2 Nbs isolated from immunized alpaca and two engineered hetero-bivalent Nbs. These potent neutralizing Nbs showed promise as potential therapeutics against COVID-19.

Application value of metagenomic next generation sequencing in diagnosis of osteoarticular infections / 中华临床感染病杂志

Objective:To evaluate the application of metagenomic next-generation sequencing (mNGS) in the diagnosis of osteoarticular infection.Methods:The clinical data of 37 inpatients aged 32-90 year with osteoarticular infection admitted in the Department of Spine Surgery of Qingdao Chest Hospital from January to December 2019 were retrospectively analyzed. There were 31 cases of spine infection and 6 cases of other joint infection. The tissue samples were obtained from the infected sites through puncture or surgical approach in all patients. The tissue samples were subjected to routine culture of mycobacteria, aerobic bacteria and anaerobic bacteria, respectively. The gene amplification and mNGS were performed for detection of mycobacterium tuberculosis DNA (MTB-DNA). The chi-square test or Fisher’s exact test were used to compare the detection rates of pathogen and simple bacterial infection between mNGS and conventional culture. The conventional culture, mNGS and MTB-DNA amplification detection were performed for all samples; with clinical diagnosis as the gold standard, the diagnostic values of 3 methods were evaluated with receiver operating characteristic curve (ROC). Paired sample t test was used to compare white blood cell(WBC) count, erythrocyte sedimentation rate, C-reactive protein of patients before and after treatment. P<0.05 was considered statistically significant. Results:The pathogens were detected by mNGS for 42 times: bacteria for 39 times (92.8%), fungi for twice (4.8%) and Kirks body for once (2.4%). Among 37 patients there were 29 cases of pure bacterial infection (78.4%), 2 cases of pure fungi infection (5.4%), 1 case of pure Kirks body infection (2.7%), and 5 cases of mixed infection of two or more pathogens (13.5%). The detection rates of mNGS and conventional culture were 100.0% (37/37) and 67.6% (25/37), respectively ( χ2=13.987, P<0.05). The detection rates of mNGS and conventional culture in 29 patients with pure bacterial infection were 100.0% (29/29) and 69.0% (20/29), respectively ( χ2=16.913, P<0.05). The area under the ROC curve (AUC) of conventional culture, mNGS, and MTB-DNA in the diagnosis of osteoarticular tuberculosis infection was 0.958 (95% CI: 0.866-1.000, P<0.05), 1.000 (95% CI: 1.000-1.000, P<0.05) and 0.958 (95% CI: 0.866-1.000, P<0.05). All the 37 patients were treated with anti-infective drugs according to the results of mNGS and conventional culture. Among them, 28 patients received surgical intervention. The patients were followed up until April 30, 2020, 1 patient died. After 3 months of follow-up, the WBC count, erythrocyte sedimentation rate and C-reactive protein were (5.5±1.5)×10 9/L, (41±38)mm/h and (5.0±4.6) mg/L, respectively, which were lower than those before anti-infection treatment [(8.0±2.9)×10 9/L, (79±42)mm/h and(63±52)mg/L] ( t=6.536, 8.302 and 6.373, all P<0.05). Conclusion:The metagenomic next-generation sequencing may have important clinical value in the differential diagnosis of osteoarticular infection.

Tocilizumab in patients with moderate or severe COVID-19: a randomized, controlled, open-label, multicenter trial / 医学前沿

Tocilizumab has been reported to attenuate the "cytokine storm" in COVID-19 patients. We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit from this treatment. We conducted a randomized, controlled, open-label multicenter trial among COVID-19 patients. The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone. The cure rate, changes of oxygen saturation and interference, and inflammation biomarkers were observed. Thirty-three patients were randomized to the tocilizumab group, and 32 patients to the control group. The cure rate in the tocilizumab group was higher than that in the control group, but the difference was not statistically significant (94.12% vs. 87.10%, rate difference 95% CI-7.19%-21.23%, P = 0.4133). The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12 (P = 0.0359). In moderate disease patients with bilateral pulmonary lesions, the hypoxia ameliorated earlier after tocilizumab treatment, and less patients (1/12, 8.33%) needed an increase of inhaled oxygen concentration compared with the controls (4/6, 66.67%; rate difference 95% CI-99.17% to-17.50%, P = 0.0217). No severe adverse events occurred. More mild temporary adverse events were recorded in tocilizumab recipients (20/34, 58.82%) than the controls (4/31, 12.90%). Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab could be recommended to improve outcome.

Effects of Shuanghuanglian oral liquids on patients with COVID-19: a randomized, open-label, parallel-controlled, multicenter clinical trial / 医学前沿

We conducted a randomized, open-label, parallel-controlled, multicenter trial on the use of Shuanghuanglian (SHL), a traditional Chinese patent medicine, in treating cases of COVID-19. A total of 176 patients received SHL by three doses (56 in low dose, 61 in middle dose, and 59 in high dose) in addition to standard care. The control group was composed of 59 patients who received standard therapy alone. Treatment with SHL was not associated with a difference from standard care in the time to disease recovery. Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group (93.4% vs. 73.9%, P = 0.006). Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia, which was evaluated by density reduction of inflammatory focus from baseline, at day 7 (mean difference (95% CI), -46.39 (-86.83 to -5.94) HU; P = 0.025) and day 14 (mean difference (95% CI), -74.21 (-133.35 to -15.08) HU; P = 0.014). No serious adverse events occurred in the SHL groups. This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.

Decline of SARS-CoV-2 specific IgG, IgM and IgA in convalescent COVID-19 patients within 100 days after hospital discharge

Monitoring the levels of SARS-CoV-2 specific antibodies such as IgG, M and A in COVID-19 patient is an alternative method for diagnosing SARS-CoV-2 infection and an simple way to monitor immune responses in convalescent patients and after vaccination. Here, we assessed the levels of SARS-CoV-2 RBD specific antibodies in twenty-seven COVID-19 convalescent patients over 28-99 days after hospital discharge. Almost all patient who had severe or moderate COVID-19 symptoms and a high-level of IgG during the hospitalization showed a significant reduction at revisit. The remaining patients who had a low-level IgG during hospitalization stayed low at revisit. As expected, IgM levels in almost all convalescent patients reduced significantly or stayed low at revisit. The RBD-specific IgA levels were also reduced significantly at revisit. We also attempted to estimate decline rates of virus-specific antibodies using a previously established exponential decay model of antibody kinetics after infection. The predicted days when convalescent patients RBD-specific IgG reaches to an undetectable level are approximately 273 days after hospital discharge, while the predicted decay times are 150 days and 108 days for IgM and IgA, respectively. This investigation and report will aid current and future studies to develope SARS-CoV-2 vaccines that are potent and long-lasting.

Physical and bioactivities of biopolymeric films incorporated with cellulose, sodium alginate and copper oxide nanoparticles for food packaging application.

The present work prepared the antibacterial polymeric film (APF) using the different combination of sodium alginate (SA) and cellulose nano whisker (CNW) embedded with copper oxide nanoparticles (CuO NPs). Here, the SA acts as a plasticizer and provides flexibility. The CNW improves barrier properties of the film to limit moisture penetration into food. CuO NPs prevent the microbial contamination to food. Cross-linking and functional relationship of SA-CNW-CuNPs film were confirmed by adopting characterization including SEM, FTIR, EDS and XRD. The film composed with CNW (0.5%)-SA (3%)-CuNPs (5 mM) exhibited promising antibacterial activity against several pathogens in terms of higher zone of inhibition against S. aureus (27.49 ± 0.91 mm), E. coli (12.12 ± 0.58 mm), Salmonella sp. (25.21 ± 1.05 mm), C. albicans (23.35 ± 0.45 mm) and Trichoderma spp. (5.31 ± 1.16 mm). In addition, CNW (0.5%)-SA(3%)-CuO NPs (5 mM) film showed the challenging antioxidant activity in terms of DPPH and ABTS scavenging. Also, the optimized composition of film composed with CNW (0.5%)-SA (3%)-CuO NPs (5 mM) was preventing the microbial contamination in fresh cut pepper (FCP). Therefore, APF composed with CNW (0.5%)-SA (3%)-CuO NPs (5 mM) is proved to be an active food packaging system (FPS) for its utility in food industry to overcome the limitations in conventional food packaging.

Investigation and Study on the Current Situation of Chronic Disease Management Service in Social Pharmacy of Chengdu / 中国药房

OBJECTIVE：To provide reference for chronic disease man agement service develophed in social pharmacy. METHODS：Questionnaire about the Status Quo of Chronic Disease Management and Service in Social Pharmacy of Chengdu was designed，using the quota sampling method ，social pharmacies in five main urban areas of Chengdu were selected from May to July，2018 to conduct a questionnaire survey （one questionnaire by each social pharmacy ） on the basic situation of social pharmacies，the development of chronic disease management services ，the cognition of chronic disease management services ，and the challenges faced by chronic disease management services ，and suggestions were proposed. RESULTS & CONCLUSIONS ：A total of 272 questionnaires were sent out ，and 252 valid questionnaire were actually collected （effective recovery rate of 92.65％）. Totally 189 sample pharmacies （75.00％） had carried out chronic disease management services ，of which 112 （59.26％） pharmacies had been launched for 1-3 years；87（46.03％）had set up service areas ；68（35.98％）had full-time staff ，and 54 （28.57％）had part-time staff ，most of which were licensed pharmactists. 116（61.37％）had trained related staff for 1-2 times per year. 176（93.12％）pharmacies could provide services such as basic indicator testing （176，93.12％），establishing health records （142，75.13.％），and rational medication guidance for patients （163，86.24％）. According to the survey ，the substantial benefits of chronic disease management services included changing the health status of patients （163，86.24％），improving patients ’trust in the pharmacy and staff （141，74.60％），improving patients ’quality of life （129，68.25％），etc. More than 50％ of pharmacies faced the challenges of limited number of licensed pharmacists （102，53.97％），difficulty in establishing professional teams （112， 59.26％），and lack of trust in services （101，53.44％）. The current chronic disease management service of social pharmacy in Chengdu is in the initial stage of active exploration ，which can bring many benefits to patients and pharmacies ，and is conducive to the promotion of medical and health policies ，but there are some weak links at the same time. It is suggested that relevant government departments should strengthen the support ofpolicies and regulations ， and social pharmacies constantly 85501387。 E-mail：2191043137@qq.com improve professional level and rely on the advantages of “Internet + ”to meet the diverse needs of the public for pharmaceutical care ，and publicity efforts are intensified to · enhance the awareness and participation of patients with chronic diseases.

Analysis of KIAA0196 gene mutation in a family with hereditary spastic paraplegia / 中华医学遗传学杂志

OBJECTIVE@#To identify pathogenic mutation in a Chinese family affected with hereditary spastic paraplegia (HSP) through genetic testing and a follow-up survey.@*METHODS@#Whole exome sequencing was performed on DNA samples of two patients and one unaffected member to screen candidate mutations. Sanger sequencing was used to validate the suspected mutations in all ten family members.@*RESULTS@#Four patients and three asymptomatic members (under 25 years old) carried a c.1771T>C mutation of the KIAA0196, while the other three asymptomatic members (over 40 years old) did not carry the mutation. The mutation was predicted to be "affect protein function", "probably damaging" and "disease causing" by SIFT, PolyPhen-2 and Mutation Taster, respectively. Three asymptomatic carriers were followed up and one of them developed HSP one year later, while the other two had no signs of the disease yet.@*CONCLUSION@#The clinical phenotype of the c.1771T>C mutation of KIAA0196 has a considerable heterogeneity and this mutation may be a common pathogenic site of KIAA0196 mutations among Chinese patients with hereditary spastic paraplegia.

Analysis of TGFBI gene mutation in a pedigree affected with corneal dystrophy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect potential mutation in a large Chinese pedigree affected with congenital corneal dystrophy.</p><p><b>METHODS</b>Two patients from the pedigree were subjected to whole exome sequencing to determine the candidate gene. Suspected mutation was verified in 13 additional members by directional Sanger sequencing. Ccorrelation between genotype and phenotype was explored.</p><p><b>RESULTS</b>A missense mutation, c.1877A>C (p.His626Pro), was detected in exon 14 of the TGFBI gene in 8 patients from the pedigree, but not in five unaffected members and 100 unrelated healthy controls. Respectively, the mutation was predicted as "affecting protein function", "probably damaging" and "disease causing" by SIFT, PolyPhen-2 and MutationTaster.</p><p><b>CONCLUSION</b>The c.1877A>C mutation of the TGFBI gene probably underlies the disease in this pedigree.</p>

Biomimetic nanohydroxyapatite/gelatin composite material preparation and in vitro study / 中南大学学报(医学版)

OBJECTIVE@#To prepare nHA/gelatin porous scaffold and to evaluate its physical and chemical properties and biocompatibility.@*METHODS@#We used nano-powders of HA and gelatin to prepare 3D porous composite scaffold by freeze-drying technique, and used scanning electron microscope, fourier transform infrared spectroscopy and universal testing machine to characterize the composite material. Osteoblasts were primarily cultured, and the third-passage osteoblasts were co-cultured with the composite material. The cell adhesion and morphology were examined under scanning electron microscope. The cell viability analysis was performed by MTT assay, and the alkaline phosphatase activity was measured with alkaline phosphatase kit.@*RESULTS@#Scanning electron microscope showed that the scaffold possessed a 3-dimensional interconnected homogenous porous structure with pore sizes ranging from 150 to 400 μm. Fourier transform infrared spectroscopy showed that the composite material had a strong chemical bond between the inorganic phase and organic phase. The scaffold presented the compressive strength of (3.28 ± 0.51) MPa and porosities of (80.6 ± 4.1)%. Composite materials showed features of had good biocompatibility. Mouse osteoblasts were well adhered and spread on the materials. The grade of the cell toxicity ranged from I to II. On the 5th and 7th day the proliferative rate of osteoblasts on scaffolds in the composite materials was significantly higher than that in the control group. The activity of alkaline phosphatase was obviously higher than that in the control group on Day 1 and 3.@*CONCLUSION@#Nano-hydroxyapatite and gelatin in certain proportions and under certain conditions can be prepared into a composite biomimetic porous scaffolds with high porosity and three-dimensional structure using freeze-drying method. The scaffold shows good biocompatibility with mouse osteoblasts and may be a novel scaffolds for bone tissue engineering.

Triptolide sensitizes TRAIL-induced apoptosis in prostate cancer cells via p53-mediated DR5 up-regulation.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising agent for cancer therapy. However, a number of prostate cancer cells exhibit high resistance to TRAIL effect. In this study, we found that Triptolide, a Chinese medicine, significantly sensitizes prostate cancer cells to TRAIL-mediated cellular apoptosis by up-regulating DR5 expression. Triptolide treatment can suppress Akt/Hdm2 signaling pathway, and lead to p53 accumulation, thereby up-regulating DR5 expression. Taken together, all evidences indicate that Triptolide may become a promising therapeutic agent that prevents the progression of prostate cancer.

DNA double-strand breaks, potential targets for HBV integration / 华中科技大学学报（医学）（英德文版）

Hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC) is one of the most frequently occurring cancers. Hepadnaviral DNA integrations are considered to be essential agents which can promote the process of the hepatocarcinogenesis. More and more researches were designed to find the relationship of the two. In this study, we investigated whether HBV DNA integration occurred at sites of DNA double-strand breaks (DSBs), one of the most detrimental DNA damage. An 18-bp I-SceI homing endonuclease recognition site was introduced into the DNA of HepG2 cell line by stable DNA transfection, then cells were incubated in patients' serum with high HBV DNA copies and at the same time, DSBs were induced by transient expression of I-SceI after transfection of an I-SceI expression vector. By using nest PCR, the viral DNA was detected at the sites of the break. It appeared that integration occurred between part of HBV x gene and the I-SceI induced breaks. The results suggested that DSBs, as the DNA damages, may serve as potential targets for hepadnaviral DNA insertion and the integrants would lead to widespread host genome changes necessarily. It provided a new site to investigate the integration.

Risk factor assessment for lymph node regional metastasis of squamous cell carcinoma of tongue / 华西口腔医学杂志

<p><b>OBJECTIVE</b>The purpose of this study was to investigate the risk factors involving lymph node metastasis of squamous cell carcinoma and evaluate if the risk factors would be effective in predicting neck lymph node metastasis.</p><p><b>METHODS</b>Based on the original data of 106 cases with carcinoma of tongue, four related factors, including maximal diameter, degree of differentiation, mode of invasion and histological grade of malignancy were analyzed statistically.</p><p><b>RESULTS</b>The maximal diameter and the grade of tumor cell differentiation showed no significant correlation with cervical lymph node metastasis; but the mode of invasion and the histological grade of malignancy demonstrated a significant correlation.</p><p><b>CONCLUSION</b>The results obtained suggested that the mode of invasion and the histological grade of malignancy were closely related to cervical lymph node metastasis.</p>

Preparation and Content Determination of Cholecalciferol Microcapsules / 中国药房

OBJECTIVE:To prepare cholecalciferol(VitD3)microcapsules and establish a method for their quantitative determination.METHODS:Microcapsules were prepared by complex coacervation method and VitD3 content was determined by HPLC.RESULTS:The prepared microcapsules had well-distributed particle size with average particle size of(103.9?26.2)?m and encapsulation efficiency of(90.8?2.68)%.The linear range of VitD3 was 0.1～1.0 ?g?mL-1(r=0.999 3)with mean recovery rate of 98.65% and a dissolution rate of above 75% at 45 min.CONCLUSION:VitD3 microcapsules was successfully prepared by the established method,and the established content determination method was proved to be simple and feasible.