Lipid nanoemulsions are promising nanodrug delivery carriers that can improve the efficacy and safety of paclitaxel(PTX).However,no intravenous lipid emulsion of PTX has been approved for clinical treatment,and systemic safety profiles have not yet been reported.Here we outline the development of a PTX-loaded tumor-targeting intravenous lipid emulsion(PTX Emul)and describe its characteristics,colloidal stability,and systemic safety profiles in terms of acute toxicity,long-term toxicity,and tox-icokinetics.We also compare PTX Emul with conventional PTX injection.Results showed that PTX Emul exhibited an ideal average particle size(approximately 160 nm)with narrow size distribution and robust colloidal stability under different conditions.Hypersensitivity reaction and hemolysis tests revealed that PTX Emul did not induce hypersensitivity reactions and had no hemolytic potential.In addition,where the alleviated systemic toxicity of PTX Emul may be attributed to the altered toxicokinetic characteristics in beagle dogs,including the decreased AUC and increased plasma clearance and volume of distribution,PTX Emul alleviated acute and long-term toxicity as evidenced by the enhanced the median lethal dose and approximate lethal dose,moderate body weight change,decreased bone marrow suppression and organ toxicity compared with those under PTX injection at the same dose.A fundamental understanding of the systemic safety profiles,high tumor-targeting efficiency,and superior antitumor activity in vivo of PTX Emul can provide powerful evidence of its therapeutic potential as a future treatment for breast cancer.

Objective:To explore the efficacy and safety of TiRobot combined with three-dimensional imaging in the minimally invasive surgery for pelvic fractures.Methods:A retrospective analysis was conducted of the 40 patients with pelvic fracture who had been treated by fixation with S1 and S2 sacroiliac screws at Department of Orthopaedics and Traumatology, Yangjiang People's Hospital from January 2019 to May 2021. They were divided into 2 groups according to their treatment methods. In the TiRobot group of 20 cases subjected to percutaneous sacroiliac screw fixation assisted by TiRobot combined with three-dimensional imaging, there were 13 males and 7 females with an age of (38.2 ± 8.8) years. In the manual group of 20 cases subjected to fixation with manual placement of sacroiliac screws under conventional C-arm fluoroscopy, there were 11 males and 9 females with an age of (37.3 ± 9.2) years. The 2 groups were compared in terms of fluoroscopy time for screw placement, guide needle adjustment, operation time, intraoperative blood loss, visual analogue scale (VAS) 72 hours after operation, postoperative hospital stay, time to ambulation, excellent to good rate of screw placement, complication rate, fracture union time, Majeed score at 6 months after operation, and excellent to good rate of functional evaluation.Results:There was no significant difference between the 2 groups in their preoperative general data, showing they were comparable ( P > 0.05). In the TiRobot group, fluoroscopy time for screw placement [(8.2 ± 2.9) s], guide needle adjustment [(0.4 ± 0.2) times], operation time [(67.4 ± 5.5) min], and intraoperative blood loss [(36.5 ± 8.0) mL] were significantly less than those in the manual group [(40.4 ± 4.5) s, (8.6 ± 0.7) times, (78.4 ± 7.2) min, and (41.6 ± 7.8) mL], postoperative VAS [3.0 (4.0, 5.0) points] was significantly lower than that in the manual group [4.0 (5.0, 6.0) points], the excellent to good rate of screw placement (100%, 40/40) was significantly higher than that in the manual group (85.0%, 34/40), and the complication rate (5.0%,1/20) was significantly lower than that in the manual group (35.0%, 7/20) (all P < 0.05). There was no significant difference between the 2 groups in postoperative hospital stay, time to ambulation, fracture union time, Majeed score, or excellent to good rate of functional evaluation ( P > 0.05). Conclusion:In the minimally invasive surgery for pelvic fractures, TiRobot combined with three-dimensional imaging leads to positive outcomes, because it can reduce operation time and radiation exposure, improve accuracy of screw placement, and increase safety.

Objective:To explore the epidemiologic characteristics and the possible risk factors of microtia in China. Meanwhile, the significant variables related to severe cases are integrated into a predictive nomogram.Methods:A total of 593 patients with congenital microtia from July 2015 to July 2018 were included. Patients conforming to congenital microtia with or without associated malformations were enrolled in this study, and patients with clear chromosomal syndromes were excluded. Questionnaire surveys were conducted among the parents to collect the demographic information and risk factors for exposure during perinatal period. Using Chi-Square and Fisher’s tests to statistically analyze the frequencies of variables. Univariate and multivariate logistic regression analysis were used to select variables related to severe cases for constructing nomogram. Concordance index (C-index), calibration plot, Hosmer-Lemeshow test, and receiver operating characteristics (ROC) curve were used to assess the nomogram model.Results:Of the patients, 456 (76.9%) were male and 137 (23.1%) were female. Right side was involved in 329 cases (55.5%), left side in 217 cases (36.6%) and both sides in 47 cases (7.9%). Among them, 16 cases were familial and the rest were sporadic. Multiple deformations were in 392 cases (66.1%). Maternal illness in early pregnancy( OR=2.205, 95% CI: 1.020-4.020)and parternal drinking history( OR=2.221, 95% CI: 1.329-3.677)were independent risk factors for severe microtia. While mother aged from 26 to 35 years old ( OR=0.507, 95% CI: 0.281-0.913; OR=0.258, 95% CI: 0.125-0.531) and father living in plain area( OR=0.512, 95% CI: 0.288-0.913)may be protective factors. All the significant predictors were combined into a predictive nomogram. The C-index was 0.703(95% CI: 0.646-0.760). The calibration plotshowed good performance of the nomogram, and the model passed Hosmer-Lemeshow goodness-of-fit test ( χ2=4.512, P=0.808). ROC curve analysis revealed a high sensitivity and specificity. Conclusions:The majority of microtia patients are male, sporadic, occur on right side, and often associated with other malformations. This nomogram predicting severe microtia based on multiple parental risk factors was with good discrimination and accuracy, which could provide scientific guidance for individualized prevention in clinical practice.

COVID-19 has swept globally and Pakistan is no exception.To investigate the initial introductions and transmissions of the SARS-CoV-2 in Pakistan,we performed the largest genomic epidemiology study of COVID-19 in Pakistan and generated 150 complete SARS-CoV-2 genome sequences from samples collected from March 16 to June 1,2020.We identified a total of 347 mutated positions,31 of which were over-represented in Pakistan.Meanwhile,we found over 1000 intra-host single-nucleotide variants(iSNVs).Several of them occurred concurrently,indicating possible interactions among them or coevolution.Some of the high-frequency iSNVs in Pakistan were not observed in the global population,suggesting strong purifying selections.The genomic epidemiology revealed five distinctive spreading clusters.The largest cluster consisted of 74 viruses which were derived from different geographic locations of Pakistan and formed a deep hierarchical structure,indicating an extensive and persistent nation-wide transmission of the virus that was probably attributed to a signature mutation(G8371T in ORF 1ab)of this cluster.Further-more,28 putative international introductions were identified,several of which are consistent with the epidemiological investigations.In all,this study has inferred the possible pathways of introduc-tions and transmissions of SARS-CoV-2 in Pakistan,which could aid ongoing and future viral surveillance and COVID-19 control.

Objective:To explore the epidemiologic characteristics and the possible risk factors of microtia in China. Meanwhile, the significant variables related to severe cases are integrated into a predictive nomogram.Methods:A total of 593 patients with congenital microtia from July 2015 to July 2018 were included. Patients conforming to congenital microtia with or without associated malformations were enrolled in this study, and patients with clear chromosomal syndromes were excluded. Questionnaire surveys were conducted among the parents to collect the demographic information and risk factors for exposure during perinatal period. Using Chi-Square and Fisher’s tests to statistically analyze the frequencies of variables. Univariate and multivariate logistic regression analysis were used to select variables related to severe cases for constructing nomogram. Concordance index (C-index), calibration plot, Hosmer-Lemeshow test, and receiver operating characteristics (ROC) curve were used to assess the nomogram model.Results:Of the patients, 456 (76.9%) were male and 137 (23.1%) were female. Right side was involved in 329 cases (55.5%), left side in 217 cases (36.6%) and both sides in 47 cases (7.9%). Among them, 16 cases were familial and the rest were sporadic. Multiple deformations were in 392 cases (66.1%). Maternal illness in early pregnancy( OR=2.205, 95% CI: 1.020-4.020)and parternal drinking history( OR=2.221, 95% CI: 1.329-3.677)were independent risk factors for severe microtia. While mother aged from 26 to 35 years old ( OR=0.507, 95% CI: 0.281-0.913; OR=0.258, 95% CI: 0.125-0.531) and father living in plain area( OR=0.512, 95% CI: 0.288-0.913)may be protective factors. All the significant predictors were combined into a predictive nomogram. The C-index was 0.703(95% CI: 0.646-0.760). The calibration plotshowed good performance of the nomogram, and the model passed Hosmer-Lemeshow goodness-of-fit test ( χ2=4.512, P=0.808). ROC curve analysis revealed a high sensitivity and specificity. Conclusions:The majority of microtia patients are male, sporadic, occur on right side, and often associated with other malformations. This nomogram predicting severe microtia based on multiple parental risk factors was with good discrimination and accuracy, which could provide scientific guidance for individualized prevention in clinical practice.

Objective:To find the chromosomal malfomations among microtia patients and the neighbouring genes of chromosomal aberrations or genes in the extra or deleted chromosome fragments would be screened to investigate the possible causative genes.Methods:According to the inclusion criteria, case group was selected from microtia patients referred to Plastic Surgery Hospital, Chinese Academy of Medical Science, between January 2012 and January 2014, and the control group was the normal people of similar age received plastic surgery in the same hospital in the same time who did not have any congenital genetic disease. Blood samples of two groups were collected, and genomic DNA was extracted, then copy number variation (CNV) analysis was performed in the two groups with gene chip technology and associated software for large fragment chromosomal malformations. The variations of chromosome copy number were recorded to further analyze the type and length of chromosome structure variation. The genes at the loci of break points were further screened referring to B allele frequency to interpret associated genes related to the occurrence of microtia. Fisher exact test were used for statistical analysis, and the difference was statistically significant ( P< 0.05). Results:942 patients with congenital microtia were included in the case group, 695 males and 247 females, aged (11.4±3.2) years; 1 802 normal controls, 1 290 males and 512 females, aged (11.6±4.9) years. Large chromosomal fragments variations were detected in 5 patients in chromosome in case group( P=0.003). The difference between the two groups was statistically significant( P=0.003). Three cases were found to carry an extra X chromosome. Among the 3 cases, one patient suffered from XXY karyotype and the other 2 patients X trisomy. Two cases were proved to be associated with chromosome structural variations. The malformations of the first case presented partial duplication of the long arm of chromosome 13 and 14. On searching for causative genes, OTX2, BMP4 and GSC were detected to be in the chromosome structural variations. The second case presented to be partial duplication of the long arm of chromosome 5. FGF pathway associated genes FGF18, FGFR4, FGF1 and BMP pathway associated genes FST, MSX2, SMAD5 were incorporated in the extra duplicated chromosome for possible gene dosage effect. Conclusions:The results indicated the possible association of chromosome abnormity and microtia and provide new insights in microtia-associated chromosome instability. Ten related genes were involved in the occurrence of microtia through various ways.

On January 22, 2020, China National Center for Bioinformation (CNCB) released the 2019 Novel Coronavirus Resource (2019nCoVR), an open-access information resource for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 2019nCoVR features a comprehensive integra-tion of sequence and clinical information for all publicly available SARS-CoV-2 isolates, which are manually curated with value-added annotations and quality evaluated by an automated in-house pipeline. Of particular note, 2019nCoVR offers systematic analyses to generate a dynamic landscape of SARS-CoV-2 genomic variations at a global scale. It provides all identified variants and their detailed statistics for each virus isolate, and congregates the quality score, functional annotation,and population frequency for each variant. Spatiotemporal change for each variant can be visualized and historical viral haplotype network maps for the course of the outbreak are also generated based on all complete and high-quality genomes available. Moreover, 2019nCoVR provides a full collection of SARS-CoV-2 relevant literature on the coronavirus disease 2019 (COVID-19), including published papers from PubMed as well as preprints from services such as bioRxiv and medRxiv through Europe PMC. Furthermore, by linking with relevant databases in CNCB, 2019nCoVR offers data submission services for raw sequence reads and assembled genomes, and data sharing with NCBI. Collectively, SARS-CoV-2 is updated daily to collect the latest information on genome sequences, variants, hap-lotypes, and literature for a timely reflection, making 2019nCoVR a valuable resource for the global research community. 2019nCoVR is accessible at https://bigd.big.ac.cn/ncov/.

Objective:To find the chromosomal malfomations among microtia patients and the neighbouring genes of chromosomal aberrations or genes in the extra or deleted chromosome fragments would be screened to investigate the possible causative genes.Methods:According to the inclusion criteria, case group was selected from microtia patients referred to Plastic Surgery Hospital, Chinese Academy of Medical Science, between January 2012 and January 2014, and the control group was the normal people of similar age received plastic surgery in the same hospital in the same time who did not have any congenital genetic disease. Blood samples of two groups were collected, and genomic DNA was extracted, then copy number variation (CNV) analysis was performed in the two groups with gene chip technology and associated software for large fragment chromosomal malformations. The variations of chromosome copy number were recorded to further analyze the type and length of chromosome structure variation. The genes at the loci of break points were further screened referring to B allele frequency to interpret associated genes related to the occurrence of microtia. Fisher exact test were used for statistical analysis, and the difference was statistically significant ( P< 0.05). Results:942 patients with congenital microtia were included in the case group, 695 males and 247 females, aged (11.4±3.2) years; 1 802 normal controls, 1 290 males and 512 females, aged (11.6±4.9) years. Large chromosomal fragments variations were detected in 5 patients in chromosome in case group( P=0.003). The difference between the two groups was statistically significant( P=0.003). Three cases were found to carry an extra X chromosome. Among the 3 cases, one patient suffered from XXY karyotype and the other 2 patients X trisomy. Two cases were proved to be associated with chromosome structural variations. The malformations of the first case presented partial duplication of the long arm of chromosome 13 and 14. On searching for causative genes, OTX2, BMP4 and GSC were detected to be in the chromosome structural variations. The second case presented to be partial duplication of the long arm of chromosome 5. FGF pathway associated genes FGF18, FGFR4, FGF1 and BMP pathway associated genes FST, MSX2, SMAD5 were incorporated in the extra duplicated chromosome for possible gene dosage effect. Conclusions:The results indicated the possible association of chromosome abnormity and microtia and provide new insights in microtia-associated chromosome instability. Ten related genes were involved in the occurrence of microtia through various ways.

OBJECTlVE To estabIish a simpIe,sensitive and quick method for determination of B7011 in rat pIasma. METHODS The method of protein precipitation with methanoI was used for pre-treatment of pIasma sampIes determined by Iiquid chromatography mass spectrometer. The Iinear reIa-tionship,intra-batch and inter-batch precision,specificity,matrix effect,recovery rate,the accuracy and stabiIity of the pIasma sampIes were vaIidated. The concentration of B7011 in pIasma was determined by LC-mS/ mS foIIowing a singIe intravenous injection of B7011 0.5 mg·kg-1 to rats. RESULTS The Iinear range of B7011 was 30-20 000 μg·L-1 ,the Iower Iimit of quantification was 30 μg·L-1 in pIasma,the in-tra-batch precision of 60,1000,16 000 and 10 000 ng·mL-1 was 5.61% -13.31%,2.31% -8.35%, 2.02%-9.47% and 4.0%-15.0% respectiveIy,and inter-batch precision was 10.05%,2.55%,3.75% and 8.58% respectiveIy. The recovery of 60,1000,and 16 000 μg·L-1 was 114.12%,109.2% and 101.06%respectiveIy. The average peak concentrations were 8373.28 and 8564.59 μg·L-1 ,the mean AUC was 98 400 and 104 000 μg·L-1·h and the t1/ 2z for B7011 was 41.7 and 63.6 h in bIood of maIe and femaIe rats, respectiveIy. CONCLUSlON The estabIished method is sensitive, fast and simpIe and concentration of B7011 in pIasma is determined by LC-mS/ mS foIIowing a singIe intravenous injection of B7011 0.5 mg·kg-1 to rats. It can satisfy the requirements of pharmacokinetic and toxicokinetic studies.

AIM: To study the bioequivalence of domestic and imported Metoprolol Tartrate Tablets in Chinese healthy volunteers.METHODS: According to the rule published by SFDA,the serum concentration of 20 selected volunteers among 18 to 40 years old was determined by HPLC-fluorescence detection after giving domestic and imported Metoprolol Tartrate Tablets 0.1g,and the pharmacokinetic parameters were calculated by DAS software.RESULTS: The method of HPLC-fluorescence detection to study the pharmakokinetics of Metoprolol Tartrate was sensitive,reliable,accurate and reasonable.The main pharmakokinetics parameters of domestic and imported Metoprolol Tartrate Tablets were T_(max):(1.11)?(0.36 h) and(1.39)?(0.65 h) respectively;C_(max):(269.20)?(87.15)(?g?L~(-1)) and(262.03)?(75.52)(?g?L~(-1)) respectively;AUC_(0-12h):(1088.91)?(510.52)(?g?L~(-1)?h) and(1098.29)?5(55.14)(?g?L~(-1)?h) respectively.The relative bioavailability of domestic Metoprolol Tartrate Tablets was(100.09)%.CONCLUSION: The domestic and imported Metoprolol Tartrate Tablets was bioequivalents.