Objective To investigate the genetic characteristics of the VP1 region of Coxsackievirus A10 (CVA10) in Yunnan Province. Methods Fecal samples of suspected hand, foot and mouth disease (HFMD) were subjected to real-time fluorescent quantitative PCR for detection of enterovirus CVA10. Positive samples were subjected to VP1 gene sequence amplification and Sanger sequencing. Sequence splicing was performed with DNAstar7.1 Seqman software, and nucleotide sequence and amino acid site analysis were performed using Mega 6.0 software. Results The sequencing of VP1 gene of CVA10 obtained a sequence of 894 nucleotides, encoding 298 amino acids. Compared with the original strain, there were mainly three active amino acid mutation regions, 13-33, 141-142, and 283-285. The nucleotide difference rate between the Yunnan isolates and the reference strain ranged from 16.92% to 30.90%, and the amino acid difference rate ranged from 2.58% to 4.00%. C1 and C2 group nucleotide difference was 10.58%, and the amino acid difference rate was 1.80%. The VP1 150-176 region exhibited highly conserved characteristics. Six CVA10 strains and Sichuan strain MW178898 belonged to the C1 group of the C genotype. The other 14 CVA10 strains belonged to the C2 group. Conclusion VP1 gene mutation is active and CVA10 is an important pathogen of HFMD in Yunnan. C2 genotype of CVA10 is dominant in this study, and C1 and C2 have co-circulated in Yunnan. It is necessary to strengthen monitoring and develop multivalent vaccines containing CVA10 epidemic genotype.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Objective:To investigate the risk factors and prognostic value of the textbook outcome (TO) in patients with advanced gastric cancer (AGC) who underwent neoadjuvant chemotherapy followed by surgical resection.Methods:This is a retrospective cohort study. A total of 253 patients with AGC who underwent neoadjuvant chemotherapy combined with gastrectomy and D2 lymphadenectomy in the Department of Gastric Surgery, Fujian Medical University Union Hospital from January 2010 to December 2019 were retrospectively included. There were 195 males and 58 females, aged (60.3±10.0) years (range: 27 to 75 years). The patients were then divided into the TO group ( n=168) and the non-TO group ( n=85). Multivariate Logistic regression was used to analyze the independent predictors of TO. Univariate and multivariate Cox analysis were used to analyze independent prognosis factors for overall survival (OS) and disease-free survival (DFS). Propensity score matching was performed to balance the TO and non-TO groups, and the Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results:Among the 253 patients, 168 patients (66.4%) achieved TO. The Eastern Cooperative Oncology Group score ( OR=0.488, 95% CI: 0.278 to 0.856, P=0.012) and ypN stage ( OR=0.626, 95% CI:0.488 to 0.805, P<0.01) were independently predictive of TO. Multivariate analysis revealed that TO was an independent risk factor for both OS ( HR=0.662, 95% CI: 0.457 to 0.959, P=0.029) and DFS ( HR=0.687, 95% CI: 0.483 to 0.976, P=0.036). After matching, the 5-year OS rate (42.2% vs. 27.8%) and the 5-year DFS rate (37.5% vs. 27.8%) were significantly higher in the TO group than in the non-TO group (both P<0.05). Furthermore, patients in the non-TO group benefited significantly from postoperative chemotherapy (both P<0.05), but those in the TO group did not (both P>0.05). Conclusion:TO is an independent prognosis factor in patients undergoing neoadjuvant chemotherapy and surgery for AGC and is associated with postoperative chemotherapy benefits.

Objective:To investigate the risk factors and prognostic value of the textbook outcome (TO) in patients with advanced gastric cancer (AGC) who underwent neoadjuvant chemotherapy followed by surgical resection.Methods:This is a retrospective cohort study. A total of 253 patients with AGC who underwent neoadjuvant chemotherapy combined with gastrectomy and D2 lymphadenectomy in the Department of Gastric Surgery, Fujian Medical University Union Hospital from January 2010 to December 2019 were retrospectively included. There were 195 males and 58 females, aged (60.3±10.0) years (range: 27 to 75 years). The patients were then divided into the TO group ( n=168) and the non-TO group ( n=85). Multivariate Logistic regression was used to analyze the independent predictors of TO. Univariate and multivariate Cox analysis were used to analyze independent prognosis factors for overall survival (OS) and disease-free survival (DFS). Propensity score matching was performed to balance the TO and non-TO groups, and the Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results:Among the 253 patients, 168 patients (66.4%) achieved TO. The Eastern Cooperative Oncology Group score ( OR=0.488, 95% CI: 0.278 to 0.856, P=0.012) and ypN stage ( OR=0.626, 95% CI:0.488 to 0.805, P<0.01) were independently predictive of TO. Multivariate analysis revealed that TO was an independent risk factor for both OS ( HR=0.662, 95% CI: 0.457 to 0.959, P=0.029) and DFS ( HR=0.687, 95% CI: 0.483 to 0.976, P=0.036). After matching, the 5-year OS rate (42.2% vs. 27.8%) and the 5-year DFS rate (37.5% vs. 27.8%) were significantly higher in the TO group than in the non-TO group (both P<0.05). Furthermore, patients in the non-TO group benefited significantly from postoperative chemotherapy (both P<0.05), but those in the TO group did not (both P>0.05). Conclusion:TO is an independent prognosis factor in patients undergoing neoadjuvant chemotherapy and surgery for AGC and is associated with postoperative chemotherapy benefits.

Objective:Analyzing the influence of morphological evaluation parameters of blastocysts, including days of blastocyst development [day 5 (D5) and day 6 (D6)], degree of blastocyst expansion (4, 5, 6), inner cell mass and trophectoderm grade, on the occurrence of chromosomal karyotype abnormalities of chorionic villi in missed abortion after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment and fresh/frozen-thawed single blastocyst transfer. Methods:The clinical data of patients with missed abortion after IVF/ICSI treatment and fresh/frozen-thawed single blastocyst transfer from February 2015 to February 2023 in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University were included. Using a case-control study, the data were divided into two groups according to the detection results of chromosomal copy number variations (CNVs) in chorionic villi of missed abortion abnormal karyotype group ( n=139) and normal karyotype group ( n=82). The baseline data between the two groups were compared. Univariate logistic regression was used to investigate the effect of blastocyst morphological rating parameters on the occurrence of chromosomal karyotype abnormalities of chorionic villi in aborted tissues, and multivariate logistic regression was also used to adjust confounding factors. Results:Male age [(34.12±6.49) years], sperm morphology rate [5.00 (4.00,6.00)%] and female age [33.00 (30.00, 37.00) years] in abnormal karyotype group were higher than those in the normal karyotype group [(32.38±4.69) years, 4.00 (2.00,5.00)% and 31.50 (29.00,34.00) years], and the differences were statistically significant ( P=0.022, P=0.020, P=0.009). Univariate and multivariate logistic regression analyses showed that days of blastocyst development, degree of blastocyst expansion, inner cell mass and trophectoderm grade did not increase the risk of chromosomal karyotype abnormalities of chorionic villi (all P>0.05). Conclusion:There is no significant correlation between blastocyst morphological evaluation parameters and chromosomal karyotype abnormalities in chorionic villi of missed abortion after fresh/frozen-thawed single blastocyst transfer with IVF/ICSI treatment.

Objective:Analyzing the influence of morphological evaluation parameters of blastocysts, including days of blastocyst development [day 5 (D5) and day 6 (D6)], degree of blastocyst expansion (4, 5, 6), inner cell mass and trophectoderm grade, on the occurrence of chromosomal karyotype abnormalities of chorionic villi in missed abortion after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment and fresh/frozen-thawed single blastocyst transfer. Methods:The clinical data of patients with missed abortion after IVF/ICSI treatment and fresh/frozen-thawed single blastocyst transfer from February 2015 to February 2023 in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University were included. Using a case-control study, the data were divided into two groups according to the detection results of chromosomal copy number variations (CNVs) in chorionic villi of missed abortion abnormal karyotype group ( n=139) and normal karyotype group ( n=82). The baseline data between the two groups were compared. Univariate logistic regression was used to investigate the effect of blastocyst morphological rating parameters on the occurrence of chromosomal karyotype abnormalities of chorionic villi in aborted tissues, and multivariate logistic regression was also used to adjust confounding factors. Results:Male age [(34.12±6.49) years], sperm morphology rate [5.00 (4.00,6.00)%] and female age [33.00 (30.00, 37.00) years] in abnormal karyotype group were higher than those in the normal karyotype group [(32.38±4.69) years, 4.00 (2.00,5.00)% and 31.50 (29.00,34.00) years], and the differences were statistically significant ( P=0.022, P=0.020, P=0.009). Univariate and multivariate logistic regression analyses showed that days of blastocyst development, degree of blastocyst expansion, inner cell mass and trophectoderm grade did not increase the risk of chromosomal karyotype abnormalities of chorionic villi (all P>0.05). Conclusion:There is no significant correlation between blastocyst morphological evaluation parameters and chromosomal karyotype abnormalities in chorionic villi of missed abortion after fresh/frozen-thawed single blastocyst transfer with IVF/ICSI treatment.

Objective:To study the genetic characteristics and genetic evolution of echovirus 30 (ECHO30) isolates in Yunnan Province, China.Methods:Virus isolation was performed on nucleic acid-positive samples for hand, foot, and mouth disease pathogen surveillance in Yunnan Province, and VP1 gene sequencing was performed. The sequences of eight ECHO30 isolates from Yunnan Province and the gene sequences of the VP1 region of the ECHO30 reference strain downloaded from GenBank were compared and analyzed using MEGA 5.0 software, and then a phylogenetic tree was constructed to measure the homology of nucleotides and amino acids between the isolates.Results:The ECHO30 virus was distributed in Wenshan, Qujing, Chuxiong, and Kunming in Yunnan Province. The ECHO30 virus was relatively common in Wenshan. ECHO30 isolates belonged to the H2 subtype of the H genotype, which was close to the local reference strain LC120939 in Yunnan Province. On the VP1 gene at site 5, the amino acid change ratio was more active, the amino acids were diverse, and mutations also occurred at sites 54, 156, 258, and so on. Nucleotide and amino acid homology were 84.0% - 100.0% and 98.4% - 100.0%, respectively.Conclusions:ECHO30 isolates from Yunnan Province have certain geographical characteristics and belong to H2 of the H genotype. The nucleotide differences in virus sequences among subtypes are small and have a close genetic relationship.

Objective:To investigate the perinatal outcome of selective fetal reduction of dizygotic twins pregnancies after double embryo transferred assisted by in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI). Methods:The clinical data of patients with single birth who underwent IVF/ICSI after double embryo transferred from September 1, 2005 to July 31, 2020 in Reproductive Center of the Third Affiliated Hospital of Zhengzhou University were retrospectively analyzed. The patients were divided into three groups according to the occurrence of fetal reduction: 80 cases of dizygotic twins to singleton by selective fetal reduction (group A), 832 cases of dizygotic twins to singleton by spontaneous fetal reduction (group B), and 6 178 cases of singleton (group C). Using group A as the reference, after approximately propensity score matching (PSM) with 1∶4 ratio, 289 cases in group B and 271 cases in group C were obtained. The differences in baseline data and perinatal outcomes between group A and group B or group C were analyzed.Results:1) Before PSM, there were statistically significant differences in patients' age, previous fertility history, type of infertility, and stage of embryo transferred between group A and group B or group C (all P<0.05); after PSM, there were no statistically significant differences in baseline data between group A and group B or group C (all P>0.05). 2) After PSM, the premature birth rate was higher in group A than in group B [17.5% (14/80) vs. 8.7% (25/289), P=0.023] and the gestational weeks [(38.18±1.98) weeks vs. (38.64±1.83) weeks, P=0.034] were lower; group A had higher incidence rates of premature birth [17.5% (14/80) vs. 7.7% (21/271), P=0.011] and premature rupture of membranes [5.0% (4/80) vs. 0.4% (1/271), P=0.002] than those in group C, but gestational weeks [(38.18±1.98) weeks vs. (38.85±1.47) weeks, P=0.002] and birth weight [(3 253.07±475.73) g vs. (3 384.89±479.54) g, P=0.029] were lower. Conclusion:Perinatal outcomes of selective fetal reduction of dizygotic twins pregnancies after assisted by IVF/ICSI were poor. Selective fetal reduction in multiple pregnancies is not the best remedy. The strategy of selective single embryo transfer should be adopted to effectively reduce the rate of multiple pregnancies and improve maternal and infant outcomes.

Objective:To investigate the perinatal outcome of selective fetal reduction of dizygotic twins pregnancies after double embryo transferred assisted by in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI). Methods:The clinical data of patients with single birth who underwent IVF/ICSI after double embryo transferred from September 1, 2005 to July 31, 2020 in Reproductive Center of the Third Affiliated Hospital of Zhengzhou University were retrospectively analyzed. The patients were divided into three groups according to the occurrence of fetal reduction: 80 cases of dizygotic twins to singleton by selective fetal reduction (group A), 832 cases of dizygotic twins to singleton by spontaneous fetal reduction (group B), and 6 178 cases of singleton (group C). Using group A as the reference, after approximately propensity score matching (PSM) with 1∶4 ratio, 289 cases in group B and 271 cases in group C were obtained. The differences in baseline data and perinatal outcomes between group A and group B or group C were analyzed.Results:1) Before PSM, there were statistically significant differences in patients' age, previous fertility history, type of infertility, and stage of embryo transferred between group A and group B or group C (all P<0.05); after PSM, there were no statistically significant differences in baseline data between group A and group B or group C (all P>0.05). 2) After PSM, the premature birth rate was higher in group A than in group B [17.5% (14/80) vs. 8.7% (25/289), P=0.023] and the gestational weeks [(38.18±1.98) weeks vs. (38.64±1.83) weeks, P=0.034] were lower; group A had higher incidence rates of premature birth [17.5% (14/80) vs. 7.7% (21/271), P=0.011] and premature rupture of membranes [5.0% (4/80) vs. 0.4% (1/271), P=0.002] than those in group C, but gestational weeks [(38.18±1.98) weeks vs. (38.85±1.47) weeks, P=0.002] and birth weight [(3 253.07±475.73) g vs. (3 384.89±479.54) g, P=0.029] were lower. Conclusion:Perinatal outcomes of selective fetal reduction of dizygotic twins pregnancies after assisted by IVF/ICSI were poor. Selective fetal reduction in multiple pregnancies is not the best remedy. The strategy of selective single embryo transfer should be adopted to effectively reduce the rate of multiple pregnancies and improve maternal and infant outcomes.

Objective:To investigate the predominant types of enteroviruses and the characteristics of the VP1 gene of coxsackievirus A4 (CVA4) causing hand, foot and mouth disease (HFMD) in Yunnan Province from 2018 to 2020.Methods:Throat swab and stool samples were collected from HFMD cases and tested by real-time quantitative PCR for nucleic acid detection. The samples positive for enterovirus nucleic acids were used for viral isolation and sent to the National Center for Disease Control and Prevention. The VP1 gene of the isolated strains was sequenced and analyzed.Results:From 2018 to 2020, a total of 21 757 HFMD samples were collected, 16 457 (75.64%) of which were positive for enteroviruses. Altogether 533 strains were isolated from 4 114 positive samples that were selected for viral isolation, including 89 strains of enterovirus 71 (EVA71, 16.70%), 180 strains of coxsackievirus A16 (CVA16, 33.77%), 76 strains of CVA10 (14.26%), 118 strains of CVA6 (22.14%), 26 strains of CVA4 (4.88%) and 44 strains of other types (8.26%). HFMD occurred mainly in children under five years old with higher incidence in males than in females (1.35∶1). The incidence of HFMD reached the peak in the second and third quarters. In Yunnan Province, CVA4 mainly circulated in Qujing and Kunming, and was sporadically detected in Wenshan and Honghe. The VP1 gene was 915 bp in length. Twenty-six CVA4 strains belonged to C2 subtype, which were genetically far from the prototype strain AY421762-HighPoint. Mutations in the VP1 gene were found at multiple sites including 18, 23, 34, 102, 148, 164, 200, 262, 174, 275, 285 and 303. These strains showed 80.4%-99.0% homology in nucleotide sequence and 95.6%-99.0% in amino acid sequence. Nucleotide mutations were mostly synonymous mutations.Conclusions:CVA16, CVA6, EVA71 and CVA10 were the predominant enteroviruses causing HFMD in Yunnan Province from 2018 to 2020. The prevalence of CVA4 was also worthy of attention. CVA4 isolates in Yunnan Province belonged to C2 subtype, mainly circulating in the east and southeast of Yunnan Province and gradually becoming a cocirculating predominant strain. Long-term dynamic monitoring would be of great public health significance for improving the sensitivity of HFMD early warning.