Objective:To investigate the application value of single-sperm sequencing in resolving the carrier status of preim-plantation genetic testing(PGT)for chromosomal structural rearrangements in Robertsonian translocations.Methods:Haplotypes were constructed by single-sperm isolation combined with single-sperm sequencing for a patient with 45,XY,der(13;14)(q10;q10).Twenty single-sperm samples were isolated by mechanical braking and subjected to whole-genome amplification(WGA),and then the Asian Screening Array(ASA)gene chip was used to detect the 183 708 single nucleotide polymorphisms(SNP)of the WGA products.The single sperm associated with the translocation that could be used as haplotype inference was detected by copy number variation(CNV)sequencing,and the chromosomal haplotypes with normal and Robertsonian translocations were inferred.Three biopsy samples of embryonic trophoblast cells were used as the objects.After whole-genome amplification,high-throughput sequencing was employed to determine the status of the translocation chromosome carried by the embryos.The available blastocysts were selected for transfer,and the amniotic fluid samples were taken at 18 weeks of gestation to confirm whether the fetus carried the pathogenic muta-tion.Results:A total of 6 037 SNP sites were screened by single-sperm sequencing,and 30 sites selected to distinguish normal and translocation haplotypes.Preimplantation haplotype analysis showed that all the three embryos were euploids without Robertsonian translocation chromosome.Genetic testing of amniotic fluid in the second trimester confirmed that the karyotype of the fetus was 46,XN,carrying no Robertsonian translocation chromosome.Conclusion:For male carriers of Robertsonian translocation,single sperm sequencing can be used to screen SNP sites to construct haplotypes for distinguishing normal and Robertsonian translocation em-bryos,and to provide a basis for embryo selection by preimplantation chromosomal structural genetic testing.

The modernization and development of traditional Chinese medicine has led to higher standards for the quality of traditional Chinese medicine products. The extraction process is a crucial component of traditional Chinese medicine production, and it directly impacts the final quality of the product. However, the currently relied upon methods for quality assurance of the extraction process, such as simple wet chemical analysis, have several limitations, including time consumption and labor intensity, and do not offer precise control of the extraction process. As a result, there is significant value in incorporating near-infrared spectroscopy (NIRS) in the production process of traditional Chinese medicine to improve the quality control of the final products. In this study, we focused on the extraction process of Xiao'er Xiaoji Zhike oral liquid (XXZOL), using near-infrared spectra collected by both a Fourier transform near-infrared spectrometer and a portable near-infrared spectrometer. We used the concentration of synephrine, a quality control index component specified by the pharmacopoeia, to achieve rapid and accurate detection in the extraction process. Moreover, we developed a model transfer method to facilitate the transfer of models between the two types of near-infrared spectrometers (analytical grade and portable), thus resolving the low resolution, poor performance, and insufficient prediction accuracy issues of portable instruments. Our findings enable the rapid screening and quality analysis of XXZOL onsite, which is significant for quality monitoring during the traditional Chinese medicine production process.

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.
Humans ; Aged ; Treatment Outcome ; Retrospective Studies ; Combined Modality Therapy ; Chemoradiotherapy/methods* ; Urinary Bladder Neoplasms/radiotherapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Neoplasm Staging

Objective: To examine the clinical efficacy of 3 anti-reflux methods of digestive tract reconstruction after proximal gastrectomy for gastric cancer. Methods: The clinical data and follow-up data of gastric cancer patients who underwent anti-reflux reconstruction after proximal gastrectomy in 11 medical centers of China from September 2016 to August 2021 were retrospectively collected, including 273 males and 65 females, aging of (63±10) years (range: 28 to 91 years). Among them, 159 cases were performed with gastric tube anastomosis (GTA), 107 cases with double tract reconstruction (DTR), and 72 cases with double-flap technique (DFT), respectively. The duration of operation, length of postoperative hospital stay and early postoperative complications (referring to Clavien-Dindo classification) of different anti-reflux reconstruction methods were assessed. Body mass index, hemoglobin and albumin were used to reflect postoperative nutritional status. Reflux esophagitis was graded according to Los Angeles criteria based on the routinely gastroscopy within 12 months after surgery. The postoperative quality of life (QoL) was evaluated by Visick score system. The ANOVA analysis, Kruskal-Wallis rank sum test, χ² test and Fisher's exact test were used for comparison between multiple groups, and further comparison among groups were performed with LSD, Tamhane's test or Bonferroni corrected χ² test. The mixed effect model was used to compare the trends of Body mass index, hemoglobin and albumin over time among different groups. Results: The operation time of DFT was significantly longer than that of GTA and DTR ((352±63) minutes vs. (221±66) minutes, (352±63) minutes vs. (234±61) minutes, both P<0.01). The incidence of early complications with Clavien-Dindo grade Ⅱ to Ⅴ in GTA, DFT and DTR groups was 17.0% (27/159), 9.7% (7/72) and 10.3% (11/107), respectively, without significant difference among these three groups (χ²=3.51, P=0.173). Body mass index decreased more significantly in GTA than DFT group at 6 and 12 months after surgery (mean difference=1.721 kg/m², P<0.01; mean difference=2.429 kg/m², P<0.01). body mass index decreased significantly in DTR compared with DFT at 12 months after surgery (mean difference=1.319 kg/m², P=0.027). There was no significant difference in hemoglobin or albumin fluctuation between different reconstruction methods perioperative. The incidence of reflux esophagitis one year after surgery in DTR group was 12.9% (4/31), which was lower than that in DFT (45.9% (17/37), χ²=8.63, P=0.003). Follow-up of postoperative quality of life showed the incidence of Visick grade 2 to 4 in DFT group was lower than that in GTA group (10.4% (7/67) vs. 34.6% (27/78), χ²=11.70, P=0.018), while there was no significant difference between DFT and DTR group (10.4% (7/67) vs. 22.2% (8/36, P>0.05). Conclusions: Compared with GTA and DTR, DFT is more time-consuming, but there is no significant difference in early complications among three methods. DFT reconstruction is more conducive to maintain postoperative nutritional status and improve QoL, especially compared with GTA. The risk of reflux esophagitis after DTR reconstruction is lower than that of DFT.
Aged ; Albumins ; Esophagitis, Peptic/surgery* ; Female ; Gastrectomy/methods* ; Hemoglobins ; Humans ; Male ; Middle Aged ; Quality of Life ; Retrospective Studies ; Stomach Neoplasms/surgery*

OBJECTIVE: To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province. METHODS: The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017. RESULTS: The clinical data of 1 442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (r=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (r=0.196, P<0.01). CONCLUSIONS Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.
Anti-Bacterial Agents ; Birth Weight ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Intensive Care Units, Neonatal ; Surveys and Questionnaires

BACKGROUNDLiquid-based cytology (LBC) offers an alternative method to biopsy in screening endometrial cancer. Cell block (CB), prepared by collecting residual cytological specimen, represents a novel method to supplement the diagnosis of endometrial cytology. This study aimed to compare the specimen adequacy and diagnostic accuracy of LBC and CB in the diagnosis of endometrial lesions.

METHODSA total of 198 women with high risks of endometrial carcinoma (EC) from May 2014 to April 2015 were enrolled in this study. The cytological specimens were collected by the endometrial sampler (SAP-1) followed by histopathologic evaluation of dilatation and curettage or biopsy guided by hysteroscopy. The residual cytological specimens were processed into paraffin-embedded CB after LBC preparation. Diagnostic accuracies of LBC and CB for detecting endometrial lesions were correlated with histological diagnoses. Chi-square test was used to compare the specimen adequacies of LBC and CB.

RESULTSThe specimen inadequate rate of CB was significantly higher than that of LBC (22.2% versus 7.1%, P < 0.01). There were 144 cases with adequate specimens for LBC and CB preparation. Among them, 29 cases were atypical endometrial hyperplasia (11 cases) or carcinoma (18 cases) confirmed by histology evaluation. Taking atypical hyperplasia and carcinoma as positive, the diagnostic accuracy of CB was 95.1% while it was 93.8% in LBC. When combined LBC with CB, the diagnostic accuracy was improved to 95.8%, with a sensitivity of 89.7% and specificity of 97.4%.

CONCLUSIONSCB is a feasible and reproducible adjuvant method for screening endometrial lesions. A combination of CB and LBC can improve the diagnostic accuracy of endometrial lesions.

Adult ; Aged ; Biopsy ; methods ; Cross-Sectional Studies ; Cytodiagnosis ; methods ; Early Detection of Cancer ; methods ; Endometrial Hyperplasia ; diagnosis ; Endometrial Neoplasms ; diagnosis ; Endometrium ; pathology ; Female ; Humans ; Middle Aged ; Sensitivity and Specificity ; Specimen Handling

OBJECTIVETo construct a breast cancer gene-drug network model for extracting and predicting the correlations between breast cancer-related genes and drugs.

METHODSWe developed an algorithm based on the ABC principle and the association rules to obtain the correlations between the biological entities. For breast cancer, we constructed 3 different correlations (gene-gene, drug-drug and gene-drug) and used the R language to implement the associated network model. The reliability of the algorithm was verified by ROC curve.

RESULTSWe identified 185 breast cancer-associated genes and 98 associations between them, 97 drugs and 170 associations between them. The breast cancer genes-drugs network contained 127 genes and 77 drugs with 384 associations between them.

CONCLUSIONSWe identified a large number of different correlations between the breast cancer-related genes and drugs and close correlations between some biological entity pairs that have not yet been reported, which may provide a new strategy for experimental design for testing personalized breast cancer treatment.

Algorithms ; Antineoplastic Agents ; pharmacology ; Breast Neoplasms ; genetics ; Female ; Gene Regulatory Networks ; Genes, Neoplasm ; Humans ; ROC Curve ; Reproducibility of Results

BACKGROUNDIn China, no multicenter double-blinded prospective randomized controlled study on labor induction has been conducted till now. This study is to evaluate the efficacy and safety of intravaginal accurate 25-μg misoprostol tablets for cervical ripening and labor induction in term pregnancy in nulliparous women.

METHODSThis was a double-blinded, prospective randomized controlled study including nulliparous women from 6 university hospitals across China. Subjects were randomized into misoprostol or placebo group with the sample size ratio set to 7:2. Intravaginal 25-μg misoprostol or placebo was applied at an interval of 4 h (repeated up to 3 times) for labor induction. Primary outcome measures were the incidence of cumulative Bishop score increases ≥3 within 12 h or vaginal delivery within 24 h. Safety assessments included the incidences of maternal morbidity and adverse fetal/neonatal outcomes.

RESULTSA total of 173 women for misoprostol group and 49 women for placebo were analyzed. The incidence of cumulative Bishop score increases ≥3 within 12 h or vaginal delivery within 24 h was higher in the misoprostol group than in the placebo (64.2% vs. 22.5%, relative risk [RR]: 2.9, 95% confidence interval [CI]: 1.4-6.0). The incidence of onset of labor within 24 h was significantly higher in the misoprostol group than in the placebo group (48.0% vs. 18.4%, RR: 2.6, 95% CI: 1.2-5.7); and the induction-onset of labor interval was significantly shorter in the misoprostol group (P = 0.0003). However, there were no significant differences in the median process time of vaginal labor (6.4 vs. 6.8 h; P = 0.695), incidence (39.3% vs. 49.0%, RR: 0.8, 95% CI: 0.4-1.5) and indications (P = 0.683) of cesarean section deliveries, and frequencies of maternal, fetal/neonatal adverse events between the groups.

CONCLUSIONIntravaginal misoprostol 25 μg every 4 h is efficacious and safe in labor induction and cervical ripening.

Administration, Intravaginal ; Adult ; Cervical Ripening ; drug effects ; Double-Blind Method ; Female ; Humans ; Labor, Induced ; methods ; Misoprostol ; administration & dosage ; therapeutic use ; Pregnancy ; Pregnancy Outcome ; Pregnancy Trimester, Third ; Young Adult