[Objective] To retrospectively analyze the detection results of alanine aminotransferase (ALT) unqualified repeat blood donors in Guangzhou, so as to provide evidence for further expanding the repeat blood donor pool, reducing the rate of blood discarding and improving the qualified rate of blood test. [Methods] Blood donors with unqualified ALT in Guangzhou Blood Center from January 2018 to April 2024 were selected as the research objects. The past blood donation and population characteristics were analyzed according to the number of blood donations and ALT unqualified times. [Results] Among repeat blood donors with previous ALT disqualification, 99.5% to 99.7% did not have reactive markers for transfusion-transmitted diseases (TTD), which was higher than the rate among first-time blood donors with unqualified ALT (95.8%) (P<0.05). The rate of single-item ALT disqualification in repeat blood donors was higher in males than in females (P<0.05); it also varied by age (18-25 years > 26-35 years > 36-45 years > over 45 years) (P<0.05); and by quarter (third and fourth quarters > first and second quarters) (P<0.05). The ALT unqualified rate was significantly higher whole blood donors than that of platelet donors and returning blood donors (P<0.05). The overall ALT level (51.0 U/L), individual ALT level (56.0 U/L) and individual ALT unqualified rate (66.7%) of repeat blood donors with multiple ALT disqualifications were higher than those of repeat blood donors with single-item ALT disqualifications (26.0 U/L, 38.5 U/L, and 33.3%, respectively) (P<0.05). Moreover, as the number of ALT disqualifications increased, the overall level of ALT in repeat blood donors also increased (P<0.05), and the average level of individual ALT and individual ALT unqualified ratio tended to increase. Repeat blood donors with frequent ALT disqualifications had higher ALT levels (69.0 U/L). [Conclusion] The ALT unqualified rates of repeat blood donors were mostly non-specific elevation without TTD. Repeat blood donors with multiple ALT disqualifications tend to have continuous high ALT. Moreover, and with the increase of ALT disqualifications times, the overall ALT levels the average individual ALT levels and individual ALT unqualified rates showed an increasing trend.

With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.

Background::In vitro fertilization (IVF) has emerged as a transformative solution for infertility. However, achieving favorable live-birth outcomes remains challenging. Current clinical IVF practices in IVF involve the collection of heterogeneous embryo data through diverse methods, including static images and temporal videos. However, traditional embryo selection methods, primarily reliant on visual inspection of morphology, exhibit variability and are contingent on the experience of practitioners. Therefore, an automated system that can evaluate heterogeneous embryo data to predict the final outcomes of live births is highly desirable. Methods::We employed artificial intelligence (AI) for embryo morphological grading, blastocyst embryo selection, aneuploidy prediction, and final live-birth outcome prediction. We developed and validated the AI models using multitask learning for embryo morphological assessment, including pronucleus type on day 1 and the number of blastomeres, asymmetry, and fragmentation of blastomeres on day 3, using 19,201 embryo photographs from 8271 patients. A neural network was trained on embryo and clinical metadata to identify good-quality embryos for implantation on day 3 or day 5, and predict live-birth outcomes. Additionally, a 3D convolutional neural network was trained on 418 time-lapse videos of preimplantation genetic testing (PGT)-based ploidy outcomes for the prediction of aneuploidy and consequent live-birth outcomes.Results::These two approaches enabled us to automatically assess the implantation potential. By combining embryo and maternal metrics in an ensemble AI model, we evaluated live-birth outcomes in a prospective cohort that achieved higher accuracy than experienced embryologists (46.1% vs. 30.7% on day 3, 55.0% vs. 40.7% on day 5). Our results demonstrate the potential for AI-based selection of embryos based on characteristics beyond the observational abilities of human clinicians (area under the curve: 0.769, 95% confidence interval: 0.709–0.820). These findings could potentially provide a noninvasive, high-throughput, and low-cost screening tool to facilitate embryo selection and achieve better outcomes. Conclusions::Our study underscores the AI model’s ability to provide interpretable evidence for clinicians in assisted reproduction, highlighting its potential as a noninvasive, efficient, and cost-effective tool for improved embryo selection and enhanced IVF outcomes. The convergence of cutting-edge technology and reproductive medicine has opened new avenues for addressing infertility challenges and optimizing IVF success rates.

Background::Breast cancer is ranked among the most prevalent malignancies in the Chinese female population. However, comprehensive reports detailing the latest epidemiological data and attributable disease burden have not been extensively documented.Methods::In 2018, high-quality cancer surveillance data were recorded in 700 population-based cancer registries in China. We extracted data on female breast cancers (International Classification of Diseases, Tenth Revision [ICD-10]: C50) and estimated the incidence and mortality in 2022 according to the baseline data and corresponding trends from 2010 to 2018. Pathological types were classified according to the ICD for Oncology, 3rd Edition codes. Disability-adjusted life years (DALYs) were calculated as the sum of the years of life lost (YLLs) and years lived with disability (YLDs).Results::In 2022, approximately 357,200 new female breast cancer cases and 75,000 deaths occurred in China, accounting for 15.59% and 7.94% of total new cancer cases and deaths, respectively. The age-standardized incidence rate (ASIR) was 33.04 per 100,000. When analyzed by pathological type, the ASIRs for papillary neoplasms, invasive breast carcinoma, rare and salivary gland-type tumors, and other types were 1.13, 29.79, 0.24, and 1.88 per 100,000, respectively. The age-standardized mortality rate (ASMR) was 6.10 per 100,000. A total of 2,628,000 DALYs were found to be attributable to female breast cancer in China, comprising 2,278,300 YLLs and 349,700 YLDs. The ASIR, ASMR, and age-standardized rate (ASR) for DALYs in urban areas were consistently higher than those in rural areas. We observed a four-fold increase in the ASIR and ASR for DALYs and an eight-fold increase in the ASMR among females over 55 years compared with those aged under 55 years.Conclusion::These data provide invaluable insights into the latest epidemiology of female breast cancer in China and highlight the urgency for disease prevention and control strategy formulation.

Background and Aims:The repair of giant incisional hernia is challenging,as closing the significant defect in the abdominal wall can lead to life-threatening complications like abdominal compartment syndrome(ACS).Botulinum toxin type A(BTA)can temporarily relax the abdominal wall muscles,facilitating defect repair,while preoperative progressive pneumoperitoneum(PPP)can increase intra-abdominal volume,reducing intra-abdominal pressure caused by hernia content reintegration.Combining BTA with PPP for the preoperative preparation of giant incisional hernia repair may have a complementary effect.This study was conducted to evaluate the clinical value of combining BTA and PPP in the repair of giant abdominal incisional hernia. Methods:The clinical data of 213 patients with giant abdominal incisional hernia treated at the Sixth Affiliated Hospital of Sun Yat-sen University from December 2015 to December 2019 were retrospectively analyzed.Two weeks after receiving combined BTA and PPP treatment,changes in bilateral abdominal wall muscle,intra-abdominal adhesions,abdominal circumference,abdominal cavity volume,and hernia sac volume ratio were assessed using CT.Intraoperative details,incidence of complications,and postoperative follow-up outcomes were recorded. Results:Following combined BTA and PPP treatment,CT scan showed a significant extension of bilateral lateral abdominal wall muscles towards the midline in all 213 patients,with an average increase of 2.45(1.53-3.29)cm on the left side and 2.54(1.68-3.40)cm on the right side;muscle thickness was reduced by an average of 0.84(0.64-1.00)cm on the left and 0.82(0.62-1.05)cm on the right,the average distance between viscera and the abdominal wall increased to(7.52±1.78)cm,with a mean increase of 6.1(4.2-6.9)cm;the mean increase in abdominal cavity volume was 1 802(1 494.98-2 316.26)mL,and the hernia sac volume ratio decreased by an average of 9％(6％-12％),all changes were statistically significant(P＜0.05).Post-PPP CT scan revealed no abdominal adhesions in 18 patients(8.45％),while 195 patients(91.55％)had varying degrees of adhesions,including 39 cases(18.31％)of sheet adhesions and 156 cases(73.24％)of mixed adhesions.Adhesions mainly consisted of omentum and intestinal tissues in 59.15％of cases.There were 43 cases(20.19％)of grade Ⅰ complications during the BTA-PPP process,including abdominal pain(28 cases),shoulder pain(9 cases),subcutaneous emphysema(6 cases),and dyspnea(3 cases).Dyspnea improved with oxygen therapy,while other complications required no special intervention.All 213 patients successfully underwent laparoscopic incisional hernia repair without conversion to open surgery or organ resection for volume reduction.Fascial closure was achieved in 209 cases(98.12％),with 4 cases(1.88％)having incomplete defect closure.The average time for adhesiolysis was 28(11.00-44.50)min,with a total operative time of 178.0(132.50-255.00)min and an average blood loss of 20(10-30)mL.The median intra-abdominal pressure(IAP)after operation was between 10 mmHg(9.00-12.00 mmHg),Among them,47 cases(22.07％)had IAP exceeding 12 mmHg,and after implementing proactive measures such as diuresis and diachoresis to reduce intra-abdominal contents,the IAP in these patients decreased to below 12 mmHg.No severe complications such as skin flap necrosis or ACS were observed.There were no deaths within postoperative 30 d,and during a follow-up period of 26(16.50-33.00)months,13 cases(6.10％)had surgical site events,including infections in 5 cases(2.35％),seromas in 7 cases(3.29％),and hematoma in 1 case(0.47％),with no hernia recurrence. Conclusion:The combination of BTA and PPP not only aids in identifying abdominal wall adhesion areas,improving preoperative surgical planning and enhancing surgical safety,but also significantly increases abdominal cavity volume and extends lateral abdominal wall muscles,facilitating the closure of giant incisional hernia defects and reducing the incidence of severe postoperative complications like ACS.This approach is worthy of clinical promotion.

Feces and intestinal contents of pigs suspected with porcine epidemic diarrhea virus were collected from a farm in Minqin County,Gansu Province,China.After the suspected positive sam-ples were detected by RT-PCR,Vero cells were used to isolate and culture them in vitro.The suc-cessfully isolated virus was identified in the laboratory,and its whole genome sequence was ana-lyzed for genetic evolution.The pathogenicity was evaluated by animal regression test.The results showed that typical syncytial lesions could be observed when the PEDV-positive treatment solu-tion was inoculated with Vero cells in the 4th generation,and the virus titer in the 6th generation reached 10-4 75TCID50/mL.PEDV-like virions with a diameter of about 100 nm and a round shape with obvious capsular membranes and spikes were observed by electron microscopy.Whole genome sequencing analysis showed that the total length of this strain was 28 085 bp,which was far from the G1 subtype represented by the classical strain CV777(96.6％),and had a high homology with the G2b strains BC-2011-1,IA1,USA/Colorado/2013 and WELL(98.6％).This indicated that the strain belonged to the G2b epidemic strain.The animal regression test showed that the 5-day-old piglets developed vomiting,acute watery diarrhea,emaciation and mental depression within 12 h after the attack,and the symptoms worsened and died within 24 h.After autopsy,the infected piglets could be observed with stomach swelling,high intestinal heave,thin and transparent intesti-nal wall,and undigested milk clots inside.In summary,a PEDV G2b epidemic strain was success-fully isolated and identified in this study,and its whole genome sequence and pathogenicity were analyzed,providing research materials for future studies on PEDV gene function,pathogenic mech-anism and vaccine development.

Fragile X syndrome (FXS) is a neurodevelopmental synaptopathy caused by loss of fragile X mental retardation protein (FMRP); abnormal synaptic plasticity is the leading pathological cause of cognitive impairment, fear and anxiety, hyperactivity and stereotyped behavior in FXS patients. In recent years, breakthroughs have been made in functional study of synaptic plasticity in FXS, providing a new theoretical basis for FXS. This article mainly summarizes the dysregulation and influencing factors of synaptic plasticity in FXS, as well as the strategy of targeted synaptic plasticity in FXS, so as to deepen the understanding of medical workers.

Objective To investigate the mechanism of Zuogui Pills (ZGP) on improving the stemness of ovarian germline stem cells (OSCs) in ovarian aging rats through the gap junction protein connexin 43 (Cx43) phosphorylation based on the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway. Methods Eight-week-old female SD rats were randomly divided into control(CON),model(cyclophosphamide,CTX),ZGP and dehydroepiandrosterone(DHEA) groups,six rats in each group. CTX was injected intraperitoneally for 15 days to establish a model for ovarian aging,and then ZGP (1.85 g·kg-1) or DHEA (8.1 mg·kg-1) was administered by gavage once daily for 30 days. Follicle count at different stages and pathological changes of ovarian tissues were observed by HE staining. ELISA was used to detect serum levels of anti-mullerian hormone (AMH),follicle-stimulating hormone (FSH),and estradiol(E2). The expression levels of related proteins (PCNA,MVH,Oct4,Cx43,p-Cx43,EGFR,AKT、p-AKT) in ovarian tissue were detected by Western Blot. Results Compared with the CON group,rats in CTX group had significantly reduced body mass(P<0.05) and ovarian mass(P<0.05). The number of primordial follicles decreased significantly(P<0.01). Serum FSH level increased remarkably(P<0.01),while AMH and E2 levels showed a downward trend (P>0.05). The protein expressions of Oct4,MVH,PCNA,EGFR,p-AKT/AKT,p-Cx43(Ser368)/Cx43 and Cx43 in ovarian tissue were obviously decreased(P<0.05,P<0.01). Compared with the model group,the body mass of rats in ZGP group was significantly increased (P<0.05),as well as ovarian mass and ovarian coefficient were remarkably increased (P<0.01). The number of primordial follicles were increased significantly (P<0.01),and E2 level increased significantly (P<0.05). The protein expressions of Oct4,MVH,PCNA,EGFR,p-AKT/AKT,p-Cx43(Ser368)/Cx43 and Cx43 in ovarian tissue were all increased significantly (P<0.05,P<0.01). Conclusion ZGP may ameliorate ovarian aging by maintaining the stemness of OSCs. Its mechanism of actions is related to the PI3K/AKT signaling pathway and gap junction protein phosphorylation.

Objective To explore the correlation between colorectal cancer tissue Janus kinase 2(JAK2)gene mutations and T cytokine 3(TCF3)protein expression with clinical pathological characteristics and prognosis,and to provide laboratory reference indicators for early evaluation of the illness severity and prognosis of colorectal cancer.Methods A retrospective analysis was conducted on the data of 50 colorectal cancer patients who were admitted from January 2016 to April 2021 and retained colon cancer and adjacent tissue wax blocks.Basic information,clinical and pathological features such as TNM staging,lymph node metastasis,and 3-year survival prognosis of the patients were collected.The wax blocks of colon cancer and adjacent tissues of patients were detected,in which Taqman fluorescence probe method was applied to detect the distribution of JAK2 gene at the rs2230724 locus AA,AG,and GG genotypes in colon cancer tissues,and immunohistochemistry method was applied to detect the positive expression rate of TCF3 protein in colon cancer and adjacent tissues.The basic information,JAK2 rs2230724 gene mutation,and TCF3 protein expression of patients with different clinical and pathological characteristics were compared,and the influencing factors of clinical and pathological characteristics of colon cancer was analyzed by logistic regression model.Kaplan Meier survival curve was applied to compare the survival prognosis of patients with JAK2 gene mutations and TCF3 protein expression in colorectal cancer tissue,and Cox regression model was applied to analyze the risk factors affecting the prognosis of colorectal cancer patients.Results The positive expression rate of TCF3 protein in colon cancer tissues was higher than that in adjacent tissues(P＜0.05).The age,BMI,proportion of GG genotype at rs2230724 locus of JAK2 gene and positive expression rate of TCF3 protein in TNM stage Ⅲ colon cancer patients were higher than those in TNM stage Ⅰ-Ⅱ patients(P＜0.05);The age,BMI,smoking rate,proportion of GG type at the rs2230724 locus of JAK2 gene in colon cancer tissue,and positive expression rate of TCF3 protein in patients with lymph node metastasis were higher than those without lymph node metastasis(P＜0.05);The results of the logistic regression model analysis showed that the influencing factors of clinical pathological features such as TNM staging and lymph node metastasis in colon cancer were age,mutation of JAK2 gene rs2230724 site in colon cancer tissue,and positive expression rate of TCF3 protein(P＜0.05).The Kaplan Meier survival curve analysis showed that patients with JAK2 gene rs2230724 GG genotype and TCF3 protein positivity in colon cancer tissue had higher cumulative all-cause mortality rates(P＜0.05).The results of univariate and multivariate Cox regression model analysis showed that independent risk factors affecting the prognosis of colorectal cancer patients include JAK2 gene rs2230724 site GG type,TCF3 protein positive expression,TNM stage Ⅲ,lymph node metastasis,and age.Conclusion The proportion of JAK2 gene rs2230724 GG type and TCF3 protein expression in colorectal cancer tissues are related to their clinical pathological characteristics and prognosis,and can be used as reference indicators for evaluating clinical pathological characteristics and predicting prognosis of colorectal cancer.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.