Objective:To compare the embryo development potential and clinical outcomes between the patients with and without oocyte degeneration.Methods:This retrospective cohort study included a total of 242 cycles underwent ICSI that cultured in time-lapse incubator from January 2019 to June 2023 at the Reproductive and Genetic Center of Suzhou Municipal Hospital and all 3 119 oocytes were evaluated. Data collection continued to February 5th,2024 until the last birthing of the study. Patients were divided into degenerated group (140 cycles) and control group (102 cycles) according to whether oocyte degenerated after ICSI. Then the embryo developmental potential and clinical outcomes were compared. Furthermore, we also investigated whether embryo morphokinetics could be different between the two groups.Results:Female age, duration of infertility, body mass index, basal follicle sitmulating hormone, basal luteinizing hormone, basal estrogen (E 2), antral follicle count, anti-Müllerian hormone, factors of infertility and source of semen were similar between the two groups ( P>0.05). E 2 on human chorionic gonadotropin triggered day [2 513.00 (1 842.20, 3 638.50) ng/L], number of oocytes retrieved (13.56±4.80) and oocyte maturation rate [84.35% (1 601/1 898)] were significantly higher in degenerated group than those in control group [2 270.50 (1 472.00, 3 044.20) ng/L, P=0.019; 11.97±4.71, P=0.011; 81.08% (990/1 221), P=0.017], while normal fertilization rate [69.33% (1 103/1 591)], day 3 (D3) good-quality embryos [57.85% (634/1 096)], blastocyst formation rate [50.87% (469/922)] and embryo utilized rate [58.30% (643/1 103)] were significantly lower in degenerated group than those in control group [85.56% (847/990), P<0.001; 65.72% (556/846), P<0.001; 61.26% (446/728), P<0.001; 66.12% (560/847), P<0.001] . In addition, the proportion of low cell number (<7) of D3 embryos [33.76% (370/1 096)] and high fragmentation (fragmentation ≥50%, fragmentation 20%-50%) of D3 embryos [10.01% (109/1 089), 18.64% (203/1 089)] in degenerated group were significantly higher than those in control group [27.19% (230/846), P=0.002; 6.06% (51/841), P=0.002; 14.15% (119/841), P=0.009], and so were the incidence of DC1 and CC [5.98% (66/1 103) vs. 2.48% (21/847), P<0.001; 2.45% (27/1 103) vs. 0.94% (8/847), P=0.013]. As regard to the utilized embryos, there were no significant differences in t5, cc2, cc3 and s2 ( P>0.05), but tPNf [22.82(21.13, 24.84) h], t2 [25.37 (23.62, 27.37) h], t3 [35.64 (33.10, 38.03) h] and t4 [36.85 (34.70, 39.52) h] in degenerated group were significantly earlier than those in control group [23.04 (21.76, 25.41) h, P=0.001; 25.91 (24.15, 28.05) h, P=0.001; 36.16 (33.11, 38.81) h, P=0.040; 37.39 (35.11, 40.27) h, P=0.026]. Further more, after the first transfer of fresh or frozen embryos, there were no significant differences in clinical pregnancy rate, implantation rate, early abortion rate, live birth rate, sex ratio, preterm birth rate, low birth weight rate and birth defect rate between the two groups (all P>0.05). ICSI degeneration was not an independent factor of implantation rate, early abortion rate and live birth rate after ICSI treatment, but number of embryos transferred was an independent factor of implantation rate and live birth rate after ICSI treatment ( OR=2.806, 95% CI: 1.179-6.677, P=0.020; OR=2.622, 95% CI: 1.129-6.090, P=0.025). Conclusion:The presence of oocyte degeneration after ICSI may affect the overall developmental potential of its sibling oocytes and may also disturb the morphokinetics of the embyos, however the pregnancy outcomes and neonatal birth outcomes may not be affected if transfer the best embryo in the first fresh or frozen cycle.

This study aims to research the relationship between arterial stiffness and serum indirect bilirub in levels(IBIL)in patients with type 2 diabetes by measuring brachial-ankle pulse wave velocity (baPWV). The clinical data of 1 327 patients with T2DM admitted to Qingdao Huangdao District People′s Hospital from July 1st, 2018 to March 1st, 2024 were retrospectively and cross-sectionally analyzed (609 men and 718 women; age range, 45.3-79.5 years; median age, 60.3 years; mean age, 61.4 years). The subjects were stratified based on gender-specific quartiles of IBIL values(male, Q1:<6.7 μmol/L, Q2:6.7-8.9 μmol/L, Q3:8.9-12.3 μmol/L, Q4:≥12.3 μmol/L;female, Q1:<6.4 μmol/L, Q2:6.4-7.9 μmol/L, Q3:7.9-10.4 μmol/L, Q4:≥10.4 μmol/L), and a high baPWV was defined as greater than 18.37 m/s (75th percentile). The results showed that the serum IBIL concentration was negatively correlated with the duration of diabetes ( r=-0.142, P=0.010), the SBP ( r=-0.158, P=0.005) and the baPWV ( r=-0.194, P<0.001) in women and was positively correlated with TC (men: r=0.282, P<0.001; women: r=0.237, P<0.001), HDL-C (men: r=0.171, P=0.011; women: r=0.287, P<0.001) and LDL-C (men: r=0.196, P=0.009; women: r=0.233, P<0.001) levels in both genders. Dividing IBIL levels into quartiles, there were significant statistical differences in the incidence of high baPWV among different subgroups of female patients ( χ 2=36.468, P<0.001), and the incidence of high baPWV showed a decreasing trend with increasing IBIL levels. After adjusting for confounding factors, the IB levels were inversely associated with a greater risk of a high baPWV both as a continuous variable [a 1-SD difference; odds ratio ( OR):0.836; 95% confidence interval ( CI):0.774-0.942; P=0.009] and when categorized in quartiles (the highest vs. the lowest quartile; OR:0.381; 95% CI:0.162-0.897; P=0.025) in women but not in men. Low IBIL levels were significantly associated with arterial stiffness in middle-aged and elderly women with type 2 diabetes. In conclusion, the serum IBIL levels were independent protective factors for macrovascular disease in middle-aged and elderly diabetic women.

Objective:To explore the risk factors of severe medication errors (ME) of tranexamic acid injection (TXAI), and put forward prevention suggestions.Methods:TXAI-related ME reports in the National Monitoring Network for Clinical Safe Medication (Monitoring Network) and medical literature databases at home and abroad were searched, and case reports of TXAI-related ME were collected; China Judgements Online and PKULAW database were searched, and TXAI-related judicial cases judged to be responsible by the hospital were collected. The retrieval time of all data was up to May 1, 2024. The severity grade, occurrence link and place, and the trigger person of TXAI-related ME reported in the Monitoring Network were retrospectively analyzed. The year of report, country of occurrence, clinical application, error content, and occurrence place of the collected severe ME cases, and the clinical characteristics of patient injury, patient outcome and the ME grading were retrospectively analyzed.Results:From September 22, 2012 to May 1, 2024, the Monitoring Network received a total of 138 TXAI-related ME reports, and there was an increasing trend in the number of reports year by year. Among 138 cases of ME, 79 (57.3%) occurred in the drug dispensing and distribution link; 58 (42.0%) occurred in the prescription/doctor's order prescribing and delivery link and mainly involved easily mixed drugs and drug overdose, of which 1 (1.7%) was a severe ME (grade E); 1 (0.7%) occurred in the drug administration link, and iodohexol was mistakenly injected as TXAI into the patient's joint cavity. A total of 29 severe ME reports related to TXAI were collected. Of them, 24 (82.8%) were due to incorrect administration routes (22 were confused with anesthetics and 2 were confused with injection catheters, all resulting in incorrect intrathecal injections) and 5 (17.2%) were due to prescription errors (3 were overdosed, 1 was used for high-risk thrombosis patient, and 1 was treated with combination use of hemocoagulase for high-risk thrombosis patient); 23 (79.3%) occurred in the operating rooms, and 6 (20.7%) occurred in the wards. The 24 patients involved in incorrect intrathecal injections of TXAI mainly developed severe pain, neurotoxicity (status epilepticus) and/or cardiotoxicity (arrhythmia and ventricular fibrillation), of which 11 (45.8%) died and 2 (8.3%) had sequelae of limb muscle weakness. Among the 5 patients with prescription errors, 4 developed severe thrombotic disease, resulting in 2 deaths and 2 cerebrovascular-related sequelae, and the other one developed palpitation, shortness of breath, nausea and vomiting. Among the 29 severe ME cases, 2 (6.9%) were grade E, 3 (10.3%) were grade F, 4 (13.8%) were grade G, 7 (24.2%) were grade H, and 13 (44.8%) were grade I.Conclusions:TXAI-related ME mainly involved easily mixed drugs and prescription errors. The severe ME main occurred in the operating room and mainly due to incorrect intrathecal injection, leading to fatal neurological and cardiac toxicity in patients.

Objective:To construct a recommended list of high-alert medication (HAM) based on big data from medication error (ME) reports in China, providing reference for preventing and reducing HAM-related risks.Methods:The drugs involved in the serious ME reports of the National Monitoring Network for Clinical Safe Medication (Monitoring Network) were collected (as of December 31, 2023), and the candidate drugs were preliminarily determined referring to the HAM list of China 2023 (Chinese list) and the latest three lists of American Institute for Safe Medication Practices (ISMP). Candidate drugs that were included in both the Chinese list and ISMP lists, as well as those existed in the Chinese list but had never been included in the ISMP lists were included in the current list, and their risk levels followed the original risks in the Chinese list. Candidate drugs that existed in the Chinese list but had been excluded from the ISMP lists, and those existed in the ISMP lists but had not been included in the Chinese list were listed as suspected drugs. For the other candidate drugs, those did not meet the definition of HAM were excluded firstly, and those related to ME that had caused serious harm were listed as suspected drugs, according to the judicial cases on ME of China Judgements Online and PKULAW database. Two methods, including Delphi expert consultation and questionnaire survey, were used to determine whether the above suspected drugs were included in the HAM list and their risk levels.Results:A total of 138 drugs were obtained through the initial screening, 106 of which were directly included in the current list, and 32 of which were listed as drugs requiring further assessment. After 2 rounds of Delphi expert consultation by 18 experts and surveys with 136 valid questionnaires, 32 suspected drugs did not meet the inclusion criteria. Finally, a total of 106 drugs were included in the current list, including 51 A-class drugs in 9 categories, 33 B-class drugs in 9 categories, and 22 C-class drugs in 5 categories.Conclusion:Based on the big data of the ME reports in China, a HAM list is constructed, which is accurate and concise and better fits the actual clinical drug risks in China, helping to improve the drug safety management.

Objective:To explore the causes of medication errors (ME) associated with deslanoside injection and put forward targeted preventive recommendations.Methods:ME reports related to deslanoside injection in the National Monitoring Network for Clinical Safe Medication (Monitoring Network) as of August 31, 2024 were collected, and sever ME cases of deslanoside injection were also collected though searching medical literature databases at home and abroad, China Judgements Online, and PKULAW database at the same period. The level of severity, occurrence link, error content, occurrence place, trigger personnel and patient outcomes of the MEs were retrospectively analyzed.Results:The Monitoring Network received a total of 41 ME reports of deslanoside injection from September 2012 to August 2024, and the number of reports showed an upward trend year by year. These MEs were classified as grade A in 1 case (2.4%), grade B in 18 cases (43.9%), grade C in 17 cases (41.5%), grade D in 4 cases (9.8%), and grade F in 1 case (2.4%). There were 63.4% (26/41) of MEs occurring in the prescription/doctor′s order prescribing and delivery links, mainly caused by physicians, and the common error contents included solvent errors, medication under contraindications, and having drug-drug interactions. In addition, 26.8% (11/41) of MEs occurred in the drug dispensing and distribution link, and 9.8% (4/41) occurred in the administration and monitoring links. A total of 4 severe MEs of deslanoside injection were collected from the Monitoring Network, medical literature and judicial cases, all of which occurred in the prescription/doctor′s order prescribing and delivery links. Among the 4 severe MEs, 2 ME cases of grade I occurred due to incorrect usage and dosage, resulting in patient death; 1 ME case of grade F was caused by interaction with traditional Chinese medicine, resulting in digitalis poisoning, and another case of grade F was that deslanoside injection was administered to a patient with digitalis poisoning (medication under contraindications).Conclusions:MEs of deslanoside injection often occurs in the prescription/doctor′s order prescribing and delivery links, mainly because of insufficient knowledge of doctors to the drug instructions. It is suggested to strengthen learning and training of medical staff centered around drug instructions, and improve the system interception and process management, so as to improve the medication safety.

Objective:To understand the prevalence and related factors of three common chronic diseases, hyperlipidemia, hypertension and diabetes in HIV-infected persons.Methods:As of December 2023, HIV-infected persons >15 years old who are receiving antiviral therapy (ART) and follow-up in Henan Province were selected as the study objects. Questionnaires, physical examinations, and blood samples were collected to collect demographic information, ART, body weight, blood lipids, blood pressure, and blood sugar of HIV-infected persons. The logistic regression model was used to analyze the related factors of hyperlipidemia, hypertension and diabetes.Results:Among 4 023 HIV-infected patients, the prevalence rates of hyperlipidemia, hypertension, and diabetes were 64.47% (2 594/4 023), 16.80% (676/4 023), and 10.54% (424/4 023), respectively. Multivariate analysis showed that hyperlipidemia was positively associated with ≥40 years of age, overweight and obesity, two nucleoside reverse transcriptase inhibitors (NRTIs) + proteasome inhibitors (PIs) regimen and two NRTIs+ integrase inhibitor regimen, and negatively associated with low body weight. Hypertension was positively correlated with the age group ≥40 years old, family history of cardiovascular and cerebrovascular diseases, overweight and obesity, ART time ≥0.5 years, and negatively correlated with low body weight. Diabetes was positively associated with age group ≥40 years, family history of cardiovascular and cerebrovascular disease, overweight and obesity, and negatively associated with the use of two NRTIs+PIs treatment regimens.Conclusions:In 2023, the prevalence of hyperlipidemia, hypertension, and diabetes among HIV-infected people in Henan Province was relatively high, and the risk of common chronic diseases among those ≥40 years old, overweight and obese, and those with a family history of cardiovascular and cerebrovascular diseases was also relatively high. It is recommended to strengthen the prevention and management of common chronic diseases among HIV-infected people.

ObjectiveStudies have shown that nuciferine has anti-cerebral ischemia effect， but the specific mechanism of action has not been elaborated. Based on the transcriptome results， the pharmacological mechanism of nuciferine against cerebral ischemia was analyzed from multiple dimensions including tissue， cell， pathological process， biological process and signaling pathway. MethodsThirty SD rats were randomly divided into the sham group， model group and nuciferine group（40 mg·kg^-1） according to weight. Except for the sham group， the model of middle cerebral artery occlusion（MCAO） was established by thread embolization method after 30 min of administration in the other two groups. Twenty-four hours after surgery， transcriptome sequencing was used to detect the gene expression profiles in the cortex penumbra of rat cerebral tissue， and gene ontology（GO） and kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis were performed for differentially expressed genes. The mechanismof nuciferine against cerebral ischemia was analyzed from 5 dimensions of tissue， cell， pathological process， biological process and signaling pathway by the transcriptome-based multi-scale network pharmacology platform（TMNP）. ResultsTranscriptome sequencing and gene quantitative analysis showed that 667 genes were significantly reversed by nuciferine. Further enrichment analysis of KEGG and GO suggested that the pathways of nuciferine involved regulating stress response， ion transport， cell proliferation and differentiation， and synaptic function. TMNP research found that at the tissue level， nuciferine could significantly improve the cerebral tissue injury caused by ischemia. At the cellular and pathological levels， nuciferine could play an anti-cerebral ischemia role by improving the state of various nerve cells， mobilizing immune cells， regulating inflammation. And at the level of biological processes and signaling pathways， nuciferine mainly acted on the processes such as vascular remodeling， inflammation-related signaling pathways， and synaptic signaling. ConclusionCombined with the results of transcriptome sequencing， gene quantitative analysis and TMNP， the mechanism of nuciferine against cerebral ischemia may be related to processes such as intervening in stress response and inflammation， affecting vascular remodeling and regulating synaptic function. These results can provide a basis and reference for further study of the pharmacological mechanism of nuciferine against cerebral ischemia.

Objective To investigate the expression levels of micro RNA-651(miR-651)and the transcrip-tion factor Forkhead Box N2(FOXN2)in lung cancer tissues and to analyse their relationship with patients' prognosis after lobectomy.Methods A total of 98 patients with lung cancer who underwent lobectomy from January 2020 to December 2021 in Nantong Cancer Hospital were selected as research objects,the lung cancer tissue specimens and corresponding paracancerous tissue specimens of patients were collected,the expression levels of miR-651 and FOXN2 were detected by real-time fluorescence quantitative PCR(qPCR),and their re-lationship with the prognosis of patients after lobectomy was analyzed.Results At 2-year follow-up,19(19.39％)of 98 patients had recurrent metastasis,and the median time to recurrent metastasis was 20 months(95％CI:18.626--21.374).qPCR assay showed that the expression levels of miR-651 and FOXN2 in lung cancer tissues were significantly lower than those in paracancerous tissues(P＜0.05).miR-651 and FOXN2 expression levels were significantly correlated with clinicopathological features such as tumour size,TNM stage and lymph node metastasis(P＜0.05).The results of univariate Cox regression analysis showed that the percentages of maximum tumor diameter ≥3 cm,TNM stage Ⅱ,lymph node metastasis,miR-651 low ex-pression and FOXN2 low expression were higher in the poor prognosis group than those in the good prognosis group(P＜0.05).Multifactorial Cox regression analysis showed that maximum tumor diameter ≥ 3 cm(HR=3.185,95％CI:1.105-9.182),TNM stage Ⅱ(HR=5.167,95％CI:1.939-13.771),lymph node metastasis(HR=2.860,95％CI:1.115-7.338),low miR-651 expression(HR=5.345,95％CI:1.845-15.483)and low FOXN2 expression(HR=5.404,95％CI:1.744-16.745)were independent risk factors for the prognosis of lung cancer patients after lobectomy(P＜0.05).Conclusion The expression levels of miR-651 and FOXN2 were reduced in the tissues of lung cancer patients,and both were associated with tumour size,TNM stage,lymph node metastasis,and patients' prognosis after lobectomy.

Objective:To compare the embryo development potential and clinical outcomes between the patients with and without oocyte degeneration.Methods:This retrospective cohort study included a total of 242 cycles underwent ICSI that cultured in time-lapse incubator from January 2019 to June 2023 at the Reproductive and Genetic Center of Suzhou Municipal Hospital and all 3 119 oocytes were evaluated. Data collection continued to February 5th,2024 until the last birthing of the study. Patients were divided into degenerated group (140 cycles) and control group (102 cycles) according to whether oocyte degenerated after ICSI. Then the embryo developmental potential and clinical outcomes were compared. Furthermore, we also investigated whether embryo morphokinetics could be different between the two groups.Results:Female age, duration of infertility, body mass index, basal follicle sitmulating hormone, basal luteinizing hormone, basal estrogen (E 2), antral follicle count, anti-Müllerian hormone, factors of infertility and source of semen were similar between the two groups ( P>0.05). E 2 on human chorionic gonadotropin triggered day [2 513.00 (1 842.20, 3 638.50) ng/L], number of oocytes retrieved (13.56±4.80) and oocyte maturation rate [84.35% (1 601/1 898)] were significantly higher in degenerated group than those in control group [2 270.50 (1 472.00, 3 044.20) ng/L, P=0.019; 11.97±4.71, P=0.011; 81.08% (990/1 221), P=0.017], while normal fertilization rate [69.33% (1 103/1 591)], day 3 (D3) good-quality embryos [57.85% (634/1 096)], blastocyst formation rate [50.87% (469/922)] and embryo utilized rate [58.30% (643/1 103)] were significantly lower in degenerated group than those in control group [85.56% (847/990), P<0.001; 65.72% (556/846), P<0.001; 61.26% (446/728), P<0.001; 66.12% (560/847), P<0.001] . In addition, the proportion of low cell number (<7) of D3 embryos [33.76% (370/1 096)] and high fragmentation (fragmentation ≥50%, fragmentation 20%-50%) of D3 embryos [10.01% (109/1 089), 18.64% (203/1 089)] in degenerated group were significantly higher than those in control group [27.19% (230/846), P=0.002; 6.06% (51/841), P=0.002; 14.15% (119/841), P=0.009], and so were the incidence of DC1 and CC [5.98% (66/1 103) vs. 2.48% (21/847), P<0.001; 2.45% (27/1 103) vs. 0.94% (8/847), P=0.013]. As regard to the utilized embryos, there were no significant differences in t5, cc2, cc3 and s2 ( P>0.05), but tPNf [22.82(21.13, 24.84) h], t2 [25.37 (23.62, 27.37) h], t3 [35.64 (33.10, 38.03) h] and t4 [36.85 (34.70, 39.52) h] in degenerated group were significantly earlier than those in control group [23.04 (21.76, 25.41) h, P=0.001; 25.91 (24.15, 28.05) h, P=0.001; 36.16 (33.11, 38.81) h, P=0.040; 37.39 (35.11, 40.27) h, P=0.026]. Further more, after the first transfer of fresh or frozen embryos, there were no significant differences in clinical pregnancy rate, implantation rate, early abortion rate, live birth rate, sex ratio, preterm birth rate, low birth weight rate and birth defect rate between the two groups (all P>0.05). ICSI degeneration was not an independent factor of implantation rate, early abortion rate and live birth rate after ICSI treatment, but number of embryos transferred was an independent factor of implantation rate and live birth rate after ICSI treatment ( OR=2.806, 95% CI: 1.179-6.677, P=0.020; OR=2.622, 95% CI: 1.129-6.090, P=0.025). Conclusion:The presence of oocyte degeneration after ICSI may affect the overall developmental potential of its sibling oocytes and may also disturb the morphokinetics of the embyos, however the pregnancy outcomes and neonatal birth outcomes may not be affected if transfer the best embryo in the first fresh or frozen cycle.

This study aims to research the relationship between arterial stiffness and serum indirect bilirub in levels(IBIL)in patients with type 2 diabetes by measuring brachial-ankle pulse wave velocity (baPWV). The clinical data of 1 327 patients with T2DM admitted to Qingdao Huangdao District People′s Hospital from July 1st, 2018 to March 1st, 2024 were retrospectively and cross-sectionally analyzed (609 men and 718 women; age range, 45.3-79.5 years; median age, 60.3 years; mean age, 61.4 years). The subjects were stratified based on gender-specific quartiles of IBIL values(male, Q1:<6.7 μmol/L, Q2:6.7-8.9 μmol/L, Q3:8.9-12.3 μmol/L, Q4:≥12.3 μmol/L;female, Q1:<6.4 μmol/L, Q2:6.4-7.9 μmol/L, Q3:7.9-10.4 μmol/L, Q4:≥10.4 μmol/L), and a high baPWV was defined as greater than 18.37 m/s (75th percentile). The results showed that the serum IBIL concentration was negatively correlated with the duration of diabetes ( r=-0.142, P=0.010), the SBP ( r=-0.158, P=0.005) and the baPWV ( r=-0.194, P<0.001) in women and was positively correlated with TC (men: r=0.282, P<0.001; women: r=0.237, P<0.001), HDL-C (men: r=0.171, P=0.011; women: r=0.287, P<0.001) and LDL-C (men: r=0.196, P=0.009; women: r=0.233, P<0.001) levels in both genders. Dividing IBIL levels into quartiles, there were significant statistical differences in the incidence of high baPWV among different subgroups of female patients ( χ 2=36.468, P<0.001), and the incidence of high baPWV showed a decreasing trend with increasing IBIL levels. After adjusting for confounding factors, the IB levels were inversely associated with a greater risk of a high baPWV both as a continuous variable [a 1-SD difference; odds ratio ( OR):0.836; 95% confidence interval ( CI):0.774-0.942; P=0.009] and when categorized in quartiles (the highest vs. the lowest quartile; OR:0.381; 95% CI:0.162-0.897; P=0.025) in women but not in men. Low IBIL levels were significantly associated with arterial stiffness in middle-aged and elderly women with type 2 diabetes. In conclusion, the serum IBIL levels were independent protective factors for macrovascular disease in middle-aged and elderly diabetic women.