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 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.

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 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 observe the clinical efficacy of Tongyuan acupuncture in the treatment of acute gouty arthritis.Methods A total of 126 cases of patients with definitive diagnosis of acute gouty arthritis admitted to the wards and outpatient clinics of Guangzhou Nansha District Hospital of Traditional Chinese Medicine from November 2023 to June 2024 were selected as the study subjects.The patients were randomly divided into observation group and control group according to the random number table method,with 63 cases in each group.The control group was given health training and conventional treatment,while the observation group was given Tongyuan acupuncture on the basis of treatment in the control group.Patients in both groups were treated for 14 consecutive days.After two weeks of treatment,the clinical efficacy of the two groups was evaluated.The changes in the clinical symptom scores,the Visual Analogue Scale(VAS)scores of pain,the levels of musculoskeletal ultrasonography(synovial proliferation,blood flow signals,and joint fluid)before and after the treatment were observed in patients of both groups.The changes of blood uric acid(UA),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),tumor necrosis factor α(TNF-α),and interleukin 1(IL-1)before and after treatment were compared between the two groups.Results(1)The total effective rate was 95.24%(60/63)in the observation group and 84.13%(53/63)in the control group.The efficacy of the observation group was superior to that of the control group,the difference being statistically significant(P<0.05).(2)After treatment,the clinical symptom scores and VAS scores of the patients in the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(3)After treatment,the serum UA,ESR,and CRP levels of patients in the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(4)After treatment,the TNF-α and IL-1 levels of patients in the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(5)After treatment,the musculoskeletal ultrasound indicators of the two groups of patients were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).Conclusion Tongyuan acupuncture in the treatment of acute gouty arthritis can significantly improve the clinical symptoms of patients,reduce the level of patients'blood UA and inflammatory factor.

Objective To explore the changes in serum epidermal growth factor receptor(EGFR)and cancer anti-gen 125(CA125)levels in pregnant women with adenomyosis(AM)and their relationship with pregnancy outcomes.Methods A total of 108 pregnant women with AM(AM pregnant women group)admitted to Baoding Maternal And Child Health Hospital from June 2021 to August 2023 were collected and divided into a good preg-nancy group(n=43)and a poor pregnancy group(n=65)based on pregnancy outcomes.Meanwhile,AM patients were selected as AM group and 108 pregnant women with normal pregnancy test were selected as control group.ELISA was applied to detect the serum level of EGFR and CA125.Pearson correlation was applied to analyze the correlation between serum EGFR and CA125 in AM pregnant women.Multivariate logistic regression was applied to analyze the factors that affected the outcome of AM pregnancy.Receiver operating characteristic(ROC)curve was applied to analyze the predictive value of serum EGFR and CA125 levels for AM pregnancy outcomes.Results Compared with the control group,serum level of EGFR and CA125 in AM group and AM pregnant women group were significantly increased and serum level of EGFR and CA125 in AM pregnant women group was higher than that in AM group(P＜0.05).As the depth grading of endometrial invasion increased,serum level of EGFR and CA125 increased sequentially;The serum level of EGFR and CA125 was obviously elevated in diffuse type and proliferate phase(P＜0.05).The expression level of EGFR and CA125 in the serum of AM pregnant women with premature rupture of membranes,premature birth,placenta previa,and miscarriage was significantly increased(P＜0.05).According to Pearson correlation analysis,there was a positive correlation between serum EGFR and CA125 in AM pregnant women(r=0.487,P＜0.05).The serum level of EGFR and CA125 in good pregnancy group was lower than that in poor pregnancy group(P＜0.05).The area under the curve(AUC)of serum EGFR,CA125,and their combined prediction for AM pregnancy outcome was 0.880,0.835,and 0.955,re-spectively and the combined prediction of AUC for AM pregnancy outcome was significantly higher than that of se-rum EGFR and CA125 alone prediction(Zcombination-EGFR=2.279,Zcombination-CA125=3.304,both P＜0.05).Conclusions Serum level of EGFR and CA125 in AM pregnant women is elevated,which is closely related to pregnancy outcomes and is potential risk factor for poor pregnancy in AM.The combination of the two is more ef-fective in predicting pregnancy outcomes in AM.

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.

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 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.

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.