Background Long-term exposure to ambient fine particulate matter (PM_2.5) is a significant risk factor for cardiometabolic disorders. However, the mechanisms of its interaction with the endogenous circadian system remain incompletely understood. Objective To investigate whether chronic PM_2.5 exposure interferes with the rhythmic expression of the cardiac circadian clock, thereby disrupting downstream antioxidant defenses and metabolic homeostasis, and ultimately driving cardiometabolic dysfunction. Methods Seventy-two male C57BL/6 mice were randomly divided into a PM_2.5 exposure group (PM group) and a filtered air control group (FA group). Whole-body exposure was conducted for 8 weeks in a meteorological environmental animal exposure system. Samples were collected at six distinct zeitgeber time (ZT) points post-exposure. The 24 h ambulatory blood pressure and serum lipid profiles were monitored. Rhythm parameters were derived via cosinor analysis to compare differences in Midline statistic of rhythm (Mesor), amplitude, and phase between the two groups. The rhythmic expression of core circadian clock genes and antioxidant genes in the myocardium was detected by quantitative polymerase chain reaction (qPCR). Myocardial reactive oxygen species (ROS) levels and downstream pathway protein expression were analyzed by immunofluorescence and Western blot (WB), respectively. The expression changes of the clock gene retinoic acid receptor-related orphan receptor α (RORα) were assessed at both the mRNA and protein levels. Finally, Spearman correlation analysis was used to explore the relationships among myocardial RORα expression, lipid profiles, and oxidative stress indicators. Results Compared to the FA group, mice in the PM group exhibited a blunted circadian rhythm in blood pressure, characterized by sustained elevation throughout the day. Chronic PM_2.5 exposure showed a significant interaction with ZT on systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) (F-interaction=9.11, 5.70, and 6.02, respectively; P<0.05), as well as on serum triglycerides (TG), total cholesterol (T-CHO), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) (F-interaction=16.32, 11.12, 15.39, and 28.09, respectively; P<0.05). Cosinor analysis further revealed that the Mesor values of T-CHO, TG, and LDL-C were significantly increased (P<0.05), while that of HDL-C was significantly decreased in the PM group (P<0.05). The oscillation amplitudes of SBP, DBP, and MAP showed a decreasing trend, whereas those of TG and LDL-C were significantly increased (P<0.05). Furthermore, SBP, T-CHO, and HDL-C all exhibited a significant phase delay (P<0.05). Mechanistically, PM_2.5 exposure significantly suppressed the expression of the positive circadian regulator RORα in the myocardium, leading to disordered rhythmic expression of core clock genes (Bmal1, Clock, Per1/2, and Cry1/2). This exposure also inhibited the rhythmic expression of antioxidant genes (GPX1, SOD2, and CAT), resulting in increased ROS generation and elevated expression of calcium/calmodulin-dependent protein kinase II (CaMKII) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) proteins. Correlation analysis further revealed that myocardial RORα expression level was negatively correlated with T-CHO, TG, and LDL-C (r=−0.55, −0.63, and −0.51, respectively; P<0.001), and positively correlated with HDL-C (r=0.37, P=0.010), and antioxidant genes GPX1, SOD2, and CAT expression (r=0.34, 0.35, and 0.56, respectively; P < 0.001). Conclusion Chronic PM_2.5 exposure induces cardiometabolic dysfunction by suppressing myocardial RORα expression. This suppression disrupts the cardiac circadian clock and the diurnal balance of oxidative stress, triggering oxidative damage and elevating expression of CaMKII/NADPH pathway proteins. Collectively, these alterations precipitate the loss of cardiac metabolic rhythms and subsequent functional impairment.

ObjectiveTo investigate the protective effect and underlying mechanisms of the Bawei Chenxiang Wan （BCW） against myocardial ischemic injury. MethodsMyocardial ischemia in vivo was induced in rats by subcutaneous injection of isoproterenol （ISO）， and ex vivo ischemia was established by coronary artery ligation in isolated rat hearts. The effects of BCW， alcohol extracts and its polar extracts were evaluated on ST segment on electrocardiogram （ECG）， myocardial damage， hemodynamic parameters， and infarct size. The phosphorylation level of phosphatidylinositol 3-kinase （PI3K）， the expression of cuproptosis-related proteins， and the content of Cu²⁺ in myocardial tissue were detected. The regulatory relationship of the signaling pathway was verified using an oxygen-glucose deprivation （OGD） myocardial cell injury model， combined with PI3K agonists and inhibitors. ResultsBCW ameliorated ST-segment elevation on electrocardiograms（P＜0.01）， reduced serum levels of myocardial injury markers， improved hemodynamic parameters， upregulated PI3K phosphorylation（P＜0.01）， and decreased Cu²⁺ accumulation in rats with myocardial ischemia（P＜0.01）. Moreover， BCW reduced the myocardial infarct size. In the isolated rat heart model of ischemia， both the ethanol extract and various solvent fractions of BCW exerted protective effects and reduced Cu²⁺ content， among which the n-butanol fraction exhibited the most potent activity（P＜0.01）. Specifically， the n-butanol fraction upregulated PI3K phosphorylation（P＜0.01） and downregulated the expression of cuproptosis-related proteins， including ferredoxin reductase 1（FDX1）（P＜0.05）， lipoic acid synthetase（LIAS）， and dihydrolipoamide S-acetyltransferase（DLAT） oligomerization（P＜0.05）. In the OGD-induced cardiomyocyte injury model， treatment with a PI3K agonist inhibited DLAT oligomerization（P＜0.05）， whereas co-administration of a PI3K inhibitor attenuated the inhibitory effect of the n-butanol fraction on DLAT oligomer formation（P＜0.05）. ConclusionThe n-butanol fraction of BCW exerts a significant protective effect against myocardial ischemic injury， and its mechanism may involve activation of the PI3K and inhibition of cuproptosis.

ObjectiveTo investigate the protective effect and underlying mechanisms of the Bawei Chenxiang Wan （BCW） against myocardial ischemic injury. MethodsMyocardial ischemia in vivo was induced in rats by subcutaneous injection of isoproterenol （ISO）， and ex vivo ischemia was established by coronary artery ligation in isolated rat hearts. The effects of BCW， alcohol extracts and its polar extracts were evaluated on ST segment on electrocardiogram （ECG）， myocardial damage， hemodynamic parameters， and infarct size. The phosphorylation level of phosphatidylinositol 3-kinase （PI3K）， the expression of cuproptosis-related proteins， and the content of Cu²⁺ in myocardial tissue were detected. The regulatory relationship of the signaling pathway was verified using an oxygen-glucose deprivation （OGD） myocardial cell injury model， combined with PI3K agonists and inhibitors. ResultsBCW ameliorated ST-segment elevation on electrocardiograms（P＜0.01）， reduced serum levels of myocardial injury markers， improved hemodynamic parameters， upregulated PI3K phosphorylation（P＜0.01）， and decreased Cu²⁺ accumulation in rats with myocardial ischemia（P＜0.01）. Moreover， BCW reduced the myocardial infarct size. In the isolated rat heart model of ischemia， both the ethanol extract and various solvent fractions of BCW exerted protective effects and reduced Cu²⁺ content， among which the n-butanol fraction exhibited the most potent activity（P＜0.01）. Specifically， the n-butanol fraction upregulated PI3K phosphorylation（P＜0.01） and downregulated the expression of cuproptosis-related proteins， including ferredoxin reductase 1（FDX1）（P＜0.05）， lipoic acid synthetase（LIAS）， and dihydrolipoamide S-acetyltransferase（DLAT） oligomerization（P＜0.05）. In the OGD-induced cardiomyocyte injury model， treatment with a PI3K agonist inhibited DLAT oligomerization（P＜0.05）， whereas co-administration of a PI3K inhibitor attenuated the inhibitory effect of the n-butanol fraction on DLAT oligomer formation（P＜0.05）. ConclusionThe n-butanol fraction of BCW exerts a significant protective effect against myocardial ischemic injury， and its mechanism may involve activation of the PI3K and inhibition of cuproptosis.

Objective:To analyze the learning curve of TiRobot-assisted lumbar pedicle screw fixation (LPSF) by cumulative sum (CUSUM) test method.Methods:The clinical data of 50 patients who underwent TiRobot-assisted LPSF from January 2020 to December 2022 in Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed. CUSUM analysis and learning curve fitting were performed with robot usage time as the main indicator with the time for each step refined (robot registration time, path planning time and guide wire placement time), to select the best learning curve fitting model with the R2 value closest to 1. Using the turning point of the learning curve as the boundary, the learning curve was divided into two stages as learning stage and maturity stage, and then the observation indexes were compared between the two stages. Results:All 50 patients successfully completed the surgery without perioperative complications, with a total of 244 pedicle screws implanted. The total robot usage time and robot registration time showed a gradually decreasing trend with the increase of case number, and the learning curves were successfully fitted and reached their peaks at the seventeenth and thirteenth cases respectively. The entire learning process was divided into learning stage (17 cases) and maturity stage (33 cases) based on the turning point of the learning curve of total robot usage time. The path planning time and guide wire placement time did not show significant changes with the increase in the case number. The total robot usage time, robot registration time and the intraoperative blood loss in the learning stage were significantly higher than those in the maturity stage: (35.35 ± 1.58) min vs. (30.61 ± 0.43) min, (20.83 ± 1.56) min vs. (14.94 ± 0.29) min and 400 (150, 500) ml vs. 200 (110, 300) ml, the guide wire placement time of per screw was significantly lower than that in the maturity stage: 2.00 (1.83, 2.34) min/screw vs. 2.33 (2.13, 2.69) min/screw, and there were statistical differences ( P<0.05 or <0.01). There were no statistical difference in the path planning time, path planning time of per screw, guide wire placement time and the accuracy of screw placement between two stages ( P>0.05). Conclusions:TiRobot-assisted LPSF is a new technology with safety and effectiveness, and it has a relatively short learning curve. To achieve technological maturity, at least 17 surgeries are required with accumulated experience, and the robot registration is the main step of the learning process. After reaching maturity stage, the robot usage time is significantly shortened and intraoperative trauma is significantly reduced while the relatively high screw placement accuracy is ensured.

Objective:To analyze the learning curve of TiRobot-assisted lumbar pedicle screw fixation (LPSF) by cumulative sum (CUSUM) test method.Methods:The clinical data of 50 patients who underwent TiRobot-assisted LPSF from January 2020 to December 2022 in Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed. CUSUM analysis and learning curve fitting were performed with robot usage time as the main indicator with the time for each step refined (robot registration time, path planning time and guide wire placement time), to select the best learning curve fitting model with the R2 value closest to 1. Using the turning point of the learning curve as the boundary, the learning curve was divided into two stages as learning stage and maturity stage, and then the observation indexes were compared between the two stages. Results:All 50 patients successfully completed the surgery without perioperative complications, with a total of 244 pedicle screws implanted. The total robot usage time and robot registration time showed a gradually decreasing trend with the increase of case number, and the learning curves were successfully fitted and reached their peaks at the seventeenth and thirteenth cases respectively. The entire learning process was divided into learning stage (17 cases) and maturity stage (33 cases) based on the turning point of the learning curve of total robot usage time. The path planning time and guide wire placement time did not show significant changes with the increase in the case number. The total robot usage time, robot registration time and the intraoperative blood loss in the learning stage were significantly higher than those in the maturity stage: (35.35 ± 1.58) min vs. (30.61 ± 0.43) min, (20.83 ± 1.56) min vs. (14.94 ± 0.29) min and 400 (150, 500) ml vs. 200 (110, 300) ml, the guide wire placement time of per screw was significantly lower than that in the maturity stage: 2.00 (1.83, 2.34) min/screw vs. 2.33 (2.13, 2.69) min/screw, and there were statistical differences ( P<0.05 or <0.01). There were no statistical difference in the path planning time, path planning time of per screw, guide wire placement time and the accuracy of screw placement between two stages ( P>0.05). Conclusions:TiRobot-assisted LPSF is a new technology with safety and effectiveness, and it has a relatively short learning curve. To achieve technological maturity, at least 17 surgeries are required with accumulated experience, and the robot registration is the main step of the learning process. After reaching maturity stage, the robot usage time is significantly shortened and intraoperative trauma is significantly reduced while the relatively high screw placement accuracy is ensured.

OBJECTIVE: To explore the genetic cause for a child featuring growth and mental retardation. METHODS: Following conventional karyotyping analysis of the trio family, next generation sequencing (NGS) was carried out to explore the origin of the supernumerary marker chromosome. Fluorescence in situ hybridization (FISH) was used to confirm the result. RESULTS: The karyotypes of both parents were normal, while the proband was found to be 47,XX,+mar. NGS showed that the supernumerary marker has originated from chromosome 9p13.1p24.3 with a size of 39.77 Mb. FISH has confirmed the above finding. CONCLUSION The 9p13.1-p24.3 trisomy probably underlies the abnormal phenotypes of the child. Cytogenetic analysis combined with NGS and FISH can provide accurate diagnosis for such disorders.
Child ; Chromosomes, Human, Pair 9 ; genetics ; Cytogenetic Analysis ; High-Throughput Nucleotide Sequencing ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Trisomy

OBJECTIVETo assess the value of next generation sequencing (NGS) for the analysis of spontaneous abortion samples.

METHODSThe NGS analysis was carried out on 85 chorionic villi samples (taken between 42 days to 12 weeks of gestation) for which conventional cell culture has failed or chromosomal karyotyping has yielded normal or uncertain result.

RESULTSAmong 68 samples with a normal karyotype, the NGS analysis has identified 2 copy number variations (CNVs) and 2 chimeras. For 16 cases with failed cell culture, the NGS has identified 4 chromosomal abnormalities including 1 copy number variation and 3 numerical chromosomal aberrations. For 1 remaining case with uncertain karyotyping result, the NGS analysis has verified it as 46,XX,del(4) (p15.1p16.3).seq[GRCh37/hg19] (57 549 - 32 371 364)×1.

CONCLUSIONThe NGS analysis is capable of identifying novel CNVs in samples for which conventional cell culture may fail or karyotyping analysis may yield a normal result.

Abortion, Spontaneous ; genetics ; Adolescent ; Adult ; Cells, Cultured ; DNA Copy Number Variations ; Female ; High-Throughput Nucleotide Sequencing ; methods ; Humans ; Karyotyping ; Middle Aged ; Pregnancy ; Young Adult

OBJECTIVETo study the association of methylenetetrahydrofolate reductase (MTHFR) gene C677T mutation and plasma homocysteine (Hcy) levels with hyperlipidemia.

METHODSBlood samples were collected from 1591 adults for detecting MTHFR gene C677T polymorphism with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), plasma Hcy levels with enzymatic cycling method, and blood lipid levels as well. The patients were divided according to the lipid levels into hyperlipidemia group (n=694) and healthy control group (n=897) and the differences in MTHFR gene C677T polymorphisms and plasma Hcy levels were compared.

RESULTSThe hyperlipidemia group and healthy control group showed no significant differences in CC, CT, or TT genotype frequencies or C and T allele frequencies of MTHFR C677T gene, and had comparable plasma Hcy levels (P>0.05). Patients with 3 different MTHFR C677T genotypes had significant differences in plasma Hcy levels (P<0.01) but not in blood lipid levels (P>0.05). Pairwise comparison indicated a significantly higher plasma Hcy level in TT genotype than in CC and CT genotypes (P<0.01), and the latter two genotypes showed no significant difference (P>0.05).

CONCLUSIONMTHFR C677T polymorphisms and plasma Hcy levels are closely related but neither of them is associated with hyperlipidemia. The TT genotype is associated with a significantly higher plasma Hcy level than CC and CT genotypes.

Adult ; Gene Frequency ; Genotype ; Homocysteine ; blood ; Humans ; Hyperlipidemias ; blood ; genetics ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Mutation ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length

ObjectiveTo evaluate the safety and effects of pseudomonas aerug PA-MSHA vaccine on cytoimmunity in advanced gastric cancer patients. MethodsSeventy two patients with advanced gastric cancer were randomly divided into experimental group and control group. Tumor bed was treated intraoperatively by pseudomonas vaccine injection in experimental group.The venous bloods were sampled prior to surgery (preoperative) and on days 10,20,and 30 postoperatively.The total lymphocyte count and lymphocyte subpopulations were detected while the postoperative complications and adverse drug reaction were observed,prognosis was evaluated. ResultsThe total lymphocyte count(P =0.042) and the counts ofCD3+ lymphocyte(P =0.027) and NK cell increased (P =0.012) obviously in experimental group.CD8+ lymphocyte decreased(P =0.037),but the counts of CI4+ lymphocyte and CD4+/CD8+ were not significantly different.Complications were not significantly different in the two groups.One year survival rate was longer ( 94.9％ ) in experimental group than that in the control group ( 83.3％ ) ( P =0.022 ).ConclusionsPeritoneal cavity administration with pseudomonas aerug vaccine was safe,and effectively helps regulate cytoimmunity in postoperative patients of advanced gastric carcinoma.

Objective To compare the efficacy of urinary type Ⅳ collagen( Ⅳ C), N-acetyl-β-D-glucosaminidase( NAG ), serum cystatin C ( CysC ), β2 microglobulin ( β2-MG ) in early diagnosis of diabetic nephropathy(DN) ,and to develop a multiple regression equation using above mentioned indices. Methods One hundred and eight cases of DM patients were enrolled in the study. All those DM patients were divided into two groups according to 24 hr urinary albumin excretion(UAE): non-DN group( UAE ＜30 mg/24 h)and DN group (UAE ≥30 mg/24 h). Receiver operating characteristics (ROC)curve was developed using urinary IVC, NAG,serum CysC and β2-MG,and the efficiency of the four indices for early diagnosis of diabetic nephropathy were assessed by area under the curve ROC (AUCROC). Furthermore, the regression equation of four indicators was developed. All statistical analyses were performed using SPSS 13.0. Results The levels of urine Ⅳ C, NAG,CysC,β2-MG,were(3.91±1.93)ng/ml, ( 12.20 ±3.46)U/L, ( 1.18 ±0.41 )mg/L , (2. 50 ±0. 74)mg/ml in the non-DN group, respectively; and ( 14.14 ± 11.17 ) ng/ml, ( 23.12 ± 13.57 ) U/L, ( 2.69 ± 1.69 ) mg/L and(5.21 ± 2.78)mg/ml in the DN group, respectively. There were significant differences in the comparison of the four indicators between the two groups ( Ps ＜ 0.01 ). AUCROC of Ⅳ C, NAG, CysC and β2-MG were 0. 747,0.732,0.764 and 0.823 respectively;which meant the diagnostic efficacy for DN decended from β2-MG, CysC,Ⅳ C, to NAG in order. All these indices showed significant efficiency in assisting diagnosis of early DN ( Ps ＜0.01 ). The regression equation of UAE and the four indices was: UAE = - 242.624 + 6.362IVC + 8.662NAG + 64. 622CysC + 29.488β2-MG, and the equation had statisticl significance( P ＜ 0.O1 ). Conclusion Urine Ⅳ C, NAG,serum CysC, and β2-MG showed significant value in assisting diagosis of early DN, and could be sensitive indices for DN.