ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

Objective·To analyze the neurodevelopmental outcomes of children after end-to-side anastomosis for coarctation of the aorta(CoA).Methods·The surgical and neurological follow-up data were collected from children who underwent end-to-side anastomosis for CoA at Shanghai Children's Medical Center,Shanghai Jiao Tong University School of Medicine from January 1,2017 to December 31,2021.Neurological assessments included magnetic resonance imaging(MRI)and Griffiths Mental Development Scale assessments.Neurodevelopmental outcomes were evaluated using Griffiths Mental Development Scale.Clinical characteristics were compared between patients with normal and abnormal MRI and Griffiths Mental Development Scale results to assess the correlation between the two assessments and their association with cardiopulmonary bypass(CPB)use and CPB modality.Results·Twenty-seven children with isolated CoA or CoA combined with simple intracardiac anomalies were included.MRI results were available for 25 cases,with 5 showing abnormalities(20.0%).Griffiths Mental Development Scale results were available for 26 cases,with 21(80.77%)showing abnormal scores,including 18 in hearing and language,and 12 in performance.No significant correlation was found between abnormal MRI or Griffiths Mental Development Scale results and the use of CPB(P=0.341,P=1.000).Among patients who underwent CPB,those in the moderate hypothermia group accounted for the majority of cases without neurological abnormalities,with proportions of 80.00%(MRI)and 100.00%(Griffiths Mental Development Scale).Conclusion·Children undergone end-to-side anastomosis for CoA are at relatively high risk for neurodevelopmental abnormalities,particularly in hearing-language and performance domains.CPB may not be a direct risk factor for poor neurodevelopmental outcome,and moderate hypothermia during CPB may be neuroprotective.

Post transplantation diabetes mellitus(PTDM)is one of the common complications after kidney transplantation,with an incidence rate of 4%to 30%.The pharmacological treatment of PTDM after kidney transplantation faces many challenges.It is necessary to consider not only the blood glucose-lowering efficacy of the drugs themselves,but also the impact of the drugs on the function of the transplant kidney.At the same time,the interaction between antihyperglycemic drugs and immunosuppressive agents should be taken into account.Glucagon-like peptide-1 receptor agonist(GLP-1RA)have been widely used for blood glucose control in patients with type 2 diabetes mellitus.Some GLP-1RA can also improve the renal and cardiovascular outcomes of patients,and they have multiple metabolic benefits,such as regulating the lipid and reducing body weight.Clinical studies have suggested that GLP-1RA can be used for blood glucose control in kidney transplant recipients with PTDM,with multiple benefits,including reducing the risk of kidney disease and adverse cardiovascular events,as well as improving metabolism.Moreover,no influence of GLP-1RA application on the blood concentration of immunosuppressive agents in kidney transplant recipients with PTDM has been found.Given the good application potential of GLP-1RA in the treatment of kidney transplant recipients with PTDM,this article reviews the current status and future prospects of GLP-1RA treatment for PTDM,analyzes the differences in effects of different GLP-1RA,and explores their potential mechanisms of action in renal protection and multiple metabolic benefits,providing a basis for clinical application.

Objective To explore the value of deep learning image reconstruction(DLIR)algorithm to improve the quality of low keV monochromatic portal vein images of energy spectrum CT.Methods Fifty patients who underwent enhanced upper abdominal energy spectrum CT scan were selected.Mixed-model adaptive statistical iterative reconstruction-Veo(50%ASIR-V)algorithm and high-deep learning image reconstruction(DLIR-H)algorithm were used to obtain monochromatic images at 40-70 keV(with intervals of 10 keV).The CT and standard deviation(SD)values of the portal vein trunk,left and right branches,and erector spinae muscle were measured in the transverse position,and the signal-to-noise ratio(SNR)and portal vein contrast-to-noise ratio(CNR)were calculated for objective evaluation.The portal vein image quality between the two algorithms and different energy was subjectively scored by two physicians.Results In terms of objective evaluation:compared with 50%ASIR-V,the CNR and SNR of portal vein in monochromatic DLIR-H images at the same keV between 40-70 keV energy levels were increased while the SD value was decreased(P＜0.05),and the CT value was unchanged;there was no statistical difference in the magnitude of change in CNR between the two algorithms at different energy levels(P＞0.05);there was a statistically significant difference in the magnitude of change in SNR and SD value(P＜0.05)and the magnitude of change was the largest at 40 keV;comparison between different energy levels of DLIR-H,the CNR and SD value of 40 keV DLIR-H were the highest(P＜0.05),and there was no significant difference in the SNR(P＞0.05).In terms of subjective evaluation:there was no significant difference between the subjective scores of the two algorithms at the same keV from 40-70 keV(P＞0.05),and the two reconstruction algorithms at 40 keV and 50 keV had the highest subjective scores between different keV.Conclusion The DLIR algorithm can reduce the noise of low keV monochromatic images,improve the image quality of portal vein.

Objective·To analyze the neurodevelopmental outcomes of children after end-to-side anastomosis for coarctation of the aorta(CoA).Methods·The surgical and neurological follow-up data were collected from children who underwent end-to-side anastomosis for CoA at Shanghai Children's Medical Center,Shanghai Jiao Tong University School of Medicine from January 1,2017 to December 31,2021.Neurological assessments included magnetic resonance imaging(MRI)and Griffiths Mental Development Scale assessments.Neurodevelopmental outcomes were evaluated using Griffiths Mental Development Scale.Clinical characteristics were compared between patients with normal and abnormal MRI and Griffiths Mental Development Scale results to assess the correlation between the two assessments and their association with cardiopulmonary bypass(CPB)use and CPB modality.Results·Twenty-seven children with isolated CoA or CoA combined with simple intracardiac anomalies were included.MRI results were available for 25 cases,with 5 showing abnormalities(20.0%).Griffiths Mental Development Scale results were available for 26 cases,with 21(80.77%)showing abnormal scores,including 18 in hearing and language,and 12 in performance.No significant correlation was found between abnormal MRI or Griffiths Mental Development Scale results and the use of CPB(P=0.341,P=1.000).Among patients who underwent CPB,those in the moderate hypothermia group accounted for the majority of cases without neurological abnormalities,with proportions of 80.00%(MRI)and 100.00%(Griffiths Mental Development Scale).Conclusion·Children undergone end-to-side anastomosis for CoA are at relatively high risk for neurodevelopmental abnormalities,particularly in hearing-language and performance domains.CPB may not be a direct risk factor for poor neurodevelopmental outcome,and moderate hypothermia during CPB may be neuroprotective.

Objective To explore the value of deep learning image reconstruction(DLIR)algorithm to improve the quality of low keV monochromatic portal vein images of energy spectrum CT.Methods Fifty patients who underwent enhanced upper abdominal energy spectrum CT scan were selected.Mixed-model adaptive statistical iterative reconstruction-Veo(50%ASIR-V)algorithm and high-deep learning image reconstruction(DLIR-H)algorithm were used to obtain monochromatic images at 40-70 keV(with intervals of 10 keV).The CT and standard deviation(SD)values of the portal vein trunk,left and right branches,and erector spinae muscle were measured in the transverse position,and the signal-to-noise ratio(SNR)and portal vein contrast-to-noise ratio(CNR)were calculated for objective evaluation.The portal vein image quality between the two algorithms and different energy was subjectively scored by two physicians.Results In terms of objective evaluation:compared with 50%ASIR-V,the CNR and SNR of portal vein in monochromatic DLIR-H images at the same keV between 40-70 keV energy levels were increased while the SD value was decreased(P＜0.05),and the CT value was unchanged;there was no statistical difference in the magnitude of change in CNR between the two algorithms at different energy levels(P＞0.05);there was a statistically significant difference in the magnitude of change in SNR and SD value(P＜0.05)and the magnitude of change was the largest at 40 keV;comparison between different energy levels of DLIR-H,the CNR and SD value of 40 keV DLIR-H were the highest(P＜0.05),and there was no significant difference in the SNR(P＞0.05).In terms of subjective evaluation:there was no significant difference between the subjective scores of the two algorithms at the same keV from 40-70 keV(P＞0.05),and the two reconstruction algorithms at 40 keV and 50 keV had the highest subjective scores between different keV.Conclusion The DLIR algorithm can reduce the noise of low keV monochromatic images,improve the image quality of portal vein.

Objective Based on the sampling test of national drugs,the quality of Huatan Pingchuan tablets was systematically evaluated,and the quality problems were analyzed to provide references and suggestions for the quality control of this variety and to improve its quality standard.Methods A total of 157 batches of samples were tested according to the statutory standard,and based on the testing results and prescription characteristics,microscopic identification and comprehensive analysis of its quality using thin-layer chromatography,high-performance liquid chromatography,and other methods were subsequently established or improved for the exploratory research.Results The established thin-layer chromatography identification for Radix Scutellariae,as well as the content determination methods for Radix Scutellariae,Syringae Cortex,and promethazine hydrochloride,are easy to operate and have good durability and specificity and can be applied to the quality control and evaluation of Huatan Pingchuan tablets.Conclusions The overall quality of the tablets is average;some enterprises should strengthen the quality control of raw medicinal materials(decoction pieces);individual enterprises have significant differences in the quality of samples from different batches,so they need to pay attention to the quality of raw materials and the stability of production processes;the inspection items of the current standards cannot fully reflect the key quality attributes of drugs,and standards improvement work needs to be carried out.

Objective To improve and refine the relevant regulations and guiding principles of warnings on drug instructions and labels in China.Methods This paper sorted out the drug instructions of small molecule anti-tumor drugs listed by the U.S.Food and Drug Administration(FDA)from 2005 to 2022,included the drugs mentioned in the QT interval prolongation risk,analyzed the clinical research and QT research results,and sorted out the identification and warning rules of the instructions.Results A total of 35 drugs were included,4 drugs wrote the risk of QT interval prolongation in the black box warning,21 drugs were wrote in the warning and precautions position,6 drugs were wrote in the adverse reaction section,and 2 drugs were only described under clinical pharmacology section.According to the severity of the QT interval prolongation caused by the drug and whether there were serious clinical consequences,they were displayed in the warnings(black box warnings),precautions(warnings and precautions)and adverse reactions in the instructions.Conclusion The aim of this article is to provide a reference for the writing of QT risk warning information of the instructions of domestic drug production enterprises and regulatory departments.It is recommended to clarify the severity of drug safety and the location of the instructions in clinical research,and continue to carry out safety monitoring and update the instructions in time after listing.

Objective:To investigate whether malignant tumors affect the laboratory outcomes of patients in their first controlled ovarian hyperstimulation (COH) cycle.Methods:This study was a retrospective case-control study that analyzed the clinical and laboratory data of patients who underwent fertility preservation before chemotherapy and radiotherapy due to malignant tumors, as well as patients with infertility caused by tubal factors who first underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) at the Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University from January 2020 to May 2024. Patients who underwent fertility preservation were designated as the research group, while patients who underwent assisted reproduction due to tubal factors during the same period were designated as control group. After 1∶3 propensity score matching (PSM), 40 patients were included in the research group and 118 patients were included in control group. The ovarian response, oocyte retrieval outcomes, and embryonic development after fertilization in the first COH cycle were compared between the two groups. Results:After PSM, the research group and control group showed statistically significant differences in the gonadotropin (Gn) starting dosage [225.00 (162.50, 300.00) U vs. 193.75 (150.00, 225.00) U, P=0.002], duration of Gn used [10.00 (8.00, 11.00) d vs. 12.00 (10.00, 13.00) d, P<0.001], and average estradiol levels on human chorionic gonadotropin trigger day [2 487.00 (1 461.25, 4 090.25) pmol/L vs. 10 738.50 (8 400.00, 16 507.25) pmol/L, P<0.001]. However, no statistically significant difference was found in the total dosages of Gn used between the two groups ( P>0.05). There were no significant differences between the groups in terms of the number of oocytes retrieved, the number of metaphase Ⅱ oocytes, two pronuclei (2PN) rate, 2PN cleavage rate, available embryo rate, high-quality embryo rate, blastocyst formation rate, and available blastocyst formation rate (all P>0.05). Conclusion:Compared with infertility patients with tubal factors, there is no significant difference in the laboratory outcomes of malignant tumor patients undergoing COH for fertility preservation prior to chemotherapy and radiation.

Objective:To investigate the effects of male body mass index (BMI) on semen parameters and perinatal outcomes following artificial insemination by husband (AIH) treatment.Methods:A retrospective cohort study was conducted to analyze the clinical data of 5 053 patients underwent AIH treatment at the Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University, from January 2017 to February 2024. The study focused on factors such as male semen parameter abnormalities, male sexual dysfunction, female cervical factors, reproductive tract malformations, and unexplained infertility. Patients were classified into three groups based on male BMI: normal weight group (18.5-23.9 kg/m2, n=1 673), overweight group (24.0-27.9 kg/m2, n=2 078), and obese group (BMI≥28.0 kg/m2, n=1 302). The primary objective was to assess the differences in semen parameters and perinatal outcomes among the three groups. Multivariable logistic regression and linear regression analyses were applied to adjust for potential confounders that could influence semen parameters and perinatal outcomes. Results:Semen volume in the normal weight group and overweight group [4.00 (3.00, 5.50) mL, 4.00 (3.00, 5.50) mL] was higher than that in the obese group [4.00 (3.00, 5.00) mL], with a significant difference among the three groups ( P<0.001, a P<0.001). The total sperm count in the normal group and overweight group [207.60 (121.90, 341.75)×10 6, 211.80 (119.88, 334.83)×10 6] was higher than that in the obese group [188.40 (110.96, 323.41)×10 6], with a significant difference among the three groups ( P=0.007, a P<0.001). The total progressive sperm motility count in the normal group [88.18 (43.63, 163.80)×10 6] was higher than that in the obese group [75.30 (40.29, 147.86)×10 6], with a significant difference among the three groups ( P=0.001, a P<0.001). The percentage of forward motile sperm in the normal group [(45.37±17.16)%] was higher than that in the overweight group [(44.03±17.36)%] and the obese group [(43.80±17.21)%], with a significant difference compared among the three groups ( P=0.020, a P=0.016]. In terms of perinatal outcomes, after multivariate logistic regression analysis, only the overweight and obese groups had higher newborn birth weights [(3 389.53±472.65) g, (3 408.57±507.90) g] compared with the normal group [(3 271.32±532.02) g], with a significant difference among the three groups ( P=0.010, a P=0.009). Conclusion:Higher male BMI is associated with decreased semen quality and may increase newborn birth weight following AIH treatment.