OBJECTIVE: To observe the effects of electroacupuncture (EA) on improving motor function and regulating microglial activation based on Notch receptor 1 (Notch1)/Hes family bHLH transcription factor 1 (Hes1) pathway in mice with Parkinson's disease (PD). METHODS: Thirty-six male C57BL/6 mice were randomly divided into a control group, a model group and an EA group, 12 mice in each group. PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days in the model group and the EA group. From the 1st day of modeling, EA was applied at "Baihui" (GV20) and bilateral "Shenshu" (BL23) in the EA group, with continuous wave, in frequency of 2 Hz and current of 2 mA, 15 min a time, once a day for 14 days continuously. The behavioral performance was evaluated by gait test, pole climbing test and hanging test, the number of positive cells of tyrosine hydroxylase (TH) and the co-expression positive cells of Notch1/ionized calcium binding adaptor molecule 1 (Iba-1) in the substantia nigra of midbrain was assessed by immunofluorescence, the protein expression of TH, α-synuclein (α-syn), Notch1, Hes1, Iba-1, inducible nitric oxide synthase (iNOS), Arginase-1 (ARG1), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-10 was detected by Western blot, the mRNA expression of Notch1 and Hes1 was detected by real-time PCR. RESULTS: Compared with the control group, in the model group, the stride frequency was accelerated (P<0.001) and the stride length was shortened (P<0.001) for the four limbs, the pole climbing test time was prolonged (P<0.01) and the grip level was reduced (P<0.01); in the substantia nigra of midbrain, the number of positive cells of TH was decreased (P<0.001), the number of co-expression positive cells of Notch1/Iba-1 was increased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-1βand IL-6 was increased (P<0.01, P<0.05, P<0.001), the protein expression of TH, ARG1 and IL-10 was decreased (P<0.01, P<0.001), the mRNA expression of Notch1 and Hes1 was increased (P<0.01). Compared with the model group, in the EA group, the stride frequency was decelerated (P<0.001) and the stride length was increased (P<0.05, P<0.01, P<0.001) for the four limbs, the pole climbing test time was shortened (P<0.05) and the grip level was increased (P<0.05); in the substantia nigra of midbrain, the number of positive cells of TH was increased (P<0.01), the number of co-expression positive cells of Notch1/Iba-1 was decreased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-6 and IL-1β was decreased (P<0.05, P<0.01), the protein expression of TH, ARG1 and IL-10 was increased (P<0.05, P<0.001, P<0.01), the mRNA expression of Notch1 and Hes1 was decreased (P<0.05). CONCLUSION EA can improve the behavioral performance and protect the dopaminergic neurons in PD mice, its mechanism may relate to the inhibition of Notch1/Hes1-mediated neuroinflammation, thus inhibiting the microglial activation.
Animals ; Electroacupuncture ; Microglia/metabolism* ; Male ; Receptor, Notch1/metabolism* ; Parkinson Disease/physiopathology* ; Transcription Factor HES-1/metabolism* ; Mice ; Mice, Inbred C57BL ; Humans ; Signal Transduction

Objective To explore the prognostic value of combined serum oxidized low-density lipoprotein(ox-LDL),remnant cholesterol(RC)and neutrophil-to-lymphocyte ratio(NLR)tests for clinical prognosis in patients with intracranial atherosclerotic stenosis(ICAS).Methods Patients with acute cerebral infarction were admitted to Cangzhou Central Hospital from June 2022 to December 2023 and diagnosed with ICAS by head MRI.A clinical diagnosis was selected(observation group,n=160).According to the modified Rankin scale(mRS)score,they were separated into a good prognosis group(mRS 0～2 points,n=52)and a poor prognosis group(mRS≥3 points,n=108).160 healthy volunteers who underwent physical examinations were used as a reference group.Magnetic particle immunochromatography was applied to detect serum ox-LDL levels.Clinical data of patients were collected,and the levels of RC and NLR were calculated.The Spearman method was used to analyze the correlation between serum ox-LDL,RC,NLR levels and mRS scores.Logistic regression was applied to analyze the factors influencing prognosis in ICAS patients.Receiver operating characteristic curve(ROC)was used to analyze the predictive value of serum ox-LDL,RC and NLR levels for the prognosis of ICAS patients.Results Compared with reference group,the serum levels of ox-LDL(53.65±8.35 U/L vs 33.23±6.42 U/L),RC(0.82±0.15 mmol/L vs 0.52±0.13 mmol/L)and NLR(2.84±0.38 vs 1.95±0.26)in observation group were obviously increased,and the differences were statistically significant(t=24.523,65.079,62.911,all P<0.05).The serum levels of ox-LDL(57.52±8.72 U/L),RC(0.84±0.14 mmol/L)and NLR(3.02±0.45)in the poor prognosis group were higher than those in the good prognosis group(45.62±6.63 U/L,0.79±0.12 mmol/L,2.48±0.36),and the differences were statistically significant(t=8.699,8.507,7.562,all P＜0.05),and there were differences in TC,LDL-C,HDL-C levels and mRS scores between the two groups,and the differences were statistically significant(t=15.755～27.072,all P<0.05).The serum levels of ox-LDL,RC,NLR were positively correlated with mRS scores(r=0.612,0.623,0.653,all P<0.05).The levels of TC,LDL-C,HDL-C,ox-LDL,RC and NLR were all factors that affected the prognosis of ICAS(all P<0.05).The AUC of serum ox-LDL,RC and NLR for predicting prognosis in ICAS patients were 0.894(0.835～0.937),0.860(0.797～0.910)and 0.817(0.748～0.874),respectively.The combined AUC(95%CI)of the three was 0.965(0.923～0.987),the combination of the three was more valuable than predicting serum ox-LDL,RC and NLR alone(Z=3.030,3.969,4.839,all P<0.05).Conclusion The serum levels of ox-LDL,RC and NLR in ICAS patients have all increased and are positively correlated with mRs scores.The three have predictive value for the prognosis of ICAS patients,and the combined detection of the three has higher clinical value.

Objective To explore the prognostic value of combined serum oxidized low-density lipoprotein(ox-LDL),remnant cholesterol(RC)and neutrophil-to-lymphocyte ratio(NLR)tests for clinical prognosis in patients with intracranial atherosclerotic stenosis(ICAS).Methods Patients with acute cerebral infarction were admitted to Cangzhou Central Hospital from June 2022 to December 2023 and diagnosed with ICAS by head MRI.A clinical diagnosis was selected(observation group,n=160).According to the modified Rankin scale(mRS)score,they were separated into a good prognosis group(mRS 0～2 points,n=52)and a poor prognosis group(mRS≥3 points,n=108).160 healthy volunteers who underwent physical examinations were used as a reference group.Magnetic particle immunochromatography was applied to detect serum ox-LDL levels.Clinical data of patients were collected,and the levels of RC and NLR were calculated.The Spearman method was used to analyze the correlation between serum ox-LDL,RC,NLR levels and mRS scores.Logistic regression was applied to analyze the factors influencing prognosis in ICAS patients.Receiver operating characteristic curve(ROC)was used to analyze the predictive value of serum ox-LDL,RC and NLR levels for the prognosis of ICAS patients.Results Compared with reference group,the serum levels of ox-LDL(53.65±8.35 U/L vs 33.23±6.42 U/L),RC(0.82±0.15 mmol/L vs 0.52±0.13 mmol/L)and NLR(2.84±0.38 vs 1.95±0.26)in observation group were obviously increased,and the differences were statistically significant(t=24.523,65.079,62.911,all P<0.05).The serum levels of ox-LDL(57.52±8.72 U/L),RC(0.84±0.14 mmol/L)and NLR(3.02±0.45)in the poor prognosis group were higher than those in the good prognosis group(45.62±6.63 U/L,0.79±0.12 mmol/L,2.48±0.36),and the differences were statistically significant(t=8.699,8.507,7.562,all P＜0.05),and there were differences in TC,LDL-C,HDL-C levels and mRS scores between the two groups,and the differences were statistically significant(t=15.755～27.072,all P<0.05).The serum levels of ox-LDL,RC,NLR were positively correlated with mRS scores(r=0.612,0.623,0.653,all P<0.05).The levels of TC,LDL-C,HDL-C,ox-LDL,RC and NLR were all factors that affected the prognosis of ICAS(all P<0.05).The AUC of serum ox-LDL,RC and NLR for predicting prognosis in ICAS patients were 0.894(0.835～0.937),0.860(0.797～0.910)and 0.817(0.748～0.874),respectively.The combined AUC(95%CI)of the three was 0.965(0.923～0.987),the combination of the three was more valuable than predicting serum ox-LDL,RC and NLR alone(Z=3.030,3.969,4.839,all P<0.05).Conclusion The serum levels of ox-LDL,RC and NLR in ICAS patients have all increased and are positively correlated with mRs scores.The three have predictive value for the prognosis of ICAS patients,and the combined detection of the three has higher clinical value.

[Objective] To explore the clinical characteristics, diagnosis and treatment of benign liver tissue ectopia in adrenal tumor, so as to improve the understanding of this disease. [Methods] We reported the data of a rare patient with ectopic liver tissue to adrenal gland admitted in the Department of Urology, Liaocheng Second Hospital Affiliated to Shandong First Medical University and discussed it in conjunction with literature. [Results] The patient was a 32-year-old male who sought medical attention for more than half a year due to elevated blood pressure and detection of a tumor in the right adrenal gland.Ultrasound and CT examinations showed a tumor in the right adrenal gland, suggesting myeloid lipoma.Laparoscopic right adrenalectomy was performed, and the postoperative pathology showed benign liver tissue ectopia in adrenal tumor, hepatocyte proliferation, steatosis, and slight lymphocyte infiltration.Immunohistochemistry suggested Hep-1 (+ ). During the follow-up of 12 months, the patient recovered well with no complications.Imaging examinations showed no signs of recurrence. [Conclusion] Benign liver tissue ectopia in adrenal tumor is very rare and is difficult to diagnose preoperatively.Diagnosis is mainly based on pathology, and surgical resection is usually chosen.

Objective:To explore the effectiveness, safety and cost between urinary follicle stimulating hormone (uFSH) and recombinant follicle stimulating hormone (rFSH) in controlled ovarian stimulation (COS) in China.Methods:Data were collected from 16 reproductive centers in China covering oocytes collection time from May 1, 2015 to June 30, 2018. Eligible patients were over 18 years old, adopting COS with uFSH (uFSH group) or rFSH (rFSH group) as start gonadotropins (Gn), and using in vitro fertilization (IVF) and (or) intracytoplasmic sperm injection for fertilisation, excluding frozen embryo recovery cycle. Generalised estimating equation was used to address the violation of independency assumption between cycles due to multiple IVF cycles for one person and clustering nature of cycles carried out within one center. Controlling variables included age, body mass index, anti-Müllerian hormone level, cause of infertility, ovulation protocol, type of fertilisation, number of embryos transferred, number of days of Gn use.Results:Totally 102 061 cycles met eligibility criteria and were included in the analyses. In terms of effectiveness, after controlling relevant unbalanced baseline characteristics, compared with rFSH group, the high oocyte retrieval (>15 oocytes was considered high retrieval) rate of uFSH group significantly decreased in gonadotropin-releasing hormone agonist protocol ( OR=0.642, P<0.01) and in gonadotropin-releasing hormone antagonist protocol ( OR=0.556, P=0.001), but the clinical pregnancy rate per transfer cycle and the live birth rate per transfer cycle significantly increased ( OR=1.179, OR=1.169, both P<0.01) in both agonist and antagonist protocols. For safety, multiple analysis result demonstrated that in the agonist protocol, compared with rFSH group, the incidence of moderate to severe ovarian hyperstimulation syndrome of uFSH group significantly decreased ( OR=0.644, P=0.002). The differences in ectopic pregnancy rate and multiple pregnancy rate between the uFSH and rFSH groups were not significant ( P=0.890, P=0.470) in all patients. In terms of cost, compared with rFSH group, the uFSH group had lower total Gn costs for each patient ( P<0.01). Conclusion:For patients who underwent COS, uFSH has better safety, and economic profiles over rFSH in China.

Antibodies, Neutralizing ; Antibodies, Viral/isolation & purification* ; B-Lymphocytes/virology* ; COVID-19/virology* ; Humans ; Immunity/genetics* ; RNA, Viral/immunology* ; SARS-CoV-2/pathogenicity* ; Single-Cell Analysis

Objective To assess effectiveness of ketogenic diet on improving polycystic ovary syndrome (PCOS) patients accompanying with overweight and obesity. Methods A total of 72 PCOS patients planned to recruit in our study from December 29, 2018 to June 2019 were selected, and were randomly divided into experimental group and control group. The control group was given routine treatment and suggestions of life style, while the experimental group carried out ketogenic diet intervention alone for three months. All patients were followed up every day and rechecked monthly. The safety and effectiveness indexes of the two groups were observed. Results A total of fifty patients had been recruited until March 30, 2019, but one patient was lost in the follow-up. As a result, there were totally twenty-five patients in the experimental group with one patient lost in follow-up. In the remaining twenty-four patients, 75％ of these patients had recovered spontaneous menstruation in good condition. Ten patients who have been intervened over one month accepted the first re-examination. The results showed that the patient's weight, the body fat rate and the level of androgen detected in venous blood were all reduced after ketogenic diet after the intervention (P ＜ 0. 01), which revealed that the effect of ketogenic diet's intervention for PCOS was significant in the short term. Conclusion Ketogenic diet intervene in PCOS effectively restore spontaneous menstruation in patients for one month, the state of hyperandrogenism is significantly improved. Other hormones show improvement trends, but no significant difference compared with baseline. The mid-term and final reports of KIDs-001 are worthy of the wait.

Objective To assess effectiveness of ketogenic diet on improving polycystic ovary syndrome (PCOS) patients accompanying with overweight and obesity. Methods A total of 72 PCOS patients planned to recruit in our study from December 29, 2018 to June 2019 were selected, and were randomly divided into experimental group and control group. The control group was given routine treatment and suggestions of life style, while the experimental group carried out ketogenic diet intervention alone for three months. All patients were followed up every day and rechecked monthly. The safety and effectiveness indexes of the two groups were observed. Results A total of fifty patients had been recruited until March 30, 2019, but one patient was lost in the follow-up. As a result, there were totally twenty-five patients in the experimental group with one patient lost in follow-up. In the remaining twenty-four patients, 75％ of these patients had recovered spontaneous menstruation in good condition. Ten patients who have been intervened over one month accepted the first re-examination. The results showed that the patient's weight, the body fat rate and the level of androgen detected in venous blood were all reduced after ketogenic diet after the intervention (P ＜ 0. 01), which revealed that the effect of ketogenic diet's intervention for PCOS was significant in the short term. Conclusion Ketogenic diet intervene in PCOS effectively restore spontaneous menstruation in patients for one month, the state of hyperandrogenism is significantly improved. Other hormones show improvement trends, but no significant difference compared with baseline. The mid-term and final reports of KIDs-001 are worthy of the wait.

Objective To study the clinical effect of Yiqi-Huoxue decoctions combined with exercise rehabilitation training for patients with chronic heart failure and its effect on serum MMP-1, TIMP-1. Methods A total of 120 patients with chronic heart failure in our hospital from February 2016 to January 2017 were enrolled in this study. The subjects were randomly divided into the control group (n=60) and the treatment group (n=60). The control group were treated with conventional treatment, and the treatment group were treated with Yiqi-Huoxue decoctions combined with exercise training. The two groups were treated for 30 days. The clinical effects of the two groups after treatment were compared. The SBP, DBP, LVESD, LVEDD and LVEF of the two groups before and after treatment were compared. The serum MMP-1, TIMP-1 of the two groups before and after treatment were compared. The adverse reaction rates of the two groups during treatment were compared. Results The total effect rate of the treatment group was 93.3％ (56/60), significantly higher than 73.3％ (44/60)of the control group (χ2=8.640, P=0.003). After treatment, the SBP (125.17 ± 13.51 mmHg vs. 140.82 ± 14.63 mmHg, t=6.087), DBP (74.36 ± 10.31 mmHg vs. 86.29 ± 11.17 mmHg, t=6.079), LVESD (41.11 ± 3.23 mm vs. 49.69 ± 4.99 mm, t=11.181) and LVEDD (57.36 ± 3.28 mm vs. 64.16 ± 4.05 mm, t=10.107) of the treatment group were significantly lower than those of the control group (P<0.05). The LVEF (69.82％ ± 5.05％ vs. 51.40％ ± 4.11％, t=21.913) of the treatment group was significantly higher than the control group (P<0.05). After treatment, the serum MMP-1 (141.52 ± 15.22 μg/L vs. 164.10 ± 16.18 μg/L, t=7.874) of the treatment group were significantly lower than those of the control group (P<0.05), and the serum TIMP-1 (3.98 ± 0.22 μg/L vs. 3.51 ± 0.16 μg/L, t=13.383) of the treatment group were significantly higher than those of the control group (P<0.05). There was no significant differences of the adverse reaction rates of the two groups during treatment (χ2=0.152, P=0.697). Conclusions The Yiqi-Huoxue decoctions combined with exercise rehabilitation training for patients with chronic heart failure showed good efficacy and low incidence of adverse reactions, can significantly improve cardiac function and the cardiac remodeling.

Objective To evaluate the accuracy in placement of cervical anterior transpedicular screws (ATPS) under the guidance of our modified drilling template.Methods Eight wet cadaveric specimens of adult cervical spine,4 male and 4 female ones,were used for this experiment.Data of CT thin layer scanning of the cervical specimens in DICOM format were imported into software Mimics 17.0.After 3D models of the cervical vertebrae were reconstructed,the optimal trajectory was designed for ATPS placement in the transparent mode of the 3D models.Normal and our modified drilling templates for ATPS placement were designed and manufactured by 3D printing.The 2 kinds of drilling templates were used to assist ATPS placement onto one cervical vertebra,with laterality randomized.Altogether 64 pieces of ATPS were placed,with 32 ones for each drilling template.Postoperative CT scanning was conducted to evaluate the accuracy in ATPS placement.The 2 kinds of ATPS template were compared in terms of the deviations between actual and ideal trajectories in direction (caudal-angle and extroversive-angle) and position (X and Y axes) of the entry point.Results Our modified drilling template led to one screw penetrating the pedicle cortical bone while the normal drilling template led to 4 screws penetrating the pedicle cortical bone,yielding an accuracy rate of 96.9％ and of 87.5％ respectively.The extroversive-angle deviation (0.72°±0.69°),caudal-angle deviation (0.91°±0.70°),X axis shift (0.53 ±0.40 mm) and Y axis shift (0.54 ±0.42 mm) related to the modified template were all significantly smaller than those related to the normal template (1.16° ± 0.70°,1.49°±0.68°,0.88±0.40mm,1.22±0.42mm,respectively) (P ＜0.05).Conclusion Compared with a normal ATPS template,our modified drilling template for ATPS may be advantageous in better fitness,greater stability,increased accuracy in screw placement,and protection of adjacent discs.