Objective To clarify the clinical features and genetic background of a kindred of primary pigmented nodular adrenocortical disease (PPNAD).Methods Detailed clinical characteristics and laboratory test results from a ten-year old girl diagnosed as PPNAD were collected.Seven members of her family were screened for Cushing syndrome and Carney complex,and their blood DNA was extracted and sequenced for PRKAR1A,PDE11A,PDE8B and CTNNB1 mutations with ABI3730.Results The girl presented with symptoms and signs of hypercortisolism,while no features of Carney complex were observed.Hypercortisolemia,suppressed corticotrophin and high urinary free cortisol level were revealed.Cortisol level could not be suppressed both in high and low dose dexamethasone suppression test.The diagnosis of adrenocorticotrophic hormone (ACTH)-independent Cushing syndrome was established.Image and pathology of adrenal glands were in accordance with PPNAD.Other family members showed no evidence of Cushing syndrome or Carney complex.DNA sequencing showed that the patient harbored a missense mutation,C18G.Her father and younger sister were proved to be carriers of this mutation.Conclusion A Chinese PPNAD family was identified clinically and genetically,and a novel missense mutation of PRKAR1A was found.

Objective To evaluate the diagnostic value of triptorelin stimulation test in disorders due to delayed puberty.Methods Triptorelin stimulation test was carried out in 128 teenagers with delayed puberty,due to idiopathic hypogonadotropic hypogonadism(IHH) in 77 cases and constitutional delayed puberty(CDP) in 51.Blood samples were obtained 15 min before and 0,30,60,and 120 min after tripotorelin administration,and the levels of LH and FSH were determined.An extended GnRH stimulation test was carried out in 3 patients with IHH.Results Peak LH,peak FSH,and LH increment were parameters with high diagnostic value.A cut-off point at 8.2 IU/L of peak LH showed a sensitivity of 87％ and a specificity of 80.4％ in the differential diagnosis of IHH and CDP.Conclusion Peak LH cut-off point at 8.2 IU/L of triptorelin stimulation test seems to be sufficient to confirm diagnosis of IHH and CDP.An extended GnRH stimulation test may distinguish hypothalamic from the pituitary hypogonadotropic hypogonadism.

Objective To explore the value of three-dimensional DSA (3D-DSA) in displaying the location of the origin of uterine artery.Methods A total of 90 female patients underwent uterine artery (UA) embolization were enrolled.The bilateral internal iliac artery catheterization were performed by 3D-DSA,then the images were reconstructed in every 5 degree interval to choose the optimum range of viewing angle.The origination and the degree of the origin artery and UA were calculated.The distance between the origin of UA and superior glutea artery which was identified as the locating point was measured.Results Bilateral and contralateral oblique position of ＞30°-60°were the optimal projection positions of UA.Totally 64.44％ (116/180) of UA originated from the anterior trunk of internal iliac artery,18.33％ (33/180) originated from the inferior gluteal trunk,9.44 ％ (17 / 180) originated from the internal pundenal artery,5.56 ％ (10 / 180) originated from internal iliac artery,and 2.22％ (4/180) originated from the superior gluteal artery;10.56％ (19/180) of the angle of the origin artery and UA were 0-30°,38.89％ (70/180) were ＞30°-60°,41.11％ (74/180) were ＞60°-90°,4.44％ (8/180) were＞90°-120°,2.78％ (5/180) were＞120°-150°,2.22％ (4/180) were＞150°-180°.Distance between the origin of UA and superior gluteal artery was 3.04-18.31 mm,average was (11.71±4.28)mm.Conclusion 3D-DSA can clearly display the origination,viewing angle and the distance away from superior gluteal artery.

Objective To investigate the biomechanical stability of 5 kinds of internal fixation for acetabular T-shaped fractures using finite element analysis.Methods After a three-dimensional model of normal pelvis was reconstructed using Mimics software,the model of acetabular T-shaped fracture was divided by Solidworks software.Models of acetabular T-shaped fracture fixated by 5 methods were reconstructed:(A) a reconstruction plate for anterior column + lag screws for posterior column,(B) lag screws for anterior column + a reconstruction plate for posterior column,(C) a reconstruction plate for anterior column + a medial ilioischial plate for posterior column (combination plating),(D) retrograde lag screws for 2 columns,and (E) a reconstruction plate for anterior column + and a posterior ilioischial plate for posterior column.Valuation was conducted with software Ansys to simulate 600 N loading on the terminal plate of S1 vertebral body at standing and sitting positions.The biomechanical stabilities were compared between the 5 models of internal fixation.Results At standing and sitting positions,the displacements of anterior column in modelA (0.522±0.121 mmand0.762±0.181 mm),modelC (0.512±0.207mmand0.730±0.181mm) and model E (0.513 ± 0.184 mm and 0.733 ± 0.166 mm) were significantly smaller than those in model B (0.622±0.224 mmand 1.328±0.537 mm) and in modelD (0.655±0.174mm and 1.591± 0.270 mm) (P ＜ 0.05).However,there were no statistically significant differences in anterior column displacements between models A,C and E or between models B and D (P ＞ 0.05).At standing and sitting positions,the displacements of posterior column in model B (0.631 ± 0.151 mm and 0.572 ± 0.693 mm),in model C (0.621 ± 0.195 mm and 0.538 ± 0.075 mm) and in model E (0.625 ± 0.192 mm and 0.544 ± 0.063 mm) were significantly smaller than those in model A (0.742 ±0.140 mm and 0.715 ±0.072 mm)and in modelD (0.754±0.247 mm and 0.717 ± 0.071 mm) (P ＜0.05).However,there were no statistically significant differences in posterior column displacements between models B,C and E or between models A and D (P ＞ 0.05).Conclusions In the treatment of acetabular T-shaped fractures,reconstruction plating has better stability than screwing.Reconstructive plating shows the best stability for anterior and posterior columns,followed by combination plating which is the best choice for reducing surgical injury.

Severe acute pancreatitis is a common clinical acute abdominal disease, characterized by acute onset, rapid progression, high risk, poor prognosis and so on. Due to the high mortality of this disease, it has been the focus and difficulty of clinical research. The traditional treatment of severe acute pancreatitis mainly include fasting and parenteral nutrition. However, recently, international and national consensus suggest that early enteral nutrition is fit for severe acute pancreatitis, although the timing of early enteral nutrition has been controversial. The article summarizes the optimal timing of early enteral nutrition for severe acute pancreatitis.

Objective:To observe the effects of acupuncture and moxibustion on phosphatase and PTEN-induced putative kinase 1(PINK1)/Parkin signaling pathway in the midbrain substantia nigra of Thy1-α synuclein(αSyn)transgenic model mice with Parkinson disease(PD). Methods:Twenty-four Thy1-αSyn transgenic mice were randomly divided into a model group,an acupuncture group,an acupuncture + moxibustion group,and a Western medicine group.Six wild-type mice in the same litter were used as the wild-type group.In the acupuncture group,Baihui(GV20)and Yanglingquan(GB34)were selected for acupuncture.In the acupuncture + moxibustion group,Guanyuan(CV4)was added on the basis of the acupuncture group.The Western medicine group was given rapamycin intraperitoneal injection at a dose of 10 mg/(kg·bw).The wild-type group and the model group were fixed without intervention.The overall rod performance(ORP)score of mice was observed in each group.The immunohistochemical method was used to detect the tyrosine hydroxylase(TH)positive neurons in the substantia nigra of mice in each group.The αSyn was detected by the immunofluorescence chemical method.The expression levels of αSyn,microtubule-associated protein 1 light chain 3(LC3)-Ⅱ/LC3-Ⅰ,autophagy protein sequestosome-1/protein 62(SQSTM-1/p62),PINK1,Parkin,and ubiquitin-specific protease 30(USP30)proteins were detected by Western blotting assay.The expression levels of LC3B,p62,PINK1,Parkin,and USP30 mRNAs were detected by fluorescence quantitative polymerase chain reaction. Results:Compared with the wild-type group,the ORP score,the p62,PINK1,and Parkin protein expression levels decreased significantly(P<0.01),the PINK1 mRNA expression level decreased(P<0.05),while the protein and mRNA expression levels of USP30 increased(P<0.05)in the model group.Compared with the model group,the ORP score in the acupuncture group and the acupuncture + moxibustion group increased(P<0.05);the expression level of LC3-Ⅱ/LC3-Ⅰ protein in the acupuncture + moxibustion group and the Western medicine group increased(P<0.05);the protein expression levels of p62,PINK1,and Parkin increased(P<0.05),while the USP30 protein expression level decreased significantly(P<0.01)in the acupuncture group,the acupuncture + moxibustion group,and the Western medicine group;the Parkin mRNA expression level in the acupuncture group and the acupuncture + moxibustion group increased(P<0.05);the USP30 mRNA expression level in the acupuncture + moxibustion group decreased(P<0.05). Conclusion:Acupuncture and moxibustion regulate the related molecule expression levels of PINK1/Parkin signaling pathway in the Thy1-αSyn transgenic PD model mice and promote the autophagy degradation of αSyn to exert the protective effect of dopaminergic neurons.

Objective To explore the effectiveness of Failure Modes and Effects Analysis(FMEA)in emergency man-agement of sudden incidents involving outpatient and emergency patients in general hospitals,to provide references for the optimi-zation of emergency response process for such incidents.Methods Based on FMEA,we identified and evaluated risks in the e-mergency response procedures for sudden incidents involving outpatient and emergency patients in general hospitals.Potential fail-ure modes were analyzed to identify key risks with a Risk Priority Number(RPN)greater than 125.Continuous quality improve-ment measures were implemented to control these risks,and the effectiveness of these controls was evaluated using chi-square tests for statistical analysis.Results A total of 16 risk points in 4 major areas were identified.After implementing continuous quality improvement measures,the RPNs of these high-risk points decreased to below 125,effectively controlling the potential risks.This intervention significantly improved the utilization rate of emergency equipment,the timely reporting rate of sudden in-cidents,the timely feedback rate of emergency response,with statistically significant differences(P＜0.01).Conclusion The application of FMEA to outpatient and emergency management of sudden incidents helps optimize the emergency response process,thus enhancing the emergency response capability of general hospitals and ensuring effective handling of such incidents.

OBJECTIVE To analyze the clinical manifestation and characteristics of ocular adverse drug reaction （ADR） related to dupilumab， so as to provide reference for clinically safe drug use. METHODS Retrieved from CNKI， Wanfang data， VIP and PubMed databases， the case reports about ocular ADR caused by dupilumab were collected， and then analyzed statistically in terms of gender， age， primary disease， drug use， occurrence time of ADR， main clinical manifestations， treatment or outcome， etc. RESULTS A total of 20 pieces of literature were selected， involving 46 patients， among which there were 29 males and 17 females. Mainly patients were under 60 years old. The results of the association evaluation was given as follows： 13 were “very likely” and 33 were “likely”. All patients were treated with dupilumab for atopic dermatitis （AD） without off-label medication. The occurrence time of ADR was 2 weeks to 2 years after administration， mainly within 6 months after medication. All patients received dupilumab monotherapy except that 3 patients with hypertension and 1 patient with chronic obstructive pulmonary disease and human immunodeficiency virus received other drugs simultaneously. Twenty-eight patients had a history of allergic disease， and 11 patients had a history of eye disease. Ocular ADRs were mainly conjunctivitis and uveitis， and the clinical manifestations mainly included conjunctival congestion， swelling， eye secretions， etc. Ten patients developed severe ADR， including uveitis， severe conjunctivitis， and tear point stenosis； 45 patients were improved after symptomatic treatment. AD， serious initial symptoms of AD， allergic disease and underlying ocular diseases might be the high-risk factors of ocular ADR caused by dupilumab. CONCLUSIONS Whether the patient has the history of allergic diseases and basic eye diseases should be asked in detail before clinical use of dupilumab. When using the drug， attention should be paid to monitoring whether the patient has intraocular inflammation， be alert to the occurrence of new or serious ADR， and give timely symptomatic treatment to ensure the safety of drug use.

Objective:The purpose of this study was to investigate the characteristics of distortion product otoacoustic emissions (DPOAE) in patients with auditory neuropathy (AN). The factors affecting DPOAE elicitation rate of each frequency, elicitation rate of each ear and change rate of first and last diagnosis in the natural course were analyzed.Methods:The sample was obtained from the Multicenter Study on Clinical Diagnosis and Intervention of AN (registration number: ChiCTR2100050125), and the diagnostic criteria for AN were based on the Chinese Clinical Practice Guidelines of Auditory Neuropathy (version 2022). Patients with bilateral AN who underwent 2 or more DPOAE tests were screened and divided into infant groups (≤3 years old) and non-infant groups (>3 years old) according to the age of detection, and the trend of DPOAE elicitation rate of each frequency, elicitation rate of each ear and change rate in the natural course of disease were analyzed, in order to explore the relevant influencing factors.Results:A total of 165 patients (330 ears) with AN were included in the study. The overall DPOAE elicitation rate per ear was 77.0%±29.4% at the initial diagnosis and 65.1%±35.2% at the final diagnosis, with a reduction observed in the elicitation rate of 171 ears (51.82%). In the infant group, there were 49 cases (98 ears), including 28 males and 21 females, whose found age ranged from 0 to 3 years old, with a median age of 0.7 years. DPOAE elicitation rate per ear was 57.9%±35.5% in the initial diagnosis, and 32.4%±32.1% in the final diagnosis, with a reduction observed in the elicitation rate of 69 ears (70.41%). In the non-infant group, there were 116 cases (232 ears), including 59 males and 57 females, ranging in found age from 3.9 to 40 years old, with a median age of 14 years old. DPOAE elicitation rate per ear was 84.6%±23.4% in the initial diagnosis, and 78.3%±27.1% in the final diagnosis, with a reduction observed in the elicitation rate of 102 ears (43.97%). Age was found to be correlated with DPOAE changes by multicategorical unordered logistic regression analysis ( B=-0.224, OR=0.799, P<0.001). Conclusions:The elicitation rate of DPOAE in AN patients decreases or even disappears with increasing disease duration; The rate of DPOAE extraction is found to be lower in infant patients with auditory neuropathy (AN) compared to non-infant AN patients. Additionally, it is observed that the decrease in DPOAE extraction rate is more pronounced in infant AN patients as the disease progressed, as compared to non-infant AN patients. DPOAE and cochlear microphonic potentials should be fully combined for accurate diagnosis, and regular follow-up should be conducted to understand the natural course of the disease and give personalized guidance and assistance.

Objective:To investigate the effects of single intermittent theta-burst stimulation on functional connectivity in patients with mild cognitive impairment(MCI).Methods:From July to November 2020, forty MCI patients were selected and randomly divided into iTBS true stimulation group and iTBS sham-stimulation group, with 20 patients in each group.iTBS targeted the left dorsolateral prefrontal cortex (DLPFC). Montreal cognitive assessment (MoCA), mini-mental state examination (MMSE), activity of daily living scale(ADL), Hamilton depression scale (HAMD) and Hamilton anxiety scale (HAMA) were evaluated at baseline.The resting state electroencephalography (rsEEG) was collected for 5 minutes before and after iTBS in the two groups.The phase lag index(PLI) of EEG functional connectivity was calculated, and the functional connectivity matrix diagram was drawn.SPSS 26.0 software was used for statistical analysis.Data were statistically analyzed by χ2 test, Wilcoxon rank sum test and independent sample t-test. Results:There were no significant differences in scores of MoCA, ADL, HAMD and HAMA between the two groups(all P>0.05). In the iTBS true stimulation group, compared with that before iTBS treatment(0.140(0.133, 0.144)), the PLI of β band increased significantly after iTBS treatment(0.146(0.136, 0.167))( P<0.05). The region of increased PLI was mainly concentrated in the central region(C3/C4-T7/T8). Compared with that before iTBS treatment(0.251(0.232, 0.299)), the PLI of α band increased after iTBS treatment(0.286(0.241, 0.359)), but the difference was not statistically significant( P>0.05). Conclusion:Single iTBS treatment can significantly increase the EEG functional connectivity in patients with MCI, indicating that iTBS targeting the left DLPFC can effectively regulate the EEG functional connectivity in patients with MCI, which may reveal the mechanism of iTBS in improving cognitive function in patients with MCI.