OBJECTIVE: To explore the clinical features and genetic basis of a male patient with Kennedy disease(KD) presenting as secondary infertility. METHODS: A male patient who had presented at Yantai Yuhuangding Hospital in August 2023 for secondary infertility for 5 years was selected as the study subject. Clinical data, laboratory findings, and auxiliary examination of the patient were collected. Peripheral blood samples were obtained from the patient and his family members. Following DNA extraction, whole-exome sequencing (WES) was carried out. Pathogenicity of candidate variant was predicted by bioinformatics analysis. Fluorescence probe PCR-capillary electrophoresis was employed to analyze the trinucleotide CAG repeat sequence variation in the AR gene to rule out dynamic mutation. This study was approved by the Ethics Committee of Yantai Yuhuangding Hospital (Ethics No.: 2024-697). RESULTS: The patient had presented with non-obstructive azoospermia and elevated androgen sensitivity index. Ultrasound scan indicated small testicular volume and seminal vesicle atrophy. WES and bioinformatics analysis revealed abnormal amplification in the patient's AR gene. Fluorescence probe PCR and capillary electrophoresis confirmed that both the proband and his nephew had harbored 52 CAG trinucleotide repeats in exon 1 of the AR gene, confirming the diagnosis of KD. The proband's mother, elder sister, and daughter were identified as carriers of the variant, while his second elder sister did not carry the mutation. CONCLUSION As a rare X-linked recessive genetic disease, KD mainly manifests with muscle weakness, myasthenia gravis and myofascial tremor, while cases with infertility and non-obstructive azoospermia as the initial symptoms are rare and can be easily missed. Diagnosis made by genetic testing needs to be taken seriously by the clinicians.
Humans ; Male ; Bulbo-Spinal Atrophy, X-Linked/diagnosis* ; Adult ; Infertility, Male/genetics* ; Receptors, Androgen/genetics* ; Exome Sequencing ; Mutation ; Pedigree ; Trinucleotide Repeats

Objective:To explore the risk factors for primary Sjogren′s syndrome-associated interstitial lung diseases (pSS-ILD) and to evaluate the diagnostic value of NLR and other predictors of pSS-ILD.Methods:A retrospective study of 63 patients with pSS-ILD and 201 patients with pSS visited our hospital from January 2016 to December 2023 was conducted. The general characteristics, clinical symptoms, laboratory indicators and treatment of the patients were collected. Correlation analyses were performed using the point bi-serial correlation test and Spearman′s Rho test, and binary logistic regression analysis was applied to explore the risk factors for the development of pSS-ILD. We assessed the value of diagnostic tools in relation to pSS-ILD by plotting receiver operating characteristic (ROC) curves.Results:①The proportion of males(14.29% vs. 4.48%, χ2=7.26, P=0.007), age at onset [(53±13)years old vs. (47±15)years old, t=2.55, P=0.011], neutrophil-to-lymphocyte ratio (NLR)[3.52(2.28, 6.49) vs. 1.64(1.23, 3.12), Z=-5.94, P<0.001], systemic immune-inflammatory index (SII) [653.34(328.08, 1 393.54) vs. 316.56(185.57, 593.65), Z=-5.26, P<0.001], C-reactive protein (CRP) [3.53(2.95, 9.76)mg/L vs. 2.82(1.67, 5.00)g/L, Z=-2.24, P=0.025], complement C3 [0.93(0.84, 1.02)g/L vs. 0.76(0.66, 0.85)g/L, Z=-5.33, P<0.001], and ESSDAI [4(3, 6) vs. 2(2, 4), Z=-5.70, P<0.001] levels were higher in the pSS-ILD than in non-ILD group, while the proportion of dry eyes (62.7%, χ2=13.37, P<0.001), proportion of anti-SSA/Ro60 antibody positivity (76.1%, χ2=8.77, P=0.012), rheumatoid factor (RF) positiveity [25.90(20.00, 83.30)U/ml, Z=-3.58, P<0.001], immunoglobulin G (IgG)[15.60(12.30, 21.90)g/L, Z=-3.28, P=0.001], immunoglobulin A (IgA)[3.21(2.32, 3.76)g/L, Z=-2.22, P=0.026], and immunoglobulin M (IgM)[1.29(0.93, 1.86)g/L, Z=-4.02, P<0.001) levels were higher in the non-ILD group. ②Correlation analysis showed that age at onset ( r=0.16, P<0.011), NLR ( r=0.43, P<0.001), SII ( r=0.41, P<0.001), and C3 ( r=0.27, P<0.001) were positively correlated with pSS-ILD, whereas IgG ( r=-0.18, P=0.005), IgM ( r=-0.19, P=0.002) were negatively correlated with pSS-ILD. Meanwhile, age at onset ( r=0.27, P<0.001), NLR ( r=0.30, P<0.001), and SII ( r=0.27, P<0.001) were positively correlated with ESSDAI score. ③Regression analysis showed that high levels of NLR[ OR(95% CI)=2.559(1.650, 3.969), P<0.001], C3[ OR(95% CI)=35.228(5.685, 218.309), P<0.001] might be risk factors for pSS-ILD. ④The area under the curve (AUC) for the diagnosis of pSS-ILD by NLR was 0.748, with a diagnostic sensitivity and specificity of 97.01% and 39.68%, respectively; the AUC for C3 was 0.727, with a diagnostic sensitivity and specificity of 66.67% and 79.03%, respectively; and the AUC for the joint predictive probability (Pre_1) of NLR and C3 was 0.812, with a sensitivity and specificity of 93.33% and 54.84%, respectively. Conclusion:High levels of NLR, C3 may be risk factors for pSS-ILD. NLR and C3 are adjunctive tools for the diagnosis of pSS-ILD, and the combination of the two increases the predictive value.

Objective:To explore the risk factors for primary Sjogren′s syndrome-associated interstitial lung diseases (pSS-ILD) and to evaluate the diagnostic value of NLR and other predictors of pSS-ILD.Methods:A retrospective study of 63 patients with pSS-ILD and 201 patients with pSS visited our hospital from January 2016 to December 2023 was conducted. The general characteristics, clinical symptoms, laboratory indicators and treatment of the patients were collected. Correlation analyses were performed using the point bi-serial correlation test and Spearman′s Rho test, and binary logistic regression analysis was applied to explore the risk factors for the development of pSS-ILD. We assessed the value of diagnostic tools in relation to pSS-ILD by plotting receiver operating characteristic (ROC) curves.Results:①The proportion of males(14.29% vs. 4.48%, χ2=7.26, P=0.007), age at onset [(53±13)years old vs. (47±15)years old, t=2.55, P=0.011], neutrophil-to-lymphocyte ratio (NLR)[3.52(2.28, 6.49) vs. 1.64(1.23, 3.12), Z=-5.94, P<0.001], systemic immune-inflammatory index (SII) [653.34(328.08, 1 393.54) vs. 316.56(185.57, 593.65), Z=-5.26, P<0.001], C-reactive protein (CRP) [3.53(2.95, 9.76)mg/L vs. 2.82(1.67, 5.00)g/L, Z=-2.24, P=0.025], complement C3 [0.93(0.84, 1.02)g/L vs. 0.76(0.66, 0.85)g/L, Z=-5.33, P<0.001], and ESSDAI [4(3, 6) vs. 2(2, 4), Z=-5.70, P<0.001] levels were higher in the pSS-ILD than in non-ILD group, while the proportion of dry eyes (62.7%, χ2=13.37, P<0.001), proportion of anti-SSA/Ro60 antibody positivity (76.1%, χ2=8.77, P=0.012), rheumatoid factor (RF) positiveity [25.90(20.00, 83.30)U/ml, Z=-3.58, P<0.001], immunoglobulin G (IgG)[15.60(12.30, 21.90)g/L, Z=-3.28, P=0.001], immunoglobulin A (IgA)[3.21(2.32, 3.76)g/L, Z=-2.22, P=0.026], and immunoglobulin M (IgM)[1.29(0.93, 1.86)g/L, Z=-4.02, P<0.001) levels were higher in the non-ILD group. ②Correlation analysis showed that age at onset ( r=0.16, P<0.011), NLR ( r=0.43, P<0.001), SII ( r=0.41, P<0.001), and C3 ( r=0.27, P<0.001) were positively correlated with pSS-ILD, whereas IgG ( r=-0.18, P=0.005), IgM ( r=-0.19, P=0.002) were negatively correlated with pSS-ILD. Meanwhile, age at onset ( r=0.27, P<0.001), NLR ( r=0.30, P<0.001), and SII ( r=0.27, P<0.001) were positively correlated with ESSDAI score. ③Regression analysis showed that high levels of NLR[ OR(95% CI)=2.559(1.650, 3.969), P<0.001], C3[ OR(95% CI)=35.228(5.685, 218.309), P<0.001] might be risk factors for pSS-ILD. ④The area under the curve (AUC) for the diagnosis of pSS-ILD by NLR was 0.748, with a diagnostic sensitivity and specificity of 97.01% and 39.68%, respectively; the AUC for C3 was 0.727, with a diagnostic sensitivity and specificity of 66.67% and 79.03%, respectively; and the AUC for the joint predictive probability (Pre_1) of NLR and C3 was 0.812, with a sensitivity and specificity of 93.33% and 54.84%, respectively. Conclusion:High levels of NLR, C3 may be risk factors for pSS-ILD. NLR and C3 are adjunctive tools for the diagnosis of pSS-ILD, and the combination of the two increases the predictive value.

The senescence accelerate mouse prone strain was identified by Professor T.Takeda's laboratory in Japan from the offspring produced by the brother-sister inbred line of AKR/J mice donated by Jackson Laboratory in the United States SAMP),and SAMP8 mice showed a variety of aging characteristics,such as:Pathological changes such as memory and learning disorders,behavioral abnormalities,skin roughness,aging,hair loss,eye lesions(visual impairment,cataract,periocular lesions),hearing impairment,weight loss,muscle strength loss,reproductive system aging,liver and fat metabolism disorders,etc.,are widely used in experimental studies of related diseases or pathology,and have made considerable contributions to the research of diseases.However,there are also many problems in its application,such as the selection of month age,the use of intervention methods,the suitability of pathological changes and research content,and the understanding of models under different theoretical backgrounds,which are of great research value.Therefore,this paper systematically analyzes the above problems based on existing literature,in order to provide relevant basis for the application of SAMP8 mice in different fields and different mechanisms.

The senescence accelerate mouse prone strain was identified by Professor T.Takeda's laboratory in Japan from the offspring produced by the brother-sister inbred line of AKR/J mice donated by Jackson Laboratory in the United States SAMP),and SAMP8 mice showed a variety of aging characteristics,such as:Pathological changes such as memory and learning disorders,behavioral abnormalities,skin roughness,aging,hair loss,eye lesions(visual impairment,cataract,periocular lesions),hearing impairment,weight loss,muscle strength loss,reproductive system aging,liver and fat metabolism disorders,etc.,are widely used in experimental studies of related diseases or pathology,and have made considerable contributions to the research of diseases.However,there are also many problems in its application,such as the selection of month age,the use of intervention methods,the suitability of pathological changes and research content,and the understanding of models under different theoretical backgrounds,which are of great research value.Therefore,this paper systematically analyzes the above problems based on existing literature,in order to provide relevant basis for the application of SAMP8 mice in different fields and different mechanisms.

Objective To explore the effects and the underlying mechanisms by which paired associative stimulation ( PAS) of tibial nerve electrostimulation and M1 cortex transcranial magnetic stimulation ( TMS) in pro-moting the recovery of forelimb dysfunction in rats with cerebral ischemic stroke. Methods Resting motor thresholds of left extensor carpi radialis muscle ( ECR) were determined 5 min before and 5 min, 30 min, 60 min after PAS,respectively, in 8 male Sprague-Dawley ( SD) rats. Then 48 male SD rats were divided into a sham group ( n=16) subject to sham surgery, an experimental group (n=32) which was further divided into a MCAO group (n=16) and a PAS group (n=16) after cerebral ischemic stroke model was established successfully by occluding the right middle cerebral artery. 24 hours after surgery, PAS consisting of left tibial nerve stimulation and right M1 cortex area TMS was applied to PAS group once daily for 7 consecutive days. The corner tests and grip strength tests were per-formed before and after 7 days of PAS treatment in each group. The RMTs of left ECR were determined, metabolites of the left area tissue of cervical spinal cord were measured by nuclear magnetic resonance spectrum, and expressions of Bcl-2 and Bax of left and right area tissue of cervical spinal cord enlargement were detected by Western Blot tech-nique after 7 days of intervention. Results The average RMTs of left ECR at 5 min, 30 min, 60 min after PAS were significantly lower than those at 5 min before PAS ( P<0.05) . All rats in experimental group showed significant higher turning scores and lower grip strength when compared with sham group (P<0.001 or P<0.01). After PAS interven-tion, PAS group demonstrated lower turning scores, higher grip strength and lower RMT of left ECR as compared with MCAO group ( P<0.05 or P<0.01) . The expression of GABA of left cervical enlargment was significantly decreased in MCAO group when compared with the sham group ( P<0.05) , and there was no significant difference between MCAO group and PAS group. Meanwhile, other metabolites showed no significant difference among the three groups. The av-erage expression level of Bcl-2 and Bax proteins in both sides of cervical spinal cord enlargment showed no significant difference among three groups either. Conclusions Tibial nerve-M1 cortex area PAS may increase the excitability of motor cortical representation of forelimbs in rats, by which PAS promotes the recovery of forelimb dysfunction in rats with cerebral ischemic stroke.

Objective To explore a kind of comfortable medical for ervical plexus anesthesia auxiliary anesthesia .Methods 80 thyroidectomy female patients were randomly divided into normal saline group (group A) ,droperidol-fentanyl group (group B) ,bu-torphanol group (group C) ,dex group (group D) ,20 cases in each group .The change of systolic blood pressure (SBP) ,diastolic blood pressure (DBP) ,heart rate (HR) ,blood oxygen saturation (SpO2 ) ,narcotrend index (NTI) were monitored .The above pa-rameters were recorded at 10 min before cervical plexus(T0 ) ,cervical plexus operation(T1 ) ,skin incision(T2 ) ,separation of thyroid upper extreme(T3 )and suture(T4 ) .Results There was no significant difference between the groups A and B at the same time point (P>0 .05) .In group C ,the SBP、DBP、HR at T3 and T4 were significant higher than at T0 ,and at the same point the A and B group decreased statistically significant (P<0 .05) .In group D ,the SBP、DBP、HR at T2 、T3 、T4 were significant lower than at T1 ,espe-cially at T4 compared to at T0 (P<0 .05) .Compared to group A ,B ,C ,the SBP、DBP、HR in group D were lower at T3 and T4(P<0 .05) .NTI in group D at T1 、T2 had significant difference compared with group A and B (P<0 .05) ,especially at T3 、T4 were sta-tistically significant than the other three groups(P<0 .05) ,sedation was better than the other groups .Conclusion Cervical plexus block supplemented by dex can reduce the patient′s stress response and reach moderate sedation analgesia to comfortable medical purposes .