Objective:To investigate the expression of MKK 4 protein in the nasopharyngeal carcinoma and its clinical significance.Methods:Immunohistochemical methods were employed to analyze MKK 4 positive expression intensity and positive cells in freshly collected nasopharyngeal carcinoma of both 90nasopharyngeal carcinoma cases and 20 chronic nasopharyngitis control.The clinical pathological characteristic were analyzed.Results:The data obtained by MKK4 immunohistochemistry showed that the MKK 4 positive rate was higher in control group than in the NPC group (95.5%vs 75.6%,P<0.05).The expression of MKK4 was related to tumor differentiation and lymph node metastasis ( P<0.05 ) , but not to gender , age, tumor volum and TNM stage ( P>0.05 ) . Conclusion:Positive rate of MKK4 protein in nasopharyngeal carcinoma tissues is lower than in chronic nasopharyngitis.MKK4 protein expressions in nasopharyngeal carcinoma tissues negatively correlated with lymph node metastasis ,clincal stage ,invasive depth ,and TTP (Time to progression),but not with age,gender,location and tumor volume.

OBJECTIVE: To investigate the association between-1304T/G polymorphism in the promoter of MKK4 gene and the susceptibility in sporadic nasopharyngeal carcinoma. METHOD: MKK4-1304T/G genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 90 NPC cases and 30 healthy controls. RESULT: The number of nasopharyngeal carcinoma patients carrying with TG+GG genotype was much higher than those of controls (82.2% vs 66.7%, χ² =10.076, P < 0.05). Analysis showed that compared with the-1304TT genotype, -1304TG heterozygous reduced risk of nasopharyngeal carcinoma 0.56 fold (95% CI = 0.164-1.178, P < 0.01) and-1304GG lower 0.58 fold (95% CI = 0.126-1.381, P < 0.01), TG+ GG genotype variation risk of nasopharyngeal carcinoma decreased 0.72 fold (95% CI = 0.105-0.753, P < 0.01). CONCLUSION MKK4 gene-1304TG genotype can reduce risk of nasopharyngeal carcinoma, and it may be an independent protection factor in sporadic nasopharyngeal carcinoma.
Carcinoma ; Genetic Predisposition to Disease ; Genotype ; Heterozygote ; Humans ; MAP Kinase Kinase 4 ; genetics ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; genetics ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Promoter Regions, Genetic

Objective:Discussion MKK4 protein expression in nasopharyngeal carcinoma and -1044 A/T polymorphism correlation.Methods:90 patients with nasopharyngeal carcinoma , MKK4 protein expression was determined by immunohistochemical staining,polymerase chain reaction-restriction fragment length polymorphism ( PCR-RFLP ) to detect the gene -1044A/T sites monocytes nucleotide polymorphism.Results:MKK4 protein expression in nasopharyngeal carcinoma (-) was 24.4%(22/90),(+) was 15.6%(14/90),(++) was 34.4%(31/90),(+++) was 25.6% (23/90).Low expression (-/+) patients with a total of 36 cases,-1044AA genotype accounted for 22 cases (61.11%),AT genotype accounted for 12 cases (33.33%),TT genotype accounted for two cases (5.56%),AT+TT gene type accounted for 14 cases (38.89%).The patients with high MKK4 expression of 54 cases,of which accounted for 38 cases of AA genotype (70.37%),AT genotype accounted with 15 cases (27.78%),TT genotype accounted for one case (1.85%),AT +TT genotype accounted for 16 cases (29.63%).Low expression and high expression of T gene mutation occurs no significant ( Z=0.323 , P=0.747 ) .Conclusion: MKK4 protein expression correlated with -1044 A/T gene promoter polymorphisms was no significant correlation .

Objective To translate and revise the Atrial Fibrillation-Quality of Life -18 (AF-QoL-18),and to test its reliability and validity. Methods The Chinese version of AF-QoL-18 was developed through the process of translation, back- translation, cultural adaptation, and preliminary experiment. A total of 187 atrial fibrillation (AF) patients in eight hospitals in Jiangsu province were investigated using the Chinese version to test the reliability and validity. Results Exploratory factor analysis identified three factors, including physiological, psychological and sexual dimensions, which could explain 65.055%of the total variance. The content validity index was 0.969. The Cronbach α coefficient was 0.915 and the retest reliability was 0.948 for the total scale. Conclusions The Chinese version AF-QoL-18 has proved to be reliable and valid.It can be used to measure the quality of life of AF patients in China.

Objective To analyze relation of comprehensive parameters of the dose-volume V5,V10 and V20 with radiation pneumonitis (RP) in patients with advanced stage non-small-cell lung cancer (NSCLC) treated with three-dimensional conformal (3DCRT) or intensity-modulated radiation therapy (IMRT).Methods Data of 90 patients with histologically proved NSCLC treated with 3DCRT or IMRT between November 2006 and July 2009 were collected.The median radiation dose of 70 Gy (range, 61 - 80 Gy) was delivered with late-course accelerated hyperfractionated radiotherapy (LAHRT).The V5 ,V10 ,V20,V30 and mean lung dose (MLD) were calculated from the dose-volume histogram system.The RP was evaluated according to the common toxicity criteria 3.0(CTC 3.0).Results The range of V5 ,V10 and V20 was 36% - 98%, 27% - 78% and 19% - 54%, respectively, with a median value of 66%, 48% and 31%, respectively.The RP of grade 1,2,3,4 and 5 was observed in 29,23,5,1 and 1 patients.The V5,V10 ,V20, contralateral V10, GTV,PTV, and numbers of fields were all significantly associated with RP of ≥grade 1 (χ2=2.04, 2.05, 2.01, 4.62, 6.50, 5.61, 5.61, and P= 0.044, 0.043, 0.047, 0.030,0.010,0.020,0.020).The V5, V10, V20, V30, and MLD were all significantly associated with RP of ≥ grade 2 (χ2= 2.05,2.20,2.96,4.96,5.20, and P = 0.040,0.030,0.000,0.030,0.020).In Logistic regression analysis, GTV was the only factor significantly associated with RP of ≥ grade 1 (χ2= 4.06, P =0.044).The V20 was the only factor significantly associated with RP of ≥grade 2(χ2=9.61,P=0.002).The RP of ≥grade 2 was significantly increased when V20 was more than 31%.The RP of ≥grade 2 was significantly increased when V20, V10 and V5 were more than 31%, 48% and 66%, respectively.The RP of ≥ grade 2 was significantly increased when V20 was more than 31% and V5 was more than 66%.Conclusions The comprehensive parameters combined with V5, V10 and V20 are effective in predicting RP.

Objective To analyze the low dose-volume associated with radiation-induced lung injury (RILI) in patients with advanced non-small cell lung cancer (NSCLC) treated by three-dimensional confor-real radiation therapy (3DCRT). Methods Data of 100 patients with histologically proved NSCLC treated with 3DCRT or IMRT between November 2006 and January 2009 were collected. Nine patients treated with radiotherapy alone and 91 with radiotherapy combined with chemotherapy. A median dose of 70 Gy (range,60-80 Gy) was delivered with late-course accelerated hyperfractionated radiotherapy (LAHRT). Twenty-four patients received dose of 61-69 Gy and 76 received more than 70 Gy. The V_5 ,V_(10) ,V_(20) ,V_(30)and mean lung dose (MLD) were calculated from the dose volume histogram system. The RILI was evaluated according to Common Toxicity Criteria 3.0(CTC 3.0). Results The range of V_5 ,V_(10) ,V_(20) ,V_(30) was 37%-98%,27%-78%, 17%-54% and 9%-31%, respectively, with a median value of 65%, 47.5%, 31% and 24%, respectively. The acute RILI of grade 1, 2, 3, 4 and 5 was observed in 34, 27, 8, 1 and 1 patients,respectively. The chronic RILI of grade 1, 2 and 3 was observed in 46, 14 and 2 patients, respectively. V_5 ,V_(10) ,V_(20) and MLD were significantly correlated with acute RILI of ≥ grade 1. V_5 ,V_(20) ,V_(30) and MLD were significantly correlated with acute RILI of ≥ grade 2. The acute RILI of ≥ grade 2 was significantly in-creased when V_5, V_(20) and V_(30) were more than 65%, 31% and 24%, respectively. The acute RILI of ≥ grade 3 was significantly increased when V_5 was more than 65%. The acute RILI of ≥ grade 1 was signifi-candy increased when V_(20)was more than 31%. The gross tumor volume and planning target volume were sig-nificantly correlated with the acute RILI of ≥ grade 1 and chronic RILI of ≥ grade 2. Conclusions The dose-volume V_5 and V_(10) are effective in predicting RILI.

Objective:To investigate the effects of repetitive transcranial magnetic stimulation combined with paroxetine hydrochloride on executive function in depressed adolescents with non-suicidal self-injury.Methods:The clinical data of 120 depressed adolescents with depressive disorders who were admitted to The Second Hospital of Jinhua from August 2021 to July 2022 were retrospectively analyzed. They were randomly assigned to undergo treatment either with paroxetine hydrochloride (control group, n = 60) or repetitive transcranial magnetic stimulation combined with paroxetine hydrochloride (observation group, n = 60). All patients were treated for 2 months. Hamilton Depression Rating Scale-24 (HAMD-24) score, Non-suicidal Self-injury Behavior and Function Scale for Adolescents (ANSSIQ) score, executive function, brain-derived neurotrophic factor, 5-hydroxytryptamine, and clinical efficacy were determined in each group. Results:After treatment, the Hamilton Depression Rating Scale-24 score in the observation group was significantly lower than that in the control group [(15.85 ± 1.08) points) vs. (18.72±1.21) points, t = 13.71, P < 0.001). After treatment, the number of self-injury attacks, number of self-injury impulsions, and the intensity of self-injury thought within 2 weeks in the observation group were significantly lower than those in the control group ( t = 3.42, 3.03, 1.92, all P < 0.05). The scores of the Trail Making Test, Stroop Word test, Stroop Color test, and Stroop Color-Word Interference Test were significantly higher in the observation group than those in the control group ( t = 2.66, 3.33, 3.97, 4.64, all P < 0.01). Brain-derived neurotrophic factor and 5-hydroxytryptamine levels in the observation group were (11.45 ± 1.79) μg/L and (136.68 ± 11.90) μg/L, respectively, which were significantly higher than (9.06±2.21) μg/L and (124.82 ± 10.34) μg/L in the control group ( t = 6.51, 5.83, both P < 0.001). The total response rate in the observation group was significantly higher than that in the control group (91.7% vs. 78.3%, Z = 2.73, P = 0.006). Conclusion:Repetitive transcranial magnetic stimulation combined with paroxetine hydrochloride is highly effective on depressive disorders in adolescents with non-suicidal self-injury. The combined therapy can reduce symptoms, improve executive function and cognitive function, and optimize serological indicators, and thereby deserves the clinical promotion.

Objective:To investigate the clinical efficacy of multi-point acupuncture and lavage on removing facial filling material.Methods:From May 2015 to May 2020, the Department of Plastic Surgery of Tianjin Time Plastic Aesthetic Clinic removed the filling materials from 38 patients (4 males, 34 females; 19-55 years, with average 28 years). During the operation, multi-point acupuncture were performed with an 18G needle to perforate different cavities of the fillers to press them out; with injection syringe flushing fluid was injected with a needle into the filling material area with repeated lavage through puncture points.Results:On average, 90% of the filling materials were recovered by this method, 5 cases were removed twice; follow-up for 6-12 months after operation showed that postoperative appearance was natural, and no scar and hyperpigmentation occurred; there were no cases of postoperative infection with ideal effects.Conclusions:Multi-point acupuncture and lavage treatment can remove more facial filling material; although there is also small amount of filling material left, it is not affect clinical efficacy. This method basically does not damage the surrounding normal tissue, and therefore it is worthy of clinical application.

Objective:To study the clinical characteristics and prognosis of Brucella and other pathogens infections complicated with anti-myelin oligodendrocyte glycoprotein-IgG associated disorders (MOGAD). Methods:The clinical data of a patient with brucellosis complicated with MOGAD diagnosed in the Department of Neurology of the First Affiliated Hospital of Zhengzhou University in April 2022 were reported, and related case reports of infection coexisting with MOGAD were reviewed and summarized.Results:This case was a 44-year-old male, with recurrent fever and anorexia, followed by sudden weakness, numbness, pain in both lower limbs and dysuria, and then pain in the right neck. Magnetic resonance imaging showed lesions in the spine and spinal cord. Due to the positive myelin oligodendrocyte glycoprotein antibodies in cerebrospinal fluid and serum, and the growth of Brucella in blood culture, he was diagnosed as brucellosis complicated with MOGAD. After anti-brucellosis and glucocorticoid therapy, his symptoms improved. The literature on infection coexisting with MOGAD was reviewed and 22 cases were included. The infection sources included COVID-19, Borrelia burgdorferi, etc. No case of Brucella infection complicated with MOGAD had been reported. The main clinical manifestations of the 22 cases included myelitis (63.6%, 14/22), optic neuritis (40.9%, 9/22), acute disseminated encephalomyelitis (18.2%, 4/22), multiphasic disseminated encephalomyelitis (4.5%, 1/22) and meningoencephalitis (4.5%, 1/22). Magnetic resonance imaging was performed in 20 cases, showing spinal cord lesions in 12 cases (60.0%, 12/20), intracranial lesions in 10 cases (50.0%, 10/20) and optic nerve lesions in 6 cases (30.0%, 6/20). Cerebrospinal fluid examination was performed in 19 patients, of whom 13 (13/19) had increased cerebrospinal fluid cell count and 10 (10/18) had increased cerebrospinal fluid protein. Twenty-two patients received glucocorticoid therapy, of which 95.5% (21/22) responded well and 95.5% (21/22) had a good prognosis. Conclusions:Brucella and other pathogens infection may complicate with MOGAD, with similar clinical manifestations, and glucocorticoid therapy is effective.

In recent years， adaptive design has gradually emerged in clinical trials， gaining widespread application and expansion. Compared with traditional randomized controlled trials， appropriate adaptive design can save time and resources to some extent， improve the validity of the trial results and strength of the evidence， align better with ethical requirements， and facilitate subsequent drug market research. However， due to the greater flexibility of adaptive design， controlling type Ⅰ error rates and truly enhancing research efficiency are challenging aspects of its application. Therefore， the normative application and optimization of adaptive design in research deserve early focus， including adhering to good adaptive design principles， conducting rigorous pre-design planning， scientifically applying various statistical methods such as Bayesian dynamic models and simulation methods， and utilizing monitoring tools like monitoring committees to ensure the scientific integrity of the research process. Moreover， the flexibility of adaptive design aligns well with the practical realities of traditional Chinese medicine （TCM） clinical practice. The main characteristics of TCM， such as the holistic concept and treatment based on syndrome differentiation， determine that TCM provides a dynamic and personalized treatment plan. In contrast， the traditional fixed development approach of western medicine limits the application of "human experience" in TCM. To address this bottleneck in TCM research and development， the innovative use of adaptive design， a modern scientific theory and methodology with multiplicity and variability， offers a feasible new approach for TCM clinical research and the innovation of Chinese herbal medicine. By learning from successful cases such as the first Food and Drug Administration （FDA）-approved oral botanical drug， Crofelemer， researchers can explore optimal solutions for adaptive design in clinical research protocols and its role in the "three-combination" evaluation system for Chinese herbal medicines， further refine trial design， clarify key trial points， and develop innovative research and development applications that adapt to the clinical positioning of TCM and highlight the characteristics and advantages of TCM， paving the way for the clinical efficacy， pharmacological mechanism exploration， and post-market efficacy evaluation of Chinese herbal compounds.