Objective:To construct the intracranial venous sinus thrombosis (CVST) models under plateau hypoxia by simulating plateau hypoxic condition, and further clarify the role of plateau hypoxa in CVST.Methods:Forty-eight 8-week-old male SD rats were randomly divided into sham-operated group, plateau sham-operated group, CVST group, and plateau CVST group ( n=12). CVST models in the CVST group and plateau CVST group were established by ferric chloride wet dressing, and rats in the plateau CVST group were kept in a low-pressure oxygen chamber for 2 d immediately after modeling to simulate plateau hypoxic condition at an altitude of 5,000 m (barometric pressure of 54.047 kPa, oxygen concentration of 10%-11%, and temperature of 18-23 °C). Only the bone flap and dura mater were separated in rats of the sham-operated group, without low-pressure oxygen condition or filter paper dressing. Only the bone flap and dura mater were separated in rats of the plateau sham-operated group, with plateau hypoxic condition at an altitude of 5,000 m for 2 d and without filter paper dressing. Intracranial venous sinus blood flow was detected by Doppler flowmetry before and 48 h after modeling. At 6, 24, and 48 h after modeling, 4 rats in each group were sacrificed; blood vessels at the thrombus of superior sagittal sinus (blood vessels at the superior sagittal sinus in the sham-operated group and plateau sham-operated group) were cut out and weighed; meanwhile, water contents of the brain tissues were calculated. HE staining was employed in the brain, heart, liver, lung, and kidney tissues and veins, and toluidine blue staining was peformed in the brain tissues only at 48 h after modeling. Results:(1) Doppler flowmetry indicated that intracranial venous sinus blood flow was normal in the 4 groups before modeling; intracranial venous sinus blood flow signals were normal in the sham-operated group and plateau sham-operated group and obviously weakened in the CVST group and plateau CVST group 48 h after modeling. (2) No thrombus was formed in the sham-operated group 48 h after modeling. At 6, 24 and 48 h after modeling, the thrombus in the CVST group ([15.44±1.90] mg, [12.63±1.26] mg, and [7.85±0.68] mg) and plateau CVST group ([20.38±1.67] mg, [24.93±2.37] mg, and [20.90±1.30] mg) weighted significantly heavier than those in the plateau sham-operated group ([2.55±0.38] mg, [2.19±0.30] mg, [1.75±0.31] mg), and that in the plateau CVST group weighted significantly heavier than that in the CVST group ( P<0.05); the thrombus weight in both plateau sham-operated group and CVST group decreased sequentially at 6, 24 and 48 h after modeling, with significant differences ( P<0.05); whereas, the thrombus weight in the plateau CVST group at 24 h after modeling increased compared with that at 6 h after modeling, and that at 48 h after modeling decreased compared with that at 24 h after modeling, with significant differences ( P<0.05). (3) At 6 h after modeling, the brain water contents in the sham-operated group, plateau sham-operated group, CVST group and plateau CVST group were (77.56±0.52)%, (77.57±0.92)%, (78.91±0.53)%, and (78.90±0.63)%, respectively, with statistical differences ( P<0.05); the CVST group and plateau CVST group had increased water content compared with the sham-operated group and plateau sham-operated group without significant differences ( P>0.05). At 24 and 48 h after modeling, the brain water content among the 4 groups was not statistically different ( P>0.05). (4) HE staining and toluidine blue staining indicated limited infarction, neuronal edema, and necrotic apoptosis in the brain tissues of plateau CVST group at 24 h after modeling. HE staining showed no obvious pathological changes in the myocardium, liver, lung, or kidney tissues in the 4 groups. Conclusion:CVST models can be successfully established by simulating plateau hypoxic condition through ferric chloride wet dressing and feeding in low-pressure oxygen chamber.

Objective:To investigate the influence of Kruppel-like factor 16 (KLF16) on the proliferation and migration of pancreatic cancer cells.Methods:Immunohistochemical images of KLF16 were collected from 171 pancreatic cancer tissues and their matched paracarcinoma normal pancreas tissues and 8 pancreatic cancer tissues only in GEPIA database. The expression of KLF16 protein was detected by immunohistochemical imaging software. The protein and mRNA expressions of pancreatic cancer cell lines AsPC-1 and MIA PaCa-2 KLF16 were detected by Western blot and quantitative fluorescence PCR. By knockdown or exogenous overexpression of KLF16, the two cells were divided into blank control group (NC group), negative control group (siRNA-NC group), downexpression KLF16 group (siKLF16 group), overexpression control group (OE-NC group) and ovexpression KLF16-OE group (KLF16-OE group). CCK-8 assay, colony formation assay and transwell chamber were used to detect cell proliferation and migration.Results:The KLF16 protein expression level (4.02±1.26 vs 1.73±1.07) and positive expression rate (91.6% vs 13.5%) in pancreatic cancer tissues were significantly higher than those in paracancer normal pancreas tissues, with statistical significance ( P<0.05). After downregulating KLF16 expression and culturing for 24, 48, 72, and 96 hours, the A450 values of both AsPC-1 (0.19±0.02 vs 0.23±0.03, 0.24±0.06 vs 0.36±0.06, 0.45±0.09 vs 0.78±0.10, 0.69±0.04 vs 0.88±0.07) and MIA PaCa-2 cells (0.20±0.03 vs 0.22±0.02, 0.29±0.05 vs 0.31±0.04, 0.47±0.06 vs 0.78±0.10, 0.71±0.02 vs 0.90±0.07) and colony counts [(36±4.32) per well vs (118.51±10.01) per well, (13.6±2.62) per well vs (83.1±9.11) per well], and the number of migrated cells [(16.67±2.05) vs (46.67±5.91), (19.67±1.69) vs (55±4.89)] all decreased significantly. However, after up-regulating the expression of KLF16 and culturing for 24, 48, 72 and 96 h, the A450 value of both AsPC-1 (0.21±0.05 vs 0.20±0.04, 0.48±0.03 vs 0.31±0.04, 0.91±0.09 vs 0.72±0.03, 1.28±0.10 vs 1.05±0.02) and MIA PaCa-2 cells (0.20±0.01 vs 0.19±0.05, 0.44±0.03 vs 0.30±0.04, 0.89±0.06 vs 0.72±0.03, 1.19±0.05 vs 1.01±0.10), and the number of cell colonies [(189±6.37)/per hole vs (108±9.62)/ per hole, (141±12.56)/ per hole vs (80.69±10.32)/ per hole]], migration cell numbers [(79±4.89) per hole vs (50.33±4.11) per hole, (79.66±3.85) per hole vs (51±4.08) per hole] all increased significantly. Conclusions:KLF16 is highly expressed in pancreatic cancer. The up-regulated expression of KLF16 in pancreatic cancer cell lines can promote the proliferation and migration of pancreatic cancer cells.

Purpose: This study aims to explore whether neoadjuvant chemotherapy with immunotherapy (NACI) leads to different tumor shrinkage patterns, based on magnetic resonance imaging (MRI), compared to neoadjuvant chemotherapy (NAC) alone in patients with triple-negative breast cancer (TNBC). Additionally, the study investigates the relationship between tumor shrinkage patterns and treatment efficacy was investigated. Methods: This retrospective study included patients with TNBC patients receiving NAC or NACI from January 2019 until July 2021 at our center. Pre- and post-treatment MRI results were obtained for each patient, and tumor shrinkage patterns were classified into three categories as follows: 1) concentric shrinkage (CS); 2) diffuse decrease; and 3) no change.Tumor shrinkage patterns were compared between the NAC and NACI groups, and the relevance of the patterns to treatment efficacy was assessed. Results: Of the 99 patients, 65 received NAC and 34 received NACI. The CS pattern was observed in 53% and 20% of patients in the NAC and NACI groups, respectively. Diffuse decrease pattern was observed in 36% and 68% of patients in the NAC and NACI groups. The association between the treatment regimens (NAC and NACI) and tumor shrinkage patterns was statistically significant (p = 0.004). The postoperative pathological complete response (pCR) rate was 45% and 82% in the NAC and NACI groups (p < 0.001), respectively. In the NACI group, 17% of patients with the CS pattern and 56% of those with the diffuse decrease pattern achieved pCR (p = 0.903). All tumor shrinkage patterns were associated with achieved a high pCR rate in the NACI group. Conclusion Our study demonstrates that the diffuse decrease pattern of tumor shrinkage is more common following NACI than that following NAC. Furthermore, our findings suggest that all tumor shrinkage patterns are associated with a high pCR rate in patients with TNBC treated with NACI.

Objective:To explore the risk factors and prognosis of lymph node metastasis and residual cancer following additional surgery after endoscopic submucosal dissection (ESD) in early gastric cancer (EGC).Methods:Retrospective analysis was performed on the data of 42 patients with EGC who received additional surgery after ESD in General Surgery Department of Beijing Friendship Hospital, Capital Medical University from August 2012 to August 2019, including 35 males and 7 females, with a male to female ratio of 5∶1 and an average age of 62 (32 to 82 years old). The primary outcomes were lymph node metastasis risk and residual cancer risk, while the secondary outcomes were 3-year and 5-year overall survival. Logistic regression model was used to analyze the risk factors of lymph node metastasis and residual cancer, and Kaplan-Meier survival analysis was performed.Results:Multivariate analysis showed that gender ( OR: 45.3, 95% CI: 3.762-546.250, P=0.003), invasion depth ( OR: 3.965, 95% CI: 1.1019-15.432, P=0.047) and histological type ( OR: 9.455, 95% CI: 0.946-94.482, P=0.049) were independent risk factors for lymph node metastasis of early gastric cancer. The type of tumor invasion ( OR: 10.675, 95% CI: 1.840-61.932, P=0.008) and the horizontal resection margin ( OR: 9.341, 95% CI: 1.47-59.346, P=0.018) were independent risk factors affecting the occurrence of residual cancer. Stratified analysis showed that in men, the tumor invaded to T 1b-SM1, and the pathological type was undifferentiated; and in women, the tumor invaded to T 1b-SM2, regardless of the pathological type, lymph node metastasis occurred. When the horizontal margin was positive, regardless of the infiltration pattern; and the infiltration pattern is INF-c, regardless of the horizontal margin, residual cancer occurred. Survival analysis showed that the 3-year (100% vs 60%, P< 0.001) and 5-year overall survival rate (100% vs 25%, P< 0.001) were better than those with lymph node metastasis.The 3-year (100% vs 80%) and 5-year overall survival rates (100% vs 62.5%) of patients without residual cancer were significantly better than those with residual cancer, with statistically significant differences ( P<0.001). Conclusions:Gender, invasion depth and histological type are independent risk factors for lymph node metastasis of early gastric cancer, and tumor invasion form and horizontal incision margin are independent risk factors for the appearance of residual cancer. The long-term survival rate of patients with early gastric cancer without lymph node metastasis and residual cancer was significantly better than that of patients with lymph node metastasis and residual cancer. Therefore, ESD is one of the safe and effective treatment methods for patients with early gastric cancer, but some patients need additional surgery according to the specific situation in order to improve the prognosis.

OBJECTIVE: To explore the genetic basis of a patient with early-onset Parkinson disease from a consanguineous family. METHODS: Homozygosity mapping and Sanger sequencing of cDNA were used to identify the causative mutation. RESULTS: A homozygous missense variation (c.56C>G, p.Thr19Arg) in the PARK7 gene was identified in the patient. In silico analysis suggested the c.56C>G variation to be pathogenic. CONCLUSION Homozygous c.56C>G variation of the PARK7 gene was the disease-causing variation in this family.
Consanguinity ; Homozygote ; Humans ; Mutation, Missense ; Parkinson Disease ; genetics ; Pedigree ; Protein Deglycase DJ-1 ; genetics

Objective: To explore the genetic basis for a pedigree affected with X-linked adrenoleukodystrophy presenting as spastic paraplegia of the lower limbs. Methods: Genomic DNA was extracted from peripheral blood samples of the patient and his mother. Potential variant was detected with a panel for genes associated with spastic paraplegia. Candidate variant was verified by PCR and Sanger sequencing. Results: Both the proband and his mother presented with walking difficulty. A previously known variant, c. 623T>A (p.V208E), was identified in the ABCD1 gene mapped on chromosome X in both. Conclusion X-link adrenoleukodystrophy should be taken into account as a possible diagnosis for this pedigree.

Objective: To explore the genetic basis of a patient with early-onset Parkinson disease from a consanguineous family. Methods: Homozygosity mapping and Sanger sequencing of cDNA were used to identify the causative mutation. Results: A homozygous missense variation (c.56C>G, p. Thr19Arg) in the PARK7 gene was identified in the patient. In silico analysis suggested the c. 56C>G variation to be pathogenic. Conclusion Homozygous c. 56C>G variation of the PARK7 gene was the disease-causing variation in this family.

No abstract available.
Asian Continental Ancestry Group ; Humans ; Spastic Paraplegia, Hereditary

Objective　To establish Huashan diagnostic criteria and clinical classification system for Hirayama disease.Methods　Retrospective analysis 359 cases of puberty onset,upper extremity muscle atrophy as main clinical manifestations,and complete clinical data from September 2007 to August 2018.There were 348 males and 11 females(31.6:1 male and female)in this group.The average age of onset was 16.7±2.2 years,the average age of visits was 19.2±4.5 years,and the average duration of treatment was 29.3±45.4 months.Descriptive study of the clinical manifestations,radiologic and neurophysiological findings of this group of patients,the Huashan clinical diagnostic criteria of Hirayama disease were established by including 100% of the clinical manifestations,imaging and neurophysiological findings.According to the following parameters,the clinical classification system of Hirayama disease was proposed.The parameters specifically included:the muscle atrophy involves the upper limbs,whether the quadriplegia was active or hyperactive,the Babinski sign positive and other pyramidal tract damage,whether it was accompanied by sensory dysfunction such as upper limb numbness,muscle atrophy location,and the progress of clinical symptoms or electrophysiological examination within 6 months.Thirty patients were randomly selected from the above 359 cases.Four orthopedic surgeons who were not involved in the classification system completed the clinical classification within the specified time.The Kappa value was used for the credibility evaluation.Results　The Huashan diagnostic criteria of Hirayama disease included clinical manifestations,imaging examinations and neurophysiological examinations.The main diagnostic indicators were:1)occult onset puberty,more common in men;2)localized muscle atrophy and weakness in the upper extremities;3)compared with the cervical neutral MRI,the MRI of cervical flexion showed that spinal cord was significantly shift forward and the anterior spinal cord was narrowed or disappeared.4)MRI T2 weighting of the cervical flexion showed cyst-wall separation behind the spinal cord;5)Neurophysiological examination showed that the affected muscles were neurogenic damage.6)The affected parts are limited to the middle and lower neck segment.At the same time,it was necessary to combine imaging and neurophysiological manifestations to distinguish cervical spondylosis with upper limb muscle atrophy and motor neuron disease.According to the clinical characteristics of different patients,Hirayama disease can be divided into type I-III.Type I:72.1%,one-sided upper limb or one upper limb-based hand inner muscle and forearm muscle atrophy.According to whether progress of symptoms or electrophysiological examination was seen in the past 6 months,type I can be divided into:Ia.stable period.Regular follow-up assessment was recommended.If the disease progressed,to wear a cervical collar was suggested;surgery could be done if necessary;Ib.progression period,it was recommended to use a cervical collar,and regularly evaluate,if patients could not wear cervical collar for long,it was recommended to operate.Type II:14.2%,unilateral upper limb or one upper limb-based hand inner muscle and forearm muscle atrophy with pyramidal tract injury.Surgery was recommended.Type II:13.7%,atypical Hirayama disease,including upper limb proximal muscle atrophy,symmetrical double upper limb muscle atrophy,and sensory disturbances associated with upper limb numbness.Wear a cervical collar,and follow-up and assess closely,and choose surgical treatment if necessary.The credibility evaluation showed that the average Kappa value of the classification was 0.732(0.688-0.834),which is a basic credibility.Conclusion　The Huashan diagnostic criteria of Hirayama disease was conducive to the early diagnosis.The clinical classification system of Hirayama disease has good credibility and good clinical intervention guidance value.

Objective　To investigate the impact of the loss of attachment on the outcomes in Hirayama disease(HD)patients treated with anterior cervical discectomy and fusion(ACDF).Methods　A total of 26 patients(23 males and 3 females)who were diagnosed as HD and received 2 levels of ACDF surgery from February 2014 to November 2016 were enrolled in the present study.All patients took the MRI at both flexion and neutral position pre-operation and MRI at flexion position post-operation.The measured parameters related to performance of "loss of attachment" include:the distances between the posterior edge of the spinal cord and the cervical spinal canal(x),the anterior and posterior wall of the cervical spinal canal(y),the anterior-posterior(a)and the transverse diameter(b)of spinal cord cross sections.The value of the cervical spinal cord deformation(flexion position a/b)and the cervical spinal cord forward movement(flexion position x/y-neutral position x/y)were calculated,and the centrums refer to the performance of "loss of attachment" were also recorded.DASH scores and grip strength on both sides were recorded before and 1 year after operation.The 26 patients were divided into two groups,17 patients(17/26,65.4%)in improvement group with the decreased DASH scores and the other 9 patients(9/26,34.6%)in no improvement group.Logistic regression and ROC curve were used to analyze the influence factor of anterior cervical discectomy and fusion(ACDF)surgery on patients with Hirayama disease.Results　After surgery,the value of a/b significantly increased(t=4.27,P=0.001)and x/y significantly decreased(t=10.25,P=0.001).The performance of "loss of attachment" in 88.5%(23 of 26)patients disappeared after surgery,while the DASH score(P=0.06),and the grip strength of severe and mild side(P=0.36 and P=0.42)shew no obvious change.65.4%(17 of 26)patients shew a decrease in DASH scores after operation,the remaining 34.6%(9 of 26)patients shew no obvious change,several even with a mild increase.The segments refer to performance of "loss of attachment",the value of the cervical spinal cord de-formation and the cervical spinal cord forward movement shew a difference between the two group(t=-5.56,P=0.001;t=3.06,P=0.005;t=-3.76,P=0.001).The logistics regression analysis with the above three independent variable confirmed that the value of segments that refer to "loss of attachment" was the factor of the post-operative efficacy of ACDF surgery on patients with Hirayama disease(OR=6.963,P=0.001).And the ROC curve shew AUC=0.902,Jordan index=0.83,critical value=4.5.Conclusion　The anterior cervical discectomy and fusion(ACDF)surgery can effectively improve the loss of attachment at the surgical segments,and prevent the progress of upper limb dyskinesia.And range of the longitudinal separation refers to "loss of attachment" can impact the outcomes of ACDF surgery,more segments for fusion may be need in order to improve the outcomes of those patients with the range more than 5 segments.