【Objective】 To explore the causal association between the onset of gastroesophageal reflux disease (GERD) and migraine and to provide genetic evidence, a two-sample bidirectional Mendelian randomization (MR) method was used in this study. 【Methods】 Single nucleotide polymorphism (SNP) information for both samples was obtained from publicly available genome-wide association study (GWAS) databases, in which the appropriate SNPs were selected as instrumental variables, and then bidirectional MR analysis used five MR analysis methods including inverse variance weighting (IVW), MR-Egger regression, weighted median, weighted mode and simple mode methods, followed by sensitivity analysis. 【Results】 IVW showed positive results of forward MR analysis with GERD as exposure [OR=1.398 7, 95%CI (1.181 7-1.655 6), P=9.59×10^-5] , while no positive significance of reverse MR analysis results with migraine as exposure (P>0.05). The same results were obtained in methods other than MR-Egger method. Meanwhile, none of the instrumental variables were found to be horizontally polytomous (P=0.92, P=0.64), and the results were robust after the leave-one-out method to exclude single SNPs. 【Conclusion】 There may be a unidirectional causal association between GERD and migraine, and GERD is a risk factor for migraine development.

Objective To investigate the liver disease phenotypes and clinical features of patients with different genotypes of Wilson's disease(WD).Methods A retrospective analysis was performed for 163 patients with WD who were diagnosed and underwent genetic testing in The Fifth Medical Center of Chinese PLA General Hospital from August 2008 to June 2023,and clinical manifestations,laboratory examination,pathological examination,imaging examination,and ATP7B genetic testing results were collected.According to ATP7B gene mutation,the patients were divided into groups as follows:R778L mutation group and non-R778L mutation group;P992L mutation group and non-P992L mutation group;truncation mutation group and non-truncation mutation group.Liver disease phenotypes and clinical features were analyzed for the patients with c.2333G>T/p.R778L mutation(R778L mutation),c.2975C>T/p.P992L mutation(P992L mutation),and truncation mutation of the ATP7B gene.The Mann-Whitney U test or the Kruskal-Wallis H test was used for comparison of continuous data between groups,and the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.Results The 163 patients with WD had varying severities of liver disease phenotypes,among whom 121(74.23%)were diagnosed with chronic liver disease,36(22.09%)were diagnosed with decompensated cirrhosis,and 6(3.68%)were diagnosed with fulminant WD,and in addition,there were 5 patients(2 with chronic liver disease and 3 with decompensated cirrhosis)with neurological abnormalities.For the 163 patients with WD,R778L mutation(with an allele frequency of 28.2%)was the most common mutation in the ATP7B gene,followed by P992L mutation(with an allele frequency of 12.6%),and truncation mutation showed an allele frequency of 11.0%.There was no significant difference in the distribution of the three mutations across different liver disease phenotypes(P>0.05).The R778L mutation group had a significantly lower level of ceruloplasmin(CP)than the non-R778L mutation group[0.04(0.02-0.08)g/L vs 0.08(0.03-0.13)g/L,Z=-2.889,P=0.004].Compared with the non-P992L mutation group,the P992L mutation group had significantly higher levels of alanine aminotransferase[135.0(80.5-237.0)U/L vs 80.5(36.0-173.3)U/L,Z=2.684,P=0.007]and aspartate aminotransferase[121.4(77.0-195.0)U/L vs 84.0(39.0-123.3)U/L,Z=3.388,P<0.001].Compared with the non-truncation mutation group,the truncation mutation group had significantly lower levels of CP[0.03(0.02-0.08)g/L vs 0.06(0.03-0.11)g/L,Z=-3.136,P=0.002]and serum copper[3.20(2.15-5.00)mg/L vs 4.20(2.60-7.50)mg/L,Z=-2.296,P=0.025].Conclusion R778L mutation,P992L mutation and truncation mutation are not associated with liver disease phenotype in WD patients;however,R778L mutation is associated with a lower level of CP,P992L mutation is associated with higher levels of ALT and AST,and truncation mutation is associated with lower levels of CP and serum copper.

Objective To investigate ecological isolation between Oncomelania hupensis snail populations in hilly regions and marshland and lake regions in Yuanjiang valley, Changde City, Hunan Province, and to unravel its underlying mechanisms. Methods Taoyuan County, Shimen County, Linli County and Lixian County in Changde City were selected as snail sampling sites in hilly regions, and Lixian County, Jinshi City, West Lake Administration District, Hanshou County and Dingcheng District were selected as snail sampling sites in marshland and lake areas. Cytochrome C oxidase 1 (cox 1) gene was amplified in snail samples and sequenced. The genetic sequences of O. hupensis snails were aligned using the software MEGA 11, and the haplotypes of O. hupensis snails were determined using the software DNASP 5.10.01. The phylogenetic tree was generated using Bayesian inference with the software MrBayes 3.2, and analysis of molecular variance (AMOVA) was performed to analyze the source of genetic divergence and estimate the genetic divergence index (F_ST) among snail populations with the software Arlequin 3.5.2.2. The genetic barrier among 11 O. hupensis snail populations was estimated using the Monmonier algorithm of adegenet toolkit in R package. The settings with “land in winter and water in summer” in the Yuanjian River section were divided into two categories according to the upstream and downstream, and the areas with “land in winter and water in summer” in the upstream and downstream were transformed into raster data, and then loaded into the software Fragstats 4 for analysis of landscape indicators. The trends in changes of digital elevation were extracted from the Yuanjiang River section based on the digital elevation model, and made three-dimensional visualization using the R package. Results The mitochondrial cox 1 gene were amplified in 165 O. hupensis snais from 11 sampling sites and sequenced, and a total of 152 valid gene sequences were obtained, with 46 haplotypes or 9 populations determined. No haplotype was shared in snails between Taoyuan County and Dingcheng District and Hanshou County along the downstream of the Yuanjiang River. The total area of settings with “land in winter and water in summer” was 617.66 hm² in the upsteram of the Yuanjiang River, which consisted of 473 patches, with each patch measuring 1.31 hm², the largest area index of 0.735 2, the landscape division index of 0.999 9, and the landscape shape index of 45.293 7. The total area of settings with “land in winter and water in summer” was 9 956.92 hm² in the downstream of the Yuanjiang River, which consisted of 771 patches, with each patch measuring 12.91 hm², the largest area index of 97.839 9, the landscape division index of 0.042 7, and the landscape shape index of 7.249 6. The area of settings with “land in winter and water in summer” was much larger in the downstream than that in the upstream of the Yuanjiang River, and the stronger landscape connectivity and non-remarkable alteration of riverbed elevation provided suitable habitats for snail breeding. Conclusion The hydrological and environmental characteristics of the upstream of the Yuanjiang River restrain the breeding and spread of O. hupensis, resulting in ecological isolation between Oncomelania hupensis in Taoyuan County and those in the downstream of Yuanjiang River.

As an important part of tumor microenvironment, neutrophils are poorly understood due to their spatiotemporal heterogeneity in tumorigenesis. Here we defined, at single-cell resolution, CD44-CXCR2- neutrophils as tumor-specific neutrophils (tsNeus) in both mouse and human gastric cancer (GC). We uncovered a Hippo regulon in neutrophils with unique YAP signature genes (e.g., ICAM1, CD14, EGR1) distinct from those identified in epithelial and/or cancer cells. Importantly, knockout of YAP/TAZ in neutrophils impaired their differentiation into CD54+ tsNeus and reduced their antitumor activity, leading to accelerated GC progression. Moreover, the relative amounts of CD54+ tsNeus were found to be negatively associated with GC progression and positively associated with patient survival. Interestingly, GC patients receiving neoadjuvant chemotherapy had increased numbers of CD54+ tsNeus. Furthermore, pharmacologically enhancing YAP activity selectively activated neutrophils to suppress refractory GC, with no significant inflammation-related side effects. Thus, our work characterized tumor-specific neutrophils in GC and revealed an essential role of YAP/TAZ-CD54 axis in tsNeus, opening a new possibility to develop neutrophil-based antitumor therapeutics.
Humans ; Animals ; Mice ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Stomach Neoplasms/pathology* ; Neutrophils/pathology* ; Signal Transduction/genetics* ; YAP-Signaling Proteins ; Tumor Microenvironment ; Hyaluronan Receptors/genetics*

【Objective】 To explore the surgical characteristics and clinical efficacy of percutaneous endoscopic visualization trephine for thoracic spinal stenosis. 【Methods】 We made a retrospective analysis of 37 patients with single-segment thoracic spinal stenosis treated with percutaneous endoscopic visualization trephine from January 2019 to June 2020. Among them， there were 14 males and 23 females； their age ranged from 31 to 82 years old， with an average of （57.6±11.8） years old. Their posture， length of hospital stay， length of operation and blood loss were recorded. The visual analogue scale （VAS）， Oswestry disability index （ODI） and the modified Japanese Orthopaedic Association （JOA） score were used to evaluate the preoperative and final conditions of patients and calculate the improvement rate. 【Results】 The operation was successfully completed in all the patients， and no patients developed epidural hematoma， incision infection or postoperative paralysis. Among the 37 patients， 24 ones with ossification of ligamentum flavum （OLF） were in the prone position， and 13 patients had lateral surgery. Among them， thoracic disc herniation （TDH） occurred in 3 cases， OPLL in 5 cases and OLF+OPLL in 5 cases. The hospital stay was （7.2±1.6） days， the operation time was （96.5±20.0） min， and the blood loss was （41.9±10.8） mL. VAS score decreased from （7.0±0.9） to （1.9±0.8）； ODI improved from （41.7±2.1） to （16.1±1.7）； and JOA score increased from （5.8±1.4） to （8.6±1.4）. The preoperative and postoperative differences were statistically significant （P<0.05）. 【Conclusion】 Percutaneous endoscopic visualization of thoracic spinal stenosis is treated by choosing different positions according to the type of compression. The spinal canal is fully decompressed. The surgical method is safe and minimally invasive， and the postoperative effect is satisfactory.

Objective:To investigate the clinical effects of robot-assisted minimally invasive percutaneous pedicle screwing in the treatment of multi-segmental thoracolumbar burst fractures without neurological dysfunction.Methods:A retrospective analysis was conducted of the 24 patients who had been treated at Department of Orthopaedics, Hospital Affiliated to Inner Mongolia Medical University for multi-segmental thoracolumbar fractures from January 2019 to December 2020. They were randomly divided into a robot group ( n=12) in which the minimally invasive percutaneous pedicle screwing was assisted by a surgical robot and a manual group ( n=12) in which the minimally invasive percutaneous pedicle screwing was performed manually. There were 8 males and 4 females in the robot group, aged from 35 to 74 years; there were 7 males and 5 females in the manual group, aged from 36 to 69 years. The clinical effects were evaluated by comparing the 2 groups in terms of operation time, fluoroscopy frequency, fluoroscopy time, intra-operative needle adjustments, intra-operative blood loss, screwing accuracy, and visual analogue scale (VAS) scores, anterior vertebral height ratios and sagittal cobb angles at preoperation, postoperative 3 days and the last follow-up. Results:There was no statistically significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). A total of 128 screws were implanted in the robot group and 126 ones in the manual group. In the robotic group, operation time [(129.2±10.5) min], fluoroscopy frequency [(8.5±2.1) times], fluoroscopy time [(9.8±1.9) s], guide needle adjustments [(2.3±1.4) times], and intraoperative blood loss [(65.3±9.8) mL] were significantly less than those in the manual group [(153.8±18.1) min, (39.8±5.1) times, (43.9±4.8) s, (18.6±2.6) times and (96.8±10.9) mL] (all P<0.05). Regarding the screwing accuracy evaluated using CT scanning, the robot group was significantly higher (93.75%, 120/128) than the manual group (84.92%, 107/126) ( P<0.05). There was no significant difference between the 2 groups in VAS score, anterior vertebral height ratio or sagittal cobb angle at postoperative 3 days or the last follow-up ( P>0.05). The VAS scores, anterior vertebral height ratios and sagittal cobb angles at postoperative 3 days and the last follow-up were significantly improved than the preoperative values in all patients ( P<0.05). There was no supplementary surgery or screw loosening in either of the 2 groups. Conclusion:In the treatment of multi-segmental thoracolumbar fractures, robot-assisted percutaneous pedicle screwing can achieve satisfactory clinical effects, because, compared with traditional open surgery, it has exhibited advantages of less operation time, lower radiation exposure, less intraoperative blood loss, and higher screwing accuracy.

To date, there is no report on the genetic diversity of ticks in these regions. A total of 370 representative ticks from the south and east regions of Kazakhstan (SERK) and Xinjiang Uygur Autonomous Region (XUAR) were selected for molecular comparison. A fragment of the mitochondrial cytochrome c oxidase subunit I (cox1) gene, ranging from 631 bp to 889 bp, was used to analyze genetic diversity among these ticks. Phylogenetic analyses indicated 7 tick species including Hyalomma asiaticum, Hyalomma detritum, Hyalomma anatolicum, Dermacentor marginatus, Rhipicephalus sanguineus, Rhipicephalus turanicus and Haemaphysalis erinacei from the SERK clustered together with conspecific ticks from the XUAR. The network diagram of haplotypes showed that i) Hy. asiaticum from Almaty and Kyzylorda Oblasts together with that from Yuli County of XUAR constituted haplogroup H-2, and the lineage from Chimkent City of South Kazakhstan was newly evolved; and ii) the R. turanicus ticks sampled in Israel, Almaty, South Kazakhstan, Usu City, Ulugqat and Baicheng Counties of XUAR were derivated from an old lineage in Alataw City of XUAR. These findings indicate that: i) Hy. asiaticum, R. turanicus and Ha. erinacei shared genetic similarities between the SERK and XUAR; and ii) Hy. marginatum and D. reticulatus show differences in their evolution.

Objective To explore the effects of the interfacial debonding caused by water environment in the mouth and the interfacial defects between the crown and cement on stress distributions in all-ceramic crowns. Methods The three-dimensional solid model of lithium disilicate CAD/CAM crowns for the first mandibular molar was established. Seven debonding states between inferior surface of the crown and top surface of the cement (Stage 1-7) as well as two interfacial defects (Case I and II) were defined in finite element software ABAQUS. The bottom of nine models was completely constrained. For stress calculation, the 600 N vertical load was applied at occlusal surface via an analytical rigid hemisphere with the diameter of 5 mm. Results Under occlusal vertical load, the stress on interior of the crown and top surface of the cement was mainly distributed at the boundary of the debonding areas and margin of the defects. The first principle stress on interior of the crown did not exceed its ultimate tensile strength, but the maximum tensile stress of the cement exceeded its ultimate tensile strength, leading to cohesive failure in the cement. Conclusions The axial wall played a critical role in maintaining the principal tensile stress of the crown at a lower level. The defects at bonding interface between the crown and cement had a more significantly impact on load capacity of the crown than the increase in debonding areas. In order to improve load bearing capacities of all-ceramic crowns, attention should be paid to avoid defects in clinical prosthodontic practices.

Objective: To observe the clinical efficacy and safety of transhepatic arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) in the treatment of colorectal cancer with liver metastasis. Methods: The data of 92 patients with colorectal cancer with liver metastasis admitted to Nanyang First People′s Hospital of Henan Province from January 2014 to January 2016 were retrospectively analyzed. A total of 46 patients treated with TACE were selected as the TACE group, and another 46 patients treated with TACE and RFA were selected as the combined group. The clinical efficacies of the two groups were compared, and the changes of Karnofsky functional status (KPS) scores before and after treatment in the two groups were analyzed. The incidences of complications in the two groups were calculated. Patients in the two groups were followed up, and the progress-free survival (PFS) and overall survival (OS) were calculated. Results: The disease control rate of the combined group was 82.61% (38/46), and that of the TACE group was 63.04% (29/46). The disease control rate of the combined group was higher than that of the TACE group (χ²=4.449, P=0.035). Before treatment, the KPS scores of the combined group and the TACE group were 71.84±4.37, 72.22±4.26, with no statistically significant difference (t=0.423, P=0.673). After treatment, the KPS scores of the two groups were higher than those before treatment, and the KPS score of the combined group was higher than that of the TACE group (79.81±6.15 vs. 75.86±6.02; t=3.108, P=0.003). The incidence of complications was 54.35% (25/46) in the combined group and 41.30% (19/46) in the TACE group. The difference between the two groups was not statistically significant (χ²=1.568, P=0.210). The median PFS and OS in the TACE group were 12.6 and 20.7 months, and those in the combined group were 18.9 and 28.2 months. The PFS and OS of the combined group were longer than those of the TACE group (χ²=72.025, P<0.001; χ²=26.580, P<0.001). Conclusion TACE combined with RFA is effective in the treatment of liver metastasis of colorectal cancer, which can effectively improve the KPS score of patients, prolong the PFS and OS, and do not increase the risk of complications.

Objective To analyze and determine the optimal osseous pathway for anterograde screwing in the acetabulum posterior column.Methods Recruited for this study were 40 healthy adult volunteers,20 nales and 20 females,aged from 18 to 56 years (average,34.6 years).Firstly,their abdomen CT scanning images were transformed into Materialise Mimics Innovation Suite 16.0 software to obtain the 3D reconstruction images of the pelvis (.stl file).The Imageware 12.0 software (EDS,USA) was used to produce the optimal osseous pathway for anterograde screwing in the acetabulum posterior column.The diameter and length of the pathway were measured and statistically analyzed.Secondly,after 10 adult fresh pelvic specimens were scanned,the optimal osseous pathway for anterograde screwing in the acetabulum posterior column was determined in the same way as the above.A navigation template for anterograde screwing in the acetabular posterior column was manufactured.The screwing in the posterior column of the acetabulum was conducted using Kirschner wire with the aid of the navigation template.Imaging evaluation was performed after fixation.Results The projection of the safe zone in the acetabular posterior column was irregularly triangle;there were no significant differences regarding the projection size between different ages (P ＞ 0.05).The maximum diameter and the maximum length of the left optimal pathway in males were respectively 22.37 ± 1.42 mm and 131.27 ± 3.63 mm,and those of the right optimal pathway in males respectively 23.16 ± 1.39 mm and 129.23 ± 3.27 mm.The maximum diameter and the maximum length of the left optimal pathway in females were respectively 17.58 ± 1.83 mm and 112.56 ±2.77 mm,and those of the right optimal pathway in females respectively 16.92 ± 1.66 mm and 114.41 ± 2.98 mm.There were no significant differences between the left and right sides for the same item in the same gender (P ＞ 0.05).There were significant differences between males and females for the same item in the same side (P ＜ 0.05).No penetration into the cortex or the hip joint happened.Conclusion The optimal osseous pathway for anterograde screwing in the acetabulum posterior column can be determined by digital techniques,leading to a simple and safe procedure for the treatment of fractures of the acetabular posterior column.