Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

OBJECTIVES: To analyze the potential causal relationship between gut microbiota and food allergy (FA) using two-sample Mendelian randomization (MR) methods. METHODS: Data from genome-wide association studies on gut microbiota and FA were utilized. MR analysis was conducted employing inverse variance weighting, MR-Egger regression, and weighted median methods to assess the causal relationship between gut microbiota and FA. Cochrane's Q test was used to evaluate heterogeneity of instrumental variables, MR-PRESSO analysis was conducted to test for outliers and pleiotropy, and MR-Egger regression was employed to assess horizontal pleiotropy. The "leave-one-out" method was used to evaluate the impact of removing individual single nucleotide polymorphisms on the causal relationship. RESULTS: Inverse variance weighting analysis revealed that the phylum Verrucomicrobia, family Verrucomicrobiaceae, order Verrucomicrobiales, genus Ruminococcaceae UCG013, and genus Akkermansia were negatively associated with FA (P<0.05). Sensitivity analyses confirmed the reliability of the findings, indicating no heterogeneity or pleiotropy present. CONCLUSIONS There is a causal relationship between gut microbiota and FA, with Verrucomicrobia, Verrucomicrobiaceae, Verrucomicrobiales, Ruminococcaceae UCG013, and Akkermansia potentially reducing the risk of developing FA. These findings provide potential targets for the treatment and prevention of FA; however, further research is needed to explore the specific mechanisms by which the microbiota influence FA.
Humans ; Mendelian Randomization Analysis ; Gastrointestinal Microbiome ; Food Hypersensitivity/microbiology* ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide

OBJECTIVE: To investigate the effectiveness of Xuanshen Yishen Decoction (XYD) in the treatment of hypertension. METHODS: Hospital electronic medical records from 2019-2023 were utilized to emulate a randomized pragmatic clinical trial. Hypertensive participants were eligible if they were aged ⩾40 years with baseline systolic blood pressure (BP) ⩾140 mm Hg. Patients treated with XYD plus antihypertensive regimen were assigned to the treatment group, whereas those who followed only antihypertensive regimen were assigned to the control group. The primary outcome assessed was the attainment rate of intensive BP control at discharge, with the secondary outcome focusing on the 6-month all-cause readmission rate. RESULTS: The study included 3,302 patients, comprising 2,943 individuals in the control group and 359 in the treatment group. Compared with the control group, a higher proportion in the treatment group achieved the target BP for intensive BP control [8.09% vs. 17.5%; odds ratio (OR)=2.29, 95% confidence interval (CI)=1.68 to 3.13; P<0.001], particularly in individuals with high homocysteine levels (OR=3.13; 95% CI=1.72 to 5.71; P<0.001; P for interaction=0.041). Furthermore, the 6-month all-cause readmission rate in the treatment group was lower than in the control group (hazard ratio=0.58; 95% CI=0.36 to 0.91; P=0.019), and the robustness of the results was confirmed by sensitivity analyse. CONCLUSIONS XYD could be a complementary therapy for intensive BP control. Our study offers real-world evidence and guides the choice of complementary and alternative therapies. (Registration No. ChiCTR2400086589).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Antihypertensive Agents/pharmacology* ; Blood Pressure/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Hypertension/physiopathology* ; Patient Readmission ; Treatment Outcome

Social working memory (SWM)-the ability to maintain and manipulate social information in the brain-plays a crucial role in social interactions. However, research on SWM is still in its infancy and is often treated as a unitary construct. In the present study, we propose that SWM can be conceptualized as having two relatively independent components: "externally oriented SWM" (e-SWM) and "internally oriented SWM" (i-SWM). To test this external-internal hypothesis, participants were tasked with memorizing and ranking either facial expressions (e-SWM) or personality traits (i-SWM) associated with images of faces. We then examined the neural correlates of these two SWM components and their functional roles in empathy. The results showed distinct activations as the e-SWM task activated the postcentral and precentral gyri while the i-SWM task activated the precuneus/posterior cingulate cortex and superior frontal gyrus. Distinct multivariate activation patterns were also found within the dorsal medial prefrontal cortex in the two tasks. Moreover, partial least squares analyses combining brain activation and individual differences in empathy showed that e-SWM and i-SWM brain activities were mainly correlated with affective empathy and cognitive empathy, respectively. These findings implicate distinct brain processes as well as functional roles of the two types of SWM, providing support for the internal-external hypothesis of SWM.
Humans ; Memory, Short-Term/physiology* ; Male ; Female ; Empathy/physiology* ; Young Adult ; Magnetic Resonance Imaging ; Adult ; Brain/diagnostic imaging* ; Brain Mapping ; Facial Expression ; Social Behavior ; Facial Recognition/physiology* ; Social Perception ; Personality/physiology*

Objective To evaluate the efficacy and safety of a novel intravascular lithotripsy(IVL)balloon—Vesscrack shockwave balloon—for vascular preparation before stent implantation in patients with severe coronary artery calcification(CAC).Methods This was a prospective,single-arm,multicenter study conducted in China from June 2022 to October 2022.Patients with severe CAC were treated with the Vesscrack shockwave balloon for lesion preparation,followed by drug-eluting stent(DES)implantation.Of these,33 patients underwent optical coherence tomography(OCT).The primary endpoint was procedural success,defined as successful stent implantation with residual stenosis≤30％and the absence of in-hospital major adverse events,including cardiac death,target vessel-related myocardial infarction,or target lesion revascularization.Results A total of 170 patients[mean age:(65.9±7.9)years,116 males]were enrolled.After treatment with IVL and DES,the minimum lumen diameter increased significantly compared to baseline[(2.34±0.40)mm vs.(0.95±0.33)mm,P＜0.001],the degree of stenosis was significantly reduced[(13.24±6.60)％vs.(65.18±10.59)％,P＜0.001].Procedural success was achieved in 100％of cases,and device success was 98.8％.The 30-day patient-related cardiovascular clinical composite endpoint(POCE)rate was 0.0,with no target lesion failure,no confirmed or potential thrombotic events were observed.The shockwave energy generator demonstrated excellent stability and ease of use.Among the 33 patients assessed with OCT,after IVL intervention,the maximum calcified area of the lumen[(3.51±1.51)mm2 vs.(2.85±1.80)mm2,P＜0.001],and the minimum lumen area within the target lesion[(3.08±1.04)mm2 vs.(2.02±0.75)mm2,P＜0.001],and after DES intervention,the luminal area of the largest calcified site[(6.59±1.64)mm2 vs.(2.85±1.80)mm2,P＜0.001]and the minimum luminal area within the target lesion[(6.19±1.45)mm2 vs.(2.02±0.75)mm2,P＜0.001]were significantly increased,and the differences were statistically significant.Conclusions The Vesscrack shockwave balloon is effective and safe for vascular preparation in patients with severe CAC prior to stent implantation.It achieves significant calcified plaque modification,high procedural success rates,and minimal complications.

T7 RNA polymerase (T7 RNAP) is one of the simplest known RNA polymerases. Its unique structural features make it a critical model for studying the mechanisms of RNA synthesis. This review systematically examines the static crystal structure of T7 RNAP, beginning with an in-depth examination of its characteristic “thumb”, “palm”, and “finger” domains, which form the classic “right-hand-like” architecture. By detailing these structural elements, this review establishes a foundation for understanding the overall organization of T7 RNAP. This review systematically maps the functional roles of secondary structural elements and their subdomains in transcriptional catalysis, progressively elucidating the fundamental relationships between structure and function. Further, the intrinsic flexibility of T7 RNAP and its applications in research are also discussed. Additionally, the review presents the structural diagrams of the enzyme at different stages of the transcription process, and through these diagrams, it provides a detailed description of the complete transcription process of T7 RNAP. By integrating structural dynamics and kinetics analyses, the review constructs a comprehensive framework that bridges static structure to dynamic processes. Despite its advantages, T7 RNAP has a notable limitation: it generates double-stranded RNA (dsRNA) as a byproduct. The presence of dsRNA not only compromises the purity of mRNA products but also elicits nonspecific immune responses, which pose significant challenges for biotechnological and therapeutic applications. The review provides a detailed exploration of the mechanisms underlying dsRNA formation during T7 RNAP catalysis, reviews current strategies to mitigate this issue, and highlights recent progress in the field. A key focus is the semi-rational design of T7 RNAP mutants engineered to minimize dsRNA generation and enhance catalytic performance. Beyond its role in transcription, T7 RNAP exhibits rapid development and extensive application in fields, including gene editing, biosensing, and mRNA vaccines. This review systematically examines the structure-function relationships of T7 RNAP, elucidates the mechanisms of dsRNA formation, and discusses engineering strategies to optimize its performance. It further explores the engineering optimization and functional expansion of T7 RNAP. Furthermore, this review also addresses the pressing issues that currently need resolution, discusses the major challenges in the practical application of T7 RNAP, and provides an outlook on potential future research directions. In summary, this review provides a comprehensive analysis of T7 RNAP, ranging from its structural architecture to cutting-edge applications. We systematically examine: (1) the characteristic right-hand domains (thumb, palm, fingers) that define its minimalistic structure; (2) the structure-function relationships underlying transcriptional catalysis; and (3) the dynamic transitions during the complete transcription cycle. While highlighting T7 RNAP’s versatility in gene editing, biosensing, and mRNA vaccine production, we critically address its major limitation—dsRNA byproduct formation—and evaluate engineering solutions including semi-rationally designed mutants. By synthesizing current knowledge and identifying key challenges, this work aims to provide novel insights for the development and application of T7 RNAP and to foster further thought and progress in related fields.

Objective:To evaluate the clinical outcomes of corrective surgery in patients with different subtypes of "Ω"-type severe scoliosis.Methods:A retrospective analysis was conducted on 79 patients with "Ω"-type severe scoliosis treated at Nanjing Drum Tower Hospital from August 2010 to July 2020. The cohort included 37 males and 42 females, with a mean age of 21.4±7.4 years (range, 8-52 years). The mean duration of preoperative halo traction was 72.6±27.5 days (range, 14-150 days). Etiologies included congenital scoliosis (33 cases), idiopathic scoliosis (27 cases), Marfan syndrome (9 cases), neurofibromatosis (8 cases), and neuromuscular disorders (2 cases). Based on the classification by Karikari et al., 58 patients were classified as type 2P, 13 as type 2D, and 8 as type 2PD. Outcome measures included coronal and kyphotic Cobb angles, the Scoliosis Research Society-22 (SRS-22) questionnaire, Oswestry disability index (ODI), and visual analog scale (VAS).Results:All surgical procedures were successfully completed, and all patients were followed up for an average of 27.5±3.9 months (range, 24 to 40 months). The duration of Halo gravity traction was 72.6±27.5 days (range, 14-150 days). In the 2D group, the changes after traction were 26.0°±12.5° for the coronal Cobb angle and 10.1°±7.9° for the kyphotic Cobb angle. In the 2PD group, the traction effect was 13.4°±5.7° for the coronal and 8.3°±5.9° for the kyphotic Cobb angle. In the 2P group, the preoperative coronal Cobb angle was 128.9°±29.1°, postoperative was 84.5°±24.5°, and at the last follow-up was 87.7°±25.0°, yielding a correction rate of 34%±12%. The kyphotic Cobb angle in this group changed from 112.9°±27.1° preoperatively to 77.6°±22.9° postoperatively, and 80.2°±22.8° at the final follow-up, corresponding to a correction rate of 30%±16%. In the 2D group, the coronal Cobb angle was 113.1°±19.9° preoperatively, 71.2°±16.3° postoperatively, and 73.8°±16.3° at the final follow-up, with a correction rate of 37%±11%. The kyphotic Cobb angle in this group was 87.2°±14.0° preoperatively, 61.6°±18.5° postoperatively, and 65.1°±18.5° at the final follow-up, with a correction rate of 31%±22%. In the 2PD group, the coronal Cobb angle improved from 119.6°±29.0° preoperatively to 78.3°±20.8° postoperatively, and 87.0°±23.0° at the last follow-up, corresponding to a correction rate of 35%±8%. The kyphotic Cobb angle in this group was 124.6°±16.8° preoperatively, 82.1°±19.9° postoperatively, and 90.9°±16.9° at the final follow-up, with a correction rate of 33%±16%. At the last follow-up, SRS-22 scores across all four domains had improved in all three groups compared to preoperative values. In the 2PD group, however, the differences in the pain and self-image domains before and after surgery were not statistically significant ( P>0.05), while improvements in the other domains were significant ( P<0.05). No statistically significant differences were observed among the three groups either preoperatively or at the final follow-up ( P>0.05). Conclusion:Combined Halo-gravity traction and spinal corrective surgery are effective in improving both radiographic and functional outcomes in patients with "Ω"-type severe scoliosis. Nonetheless, patients in the 2PD subtype demonstrate reduced traction responsiveness and relatively limited postoperative recovery compared to the 2P and 2D subtypes.

Objective To investigate the mechanism of action of circ-0058063 regulating ERK/MAPK signaling pathway on ferroptosis in esophageal cancer cells.Methods EC9706 cells were randomly divided into the Control group,the si-NC group,the si-circ-0058063 group,and the si-circ-0058063+ISO group.qRT-PCR was used to detect the expression of circ-0058063 in esophageal cancer tissues and cells;CCK-8 and clone formation assay were used to detect the cell proliferation ability.The levels of Fe2+,malondialdehyde(MDA),glutathione(GSH),and reactive oxygen species(ROS)in cells were detected.Western blot was used to detect the ERK/MAPK signaling pathway and the expression of ferroptosis-related protein in cells.Results The expression level of circ-0058063 in esophageal cancer tissue was significantly higher than that in adjacent tissues(P<0.05);the expression level of circ-0058063 in human esophageal cancer cell EC9706 was significantly higher than that in human normal esophageal epithelial cell HEEC(P<0.05).Compared with the Control group,the expression level of circ-0058063 in cells,cell survival rate,number of cloned cells,GSH level,ratios of p-ERK1/2/ERK1/2 and p-p38MAPK/p38MAPK,as well as the expression levels of SLC7A11 and GPX4 protein in the si-circ-0058063 group were significantly reduced(P<0.05),while the levels of Fe2+,MDA,and ROS in cells were significantly increased(P<0.05).Compared with the si-circ-0058063 group,the expression level of circ-0058063 in cells,cell survival rate,number of cloned cells,GSH level,ratios of p-ERK1/2/ERK1/2 and p-p38MAPK/p38MAPK,as well as the expression levels of SLC7A11 and GPX4 protein in the si-circ-0058063+ISO group were significantly increased(P<0.05),while the levels of Fe2+,MDA,and ROS in cells were significantly decreased(P<0.05).Conclusion Knockdown of circ-0058063 can inhibit the proliferation of esophageal cancer cells and induce ferroptosis,and its mechanism of action may be related to the inhibition of ERK/MAPK signaling pathway activation.

Objective:To evaluate the clinical outcomes of corrective surgery in patients with different subtypes of "Ω"-type severe scoliosis.Methods:A retrospective analysis was conducted on 79 patients with "Ω"-type severe scoliosis treated at Nanjing Drum Tower Hospital from August 2010 to July 2020. The cohort included 37 males and 42 females, with a mean age of 21.4±7.4 years (range, 8-52 years). The mean duration of preoperative halo traction was 72.6±27.5 days (range, 14-150 days). Etiologies included congenital scoliosis (33 cases), idiopathic scoliosis (27 cases), Marfan syndrome (9 cases), neurofibromatosis (8 cases), and neuromuscular disorders (2 cases). Based on the classification by Karikari et al., 58 patients were classified as type 2P, 13 as type 2D, and 8 as type 2PD. Outcome measures included coronal and kyphotic Cobb angles, the Scoliosis Research Society-22 (SRS-22) questionnaire, Oswestry disability index (ODI), and visual analog scale (VAS).Results:All surgical procedures were successfully completed, and all patients were followed up for an average of 27.5±3.9 months (range, 24 to 40 months). The duration of Halo gravity traction was 72.6±27.5 days (range, 14-150 days). In the 2D group, the changes after traction were 26.0°±12.5° for the coronal Cobb angle and 10.1°±7.9° for the kyphotic Cobb angle. In the 2PD group, the traction effect was 13.4°±5.7° for the coronal and 8.3°±5.9° for the kyphotic Cobb angle. In the 2P group, the preoperative coronal Cobb angle was 128.9°±29.1°, postoperative was 84.5°±24.5°, and at the last follow-up was 87.7°±25.0°, yielding a correction rate of 34%±12%. The kyphotic Cobb angle in this group changed from 112.9°±27.1° preoperatively to 77.6°±22.9° postoperatively, and 80.2°±22.8° at the final follow-up, corresponding to a correction rate of 30%±16%. In the 2D group, the coronal Cobb angle was 113.1°±19.9° preoperatively, 71.2°±16.3° postoperatively, and 73.8°±16.3° at the final follow-up, with a correction rate of 37%±11%. The kyphotic Cobb angle in this group was 87.2°±14.0° preoperatively, 61.6°±18.5° postoperatively, and 65.1°±18.5° at the final follow-up, with a correction rate of 31%±22%. In the 2PD group, the coronal Cobb angle improved from 119.6°±29.0° preoperatively to 78.3°±20.8° postoperatively, and 87.0°±23.0° at the last follow-up, corresponding to a correction rate of 35%±8%. The kyphotic Cobb angle in this group was 124.6°±16.8° preoperatively, 82.1°±19.9° postoperatively, and 90.9°±16.9° at the final follow-up, with a correction rate of 33%±16%. At the last follow-up, SRS-22 scores across all four domains had improved in all three groups compared to preoperative values. In the 2PD group, however, the differences in the pain and self-image domains before and after surgery were not statistically significant ( P>0.05), while improvements in the other domains were significant ( P<0.05). No statistically significant differences were observed among the three groups either preoperatively or at the final follow-up ( P>0.05). Conclusion:Combined Halo-gravity traction and spinal corrective surgery are effective in improving both radiographic and functional outcomes in patients with "Ω"-type severe scoliosis. Nonetheless, patients in the 2PD subtype demonstrate reduced traction responsiveness and relatively limited postoperative recovery compared to the 2P and 2D subtypes.

Objective To investigate the mechanism of action of circ-0058063 regulating ERK/MAPK signaling pathway on ferroptosis in esophageal cancer cells.Methods EC9706 cells were randomly divided into the Control group,the si-NC group,the si-circ-0058063 group,and the si-circ-0058063+ISO group.qRT-PCR was used to detect the expression of circ-0058063 in esophageal cancer tissues and cells;CCK-8 and clone formation assay were used to detect the cell proliferation ability.The levels of Fe2+,malondialdehyde(MDA),glutathione(GSH),and reactive oxygen species(ROS)in cells were detected.Western blot was used to detect the ERK/MAPK signaling pathway and the expression of ferroptosis-related protein in cells.Results The expression level of circ-0058063 in esophageal cancer tissue was significantly higher than that in adjacent tissues(P<0.05);the expression level of circ-0058063 in human esophageal cancer cell EC9706 was significantly higher than that in human normal esophageal epithelial cell HEEC(P<0.05).Compared with the Control group,the expression level of circ-0058063 in cells,cell survival rate,number of cloned cells,GSH level,ratios of p-ERK1/2/ERK1/2 and p-p38MAPK/p38MAPK,as well as the expression levels of SLC7A11 and GPX4 protein in the si-circ-0058063 group were significantly reduced(P<0.05),while the levels of Fe2+,MDA,and ROS in cells were significantly increased(P<0.05).Compared with the si-circ-0058063 group,the expression level of circ-0058063 in cells,cell survival rate,number of cloned cells,GSH level,ratios of p-ERK1/2/ERK1/2 and p-p38MAPK/p38MAPK,as well as the expression levels of SLC7A11 and GPX4 protein in the si-circ-0058063+ISO group were significantly increased(P<0.05),while the levels of Fe2+,MDA,and ROS in cells were significantly decreased(P<0.05).Conclusion Knockdown of circ-0058063 can inhibit the proliferation of esophageal cancer cells and induce ferroptosis,and its mechanism of action may be related to the inhibition of ERK/MAPK signaling pathway activation.