ObjectiveTo observe the effects of the Fuyuan Tongluo prescription （composed of Astragali Radix， Carthami Flos， Spatholobi Caulis， Liquidambaris Fructus， Lycopodii Herba， Centellae Herba， etc.） in the treatment of restenosis with collateral obstruction syndrome after interventional operation of lower limb arteriosclerosis obliterans， and its impact on the primary patency rate. MethodsA total of 88 patients with collateral obstruction syndrome after interventional surgery for lower limb arteriosclerosis obliterans were randomly divided into two groups. The control group （n₁=44） received dual antiplatelet therapy with aspirin and clopidogrel. The observation group （n₂=44） was treated with Fuyuan Tongluo prescription non-decocted granules in addition to aspirin and clopidogrel. Both groups received treatment for 24 weeks and were followed up for 36 weeks. The changes in primary patency rate， symptom scores， ankle-brachial index （ABI）， coagulation function， and inflammatory markers before and after treatment were compared between the two groups. ResultsFor primary patency rate， after 36 weeks of treatment， the observation group had a significantly better primary patency rate than the control group （χ²=4.14，P<0.05）. After 24 weeks of treatment， there was no significant difference in primary patency rate between the two groups. Clinical efficacy comparison： Based on symptom quantification scores， and using the Nimodipine method as a reference， the overall efficacy of the observation group was superior to that of the control group after 24 weeks of treatment （χ²=2.24，P<0.05）. ABI levels： The observation group had a higher ABI than the control group after 24 and 36 weeks of treatment （P<0.05）. Coagulation function indicators： After 24 and 36 weeks of treatment， D-dimer and fibrinogen levels in both groups were lower than before treatment （P<0.05）. Inflammatory markers： After 24 and 36 weeks of treatment， CRP levels in the observation group were lower than those in the control group （P<0.05）. There were no significant differences in white blood cell （WBC） and erythrocyte sedimentation rate （ESR） levels before and after treatment between the two groups. ConclusionAdding Fuyuan Tongluo prescription non-decocted granules to dual antiplatelet therapy can improve the primary patency rate of the affected vessels in patients with lower limb arteriosclerosis obliterans after interventional surgery. Longer use of Fuyuan Tongluo prescription can significantly improve clinical symptoms， demonstrating clinical application value.

ObjectiveTo observe the effects of the Fuyuan Tongluo prescription （composed of Astragali Radix， Carthami Flos， Spatholobi Caulis， Liquidambaris Fructus， Lycopodii Herba， Centellae Herba， etc.） in the treatment of restenosis with collateral obstruction syndrome after interventional operation of lower limb arteriosclerosis obliterans， and its impact on the primary patency rate. MethodsA total of 88 patients with collateral obstruction syndrome after interventional surgery for lower limb arteriosclerosis obliterans were randomly divided into two groups. The control group （n₁=44） received dual antiplatelet therapy with aspirin and clopidogrel. The observation group （n₂=44） was treated with Fuyuan Tongluo prescription non-decocted granules in addition to aspirin and clopidogrel. Both groups received treatment for 24 weeks and were followed up for 36 weeks. The changes in primary patency rate， symptom scores， ankle-brachial index （ABI）， coagulation function， and inflammatory markers before and after treatment were compared between the two groups. ResultsFor primary patency rate， after 36 weeks of treatment， the observation group had a significantly better primary patency rate than the control group （χ²=4.14，P<0.05）. After 24 weeks of treatment， there was no significant difference in primary patency rate between the two groups. Clinical efficacy comparison： Based on symptom quantification scores， and using the Nimodipine method as a reference， the overall efficacy of the observation group was superior to that of the control group after 24 weeks of treatment （χ²=2.24，P<0.05）. ABI levels： The observation group had a higher ABI than the control group after 24 and 36 weeks of treatment （P<0.05）. Coagulation function indicators： After 24 and 36 weeks of treatment， D-dimer and fibrinogen levels in both groups were lower than before treatment （P<0.05）. Inflammatory markers： After 24 and 36 weeks of treatment， CRP levels in the observation group were lower than those in the control group （P<0.05）. There were no significant differences in white blood cell （WBC） and erythrocyte sedimentation rate （ESR） levels before and after treatment between the two groups. ConclusionAdding Fuyuan Tongluo prescription non-decocted granules to dual antiplatelet therapy can improve the primary patency rate of the affected vessels in patients with lower limb arteriosclerosis obliterans after interventional surgery. Longer use of Fuyuan Tongluo prescription can significantly improve clinical symptoms， demonstrating clinical application value.

OBJECTIVES: The purinergic receptor P2X2 (P2RX2) encodes an ATP-gated ion channel permeable to Na⁺, K⁺, and especially Ca²⁺. Loss-of-function mutations in P2RX2 are known to cause autosomal dominant nonsyndromic deafness 41 (DFNA41), which manifests as high-frequency hearing loss, accelerated presbycusis, and increased susceptibility to noise-induced damage. Zebrafish, owing to their small size, rapid development, high fecundity, transparent embryos, and high gene conservation with humans, provide an ideal model for studying human diseases and developmental mechanisms. This study aims to generate a p2rx2 knockout zebrafish model using CRISPR/Cas9 gene editing system to investigate the effect of p2rx2 deficiency on the auditory system, providing a basis for understanding P2RX2-related hearing loss and developing gene therapy strategies. METHODS: Two CRISPR targets (sgRNA1 and sgRNA2) spaced 47 bp apart were designed within the zebrafish p2rx2 gene. Synthesized sgRNAs and Cas9 protein were microinjected into single-cell stage Tübingen (TU)-strain zebrafish embryos. PCR and gel electrophoresis verified editing efficiency at 36 hours post-fertilization (hpf). Surviving embryos were raised to adulthood (F0), tail-clipped, genotyped, and screened for positive mosaics. F1 heterozygotes were generated by outcrossing, and F2 homozygous mutants were obtained by intercrossing. Polymerase chain reaction (PCR) combined with sequencing verified mutation type and heritability. At 5 days post-fertilization (dpf), YO-PRO-1 staining was used to examine hair cell morphology and count in lateral line neuromasts and the otolith region. Auditory evoked potential (AEP) thresholds at 600, 800, 1 000, and 2 000 Hz were measured in nine 4-month-old wild type and mutant zebrafish per group. RESULTS: A stable p2rx2 knockout zebrafish line was successfully established. Sequencing revealed a 66 bp insertion at the first target site introducing a premature stop codon (TAA), leading to early termination of protein translation and loss of function. Embryos developed normally with no gross malformations. At 5 dpf, mutants exhibited significantly reduced hair cell density in the otolith region compared with wild type, although lateral line neuromasts were unaffected. AEP testing showed significantly elevated auditory thresholds at all 4 frequencies in homozygous mutants compared with wild type (all P<0.001), indicating reduced hearing sensitivity. CONCLUSIONS We successfully generated a p2rx2 loss-of-function zebrafish model using CRISPR/Cas9 technology. p2rx2 deficiency caused hair cell defects in the otolith region and increased auditory thresholds across frequencies, indicating its key role in maintaining zebrafish auditory hair cell function and hearing perception. The phenotype's restriction to the otolith region suggests tissue-specific roles of p2rx2 in sensory organs. This model provides a valuable tool for elucidating the molecular mechanisms of P2RX2-related hearing loss and for screening otoprotective drugs and developing gene therapies.
Animals ; Zebrafish/genetics* ; Receptors, Purinergic P2X2/deficiency* ; CRISPR-Cas Systems/genetics* ; Gene Knockout Techniques ; Phenotype ; Zebrafish Proteins/genetics* ; Disease Models, Animal

Objective To explore the clinical characteristics and prognostic analysis of acute corpus callosum in-farction.Methods A total of 1 466 patients with acute cerebral infarction admitted to the Neurology Department of Jiangbin Hospital in Guangxi from January 2019 to October 2023 and Neurology Department of Fuwai Hospital,Chinese Academy of Medical Sciences from January 2022 to December 2022.Among them,21 patients with acute corpus callosum infarction confirmed by MRI(observation group)and 25 patients with isolated subcortical infarction at the same period(control group)were selected.By comparing clinical data and follow-up information between two groups,we summarized the clinical characteristics of acute corpus callosum infarction,and analyzed the relevant factors affecting the prognosis of the corpus callosum infarction group.Results Acute corpus callosum infarction accounted for 1.43％(21/1 466)of patients with acute cerebral infarction in the same period.The main clinical manifestations include limb paralysis,cognitive decline,and speech impairment.Compared with the control group,the group with corpus callosum infarction had a longer onset visit time(P<0.05),more cognitive impair-ment(P<0.05),a higher proportion of mild stroke(P<0.05),more worsening symptoms during the course of the disease(P<0.05),a higher proportion of cardioembolic type(P<0.05),a lower proportion of small artery occlu?sion type(P<0.05)and a higher proportion of good prognosis(mRS score≤2 points)(P<0.05).The poor prog?nosis of corpus callosum infarction was found to be related to factors such as large lesions,multiple high?risk factors(≥3),concomitant lobar infarction and worsening of symptoms during the course of the disease.Conclusions Acute corpus callosum infarction often leads to cognitive impairment and mild limb paralysis,which frequently de?lays treatment.The poor prognosis is mainly related to factors such as lobar infarction,major lesions,and worsening of symptoms during the process.

【Objective】 To improve the understanding and diagnosis and treatment level of ALK negative anaplastic large cell lymphoma (ALK-ALCL) by sharing the diagnosis and treatment process of a patient with ALK-ALCL treated in Hangzhou Bay Hospital of Ningbo. 【Methods】 The clinical data and diagnosis and treatment process of the patient were retrospectively analyzed, and relevant literature was reviewed. 【Results】 The patient was a young male, with recurrent gross hematuria and right low back pain as the initial symptoms.Imaging examination indicated bladder tumor.After resection, the tumor was reduced and confirmed to be ALK-ALCL.After chemotherapy and autologous hematopoietic stem cell transplantation, the patient’s condition continued to improve.During the follow-up, no recurrence was observed. 【Conclusion】 Primary ALK-ALCL in the bladder is very rare and prone to misdiagnosis and missed diagnosis in clinical practice.The successful diagnosis and treatment experience of this patient can provide clinical reference.

Purpose To prepare biomimetic targeted nanobubbles(NBs)named IR780-RBCM@NBs and explore the ability of performing ultrasound enhancement,escaping immune surveillance and targeting tumor cells.Materials and Methods The red blood cell membrane(RBCM)was extracted from mouse blood,the IR780-RBCM@NBs were prepared by modified membrane hydration method,the physical and chemical properties of nanobubbles were detected.In vitro,self-made equipment was used to test the contrast-enhanced ultrasound imaging ability of the nanobubbles.Laser confocal fluorescence microscopy was used to observe the characteristics of the nanobubbles retaining CD47 on the RBCM surface,and further to observe the phagocytosis of the nanobubbles by macrophages and the targeting ability of the nanobubbles to different tumor cells.Results The newly prepared IR780-RBCM@NBs had the appearance of emulsion,the particle size was about(522.4±58.6)nm and the dispersity was good.It was spherical in uniform size under the microscope.IR-780 could be detected on the nanobubbles,which had the dual-mode imaging capabilities of near-infrared fluorescence imaging and contrast-enhanced ultrasound imaging.The RBCM-specific protein CD47 could be detected on the surface of the nanobubbles.The nanobubbles exhibited excellent immune phagocytic escape function and high efficiency to target different tumor cells.Conclusion Newly prepared biomimetic targeted IR780-RBCM@NBs,with good performance,can escape immune phagocytosis and efficiently target tumors,providing a new idea for molecular targeted accurate diagnosis and treatment of tumors.

The establishment of a traceability system for the entire industry chain of Chinese medicinal materials can enhance regional brand building,raise the quality awareness of medicinal material producers,standardize the production processes of Chinese medicinal materials,and ensure the production of high-quality medicinal materials.Sichuan Province has successfully implemented a provincial-level Traditional Chinese Medicine(TCM)tracing system that is interconnected across provinces,cities,and counties.This system enables the complete tracking of the entire supply chain,starting from seed and seedling cultivation,through planting and breeding,harvesting and processing,and finally to the production and distribution of decoction pieces in trade and medical institutions.This research provides a comprehensive overview of the progress made in establishing the Chinese herbal medicine traceability system in Sichuan Province.It analyzes the existing challenges faced by participating enterprises,such as the hierarchy of involvement,information integrity,and the overall impact of the system.Moreover,the paper presents valuable insights and suggestions for the further development of the Chinese herbal medicine traceability system in Sichuan Province.These recommendations focus on enhancing the traceability scope,improving service capabilities,promoting data sharing,and establishing standardized norms and guidelines.

Objective:To investigate the effects of improving the prenatal multidisciplinary consultation mode on the outcomes of fetuses with structural malformations.Methods:Clinical data of pregnant women attending the Prenatal Multidisciplinary Consultation Center, jointly established by the Obstetrics & Gynecology Hospital of Fudan University and the Children's Hospital of Fudan University from January 2004 to December 2019, were retrospectively collected and analyzed. In 2014, the center optimized the multidisciplinary consultation mode to achieve a more individualized approach to genetic testing based on more accurate imaging diagnosis and deeper cooperation between the obstetrics and pediatrics teams. Differences in the number of cases, structure of the diseases, genetic testing results, outcomes, and prognosis between the improved group (enrolled from January 2014 to December 2019) and the baseline group (enrolled from January 2004 to December 2013) were compared. The Chi-square test was used for statistical analysis. Results:(1) This study recruited 5 977 pregnant women, including 3 424 in the baseline group and 2 553 in the improved group. The main indications for consultation were fetal factors [97.2% (5 812/5 977)], among which congenital structural malformations accounted for 77.5% (4 503/5 812). There was a significant difference in the systematic distribution of congenital structural malformations between the two groups ( χ2=141.31, P<0.001). The proportion of malformations involving the central nervous, cardiovascular, and urinary systems ranked in the top three in both groups. (2) The percentage of women receiving genetic testing was higher in the improved group than in the baseline group [26.7% (682/2 553) vs. 15.9% (546/3 424), χ2=103.87, P<0.001] and the positive rate of genetic testing was also higher in the improved group [19.9% (136/682) vs. 9.9% (54/546). χ2=23.42, P<0.001]. (3) Among the 5 977 cases, 418 (7.0%) were lost to follow-up; 1 741 (29.1%) opted for pregnancy termination; 123 (2.2%) had intrauterine fetal death; and 3 695 (61.8%) were live births. The rate of pregnancy termination in the improved group was lower than that of the baseline group [27.7% (707/2 553) vs. 30.2% (1 034/3 424), χ2=4.45, P=0.035]. (4) In the 1 741 cases with pregnancy termination, fatal cardiovascular system malformations ( n=413, 23.7%), central nervous system malformations ( n=377, 21.7%), multiple malformations ( n=258, 14.8%), and chromosomal abnormalities ( n=162, 9.3%) were the main causes. The top five diseases leading to pregnancy termination were cleft lip and palate [59.0% (46/78)], meningocele (5/9), gastroschisis/omphalocele [49.3% (33/67)], diaphragmatic hernia [46.5% (33/71)], and skeletal malformations [40.9% (83/203)]. The rates of pregnancy termination due to gastroschisis/omphalocele, diaphragmatic hernia, and skeletal malformations in the improved group were all lower than those in the baseline group [57.4% (27/47) vs. 30.0% (6/20), χ2=4.23; 59.0% (23/39) vs. 31.3% (10/32), χ2=5.43; 51.8% (72/139) vs. 17.2% (11/64), χ2=21.72; all P<0.05]. (5) Among the 3 695 live births, 1 979 (53.6%) were delivered by cesarean section and 1 716 (46.4%) by vaginal delivery; 3 633 (98.3%) survived and 62 (1.7%) died in the neonatal period. The survival rate of newborns in the improved group was higher than that in the baseline group [98.8% (1 648/1 668) vs. 97.9% (1 985/2 027), χ2=4.23, P=0.040]. Among the 62 dead newborns, 51 (82.3%) had fatal structural or chromosomal abnormalities. (6) In the surviving neonates, 372 (10.2%) showed no abnormalities in a postnatal reexamination, and 468 (12.9%) received surgical treatment in the neonatal period. The other 2 793 cases received no treatment in the neonatal period but were followed up regularly. Conclusion:The optimized prenatal multidisciplinary consultation mode effectively reduces the rate of pregnancy termination due to non-fatal single structural malformations and increases the survival rate of newborns.

Objective To investigate the predictive value of National Institutes of Health Stroke Scale(NIHSS)score,serum brain-derived neurotrophic factor(BDNF)and interleukin-6(IL-6)in post-stroke depression(PSD).Methods A total of 180 patients with stroke were selected and divided into the PSD group(n=80,HAMD≥8 points)and the non-PSD(NPSD)group(n=100,HAMD＜8 points),according to HAMD score at 3 months after stroke.The basic information,NIHSS score,serum BDNF and IL-6 were compared between the two groups.The influencing factors of PSD were analyzed by Logistic regression method.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive value of NIHSS score,serum BDNF and IL-6 for PSD.Results Compared with the NPSD grope,low density lipoprotein cholesterol(LDL-C)and serum BDNF level were significantly lower,NIHSS score and serum IL-6 level were significantly increased in the PSD group(P＜0.05).Results of Logistic regression analysis showed that increased NIHSS score and serum IL-6 were risk factors for PSD,and increased serum BDNF was the protective factor in patents with PSD(P＜0.05).The area under curve(AUC)of NIHSS score,serum BDNF and IL-6 and their combination prediction of PSD were 0.762,0.746,0.796 and 0.839,respectively.The sensitivity of the combined prediction was 86.0%and a specificity was 95.0%.Conclusion Compared with NPSD patients,the NIHSS score and serum IL-6 level are increased,and the serum BDNF level is decreased in patients with PSD.The combination of all three has a high predictive value for patients of PSD.

Objective To investigate the effect of the loss of myeloid-derived growth factor(Mydgf)on the transformation of cardiac fibroblasts into myofibroblasts after myocardial infarction(MI).Methods Two adult mouse groups,including a wild-type(WT)group and another group with Mydgf knockout(Mydgf-KO),were examined in the study.The mice in these two groups were tested for their cardiac function by measuring left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)(n=10).Quantitative real-time PCR(qRT-PCR)(n=3)was performed to determine the mRNA expression levels of myofibroblast markers,including α-smooth muscle actin(α-SMA),periostin(postn),type Ⅷ collagen(col8al),and connective tissue growth factor(ctgf).Western blot(n=3)was performed to verify the protein expression levels of α-SMA.MI modeling was performed on the WT and the Mydgf-KO mice.Postoperative LVEF and LVFS(n=10)were then measured.The hearts were harvested and Masson staining was performed to determine the infarcted area(n=10).The heart samples of Mydgf-KO and WT mice were collected at d 7 and d 14 after MI,respectively,to verify the expression of myofibroblast markers(n=3).Results Compared with WT mice,LVEF and LVFS in adult Mydgf-KO mice showed no significant changes(all P＞0.05).However,the mRNA levels of α-SMA and postn were upregulated,and α-SMA protein expression was also increased(all P＜0.05).After MI,compared with WT mice,LVEF and LVFS in Mydgf-KO mice decreased,and the infarcted area increased significantly(all P＜0.05).Furthermore,mRNA levels of α-SMA,col8al,postn,and ctgf were increased in Mydgf-KO mice.In addition,the α-SMA protein expression level was upregulated and α-SMA-positive fibroblasts were increased(P＜0.05).Conclusion Mydgf deletion promotes the transformation of cardiac fibroblasts into myofibroblasts and aggravates myocardial fibrosis after MI.