Objectives: . This study aimed to investigate the regulatory functions of gamma-aminobutyric acid (GABA)ergic neural circuits from the inferior colliculus (IC) to the medial geniculate body (MGB) in salicylate-induced tinnitus. Methods: . Mice were treated with salicylate to induce tinnitus, and tinnitus-like behaviors were evaluated via gap prepulse inhibition of acoustic startle. Using combined viral tracing methodologies, we identified and mapped the pathways and connections from the IC to the MGB. Furthermore, we employed Gq-coupled human M3 designer receptors exclusively activated by designer drugs (DREADDs) and Gi-coupled human M4 DREADDs to achieve targeted excitation or suppression of GABAergic neurons in the IC and MGB. Following the administration of clozapine N-oxide, which binds to these receptors, we modulated these neural circuits to assess their impact on tinnitus severity in a mouse model. Results: . Our findings demonstrated that mice exposed to salicylate exhibited tinnitus-like behaviors. GABAergic neurons projecting retrogradely from the MGB to the IC were primarily concentrated in the external nucleus of the IC. After clozapine N-oxide administration, chemogenetic activation of IC-MGB GABAergic neurons aggravated salicylate-induced tinnitus. Additionally, activation of GABAergic neurons between the IC and MGB induced the perception of tinnitus even without salicylate. However, chemogenetic inhibition of the IC-MGB GABAergic circuit did not reverse salicylate-induced tinnitus. Conclusion . These findings suggest that activation of the IC-MGB GABAergic neural circuit may contribute to tinnitus generation through a mechanism distinct from that of salicylate-induced tinnitus. This study provides novel insights into the mechanisms underlying tinnitus.

Objective To evaluate the effect of Intravascular lithotripsy(IVL)in the treatment of calcified nodules,and to observe the presence of coronary dissection after IVL treatment.Methods A total of 106 patients with coronary atherosclerotic heart disease(coronary heart disease)admitted to the cardiovascular Department of Shougang Hospital,Peking University from March 2023 to July 2024 were retrospectively analyzed.A total of 106 patients with moderate to severe stenosis accompanied by calcification as detected by coronary angiography were treated with IVL after intravascular ultrasound(IVUS)examination.Patients were divided into two groups according to whether there were calcified nodules in the coronary lesions:39 cases in the calcified nodules group and 67 cases in the non-calcified nodules group.The occurrence of coronary dissection during surgery was observed between the two groups,and other perioperative related complications and major adverse cardiovascular events(MACE)within 1 month after percutaneous coronary intervention(PCI)were compared between the two groups.Results The levels of renal insufficiency(25.6％vs.9.0％,P=0.021)and creatinine[(119.71±134.75)μmol/L vs.(71.82±16.53)μmol/L,P=0.033]in the calcified nodule group were higher than those in the non-calcified nodule group,the difference was statistically significant,and there was no difference in other baseline data.The target vessels in the calcified nodule group were mainly left anterior descending branch and right coronary artery,while those in the non-calcified nodule group were mainly left anterior descending branch,with few circumflex branches in both groups,and there was statistical significance in the distribution of target vessels in the left anterior descending branch and right coronary artery between the two groups(P=0.020).In terms of eccentric calcification(P=0.048)and asymmetric calcification(48.7％vs.28.4％,P=0.035)between the two groups,the calcified nodule group was higher than the non-calcified nodule group,the difference was statistically significant(P＜0.05).In terms of whether more than 20 pulses were needed and whether there was slippage during IVL,the calcified nodule group was higher than the non-calcified nodule group,the difference was statistically significant(P=0.022).The success rate of interventional therapy was 100％in both groups.After IVL treatment,the calcified nodule group was higher than the non-calcified nodule group in terms of the occurrence of coronary artery dissection,the difference was statistically significant(P＜0.009).The MACE of the two groups within 1 month after PCI was slightly higher in the calcified nodule group than in the non-calcified nodule group,but the difference was not statistically significant(P=0.235).Conclusions IVL is feasible and effective for the treatment of calcified coronary nodules.However,in the course of treatment,the occurrence of coronary dissection should be vigilant,identified as early as possible,and treated in time.

OBJECTIVES: To assess the preliminary efficacy and safety of a dose-intensified C5VD regimen (cisplatin, 5-fluorouracil, vincristine, and doxorubicin) in children with locally advanced hepatoblastoma. METHODS: This prospective study enrolled 24 children with newly diagnosed, locally advanced hepatoblastoma who received the dose-intensified C5VD regimen at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children's Hospital between January 2020 and December 2023. Clinical characteristics, treatment outcomes, and chemotherapy-related toxicities were analyzed. RESULTS: Of the 24 patients, 13 were male and 11 were female, with a median age at diagnosis of 18.7 months (range: 3.5-79.4 months). All patients achieved complete macroscopic resection of hepatic lesions without liver transplantation. Serum alpha-fetoprotein levels decreased significantly after two chemotherapy cycles. During a median follow-up of 38.4 months (range: 15.8-50.7 months), all patients maintained continuous complete remission, with 3-year event-free survival and overall survival rates of 100%. Across 144 chemotherapy cycles, the incidence rates of grade 3-4 neutropenia, thrombocytopenia, and infections were 97%, 77%, and 71%, respectively; no treatment-related deaths occurred. Notably, 5 patients (21%) developed Brock grade ≥3 hearing loss, of whom 1 required a hearing aid. CONCLUSIONS The dose-intensified C5VD regimen demonstrates significant efficacy with an overall favorable safety profile in the treatment of newly diagnosed, locally advanced pediatric hepatoblastoma. Grade 3-4 myelosuppression and infection are the predominant toxicities. However, high‑dose cisplatin-induced ototoxicity remains a concern, highlighting the need for improved otoprotective strategies.
Humans ; Hepatoblastoma/pathology* ; Male ; Female ; Infant ; Liver Neoplasms/pathology* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child, Preschool ; Prospective Studies ; Doxorubicin/adverse effects* ; Child ; Cisplatin/adverse effects* ; Vincristine/adverse effects* ; Fluorouracil/adverse effects*

OBJECTIVE: To investigate the clinical characteristics, treatment and prognosis of adult AML patients with NUP98::HOXA9 fusion gene. METHODS: From May 2017 to October 2023， among 2 113 AML patients who visited the Hematology Department of our hospital, patients with NUP98 rearrangements were screened. The clinical characteristics, chromosome karyotypes, immunophenotypes, gene mutations, treatment efficacy and prognosis of the patients with NUP98::HOXA9 positive were analyzed. RESULTS: Among the 2 113 AML patients, there were 18 cases with NUP98 rearrangement, including 14 NUP98::HOXA9 positive cases, with a detection rate of 0.66% (14/2 113). The median age of the NUP98::HOXA9 positive patients was 42.5 (23-64) years old. The most common chromosome karyotype was t(7; 11)(p15; p15). The immunophenotypes of all patients expressed CD13, CD33, CD117 and CD38, and most patients expressed CD34 and cMPO, while only a few expressed HLA-DR. Second-generation sequencing (NGS) was performed to detect genetic mutations associated with leukemia in all 14 patients, and the genes exhibiting a high frequency of mutation were WT1 (10/14), TET2 (7/14), and FLT3-ITD (6/14). Additionally, mutations were also observed in KRAS/NRAS, IDH1, and KIT. Of the 13 patients who received treatment, 9 achieved complete remission (CR), and all 3 patients who received azacytidine(AZA)+ venetoclax (VEN) regimen achieved CR after the first course of treatment. Within this cohort, 6 patients were classified as relapsed/refractory (6/13). 4 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which two achieved long-term survival. The median follow-up time was 12 (2.1-65.0) months, while the median overall survival (OS) and relapse-free survival (RFS) were recorded as 11.4 months and 9.6 months, respectively. CONCLUSION The most common type of NUP98 rearrangement in adults AML patients is NUP98::HOXA9 , which is often accompanied by somatic mutations in WT1, TET2, and FLT3-ITD. These patients are prone to relapse, have short survival time, and generally face poor prognoses. Hopefully, utilization of the AZA+VEN regimen is anticipated to enhance the rate of induced remission in the patients, and some patients may prolong their survival through allo-HSCT. However, more effective treatment methods are still needed to improve the overall prognosis of these patients.
Humans ; Adult ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Prognosis ; Nuclear Pore Complex Proteins/genetics* ; Oncogene Proteins, Fusion/genetics* ; Mutation ; Male ; Female ; Young Adult ; Homeodomain Proteins/genetics*

Baihuasheshecao(Hedyotis diffusa) is a commonly used traditional Chinese medicine derived from the whole herb of H. diffusa and has been widely utilized in folk medicine. It possesses anti-tumor, antibacterial, and anti-inflammatory properties, making it one of the frequently used herbs in TCM clinical practice. However, Shuixiancao(H. corymbosa) and Xianhuaercao(H. tenelliflora), species of the same genus, are often used as substitutes for Baihuasheshecao. To substantiate the medicinal basis of Baihuasheshecao, this study systematically reviewed classical herbal texts and modern literature, examining its nomenclature, botanical origin, harvesting, processing, properties, meridian tropism, pharmacological effects, and clinical applications. The results indicate that Baihuasheshecao was initially recorded as "Shuixiancao" in Preface to the Indexes to the Great Chinese Botany(Zhi Wu Ming Shi Tu Kao). Based on its morphological characteristics and habitat description, it was identified as H. diffusa in the Rubiaceae family. Subsequent records predominantly refer to it as Baihuasheshecao as its official name. In most regions, Baihuasheshecao is recognized as the authentic medicinal material, distinct from Shuixiancao and Xianhuaercao. Baihuasheshecao is harvested in late summer and early autumn, and the dried whole plant, including its roots, is used medicinally. The standard processing method involves cutting. It is known for its effects in clearing heat, removing toxins, reducing swelling and pain, and promoting diuresis to resolve abscesses. Initially, it was mainly used for treating appendicitis, intestinal abscesses, and venomous snake bites, and later, it became a treatment for cancer. The excavation of its clinical value followed a process in which overseas Chinese introduced the herb from Chinese folk medicine to other countries. After its unique anti-cancer effects were recognized abroad, it was reintroduced to China and gradually became a crucial TCM for cancer treatment. The findings of this study help clarify the historical and contemporary uses of Baihuasheshecao, providing literature support and a scientific basis for its rational development and precise clinical application.
Humans ; China ; Drugs, Chinese Herbal/chemistry* ; Hedyotis/classification* ; Medicine, Chinese Traditional/history*

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To investigate the expression of small nuclear ribonucleoprotein D1 (SNRPD1) in the gastric cancer tissue and evaluate the predictive value of SNRPD1 expression level for the long-term prognosis of gastric cancer patients and the possible functioning mechanism of SNRPD1. Methods The UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) were employed to analyze the expression level of SNRPD1 in pan-cancer and its relationship with the prognosis of gastric cancer.The clinical data of 109 patients who underwent radical surgery for gastric cancer from January 2014 to January 2017 in the First Affiliated Hospital of Bengbu Medical University were retrospectively analyzed.Gastric cancer and paracancerous tissue samples were collected,and the expression of SNRPD1 was detected by immunohistochemical staining.Lentiviral transfection was employed to construct the BGC-823 gastric cancer cell models with stable high and low expression of SNRPD1,respectively.The CCK-8 assay and colony formation assay were employed to measure the proliferation of gastric cancer cells,and flow cytometry was used to analyze the cell cycle.Western blotting was employed to determine the expression levels of proteins in the signaling pathway. Results The data from UALCAN and GEPIA showed that SNRPD1 was highly expressed in the tissue of malignant tumors including gastric cancer (P<0.001).The expression level of SNRPD1 in the gastric cancer tissue was higher than that in the paracancerous tissue (P<0.001).Moreover,the expression level of SNRPD1 was positively correlated with the levels of carcinoembryonic antigen (P<0.001),carbohydrate antigen 19-9 (P<0.001),G stage (P=0.042),T stage (P=0.002),and N stage (P=0.027) in the patients with gastric cancer.The high expression of SNRPD1 had a predictive value for the long-term prognosis of gastric cancer (P<0.001),and it was an independent risk factor for the death of gastric cancer patients (P=0.003).The results of gene ontology and kyoto encyclopedia of genes and Genomes enrichment analyses showed that SNRPD1 was involved in the regulation of the cell cycle.The results of CCK-8 and colony formation assays showed that up-regulation of SNRPD1 promoted the proliferation of gastric cancer cells (P<0.001,P<0.001).The up-regulation of SNRPD1 up-regulated the expression of cyclin-dependent kinase 6 and G₁/S-specific cyclin-D1 (P<0.001,P=0.002),whereas the interference in SNRPD1 led to opposite results (P=0.004,P<0.001).SNRPD1 accelerated the G₁/S phase transition of gastric cancer cells (P<0.001).The overexpression of SNRPD1 promoted the expression of phosphorylated phosphatidylinositol 3-kinase (PI3K) and phosphorylated protein kinase B (Akt) in gastric cancer cells (P=0.043,P<0.001),whereas disruption of SNRPD1 inhibited their expression (both P<0.001).Insulin-like growth factor 1,an agonist of the PI3K/Akt signaling pathway,promoted the proliferation of gastric cancer cells with SNRPD1 disturbed (P=0.002). Conclusion High expression of SNRPD1 in the gastric cancer tissues is associated with poor prognosis,and it may promote tumor cell proliferation and regulate the cell cycle by activating the PI3K/Akt signaling pathway.
Humans ; Stomach Neoplasms/pathology* ; Prognosis ; Cell Line, Tumor ; Cell Proliferation ; Retrospective Studies ; Cell Cycle ; Male ; Female

The lesion of the left main coronary artery(LM)itself is one of the challenges of interventional therapy.If the lesion is combined with calcification,the interventional therapy is difficult to operate and extremely risky.This case report presents a 77-year-old elderly male patient.Coronary angiography(CAG)indicated severe stenosis of the LM-left anterior descending(LAD)accompanied by severe calcified bifurcation lesions.After pre-dilation,percutaneous coronary intraluminal shock wave balloon catheter angioplasty(IVL)was applied for treatment.Before IVL treatment,the LM-LAD lesion was subjected to ischemic preconditioning by using an appropriate balloon to fix the pressure and gradually upgrading the balloon dilation time.Later,a Cross-over procedure was performed to implant a single stent,achieving satisfactory results.Among them,the ischemic preconditioning methods for LM lesions can provide reference significance for clinicians.

Objective To evaluate the effect of Intravascular lithotripsy(IVL)in the treatment of calcified nodules,and to observe the presence of coronary dissection after IVL treatment.Methods A total of 106 patients with coronary atherosclerotic heart disease(coronary heart disease)admitted to the cardiovascular Department of Shougang Hospital,Peking University from March 2023 to July 2024 were retrospectively analyzed.A total of 106 patients with moderate to severe stenosis accompanied by calcification as detected by coronary angiography were treated with IVL after intravascular ultrasound(IVUS)examination.Patients were divided into two groups according to whether there were calcified nodules in the coronary lesions:39 cases in the calcified nodules group and 67 cases in the non-calcified nodules group.The occurrence of coronary dissection during surgery was observed between the two groups,and other perioperative related complications and major adverse cardiovascular events(MACE)within 1 month after percutaneous coronary intervention(PCI)were compared between the two groups.Results The levels of renal insufficiency(25.6％vs.9.0％,P=0.021)and creatinine[(119.71±134.75)μmol/L vs.(71.82±16.53)μmol/L,P=0.033]in the calcified nodule group were higher than those in the non-calcified nodule group,the difference was statistically significant,and there was no difference in other baseline data.The target vessels in the calcified nodule group were mainly left anterior descending branch and right coronary artery,while those in the non-calcified nodule group were mainly left anterior descending branch,with few circumflex branches in both groups,and there was statistical significance in the distribution of target vessels in the left anterior descending branch and right coronary artery between the two groups(P=0.020).In terms of eccentric calcification(P=0.048)and asymmetric calcification(48.7％vs.28.4％,P=0.035)between the two groups,the calcified nodule group was higher than the non-calcified nodule group,the difference was statistically significant(P＜0.05).In terms of whether more than 20 pulses were needed and whether there was slippage during IVL,the calcified nodule group was higher than the non-calcified nodule group,the difference was statistically significant(P=0.022).The success rate of interventional therapy was 100％in both groups.After IVL treatment,the calcified nodule group was higher than the non-calcified nodule group in terms of the occurrence of coronary artery dissection,the difference was statistically significant(P＜0.009).The MACE of the two groups within 1 month after PCI was slightly higher in the calcified nodule group than in the non-calcified nodule group,but the difference was not statistically significant(P=0.235).Conclusions IVL is feasible and effective for the treatment of calcified coronary nodules.However,in the course of treatment,the occurrence of coronary dissection should be vigilant,identified as early as possible,and treated in time.

The lesion of the left main coronary artery(LM)itself is one of the challenges of interventional therapy.If the lesion is combined with calcification,the interventional therapy is difficult to operate and extremely risky.This case report presents a 77-year-old elderly male patient.Coronary angiography(CAG)indicated severe stenosis of the LM-left anterior descending(LAD)accompanied by severe calcified bifurcation lesions.After pre-dilation,percutaneous coronary intraluminal shock wave balloon catheter angioplasty(IVL)was applied for treatment.Before IVL treatment,the LM-LAD lesion was subjected to ischemic preconditioning by using an appropriate balloon to fix the pressure and gradually upgrading the balloon dilation time.Later,a Cross-over procedure was performed to implant a single stent,achieving satisfactory results.Among them,the ischemic preconditioning methods for LM lesions can provide reference significance for clinicians.