OBJECTIVE To study the efficacy of Tianjiang xueshuantong pills in the treatment of coronary heart disease. METHODS In accordance with the common pathogenesis of coronary heart disease， acute myocardial ischemia model， hyperlipidemia model， blood stasis model， and carotid artery thrombosis model were established using Wistar rats or SD rats as the experimental subjects. The effects of Tianjiang xueshuantong pills administered at high， medium， and low doses （0.6， 1.2 and 2.4 g/kg） on hemodynamic parameters and myocardial enzyme markers [lactate dehydrogenase （LDH）， creatine kinase-MB （CK- MB）]， oxidative stress factors [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione （GSH）]， inflammatory cytokines [tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， IL-1β， monocyte chemotactic protein-1 （MCP-1）， intercellular adhesion molecule-1 （ICAM-1）]， myocardial infarction percentage， serum lipid indexes [total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）]， platelet aggregation function 话：022-84845240。E-mail：jiangx@tjipr.com [maximum aggregation rate （MAR）]， and thrombus formation indexes [thrombosis time， thrombus mass， thrombus protein content， plasminogen activator inhibitor-1 （PAI-1）， and tissue-type plasminogen activator （t-PA）] were evaluated in the rat models. RESULTS In myocardial ischemia tests， Tianjiang xueshuantong pills significantly reduced the percentage of myocardial infarction and the levels of CK-MB， LDH， MDA， GSH， IL-6， TNF-α， IL- 1β， and MCP-1 in serum （P＜0.05 or P＜0.01）. In hyperlipidemia tests， high dose of Tianjiang xueshuantong pills significantly reduced the serum levels of TC， LDL and significantly increased the level of HDL in rats after 2 weeks and 4 weeks of administration. In blood stasis tests， different doses of Tianjiang xueshuantong pills significantly reduced MAR of rats （P＜0.01）. In artery thrombosis tests， high dose of Tianjiang xueshuantong pills significantly prolonged the time of thrombosis formation （P＜ 0.01）， significantly reduced the weight and protein content of thrombus and the level of PAI-1 in serum （P＜0.01）. CONCLUSIONS Tianjiang xueshuantong pills exert therapeutic effects on coronary heart disease through multi-dimensional synergistic actions， including anti-myocardial ischemia， lipid-lowering， and anti-thrombotic effects.

OBJECTIVES: To investigate the role of a neural pathway from oxytocin (OXT) neurons in the paraventricular hypothalamic nucleus (PVN) to γ-aminobutyric acid (GABA) neurons (GABAergic neurons) in the trigeminal nucleus caudalis (TNC) in regulating pain sensitization in a mouse model of chronic migraine and to explore the underlying mechanisms. METHODS: A chronic migraine mouse model was established by intraperitoneal injection of nitroglycerin (NTG, 1 mg/mL, 10 mg/kg) on days 1, 3, 5, 7, and 9. The study consisted of four parts: PartⅠ: 24 male wild-type C57BL/6J mice were divided into four groups (n=6 in each), receiving single or repeated injection of NTG or saline, respectively. Immunofluorescence was used to detect c-Fos and OXT expression in the PVN. Part Ⅱ: 6 male OXT-Cre transgenic C57BL/6J mice were used for anterograde monosynaptic tracing combined with RNAscope and immunofluorescence to identify neural projections from PVN OXT neurons to TNC GABAergic neurons. Part Ⅲ: 30 male OXT-Cre transgenic C57BL/6J mice were bilaterally injected Cre-dependent chemogenetic activation virus into the PVN. These mice were randomly divided into five groups, with six mice in each group. Mice in the clozapine N-oxide (CNO) group and the control group were intra-peritoneally injected with 0.1 mg/mL of CNO solution (1 mg/kg) and the same volume of isotonic normal saline, respectively. 3 hours after the injection, the brain tissues were harvest and c-Fos immunofluorescence staining was performed to verify the efficiency of chemogenetic activation virus. Mice in the model control group and the CNO activated model group were subjected to chronic migraine modeling, with bilateral TNC injection of isotonic normal saline and CNO, respectively, on day 10. The mice in the negative control group were bilaterally intra-TNC injected with isotonic normal saline. After 30 minutes, the Von-Frey filament and acetone tests were used to assess the mechanical pain threshold and cold pain response time in the periorbital region of the mice in these three groups. Part Ⅳ: 24 male OXT-Cre transgenic C57BL/6J mice were bilaterally injected with the Cre-dependent chemogenetic activation virus into the PVN. These mice were randomly divided into four groups, with six mice in each group. Mice in the model control group, the CNO activated model group and the atosiban group were subjected to chronic migraine modeling. On day 10, mice in the negative control group and the model control group were intraperitoneally injected with isotonic normal saline, while mice in the CNO activated model group and the atosiban group were intraperitoneally injected with CNO. After 15 minutes, mice in the atosiban group were bilaterally intra-TNC injected with atosiban, while mice in other three groups were bilaterally intra-TNC injected with isotonic normal saline containing 1% dimethyl sulfoxide. After 15 minutes, the Von-Frey filament and acetone tests were used to assess the mechanical pain threshold and cold pain response time in the periorbital region of the mice. The GABA content in the bilateral TNC was detected by high-performance liquid chromatography (HPLC). RESULTS: Mice with chronic migraine models exhibited reduced periorbital mechanical pain thresholds and increased periorbital cold pain reaction time, accompanied by an increase in both the number of c-Fos⁺ neurons and the percentage of c-Fos⁺ OXT neurons in the PVN (all P<0.05). The anterograde tracing virus and RNAscope combined with immunofluorescence staining showed that PVN OXT neurons projected to TNC GABAergic neurons. Immuno-fluorescence staining demonstrated that compared with the control group, the percentage of c-Fos⁺ OXT neurons in the PVN of CNO group increased (P<0.05). In bilateral intra-TNC drug administration experiments, compared with the model control group, the periorbital mechanical pain threshold increased, and the periorbital cold pain reaction time decreased in the CNO activated model group (both P<0.05). In intraperitoneal drug administration experiments, compared with the CNO activate model group, the periorbital mechanical pain threshold decreased, and the periorbital cold pain reaction time increased in the atosiban group (both P<0.05). HPLC analysis showed that, compared with the negative control group, the model control group and the atosiban group, GABA level of TNC in the CNO activated model group increased (all P<0.05). CONCLUSIONS PVN OXT neurons exert a descending facilitatory effect on GABAergic neurons in the TNC via OXT release, thereby ameliorating pain sensitization in chronic migraine.
Animals ; Paraventricular Hypothalamic Nucleus/physiopathology* ; Male ; Mice, Inbred C57BL ; Migraine Disorders/physiopathology* ; Mice ; GABAergic Neurons/physiology* ; Oxytocin/physiology* ; Disease Models, Animal ; Neurons/physiology* ; Mice, Transgenic ; Neural Pathways ; Chronic Disease

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*

Objective： To analyze the symptoms, diagnosis and treatment of upper urinary tract calculi patients combined with mild and moderate benign prostatic hyperplasia (BPH) after ureteral stent implantation. Methods： One hundred and six BPH patients who were hospitalized for upper urinary tract calculi and had ureteral stents retained from January 2019 to December 2022 were selected and divided into 2 weeks group and 4 weeks group according to the time of removal of ureteral stents after surgery. Their general clinical data were analyzed and compared. International Prostatic Symptom Scale (IPSS), postoperative ureteral Stent Symptom Questionnaire (USSQ), and incidence of adverse events after ureteral stent removal were recorded before and after removal. Results： The scores of IPSS were significantly increased in all patients, and symptoms in urinary tract had improved significantly after discharge (P<0.05). Compared with the 2 weeks group, the USSQ score of the 4 weeks group was significantly increased (P<0.05). And no significant adverse event was observed in the 2 weeks group after the removal of ureteral sten. Conclusion： IPSS score and USSQ score increased significantly during stent implantation in BPH patients with lithiasis. And complications increased significantly over time. Following thorough clinical assessment, early ureteral stent removal demonstrates both safety and efficacy, representing an optimal therapeutic approach in selected cases.
Humans ; Male ; Prostatic Hyperplasia/surgery* ; Stents ; Ureter/surgery* ; Aged ; Middle Aged ; Urinary Calculi/surgery* ; Ureteral Calculi/surgery*

To explore the regulatory mechanism of drought stress on the synthesis of chlorogenic acid and luteoloside in Lonicera japonica, we designed five drought gradients (soil water contents of 30%, 24%, 17%, 14%, and 10%) and screened and verified the differentially expressed genes (DEGs) by RNA sequencing (RNA-seq) and reverse transcription quantitative polymerase chain reaction (RT-qPCR). Furthermore, we employed HPLC to systematically measure the content changes of chlorogenic acid and luteoloside. The results revealed that drought significantly reduced the accumulation of secondary metabolites, and severe drought led to more obvious reductions. Under extreme drought (soil water content of 10%), the content of chlorogenic acid and luteoloside decreased significantly to 25.73 mg/g and 11.33 mg/g (with the decrease rates of 37.85% and 9.58%, respectively). A total of 77 454 genes were identified via transcriptome analysis, among which the number of DEGs reached 1 128 under the extraordinary drought. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses revealed that the DEGs were mainly involved in flavonoid synthesis, secondary metabolite biosynthesis, plant hormone signal transduction and the plant-pathogen interaction pathways, and the expression of key genes regulating the synthesis of chlorogenic acid and luteoloside was significantly downregulated. RT-qPCR verified the accuracy of the RNA-seq data. This study revealed that drought stress reduced the content of chlorogenic acid and luteoloside, the main secondary metabolites, by inhibiting the expression of key genes in the secondary metabolism pathways. The findings provide candidate gene resources for molecular breeding of drought-tolerant Lonicera japonica.
Lonicera/physiology* ; Chlorogenic Acid/metabolism* ; Droughts ; Stress, Physiological ; Gene Expression Regulation, Plant ; Glucosides/metabolism* ; Luteolin

[摘 要] 目的：探讨低剂量辐射（LDR）与人端粒酶逆转录酶C末端多肽27（hTERTC27）过表达联合治疗对肺癌A549细胞增殖和凋亡的影响，同时观察LDR与常规放疗（CONV-RT）结合的体内抑瘤效应。方法：将pEgr-hTERTC27质粒转染人非小细胞肺癌A549及小鼠LLC肺癌（LLC）细胞，用G418筛选建立稳定表达C27的A549-C27细胞和LLC-C27细胞。细胞实验分为6组，分别是CONV-RT（A549-Con）、低剂量照射（A549-Low）、C27（A549-C27）、常规剂量联合C27（A549-C27-Con）、低剂量照射联合C27（A549-C27-Low）和对照（A549-Mock）组，其中Low组的辐照剂量仅为Con组的36%。MTT法检测各组细胞增殖活性，流式细胞术检测各组细胞凋亡率。通过皮下种植建立LLC肺癌移植瘤小鼠模型，动物实验分组同细胞实验；记录各组小鼠肿瘤生长情况，并检测各组肿瘤体积和质量，H-E染色观察各组移植瘤组织邻近肌肉浸润情况。结果：与A549-Mock比较，A549-Con和A549-Low组细胞增殖活性均显著降低（均P < 0.01）；而且A549-C27-Con和A549-C27-Low组细胞增殖活性显著低于A549-C27组（均P < 0.01）。与A549-Mock组比较，A549-Con组和A549-Low组细胞凋亡率均显著升高（均P < 0.01）；A549-C27、A549-C27-Con和A549-C27-Low组细胞凋亡率无显著差异（P > 0.05）。与未经照射治疗的荷瘤小鼠相比较，CONV-RT及LDR + CONV-RT均可使荷瘤小鼠肿瘤质量显著降低（均P < 0.01）。此外，LDR + CONV-RT + C27组肿瘤质量显著减小，局部浸润减少（均P < 0.01）。结论：LDR与CONV-RT相结合能够在降低辐射总剂量的同时达到与CONV-RT单独使用相似的非小细胞肺癌肿瘤抑制效果。而且，LDR与C27多肽有协同抗肿瘤作用，两者同时使用能够使移植瘤局部浸润减少。

Objective To investigate the mechanism of matrine hydrochloride injection on acetaminophen(APAP)induced liver injury in mice.Methods Sixty male Kunming mice were randomly divided into blank group,model group and experimental-L,-M,-H groups.The mice were abdominal injected 300 mg·kg-1 APAP to build the acute liver injury modeling.The experimental-L,-M,-H groups were intravenous injected matrine of 0.7,1.4,and 2.8 mg·kg-1,respectively.Blank and model groups were injected with 10％glucose solution 10 mL·kg-1·d-1 via tail vein.Enzyme-linked immunosorbent assay were used to measure the levels of glutamic oxaloacetic transaminase(GOT),glutamic oxaloacetic transaminase(GPT),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in mice serum.The kit were employed to detect the levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in liver tissue.Results The serum GOT levels in the experimental-M,-H groups,model group and blank group were(5 593.45±128.46),(2 316.24±125.37),(8 302.16±267.15)and(40.13±7.69)U·L-1;the GPT levels were(6 159.37±129.64),(2 597.10±120.37),(8 1699.54±259.87)and(36.47±9.46)U·L-1;the IL-6 levels were(159.43±26.42),(96.37±25.84),(215.34±47.68)and(83.72±26.37)pg·mL-1;the TNF-α levels were(327.68±38.37),(249.69±44.97),(477.68±58.59)and(254.35±50.67)pg·mL-1;the SOD levels were(329.46±37.49),(371.16±33.76),(246.84±38.79)and(429.67±23.76)U·mg-1;the MDA levels were(5.34±0.76),(4.09±0.54),(12.46±3.76)and(3.12±0.42)nmol·mg-1.There were significant differences between the experimental-M,-H groups and the model group(all P＜0.05).Conclusion Matrine has a significant protective effect on APAP induced drug-induced liver injury,and its protective mechanism is related to inhibiting inflammatory response and alleviating oxidative stress response.

Objective:To discuss the clinical curative effect of the treatment of bundling bone fragment with figure-of-eight suture through double bone tunnels in the chronic bong mallet finger.Methods:A retrospective analysis was performed on patients with chronic bong mallet fingers who underwent surgery in the Department of Hand and Foot Microsurgery of Nanjing Jiangbei Hospital from May 2021 to February 2023. During the procedure, made into transverse double bone tunnels on the base of the distal phalanx with 0. 8 mm Kirschner wire, bundling bone fragment with figure-of-eight suture through double bone tunnels, then fixed with Kirschner wire elastic compression. Removal of the Kirschner wire 3 weeks after the procedure, the active flexion and extension range of the joints of the affected finger and the corresponding finger were measured at the last follow-up, then the range of motion (ROM) of the distal interphalangeal joint (DIPJ) and total action movement (TAM) of the fingers (affected and healthy finger) were recorded. The curative effects were evaluated according to the TAM system of the American Association of Hand Surgeons, including 4 grades: excellent, good, fair, and poor. SPSS 13. 0 software was used for statistical analysis of the data, and the measurement data conforming to normal distribution were expressed as Mean ± SD. The ROM of DIPJ and TAM of the affected finger were compared with the corresponding healthy finger 6 months after surgery by a paired sample t test. P<0. 05 indicates that the difference is statistically significant. Results:A total of 30 patients (30 digits) were enrolled, including 19 males and 11 females, and the age ranged from 18 to 62 years old, with an average age of 31 years old. The time from injury to operation was 24 to 65 days (mean of 35 days) . According to Wehbe and Schneider classification, there were 8 cases of type Ⅰa, 6 cases of type Ⅰb, 7 cases of type Ⅱa, 5 cases of type Ⅱb, 2 cases of type Ⅲa and 2 cases of type Ⅲb. All incisions healed well, the intraoperative blood loss was minimal, with no infection. All 30 cases were followed up for 6 to 7 months. All fractures were well aligned and healed, malformed fingers were completely corrected, and no needle tunnel infection or needle breakage were observed. At the last follow-up, the differences of the ROM of the DIPJ [ (30. 2±3. 5) °vs. (30. 4±3. 3) °, t=2. 57, P=0. 463] and the TAM [ (235. 3± 3. 6) ° vs. (237. 7± 4. 2) °, t=1. 78, P= 0. 247 ] between the affected and healthy fingers were not statistically significant. Finger function assessment: 27 cases were excellent, and 3 cases were good, and the excellent and good rate was 100%. Conclusion:Satisfactory therapeutic outcome for the treatment of chronic bong mallet finger deformity can be achieved by bundling bone fragment with figure-of-eight suture through double bone tunnels. It is an effective and practical method.

Objective:To discuss the clinical curative effect of the treatment of bundling bone fragment with figure-of-eight suture through double bone tunnels in the chronic bony mallet finger.Methods:A retrospective analysis was performed on patients with chronic bony mallet fingers who underwent surgery in the Department of Hand and Foot Microsurgery of Nanjing Jiangbei Hospital from May 2021 to February 2023. During the procedure, made into transverse double bone tunnels on the base of the distal phalanx with 0.8 mm Kirschner wire, bundling bone fragment with figure-of-eight suture through double bone tunnels, then fixed with Kirschner wire elastic compression. Removal of the Kirschner wire 3 weeks after the procedure, the active flexion and extension range of the joints of the affected finger and the corresponding finger were measured at the last follow-up, then the range of motion (ROM) of the distal interphalangeal joint (DIPJ) and total action movement (TAM) of the fingers (affected and healthy finger) were recorded. The curative effects were evaluated according to the TAM system of the American Association of Hand Surgeons, including 4 grades: excellent, good, fair, and poor. SPSS 13.0 software was used for statistical analysis of the data, and the measurement data conforming to normal distribution were expressed as Mean±SD. The ROM of DIPJ and TAM of the affected finger were compared with the corresponding healthy finger 6 months after surgery by a paired sample t-test. P<0.05 indicated that the difference was statistically significant. Results:A total of 30 patients (30 digits) were enrolled, including 19 males and 11 females, and the age ranged from 18 to 62 years old, with an average age of 31 years old. The time from injury to operation was 24 to 65 days (mean of 35 days). According to Wehbe and Schneider classification, there were 8 cases of type Ⅰa, 6 cases of type Ⅰb, 7 cases of type Ⅱa, 5 cases of type Ⅱb, 2 cases of type Ⅲa and 2 cases of type Ⅲb. All incisions healed well, the intraoperative blood loss was minimal, with no infection. All 30 cases were followed up for 6 to 7 months. All fractures were well aligned and healed, malformed fingers were completely corrected, and no needle tunnel infection or needle breakage were observed. At the last follow-up, the differences of the ROM of the DIPJ [(30.2±3.5)° vs. (30.4±3.3)°, t=2.57, P=0.463] and the TAM [(235.3±3.6)° vs. (237.7±4.2)°, t=1.78, P=0.247] between the affected and healthy fingers were not statistically significant. Finger function assessment: 27 cases were excellent, and 3 cases were good, and the excellent and good rate was 100%. Conclusion:Satisfactory therapeutic outcome for the treatment of chronic bony mallet finger deformity can be achieved by bundling bone fragment with figure-of-eight suture through double bone tunnels. It is an effective and practical method.