OBJECTIVE: To elucidate the modulation mechanism of Suanzaoren Decoction (SZRD) on basolateral amygdala (BLA) neuronal activity to alleviate chronic restraint stress (CRS)-related behavioral deficits. METHODS: The male C57BL/6J mice were assigned to 4 groups using the complete randomization method, including control (CON, n=19), CRS (n=19), SZRD (n=21), and fluoxetine (Flu, n=22) groups. Mice were restrained for 6 h per day, over a 21-d period to establish CRS models. The CON group remained in their cages without food or water during the 6-h matching period. SZRD and Flu groups received intragastric administration of SZRD (4.68 g/kg) and Flu (20 mg/kg) daily, respectively, 30 min before restraint for 21 consecutive days. The therapeutic effects of SZRD were evaluated using behavioral tests including the tail suspension test, elevated plus maze test, and forced swimming test. The cellular Fletcher B. Judson murine osteosarcoma proto-oncogene (c-Fos) expression in the BLA was measured using immunofluorescence, while action potential (AP) firing and synaptic transmission in BLA pyramidal neurons were evaluated using whole-cell patch-clamp recordings. RESULTS: SZRD administration significantly increased time spent in the open arms and open-arm entries while reducing immobility time (P<0.05 or P<0.01). It downregulated CRS-induced c-Fos expression and AP firing of pyramidal neurons in the BLA (P<0.01). Additionally, SZRD selectively attenuated excitatory (P<0.01), but not inhibitory, synaptic transmission onto BLA pyramidal neurons. CONCLUSION SZRD alleviated CRS-induced anxiety- and depression-like behaviors in mice by modulating the excitability and synaptic transmission of BLA pyramidal neurons.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Depression/complications* ; Pyramidal Cells/pathology* ; Male ; Mice, Inbred C57BL ; Basolateral Nuclear Complex/pathology* ; Restraint, Physical ; Anxiety/complications* ; Behavior, Animal/drug effects* ; Stress, Psychological/physiopathology* ; Mice ; Proto-Oncogene Proteins c-fos/metabolism* ; Action Potentials/drug effects* ; Synaptic Transmission/drug effects*

The effects of different robust optimization parameters on the doses to organs-at-risk(OAR)and the clinical target volume(CTV)in proton therapy plans for localized prostate cancer are explored for identifying the optimal robust optimization parameters.A retrospective analysis is conducted on 10 cases in which proton plans with a total dose of 76 Gy delivered in 38 fractions are designed.In robust optimization,uncertainties of 3.5%in range and setup errors of 3,5 and 7 mm are considered.After being grouped by setup errors,3 groups of plans are obtained.The effects of setup errors on the doses to CTV and OAR are analyzed,and the robustness of the CTV dose is assessed,including the worst-case values of dosimetric parameters and the passing rates under different scenarios.The results show that as the setup error increased,the doses to OAR tended to rise.Compared with the 3 mm plan group,the 5 mm and 7 mm plan groups experience increases of 1.99%and 5.15%in rectal V70,3.71%and 10.01%in rectal V45,0.93%and 2.55%in bladder V70,and 1.71%and 5.27%in bladder V45,respectively;similar patterns are observed for the doses to sigmoid colon and bulbous urethra,and the differences are statistically significant(P<0.05).In robustness analysis,the CTV D99 in the 5 mm and 7 mm plan groups increases by 0.68 Gy and 0.95 Gy as compared with the 3 mm plan group,with passing rates improving by 7.2%and 9.6%,respectively(passing criterion:D95 receives at least 100%of the prescribed dose),with significant differences(P<0.05).Considering both OAR dose and CTV robustness,the setup error of 5 mm is found to be a reasonable choice for robust optimization in proton therapy plans for localized prostate cancer,as it can effectively balance the enhancement of CTV dose robustness with the control of dose escalation to OAR.

Objective:Exploring the association rules of factors influencing high hospitalization costs for cancer patients, providing references for hospitals to optimize medical cost management measures.Methods:In the inpatient case information system of a tertiary general hospital, the medical record homepages of inpatients in the DRG groups of the oncology department in 2022 were obtained. The upper four scores of hospitalization costs was used as the threshold for patient grouping. Patients with hospitalization costs≥this threshold were the high-cost group, while other patients were control group; 12 factors, including age, gender, and admission condition, etc, were considered as potential influencing factors of high hospitalization costs. FP-Growth and Apriori algorithms were used to excavate the potential association rules between the influencing factors of high hospitalization costs. Logistic regression was used to analyze the independent influencing factors of high hospitalization costs.Results:A total of 5 512 hospitalized patients were included, including 1 378 patients in the high-cost group. Thirteen validated strong association rules for factors influencing high hospitalization costs were obtained, of which the rule antecedents included age (≥70 years), number of days in hospital (≥7 days), other diagnoses (≥5), surgery, planned readmission, use of antibiotics, admission (general/critical), living admission score (61~99), level of care (level 1/level 2), non-day ward, criticality during hospitalisation. Logistic regression results showed that all nine influencing factors except gender, use of antibiotics, and readmission plans were independent influences on high hospitalization costs ( P<0.05). Conclusions:The joint application of FP-Growth and Apriori algorithm could effectively explore the association rules of high hospitalization costs for oncology patients. The early warning information mainly included the number of hospitalization days, the number of other diagnoses, surgeries, and so on. It was suggested that medical institutions can reasonably control the high hospitalization costs through clinical pathway management, diagnosis and treatment process reengineering, admission risk assessment, and multidisciplinary collaborative diagnosis and treatment strategies.

The effects of different robust optimization parameters on the doses to organs-at-risk(OAR)and the clinical target volume(CTV)in proton therapy plans for localized prostate cancer are explored for identifying the optimal robust optimization parameters.A retrospective analysis is conducted on 10 cases in which proton plans with a total dose of 76 Gy delivered in 38 fractions are designed.In robust optimization,uncertainties of 3.5%in range and setup errors of 3,5 and 7 mm are considered.After being grouped by setup errors,3 groups of plans are obtained.The effects of setup errors on the doses to CTV and OAR are analyzed,and the robustness of the CTV dose is assessed,including the worst-case values of dosimetric parameters and the passing rates under different scenarios.The results show that as the setup error increased,the doses to OAR tended to rise.Compared with the 3 mm plan group,the 5 mm and 7 mm plan groups experience increases of 1.99%and 5.15%in rectal V70,3.71%and 10.01%in rectal V45,0.93%and 2.55%in bladder V70,and 1.71%and 5.27%in bladder V45,respectively;similar patterns are observed for the doses to sigmoid colon and bulbous urethra,and the differences are statistically significant(P<0.05).In robustness analysis,the CTV D99 in the 5 mm and 7 mm plan groups increases by 0.68 Gy and 0.95 Gy as compared with the 3 mm plan group,with passing rates improving by 7.2%and 9.6%,respectively(passing criterion:D95 receives at least 100%of the prescribed dose),with significant differences(P<0.05).Considering both OAR dose and CTV robustness,the setup error of 5 mm is found to be a reasonable choice for robust optimization in proton therapy plans for localized prostate cancer,as it can effectively balance the enhancement of CTV dose robustness with the control of dose escalation to OAR.

Objective:Exploring the association rules of factors influencing high hospitalization costs for cancer patients, providing references for hospitals to optimize medical cost management measures.Methods:In the inpatient case information system of a tertiary general hospital, the medical record homepages of inpatients in the DRG groups of the oncology department in 2022 were obtained. The upper four scores of hospitalization costs was used as the threshold for patient grouping. Patients with hospitalization costs≥this threshold were the high-cost group, while other patients were control group; 12 factors, including age, gender, and admission condition, etc, were considered as potential influencing factors of high hospitalization costs. FP-Growth and Apriori algorithms were used to excavate the potential association rules between the influencing factors of high hospitalization costs. Logistic regression was used to analyze the independent influencing factors of high hospitalization costs.Results:A total of 5 512 hospitalized patients were included, including 1 378 patients in the high-cost group. Thirteen validated strong association rules for factors influencing high hospitalization costs were obtained, of which the rule antecedents included age (≥70 years), number of days in hospital (≥7 days), other diagnoses (≥5), surgery, planned readmission, use of antibiotics, admission (general/critical), living admission score (61~99), level of care (level 1/level 2), non-day ward, criticality during hospitalisation. Logistic regression results showed that all nine influencing factors except gender, use of antibiotics, and readmission plans were independent influences on high hospitalization costs ( P<0.05). Conclusions:The joint application of FP-Growth and Apriori algorithm could effectively explore the association rules of high hospitalization costs for oncology patients. The early warning information mainly included the number of hospitalization days, the number of other diagnoses, surgeries, and so on. It was suggested that medical institutions can reasonably control the high hospitalization costs through clinical pathway management, diagnosis and treatment process reengineering, admission risk assessment, and multidisciplinary collaborative diagnosis and treatment strategies.

Objective To explore the possible mechanism of Naoshuantong capsule in the treatment of cerebral infarction by network pharmacology and molecular docking technology.Methods The main active ingredients and targets of Naoshuantong Capsule were screened based on the TCMSP database.At the same time,the targets related to cerebral infarction were collected through GeneCards,OMIM,PharmGKB,TTD and DrugBank databases,and the intersection targets of drugs and diseases were obtained using InteractiVenn platform.Cytoscape software was used to construct the"active ingredient-disease target"network model.STRING database and Cytoscape software were used to construct protein interaction network diagrams,and core targets were screened according to the degree.GO functional analysis and KEGG pathway enrichment analysis were performed on inter-secting targets using R language.Finally,AutoDock Vina and Symol were used to molecularly dock the active components in the"active ingredient-disease target"network with protein targets.Results 23 active ingredients and 264 related potential targets of Naoshuantong Capsule were collected;2,043 targets related to cerebral infarction were also collected;149 common targets were obtained by the intersection of the two.It mainly acts on JUN,TNF,IL6,NFKBIA and so on,which mainly involve TNF signa-ling pathway,IL-17 signaling pathway,NF-kappa B signaling pathway and apoptosis pathway to play a role in the treatment of cerebral infarction.Molecular docking results showed that the active components of drugs in the network bind well to target pro-teins.Conclusion This study preliminarily revealed the potential multi-component,multi-target and multi-pathway mecha-nism of Naoshuantong Capsule for cerebral infarction by network pharmacology,molecular docking and bioinformatics analysis.

AIM: To investigate the application value of Worst lacrimal probe combined with modified lacrimal duct intubation in anastomosis of complex canalicular laceration.METHODS: Retrospective study. A total of 68 cases(68 eyes)with complex traumatic canalicular laceration treated in the ophthalmology department of the Second Affiliated Hospital of Zunyi Medical University from March 1, 2019 to March 31, 2021 were selected. They were divided into two groups according to the surgical methods, with 36 patients(36 eyes)who were treated with the Worst lacrimal probe to find the broken end of lacrimal duct combined with improved lacrimal duct threading intubation in group A, and 32 patients(32 eyes)who were treated with microscope to find the broken end of lacrimal duct and two-way intubation anastomosis canaliculus intubation in group B. The clinical efficacy, success rate of intraoperative search for the broken end of lacrimal duct, searching time, operation time, the degree of pain, postoperative ocular foreign body sensation and complications were compared between the two groups.RESULTS: The total effective rate of clinical efficacy in patients of group A was higher than that in group B(94% vs. 38%), the success rate of intraoperative search for broken end of lacrimal duct was higher than that in group B(100% vs. 47%), the searching time and operation time were shorter than those in group B, and the score of pain degree was lower than that in group B(all P<0.05). The postoperative follow-up for 6mo-1a showed that the ocular foreign body sensation score, the incidence of lacrimal punctum rupture and morphological change, and the degree of tear overflow in group A were all lower than those in group B(all P<0.05).CONCLUSION: Worst lacrimal probe combined with modified lacrimal duct intubation for the treatment of complex traumatic canalicular laceration can find the broken end of lacrimal duct more accurately, shorten the operation time, reduce the pain and foreign body sensation of patients, improve clinical efficacy and reduce the incidence of complications.

Objective:To observe the protective effect of Qishen Yiqi Dripping Pills on myocardial ischemia-reperfusion injury in type 2 diabetic rats and its effects on mitochondrial autophagy phosphoglycerate mutase family member 5 (PGAM5)/Fun14 domain-containing protein 1 (FUNDC1) signaling pathway.Methods:48 male SD rats were divided into a blank control group, sham operation group, No.1 myocardial ischemia reperfusion injury (MIRI) group, No.2 MIRI group, inhibitor group, and Qishen Yiqi group. In addition to the blank control group and the No.1 MIRI group, the other 32 rats were fed with a high-fat diet combined with intraperitoneal injection of streptozotocin to establish animal models of diabetes. Then, the rats in the Qishen Yiqi group were ig Qishen Yiqi Gropping Pills 450 mg/kg, once daily. The rats in the inhibitor group were given Qishen Yiqi Gropping Pills and trimethylamine (3-MA) by intraperitoneal injection 100 mmol/L, once daily. And the rats in the other four groups were ig normal saline. One week after intragastric administration, except for the blank control group and the sham operation group, the rats in the other four groups were used to establish the animal model of myocardial ischemia-reperfusion injury by ligating the anterior descending branch of the left coronary artery for 30 min and reperfusion for 2 h. Then, the materials were taken after reperfusion for 2 h. Finally, the mortality of rats was calculated, the changes in creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in myocardial tissue were detected, and the expression level of PGAM5/FUNDC1 pathway node protein in myocardial tissue was measured by real-time fluorescence quantitative PCR.Results:Compared with the No.1 MIRI group, serum indicators of the AST, LDH, CK, and MDA levels in the No.2 MIRI model group increased (all P < 0.05), while the level of SOD decreased ( P < 0.05). Compared with the No.1 MIRI group, myocardial tissue indicators of FUNDC1, PGAM5, B cell lymphoma-xL (Bcl-xL), light chain 3 (LC3), autophagy associated protein 5 (ATG5), and Beclin-1 level decreased (all P < 0.05), the level of P62 increased ( P < 0.05), while the level of cysteinyl aspartate specific proteinase-9 (Caspase-9) increased, but he difference is not statistically significant ( P > 0.05). Compared with the No.2 MIRI group and the inhibitor group, serum indicators of the AST, LDH, CK, and MDA levels in the Qishen Yiqi group decreased (all P < 0.05), and the level of SOD increased ( P < 0.05). Compared with the No.2 MIRI group and the inhibitor group, myocardial tissue indicators of FUNDC1, PGAM5, Bcl-xL, LC3, ATG5, and Beclin-1 levels increased (all P < 0.05), while the levels of P62 and Caspase-9 decreased (all P < 0.05). Conclusions:High blood sugar levels can aggravate MIRI. Qishen Yiqi Dripping Pills can regulate mitochondrial autophagy through the PGAM5/FUNDC1 pathway and alleviate myocardial ischemia-reperfusion injury. MIRI plays a protective role in the myocardium of diabetic rats.

A method based on ultra-high performance liquid chromatography coupled with triple quadrupole linear ion trap-tandem mass spectrometry(UHPLC-QTRAP-MS/MS) was developed for the simultaneous determination of 41 bioactive constituents of flavonoids, organic acids, nucleosides, and amino acids in Lysimachiae Herba. The content of multiple bioactive constituents was compared among the samples from different habitats. The chromatographic separation was performed in a Waters XBridge®C_(18) column(4.6 mm×100 mm, 3.5 μm) at 30 ℃. The gradient elution was performed with 0.4% methanol(A)-formic acid water(B) as the mobile phase at a flow rate of 0.8 mL·min~(-1), and the multiple-reaction monitoring(MRM) mode was adopted. According to the content of 41 constituents, hierarchical cluster analysis(HCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and gray relational analysis(GRA) were perfomed to comprehensively evaluate the samples from different habitats. The results showed that the 41 constituents exhibited good linear relationship within the tested concentration ranges, with the correlation coefficients(r) greater than 0.999 4. The method featured good precision, repeatability, and stability with the relative standard deviations(RSDs) less than 5.0%. The average recoveries of the 41 constituents ranged from 98.06% to 101.9%, with the RSDs of 0.62%-4.6%. HCA and OPLS-DA separated 48 batches of Lysimachiae Herba samples from different habitats into three categories: the producing areas in Sichuan and Chongqing, the producing areas in Jiangsu, Zhejiang, and Jiangxi, and the producing areas in Guizhou. The content of 41 constituents varied among the Lysimachiae Herba samples from different habitats. The GRA results revealed that the Lysimachiae Herba sample from Nanchong City, Sichuan Province had the best comprehensive quality. The method developed in this study was accurate and reliable and thus can be used for comprehensive evaluation of Lysimachiae Herba quality and provide basic information for the selection of habitats.
Tandem Mass Spectrometry/methods* ; Multivariate Analysis ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Amino Acids/analysis*

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*