OBJECTIVES: To investigate the effects of quercetin on cuproptosis and L-type calcium currents in the myocardium of diabetic rats. METHODS: Forty SD rats were randomized into control group and diabetic model groups. The rat models of diabetes mellitus (DM) induced by high-fat and high-sugar diet combined with streptozotocin (STZ) injection were further divided into DM model group, quercetin treatment group, and empagliflozin treatment group (n=10). Blood glucose and body weight were measured every other week, and cardiac function of the rats was evaluated using echocardiography. HE staining, Sirius red staining, and wheat germ agglutinin (WGA) analysis were used to observe the changes in myocardial histomorphology, and serum copper levels and myocardial FDX1 expression were detected. In cultured rat cardiomyocyte H9c2 cells with high-glucose exposure, the effects of quercetin and elesclomol, alone or in combination, on intracellular CK-MB and LDH levels and FDX1 expression were assessed, and the changes in L-type calcium currents were analyzed using patch-clamp technique. RESULTS: The diabetic rats exhibited elevated blood glucose, reduced body weight, impaired left ventricular function, increased serum copper levels and myocardial FDX1 expression, decreased L-type calcium currents, and prolonged action potential duration. Quercetin and empagliflozin treatment significantly lowered blood glucose, improved body weight, and restored cardiac function of the diabetic rats, and compared with empagliflozin, quercetin more effectively reduced serum copper levels, downregulated FDX1 expression, and enhanced myocardial L-type calcium currents in diabetic rats. In H9c2 cells, high glucose exposure significantly increased myocardial expressions of FDX1, CK-MB and LDH, which were effectively lowered by quercetin treatment; Elesclomol further elevated FDX1, CK-MB and LDH levels in the exposed cells, and these changes were not significantly affected by the application of quercetin. CONCLUSIONS Quercetin ameliorates myocardial injury in diabetic rats possibly by suppressing myocardial cuproptosis signaling and restoring L-type calcium channel activity.
Animals ; Quercetin/pharmacology* ; Calcium Channels, L-Type/metabolism* ; Diabetes Mellitus, Experimental/metabolism* ; Rats, Sprague-Dawley ; Rats ; Myocytes, Cardiac/drug effects* ; Myocardium/pathology* ; Male

Objective:To explore the short-term clinical effects of deep cervical lymph node-venous anastomosis in the treatment of Alzheimer’s disease (AD).Methods:A prospective exploratory study was conducted on the treatment of AD patients using the cervical deep lymph node-venous anastomosis technique in Scar and Wound Treatment Department, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, from September to October 2024. The patients underwent high-frequency ultrasound to locate deep cervical lymph nodes and the external jugular vein. Under general anesthesia, bilateral deep cervical lymph node-venous anastomoses were performed. Indocyanine green (ICG) lymphography was conducted via subcutaneous injection behind the ear to visualize lymph nodes in levels Ⅱ and Ⅲ. After making a skin incision along the posterior margin of the sternocleidomastoid muscle, the external jugular vein, internal jugular veins, and associated lymph nodes were exposed. Adjacent veins were selected for anastomosis of lymph node. Using microsurgical techniques, end-to-side or end-to-end anastomosis was completed for lymph nodes in levels Ⅱ and Ⅲ. Preoperative assessments included the mini-mental state examination (MMSE, a higher score indicates better cognitive function), Alzheimer’s disease assessment scale-cognitive subscale (ADAS-Cog, a higher score indicates greater impairment of cognitive function), Alzheimer’s disease cooperative study scale for activities of daily living (ADCS-ADL, a higher score indicates better ability to perform daily activity), and neuropsychiatric inventory (NPI, a higher score indicates more severe behavioral and emotional symptom). Postoperative follow-up included the same scales to observe changes in cognitive function, activities of daily living, and emotional communication.Results:Four patients (1 male, 3 females, aged 58-79 years) with AD were included. All were diagnosed based on cerebrospinal fluid biomarkers. All patients successfully underwent bilateral deep cervical lymph node-venous anastomoses. On average, 4.3 (2-7 per person) anastomoses were performed per patient. Surgical procedures lasted an average of 6.5 h (5.5-8.5 h) with minimal blood loss (less than 50 ml). Patients resumed normal activity within 6 hours postoperatively and were discharged after an average of 4.1 d (3.5-5.0 d). Postoperative complications included one case each of aspiration pneumonia, lower limb venous thrombosis, and transient delirium, all of whom resolved without long-term effects. Clinical symptoms, including memory decline, mood swings, and anxiety, showed varying degrees of improvement. Patients reported enhanced quality of life, emotional stability, and social engagement, confirming the procedure’s safety and potential cognitive benefits. At one month postoperatively, the MMSE scores of the four patients increased by an average of 0.8 points compared to preoperative levels. Additionally, the two patients who completed the ADAS-Cog assessments showed a decrease in their scores (reduced by 1.0 points and 11.3 points, respectively, compared to preoperative scores), indicating a certain degree of improvement in cognitive function during this period. The ADCS-ADL and NPI scores of four patients varied significantly, without showing any clear pattern.Conclusion:Lymphovenous anastomosis of the deep cervical lymph node-venous anastomosis may provide a new surgical intervention approach for AD, but further large-scale studies and long-term follow-up are needed to validate its safety and effectiveness.

Objective:To explore the short-term clinical effects of deep cervical lymph node-venous anastomosis in the treatment of Alzheimer’s disease (AD).Methods:A prospective exploratory study was conducted on the treatment of AD patients using the cervical deep lymph node-venous anastomosis technique in Scar and Wound Treatment Department, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, from September to October 2024. The patients underwent high-frequency ultrasound to locate deep cervical lymph nodes and the external jugular vein. Under general anesthesia, bilateral deep cervical lymph node-venous anastomoses were performed. Indocyanine green (ICG) lymphography was conducted via subcutaneous injection behind the ear to visualize lymph nodes in levels Ⅱ and Ⅲ. After making a skin incision along the posterior margin of the sternocleidomastoid muscle, the external jugular vein, internal jugular veins, and associated lymph nodes were exposed. Adjacent veins were selected for anastomosis of lymph node. Using microsurgical techniques, end-to-side or end-to-end anastomosis was completed for lymph nodes in levels Ⅱ and Ⅲ. Preoperative assessments included the mini-mental state examination (MMSE, a higher score indicates better cognitive function), Alzheimer’s disease assessment scale-cognitive subscale (ADAS-Cog, a higher score indicates greater impairment of cognitive function), Alzheimer’s disease cooperative study scale for activities of daily living (ADCS-ADL, a higher score indicates better ability to perform daily activity), and neuropsychiatric inventory (NPI, a higher score indicates more severe behavioral and emotional symptom). Postoperative follow-up included the same scales to observe changes in cognitive function, activities of daily living, and emotional communication.Results:Four patients (1 male, 3 females, aged 58-79 years) with AD were included. All were diagnosed based on cerebrospinal fluid biomarkers. All patients successfully underwent bilateral deep cervical lymph node-venous anastomoses. On average, 4.3 (2-7 per person) anastomoses were performed per patient. Surgical procedures lasted an average of 6.5 h (5.5-8.5 h) with minimal blood loss (less than 50 ml). Patients resumed normal activity within 6 hours postoperatively and were discharged after an average of 4.1 d (3.5-5.0 d). Postoperative complications included one case each of aspiration pneumonia, lower limb venous thrombosis, and transient delirium, all of whom resolved without long-term effects. Clinical symptoms, including memory decline, mood swings, and anxiety, showed varying degrees of improvement. Patients reported enhanced quality of life, emotional stability, and social engagement, confirming the procedure’s safety and potential cognitive benefits. At one month postoperatively, the MMSE scores of the four patients increased by an average of 0.8 points compared to preoperative levels. Additionally, the two patients who completed the ADAS-Cog assessments showed a decrease in their scores (reduced by 1.0 points and 11.3 points, respectively, compared to preoperative scores), indicating a certain degree of improvement in cognitive function during this period. The ADCS-ADL and NPI scores of four patients varied significantly, without showing any clear pattern.Conclusion:Lymphovenous anastomosis of the deep cervical lymph node-venous anastomosis may provide a new surgical intervention approach for AD, but further large-scale studies and long-term follow-up are needed to validate its safety and effectiveness.

This study was aimed at understanding the detection rate,drug resistance characteristics,virulence characteris-tics,multi-locus sequence typing,and other molecular epidemic and pathogenic characteristics of Campylobacter jejuni and Campylobacter coli in children in Guangdong Province from 2020 to 2022.Anal swabs or stool samples of suspected infection cases in children from 2020 to 2022 were collected from two hospitals in Guangzhou,Guangdong Province.Campylobacter was isolated and cultured through the filtration method,and identified with a microbial mass spectrometry system;antibiotic resist-ance was analyzed with the agar dilution method;bacterial genome nucleic acids were extracted,and whole-genome sequencing was conducted;and drug resistance genes,virulence genes,multi-locus sequence typing,and phylogenetic analysis based on whole-genome single nucleotide polymorphisms were analyzed from whole-genome sequencing results.First,53 strains of Campy-lobacter were detected through continuous routine monitoring in this study,with a positive detection rate of 2.94％.Among them,Campylobacter jejuni accounted for 81.13％(43/53)and Campylobacter coli accounted for 18.87％(10/53).In addition,16 strains of Campylobacter were screened through multi-pathogen surveillance,including 11 strains of Campylobacter jejuni and 5 strains of Campylobacter coli.Drug resistance ex-periments and whole genome sequencing were conducted on 46 Campylobacter isolates,including 33 isolates of Campylobacter jejuni and 13 isolates of Campylobacter coli.The resistance rate of Campylobacter to erythromycin,a widely used clinical treatment,was21.73％(10/46);that to tetracycline was 80.43％(37/46);those to the quinolone antibiotics nalidixic acid and ciprofloxacin were 76.08％(35/46)and 71.73％(33/46)respectively;and that to chloramphenicol was lowest,at 2.17％(1/46).The drug resistance rate was generally higher for Campylobacter coli than Campylobacter jejuni,and the differences in the indicators of erythromycin,gentamicin,streptomycin,telithromycin,and clindamycin were statistically significant.A total of 30 isolates of multidrug-resistant Campylobacter were detected,including nine multidrug-resistant phenotypes.Whole-ge-nome sequence analysis indicated that 46 Campylobacter isolates carried antibiotic resistance genes for antibiotics such as quino-lones,tetracyclines,β-lactams,and aminoglycosides,and carried 128 virulence factor genes in five categories.All 46 isolates of Campylobacter were identified as 35 ST type through MLST typing,and phylogenetic analysis indicated no obvious dominant ST type.Campylobacter coli had more SNPs than Campylobacter jejuni.In conclusion,the positive detection rate of Campy-lobacter in Guangzhou City,Guangdong Province stabilized from 2020 to 2022,and the detection rate of Campylobacter jejuni was higher than that of Campylobacter coli.Campylobacter isolates were resistant to tetracyclines and quinolone,and showed a wide spectrum of multi-drug resistance,which was relatively severe among Campylobacter coli.Resistance genes and drug-resistant phenotypes were correlated and had predictive significance.The virulence genes of Campylobacter jejuni were more a-bundant than those of Campylobacter coli,possibly because of the higher detection rate and pathogenicity of Campylobacter jejuni.The phylogenetic tree showed clear branches with high genetic diversity and no clearly dominant clonal group.

Objective:To compare the chemical constituents of Puerariae Flos from three different varieties of Pueraria montana var. lobata， P. montana var. thomsonii and P. montana var. montana. Method:Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF-MS） was used with the mobile phase of 0.1% formic acid aqueous solution （A）-acetonitrile （B） for gradient elution （0-20 min， 10%-30%B； 20-30 min， 30%-55%B； 30-35 min， 55%-95%B； 35-37 min， 95%B； 37-40 min， 95%-10%B）， the flow rate was 0.25 mL·min^-1. Electrospray ionization （ESI） was used to scan and collect MS data in positive and negative ion modes with scanning range of m/z 50-1 500. The chemical components from different sources of Puerariae Flos were identified in combination with the chemical composition database and literature information. After the obtained data were normalized by MarkerView^TM 1.2.1， they were imported into SICMA-P 14.1 software for principal component analysis （PCA） and orthogonal partial least squares discriminant analysis （OPLS-DA） to select the main differentiated components among the three different varieties. Result:A total of 35 compounds were identified from three different varieties of Puerariae Flos， including 22 isoflavones， 6 flavonoids and 7 saponins. The flowers of P. lobata， P. montana var. thomsonii and P. montana var. montana contained 32， 35， 33 compounds， respectively. And 18 differential compounds were screened under the positive and negative ion modes， including kakkalide， tectoridin， 6″-O-xylosyl-tectoridin， 4'-methyltectorigenin-7-glucoside， glycitin， 6″-O-xylosyl-glycitin， irisolidone， kaikasaponin Ⅲ， 6″-O-malonylglycitin， kakkalidone， tectorigenin， rutin， soyasaponin BB， vitexin， biochanin A， genistin， kakkatin， azukisaponin Ⅱ. Conclusion:This research is the first to systematically study the chemical constituents of the flower of P. montana var. montana， although the flower of P. montana var. montana is used as adulterants， it has high contents of tectoridin and 6″-O-xylosyl-tectoridin， which has great potential for development. The efficacy components such as kakkalide and tectoridin in Puerariae Flos from the three sources of varieties are obviously different， and it is necessary to carefully consider the application of these three varieties as Puerariae Flos.

Molecular pharmacognosy is a science of classification and identification, cultivation and protection, and production of active ingredients of graduated drugs at the molecular level. The proposal of molecular pharmacognosy allows the research of crude drugs to advance from the microscopic level to the genetic level. Pueraria lobata root, as a medicinal and edible plant, has high application value and economic value. There are many varieties that are easy to cause confusion, and it is not easy to distinguish and identify according to traditional identification methods. Moreover, the research of P. lobate root at the genetic level is still relatively shallow. the study received extensive attention of scholars. This article reviews recent research on molecular identification of P. lobate, transcriptome sequencing, cloning and synthesis of functional genes of P. lobate root in recent years in order to provide references for further promoting the development and utilization of P. lobate root and its active ingredients.
Pharmacognosy ; Plant Roots/genetics* ; Pueraria

Objective:To discuss the diagnostic value of the quantitative analysis of contrast-enhanced ultrasound (CEUS) in differentiating benign and malignant subpleural lung lesions.Methods:A total of 299 cases of ultrasound-guided percutaneous lung puncture in Shanghai Pulmonary Hospital Affiliated to Tongji University from January 2019 to June 2019 were selected and divided into benign group and malignant group. The time-intensity curve (TIC) parameters of CEUS before puncture in both groups were reviewed and compared with the corresponding pathological results, including the arrival time (AT), the AT intensity, the time to peak intensity (TTP), and maximum intensity (IMAX) of the lesions, the net enhancement of intensity of the lesions, the reduced-by-half intensity and the reduced-by-half time of the lesions, the AT difference between the lesions and the lung tissues, the AT difference between the chest wall and the lesions, and the time ratio. The receiver operating characteristic (ROC) curves were drawn, and the area under the curve (AUC) and the optimal cut-off point were calculated.Results:Among the quantitative parameters of CEUS, there were statistically significant differences between the benign group and malignant group in terms of the AT, AT intensity, TTP, the reduced-by-half intensity and time of the lesions, the AT difference between the lesions and the lung tissues, the AT difference between the chest wall and the lesions, and the time ratio ( P<0.05); while there was no statistically significant difference between the benign group and malignant group in terms of the IMAX and the net enhancement of intensity of the lesions ( P>0.05). The AUC of time ratio was the largest (0.845); the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 86.2%, 79.3%, 84.3%, 92%, and 68%, respectively, when the time ratio was at or above 51.89%. Conclusion:Multiple TIC parameters of CEUS quantitative analysis have shown significant differences in differentiating benign and malignant subpleural lung lesions, especially, the parameter of time ratio can provide a basis for clinical differential diagnosis.

Objective:To discuss the diagnostic value of the quantitative analysis of contrast-enhanced ultrasound (CEUS) in differentiating benign and malignant subpleural lung lesions.Methods:A total of 299 cases of ultrasound-guided percutaneous lung puncture in Shanghai Pulmonary Hospital Affiliated to Tongji University from January 2019 to June 2019 were selected and divided into benign group and malignant group. The time-intensity curve (TIC) parameters of CEUS before puncture in both groups were reviewed and compared with the corresponding pathological results, including the arrival time (AT), the AT intensity, the time to peak intensity (TTP), and maximum intensity (IMAX) of the lesions, the net enhancement of intensity of the lesions, the reduced-by-half intensity and the reduced-by-half time of the lesions, the AT difference between the lesions and the lung tissues, the AT difference between the chest wall and the lesions, and the time ratio. The receiver operating characteristic (ROC) curves were drawn, and the area under the curve (AUC) and the optimal cut-off point were calculated.Results:Among the quantitative parameters of CEUS, there were statistically significant differences between the benign group and malignant group in terms of the AT, AT intensity, TTP, the reduced-by-half intensity and time of the lesions, the AT difference between the lesions and the lung tissues, the AT difference between the chest wall and the lesions, and the time ratio ( P<0.05); while there was no statistically significant difference between the benign group and malignant group in terms of the IMAX and the net enhancement of intensity of the lesions ( P>0.05). The AUC of time ratio was the largest (0.845); the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 86.2%, 79.3%, 84.3%, 92%, and 68%, respectively, when the time ratio was at or above 51.89%. Conclusion:Multiple TIC parameters of CEUS quantitative analysis have shown significant differences in differentiating benign and malignant subpleural lung lesions, especially, the parameter of time ratio can provide a basis for clinical differential diagnosis.

Objective To investigate the application of myocardial protection technique in off-pump coronary artery bypass grafting (CABG) combined with valve surgery.Methods Forty-five patients who received CABG combined valve surgery in the cardiothoracic surgery department of our hospital from February 2015 to March 2017 were as the research object.All of the patients were treated by myocardial protection technique in off-pump CABG combined with valve surgery.The preoperative and postoperative heart function rating and color ultra results and surgical patients discharged to evaluate the method.Results There was no difference in left ventricular ejection fraction before and after surgery(P ＞ 0.05).left ventricular end diastolic diameter and left atrial end diastolic diameter at 7 days after operation was significantly lower than those before operation,the differences were significant (P ＜ 0.05).After followed up for 3 months,the level Ⅰ and level Ⅱof cardiac function increased significantly in 29 cases,heart function classification(NYHA) after 3 months was significantly better than that before the surgery,the difference was significant(P ＜ 0.05).Mediastinal infection occurred in 1 case and poor healing of wound in 1 case,healing after active treatment.Conclusion Myocardial protection technique in off-pump CABG combined with valve surgery plays an important role in the whole surgical process and ensures the operation effect.

Background: Metastatic colorectal cancer (mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promis-ing anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC. Methods: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), quality-of-life (QoL), and safety. Results: Between July 18, 2012 and Jan 22, 2014, a total of 167 patients were screened, and 154 patients were rand-omized in a 2:1 ratio to receive either famitinib (n = 99) or placebo (n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups (hazard ratio = 0.60, 95% confidence interval = 0.41–0.86, P = 0.004). The DCR was 59.8% and 31.4% (P = 0.002) and the ORR was 2.2% and 0.0% (P = 0.540) in the famitinib and placebo groups, respectively. The most frequent grade 3–4 adverse events were hypertension (11.1%), hand-foot syndrome (10.1%), thrombocytopenia (10.1%), and neutropenia (9.1%). Serious adverse events occurred in 11 (11.1%) patients in the famitinib group and 5 (9.1%) in the placebo group (P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months (P = 0.657). Conclusion: Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability. Trial registration This study was registered on ClinicalTrials.gov (NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal Symposium