OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

OBJECTIVE: To explore the role of the natural compound hesperidin in glycolysis, the key ratelimiting enzyme, in colorectal cancer (CRC) cell lines. METHODS: In vitro, HCT116 and SW620 were treated with different doses of hesperidin (0-500 µmol/L), cell counting kit-8 and colone formation assays were utilized to detected inhibition effect of hesperidin on CRC cell lines. Transwell and wound healing assays were performed to detect the ability of hesperidin (0, 25, 50 and 75 µmol/L) to migrate CRC cells. To confirm the apoptotic-inducing effect of hesperidin, apoptosis and cycle assays were employed. Western blot, glucose uptake, and lactate production determination measurements were applied to determine inhibitory effects of hesperidin (0, 25 and 50 µmol/L) on glycolysis. In vivo, according to the random number table method, nude mice with successful tumor loading were randomly divided into vehicle, low-dose hesperidin (20 mg/kg) and high-dose hesperidin (60 mg/kg) groups, with 6 mice in each group. The body weights and tumor volumes of mice were recorded during 4-week treatment. The expression of key glycolysis rate-limiting enzymes was determined using Western blot, and glucose uptake and lactate production were assessed. Finally, protein interactions were probed with DirectDIA Quantitative Proteomics, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. RESULTS: Hesperidin could inhibit CRC cell line growth (P<0.05 or P<0.01). Moreover, hesperidin presented an inhibitory effect on the migrating abilities of CRC cells. Hesperidin also promoted apoptosis and cell cycle alterations (P<0.05). The immunoblotting results manifested that hesperidin decreased the levels of hexokinase 2, glucose transporter protein 1 (GLUT1), GLUT3, L-lactate dehydrogenase A, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), PFKFB3, and pyruvate kinase isozymes M2 (P<0.01). It remarkably suppressed tumor xenograft growth in nude mice. GO and KEGG analyses showed that hesperidin treatment altered metabolic function. CONCLUSION Hesperidin inhibits glycolysis and is a potential therapeutic choice for CRC treatment.
Hesperidin/therapeutic use* ; Colorectal Neoplasms/metabolism* ; Glycolysis/drug effects* ; Animals ; Humans ; Apoptosis/drug effects* ; Mice, Nude ; Cell Movement/drug effects* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Glucose/metabolism* ; Cell Cycle/drug effects* ; Mice, Inbred BALB C ; Mice ; HCT116 Cells ; Lactic Acid

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective:To compare the safety of radial artery puncture in elderly patients aged 75 years and older who are undergoing neurointerventional procedures.Methods:A single-center retrospective study was conducted, involving 350 elderly patients aged 75 years and older who received neurointerventional treatment at Beijing Tiantan Hospital, Capital Medical University, from June to December 2022.The participants were divided into two groups based on the puncture site: femoral artery puncture and radial artery puncture.The safety indicators compared between the two groups included puncture failure, changes in puncture site, general puncture complications(such as subcutaneous bleeding, puncture site hematoma, and vasospasm), severe puncture complications(including distal limb ischemia and pseudoaneurysm), and lower limb venous thrombosis.Multivariate Logistic regression analysis was conducted to evaluate the impact of different puncture methods on the occurrence of complications.Results:Among the 350 patients, 280 underwent femoral artery puncture, while 70 underwent radial artery puncture.There were no statistically significant differences in baseline characteristics between the two groups(all P>0.05).The proportions of patients using antiplatelet drugs prior to surgery, puncture failure rates, rates of change in puncture sites, and the incidence of severe complications-including distal limb ischemia and pseudoaneurysm-were not significantly different between the two groups( χ2=2.051, 0.075, 0.588, 3.175; P=0.152, 0.784, 0.443, 0.075).In the femoral artery puncture group, 20.4%(57 cases)of patients experienced general puncture complications(including subcutaneous bleeding, puncture site hematoma, and vasospasm), whereas only 8.6%(6 cases)in the radial artery puncture group experienced such complications, revealing a statistically significant difference between the two groups( χ2=5.720, P=0.022).Multivariate Logistic regression analysis indicated that, compared to femoral artery puncture, radial artery puncture was associated with a reduced risk of all complications( OR=0.272, 95% CI: 0.139-0.532, P<0.001), general puncture complications( OR=0.375, 95% CI: 0.153-0.919, P=0.032)and lower limb venous thrombosis( OR=0.219, 95% CI: 0.050-0.954, P=0.043). Conclusions:In elderly patients aged 75 years and older who are undergoing neurointerventional procedures, radial artery puncture is associated with a reduced incidence of general puncture complications and lower limb venous thrombosis when compared to femoral artery puncture, indicating a superior safety profile.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Cryoablation therapy with explicit anti-tumor mechanisms and histopathological manifestations has a long history.A large number of clinical practice has shown that cryoablation therapy is safe and effective,making it an ideal tumor treatment method in theory.Previously,its efficacy and clinical application were constrained by the limitations of refrigerants and refrigeration equipment.With the development of the new generation of cryoablation equipment represented by argon helium knives,significant progress has been made in refrigeration efficien-cy,ablation range,and precise temperature measurement,greatly promoting the progression of tumor cryoablation technology.This consensus systematically summarizes the mechanism of cryoablation technology,indications for oral mucosal melanoma(OMM)cryotherapy,clinical treatment process,adverse reactions and management,cryotherapy combination therapy,etc.,aiming to provide reference for carrying out the standardized cryoablation therapy of OMM.

Parabacteroides distasonis is a gram-negative bacterium initially isolated from a clinical specimen in the 1930s. The strain was re-classified to form the new genus Parabacteroides in 2006. P. distasonis can regulate intestinal barrier function and plays a key role in immune response and metabolic regulation of bodies. Traditional Chinese medicine(TCM) is closely related to the intestinal microbiota. Polysaccharides, saponins, and other ingredients of TCM can treat diseases by interacting with P. distasonis, but the specific mechanisms underlying these processes are still unclear, requiring further exploration. This study reviewed the roles and related mechanisms of P. distasonis in inflammatory-immune diseases, metabolic diseases, cardiovascular disease, neuropsychiatric diseases, cancer, and other diseases and summarized the relevant research results of TCM to prevent and treat diseases by regulating P. distasonis. This study provides a reference for subsequent exploration of P. distasonis and research on the interaction between TCM and intestinal microbiota.
Humans ; Gastrointestinal Microbiome/drug effects* ; Medicine, Chinese Traditional ; Animals ; Bacteroidetes ; Drugs, Chinese Herbal/pharmacology*

PURPOSE: This study aims to elucidate the electrotaxis response of alveolar epithelial cells (AECs) in direct-current electric fields (EFs), explore the impact of EFs on the cell fate of AECs, and lay the foundation for future exploitation of EFs for the treatment of acute lung injury. METHODS: AECs were extracted from rat lung tissues using magnetic-activated cell sorting. To elucidate the electrotaxis responses of AECs, different voltages of EFs (0, 50, 100, and 200 mV/mm) were applied to two types of AECs, respectively. Cell migrations were recorded and trajectories were pooled to better demonstrate cellular activities through graphs. Cell directionality was calculated as the cosine value of the angle formed by the EF vector and cell migration. To further demonstrate the impact of EFs on the pulmonary tissue, the human bronchial epithelial cells transformed with Ad12-SV40 2B (BEAS-2B cells) were obtained and experimented under the same conditions as AECs. To determine the influence on cell fate, cells underwent electric stimulation were collected to perform Western blot analysis. RESULTS: The successful separation and culturing of AECs were confirmed through immunofluorescence staining. Compared with the control, AECs in EFs demonstrated a significant directionality in a voltage-dependent way. In general, type Ⅰ alveolar epithelial cells migrated faster than type Ⅱ alveolar epithelial cells, and under EFs, these two types of cells exhibited different response threshold. For type Ⅱ alveolar epithelial cells, only EFs at 200 mV/mm resulted a significant difference to the velocity, whereas for, EFs at both 100 mV/mm and 200 mV/mm gave rise to a significant difference. Western blotting suggested that EFs led to an increased expression of a AKT and myeloid leukemia 1 and a decreased expression of Bcl-2-associated X protein and Bcl-2-like protein 11. CONCLUSION EFs could guide and accelerate the directional migration of AECs and exert antiapoptotic effects, which indicated that EFs are important biophysical signals in the re-epithelialization of alveolar epithelium in lung injury.
Humans ; Rats ; Animals ; Alveolar Epithelial Cells ; Lung ; Lung Injury ; Cell Movement/physiology*

ObjectiveAt the end of November 2022， Guangzhou implemented the latest Covid-19 epidemic prevention policy and began to gradually lift the lockdown. However， under the new epidemic prevention situation， the situation of SARS-CoV-2 infection in hospitalized patients in China is still unclear. Accordingly， this paper aims to study the SARS-CoV-2 infection of hospitalized patients in Guangzhou under the new epidemic prevention and control situation. MethodsThe results of SARS-CoV-2 nucleic acid tests in our hospital from the end of November 2022 to the beginning of February 2023 were retrospectively analyzed. The positive rate of SARS-CoV-2 nucleic acid tests in outpatients and inpatients under the new epidemic prevention situation， and the nosocomial infection of SARS-CoV-2 in inpatients were statistically analyzed. ResultsThis study retrospectively analyzed the SARS-CoV-2 nucleic acid test results of 13 959 patients， including 6 966 outpatients and 6 993 inpatients. On November 30， 2022， the SARS-CoV-2 nucleic acid test results of outpatients began to be positive， indicating that the outbreak of the SARS-CoV-2 infection had begun. On December 7， one case of SARS-CoV-2 nucleic acid test results of hospitalized patients was positive， and nosocomial infections began to break out. On December 15， the positive rate of SARS-CoV-2 nucleic acid test among patients exceeded 40 %， and the epidemic entered its peak period. After the end of December， the test positive rate gradually decreased， but the positive rate of inpatients was always higher than that of outpatients. Compared with December 2022， the positive rate of SARS-CoV-2 nucleic acid test of patients in many departments in January 2023 decreased， but the positive rate of SARS-CoV-2 nucleic acid test of inpatients in the oncology department increased significantly （P < 0.001）. Further analysis found that the nosocomial infection rate of SARS-CoV-2 in inpatients was 86.57 % （329/380）. However， the nosocomial infection rate in lymphoma patients ［58.33 % （14/24）］ was significantly lower than that of the hospitalized patients with other disease types （P < 0.001）. ConclusionThe positive rate of SARS-CoV-2 nucleic acid testing among patients reached its peak in mid-December 2022. In January 2023， the positive rate of SARS-CoV-2 nucleic acid testing gradually decreased， while the number or positive rate of SARS-CoV-2 nucleic acid testing positive patients in some departments increased. The nosocomial infection rate among hospitalized patients is as high as 90 %. There are differences in the nosocomial infection rate of SARS-CoV-2 among inpatients with different disease types. In summary， this study provides preliminary data on the epidemiological characteristics of SARS-CoV-2 infection among hospitalized patients in Guangzhou， as well as the protection against infection among hospitalized patients and cross-infection between medical staffs and patients.

Objective:To investigate the clinical characteristics of choledocholithiasis com-bined with periampullary diverticulum and influencing factor for difficult cannulation of endoscopic retrograde cholangiopancreatography (ERCP).Methods:The retrospective case-control study was conducted. The clinical data of 1 920 patients who underwent ERCP for choledocholithiasis in 15 medical centers, including the First Hospital of Lanzhou University, et al, from July 2015 to December 2017 were collected. There were 915 males and 1 005 females, aged (63±16)years. Of 1 920 patients, there were 228 cases with periampullary diverticulum and 1 692 cases without periampullary diverticulum. Observation indicators: (1) clinical characteristics of patients with choledocholithiasis; (2) intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis; (3) influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and com-parison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Logistic regression model was used for univariate and multivariate analyses. Results:(1) Clinical characteristics of patients with choledocholithiasis. Age, body mass index, cases with complications as chronic obstructive pulmonary disease, diameter of common bile duct, cases with diameter of common bile duct as <8 mm, 8?12 mm, >12 mm, diameter of stone, cases with number of stones as single and multiple were (69±12)years, (23.3±3.0)kg/m 2, 16, (14±4)mm, 11, 95, 122, (12±4)mm, 89, 139 in patients with choledocholithiasis combined with periampullary diverticulum, versus (62±16)years, (23.8±2.8)kg/m 2, 67, (12±4)mm, 159, 892, 641, (10±4)mm, 817, 875 in patients with choledocholithiasis not combined with periampullary diver-ticulum, showing significant differences in the above indicators between the two groups ( t=?7.55, 2.45, χ2=4.54, t=?4.92, Z=4.66, t=?7.31, χ2=6.90, P<0.05). (2) Intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis. The balloon expansion diameter, cases with intraoperative bleeding, cases with hemorrhage management of submucosal injection, hemostatic clip, spray hemostasis, electrocoagulation hemostasis and other treatment, cases with endoscopic plastic stent placement, cases with endoscopic nasal bile duct drainage, cases with mechanical lithotripsy, cases with stone complete clearing, cases with difficult cannulation, cases with delayed intubation, cases undergoing >5 times of cannulation attempts, cannulation time, X-ray exposure time, operation time were 10.0(range, 8.5?12.0)mm, 56, 6, 5, 43, 1, 1, 52, 177, 67, 201, 74, 38, 74, (7.4±3.1)minutes, (6±3)minutes, (46±19)minutes in patients with choledocholithiasis combined with periampullary diverticulum, versus 9.0(range, 8.0?11.0)mm, 243, 35, 14, 109, 73, 12, 230, 1 457, 167, 1 565, 395, 171, 395, (6.6±2.9)minutes, (6±5)minutes, (41±17)minutes in patients with choledocholithiasis not combined with periampullary diverticulum, showing significant differences in the above indicators between the two groups ( Z=6.31, χ2=15.90, 26.02, 13.61, 11.40, 71.51, 5.12, 9.04, 8.92, 9.04, t=?3.89, 2.67, ?3.61, P<0.05). (3) Influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Results of multivariate analysis showed total bilirubin >30 umol/L, number of stones >1, combined with periampullary diverticulum were indepen-dent risk factors for difficult cannulation in patients with periampullary diverticulum who underwent ERCP for choledocholithiasis ( odds ratio=1.31, 1.48, 1.44, 95% confidence interval as 1.06?1.61, 1.20?1.84, 1.06?1.95, P<0.05). Results of further analysis showed that, of 1 920 patients undergoing ERCP for choledocholithiasis, the incidence of postoperative pancreatitis was 17.271%(81/469) and 8.132%(118/1 451) in the 469 cases with difficult cannulation and 1 451 cases without difficult cannula-tion, respectively, showing a significant difference between them ( χ2=31.86, P<0.05). In the 1 692 patients with choledocholithiasis not combined with periampullary diverticulum, the incidence of postopera-tive pancreatitis was 17.722%(70/395) and 8.250%(107/1 297) in 395 cases with difficult cannula-tion and 1 297 cases without difficult cannulation, respectively, showing a significant difference between them ( χ2=29.00, P<0.05). In the 228 patients with choledocholithiasis combined with peri-ampullary diverticulum, the incidence of postoperative pancreatitis was 14.865%(11/74) and 7.143%(11/154) in 74 cases with difficult cannulation and 154 cases without difficult cannulation, respectively, showing no significant difference between them ( χ2=3.42, P>0.05). Conclusions:Compared with patients with choledocholithiasis not combined with periampullary divertioulum, periampullary divertioulum often occurs in choledocholithiasis patients of elderly and low body mass index. The proportion of chronic obstructive pulmonary disease is high in choledocholithiasis patients with periampullary diverticulum, and the diameter of stone is large, the number of stone is more in these patients. Combined with periampullary diverticulum will increase the difficult of cannulation and the ratio of patient with mechanical lithotripsy, and reduce the ratio of patient with stone complete clearing without increasing postoperative complications of choledocholithiasis patients undergoing ERCP. Total bilirubin >30 μmol/L, number of stones >1, combined with periampullary diverticulum are independent risk factors for difficult cannulation in patients of periampullary diverticulum who underwent ERCP for choledocholithiasis.