ObjectiveTo explore the molecular mechanism implicated in the treatment of primary myelofibrosis （PMF） using Chinese medicinal herbs （CMH） by bioinformatics and molecular dynamics. MethodsData mining was performed to find the high-frequency CMH in treating PMF between the year of 1985 and 2024 by searching CNKI， Chinese Science and Technology Journal Database （CCD）， and China Academic Journal Database （CSPD）. TCMSP， SwissTargetPrediction and related reports were used to collect the main active ingredients of high-frequency CMH and their targets. The PMF datasets GSE44426 and GSE124281 were downloaded from GEO database， and R software was used for data normalization and differentially expressed genes （DEGs） screening. Key module hub genes were obtained by weighted gene co-expression network analysis （WGCNA） analysis. The common intersection genes of active ingredient targets， DEGs and key module hub genes of CMH were selected， and the target network was generated using Cytoscape 3.9.2 software. The core target network was generated by topological analysis， while key pathways were selected by GO and KEGG pathway enrichment analysis， and protein interaction relationships were obtained from the String database， so as to construct drug-ingredient-target network and protein interaction network （PPI） relationship diagrams. Discovery Studio 2020 software was used to perform molecular docking， and the GROMACS program was used to perform molecular dynamics simulation. ResultsA total of 21 prescriptions were collected involving 121 herbs. There were 9 herbs with a frequency ≥10 times， which were Danshen （Radix et Rhizoma Salviae Miltiorrhizae）， Huangqi （Radix Astragali）， Baizhu （Rhizoma Atractylodis Macrocephalae）， Danggui （Radix Angelicae Sinensis）， Dangshen （Radix Codonopsis）， Gancao （Radix et Rhizoma Glycyrrhizae）， Baishao （Radix Paeoniae Alba）， Fuling （Poria） and Shudihuang （Radix Rehmanniae Praeparata） from high- to low-frequency. A total of 98 active ingredients and 1125 potential targets were obtained from 9 high-frequency CMH. GSE44426 and GSE124281 data sets screened out 24 gene samples， including 14 of the healthy control group and 10 of the PMF group， and identified 319 DEGs between the two groups， including 122 up-regulated genes and 197 down-regulated genes. WGCNA screened out 24 co-expression module genes and found that the five modules closely related to the onset of PMF were MEpink， MEdarkred， MEblack， MEgrey， and MEturquoise， involving 7112 key module hub genes. The GO and KEGG enrichment analyses indicated that lipids and the atherosclerosis pathways were mainly involved in the mechanism of above high-frequency CMH in treating PMF， which included six hub protein targets： HSP90AA1， HSP90AB1， SRC， MAPK1， IL1B and IL10. From the drug-ingredient-target network， seven active ingredients of CMH targeting at these six hub targets were found， including verbascoside， verbascos isoflavone， kaempferol， luteolin， naringenin， quercetin and pachymic acid. The molecular docking and molecular dynamics analyses showed that the key CMH were Shudihuang， Huangqi， Baishao， Danshen， Gancao and Fuling， and among the seven active ingredients， calycosin had the highest binding affinity with HSP90AB1. ConclusionThe main CMH for the treatment of PMF may be Shudihuang， Huangqi， Baishao， Danshen， Gancao and Fuling， and the active ingredients include verbascoside， verbascos isoflavones， kaempferol， luteolin， naringenin， quercetin and pachymic acid. The relevant targets are HSP90AA1， HSP90AB1， SRC， MAPK1， IL-10， and IL-1β， and the most critical pathways are lipid and atherosclerosis pathways.

As an increasing number of emerging anti-tumor drugs are approved and marketed,the imperative for clinical safety monitoring and risk information management has grown significantly.Drug-induced neuropathy associated with these drugs exhibit characteristics such as insidious onset,rapid progression,and challenging treatment,ultimately leading to treatment failures.Therefore,a comprehensive understanding of the risk of neuropathy induced by emerging anti-tumor drugs,coupled with risk surveillance and early warning,as well as management and reporting,can significantly reduce the incidence and severity of drug-related diseases.This paper provides a review of the neuropathy caused by emerging anti-tumor drugs,introduces the pharmacovigilance system and risk information management measures in clinical usage,aiming to provide a reference for guiding the rational clinical use and minimizing the incidence of drug-induced diseases.

Objective:To evaluate the influencing factors and predictive value of renal function recovery in elderly patients with heart failure(HF)and acute renal injury(AKI)after intermittent veno-venous hemofiltration(IVVH)using critical care ultrasound.Methods:The clinical data of elderly patients with heart failure(NYHF grade Ⅲ~Ⅳ)complicated with acute kidney injury(stage 2~stage 3)who underwent intravenous veno-venous hemofiltration(IVVH)in the critical care unit(CCU)of our hospital were retrospectively analyzed.The demographic information of the patients and the changes in clinical biochemical and critical care ultrasound monitoring parameters before and after 7 days of IVVH were recorded.Based on the recovery of renal function, the patients were divided into two groups: a renal function recovery group and a renal function non-recovery group.Logistic regression and Receiver Operating Characteristic Curve(ROC)curve analysis were performed to determine the predictive value of various influencing factors on the recovery of renal function in patients.Results:A total of 178 patients were enrolled in this study.After starting IVVH treatment, renal function recovered in 143 cases at 30 days, and in 138 cases at 90 days.However, renal function did not recover in 35 cases at 30 days, and in 40 cases at 90 days.The proportion of NYHF Ⅲ patients、the proportion of diabetic patients、the decrease of Beta 2-microglobulin(β2-MC)、the decrease of Cystain C(CysC)、the increase of venous transit time index(VTI)、the increase of Cardiac Output(CO)and the decrease in renal blood flow resistance index(RI)in the recovery groups at both 30 days and 90 days was significantly higher than that in the non-recovery group(all P<0.05).The total treatment time of IVVH in the recovery group was significantly shorter than that in the non-recovery group, with 30 days and 90 days( P<0.05).Logistic analysis revealed that the total treatment time of IVVH( OR=1.067, P<0.001), VTI( OR=0.652, P=0.024), CO( OR=0.037, P<0.001), and RI(OR<0.001, P=0.010)of the interlobar artery were identified as independent factors influencing the recovery of renal function in AKI patients at 30 days and 90 days after IVVH treatment.The ROC curve demonstrated the predictive value of various independent influencing factors for 30-day renal function recovery.The area under the curve(AUC)for VTI was 0.610(95% CI: 0.513-0.707), for CO it was 0.760(95% CI: 0.656-0.864), and for RI it was 0.694(95% CI: 0.589-0.799).Similarly, the ROC curve showed the predictive value of these factors for renal function recovery at 90 days.The AUC for VTI was 0.654(95% CI: 0.564-0.744), for CO it was 0.697(95% CI: 0.605-0.789), and for interlobar artery RI it was 0.605(95% CI: 0.495-0.715). Conclusions:The venous transit time index(VTI), cardiac output(CO), and renal interlobar artery RI, monitored by critical care ultrasound, are independent factors that can be used to evaluate the recovery of renal function in elderly patients with HF and AKI after IVVH treatment.Additionally, the changes in these parameters within 7 days after IVVH treatment have a high predictive value for the improvement of renal function in elderly patients after 30 days and 90 days.

OBJECTIVE: Evidence that long-term exposure to ambient air pollution increases mortality among older adults, particularly those residing in low-level air pollution locations, remains scarce. This study investigated the potential links between long-term low-level air pollution exposure and mortality among Chinese older adults. METHODS: A population-based study with 317,464 individuals aged ≥ 65 years was conducted in Shenzhen, China during 2018 and 2020. Logistic regression models were used to analyze the associations between long-term exposure to air pollution and all-cause mortality, as the primary outcome, as well as non-accidental, cancer and cardiovascular mortality. RESULTS: Significant associations of PM ₁, PM _2.5, PM ₁₀, SO ₂, CO, and O ₃ exposures with a higher risk of all-cause mortality were found. Adjusted odds ratio ( OR) for each 1 µg/m ³ increment was 1.49 [95% confidence interval ( CI): 1.46, 1.53] for PM ₁, 1.30 (1.27, 1.32) for PM _2.5, 1.05 (1.04, 1.06) for PM ₁₀, 5.84 (5.39, 6.32) for SO ₂, 1.04 (1.04, 1.05) for CO, and 1.02 (1.00, 1.03) for O ₃, respectively. Long-term PM ₁, PM _2.5, PM ₁₀, SO ₂, and CO exposures also elevated the risks of non-accidental, cancer and cardiovascular mortality. CONCLUSION Long-term low-level air pollution exposure was associated with an increased mortality risk among Chinese older adults.
Humans ; Aged ; China/epidemiology* ; Male ; Female ; Air Pollution/adverse effects* ; Environmental Exposure/adverse effects* ; Air Pollutants/analysis* ; Aged, 80 and over ; Particulate Matter/adverse effects* ; Cardiovascular Diseases/mortality* ; Mortality ; Neoplasms/mortality* ; East Asian People

Objective To analyze the correlation between internal iliac artery calcification and delayed graft function (DGF) and short-term prognosis of kidney transplant recipients. Methods Clinical data of 222 kidney transplant recipients were retrospectively analyzed. According to the recovery of renal function, all recipients were divided into the DGF group (n=50) and immediate graft function (IGF) group (n=172). According to whether the recipients were complicated with severe internal iliac artery calcification, DGF and IGF groups were further divided into the high-risk DGF (n=22), low-risk DGF (n=28), high-risk IGF (n=41) and low-risk IGF(n=131) subgroups, respectively. Clinical data of donors and recipients were statistically compared between two groups. The incidences of postoperative DGF and internal iliac artery calcification were recorded. The risk factors of DGF after kidney transplantation, and the correlation between internal iliac artery calcification and clinical parameters were analyzed. Short-term prognosis of recipients with DGF complicated with severe internal iliac artery calcification was evaluated. Results The incidence of DGF was 22.5% (50/222). Among all recipients, 28.4% (63/222) were complicated with severe internal iliac artery calcification. In the DGF group, 44% (22/50) of the recipients were complicated with severe internal iliac artery calcification, higher than 23.8% (41/172) in the IGF group (P < 0.05). Univariate analysis showed that high serum creatinine (Scr) level of donors, male donor, high triglyceride level and severe internal iliac artery calcification of recipients were the risk factors for DGF after kidney transplantation (all P < 0.05). Multivariate logistic regression analysis revealed that Scr≥143 μmol/L of donors and severe internal iliac artery calcification of recipients were the independent risk factors for DGF after kidney transplantation (both P < 0.05). Correlation analysis indicated that internal iliac artery calcification was weakly correlated with the age of recipients and renal artery anastomosis (both P < 0.05). In the DGF group, the Scr level at postoperative 1 month was significantly higher, whereas the estimated glomerular filtration rate (eGFR) was significantly lower than those in the IGF group (both P < 0.05). The eGFR at postoperative 12 months in the high-risk DGF subgroup was significantly lower than those in the low-risk DGF, high-risk IGF and low-risk IGF subgroups (all P < 0.05). Conclusions Internal iliac artery calcification is not only a risk factor for recovery of renal allograft function, but also negatively affects short-term prognosis of renal allograft function.

Nasopharyngeal carcinoma (NPC) is the third most common malignancy with a high recurrence and metastasis rate in South China. Natural compounds extracted from traditional Chinese herbal medicines have been developed and utilized for the treatment of a variety of cancers with modest properties and slight side effects. Maackiain (MA) is a type of flavonoid that was first isolated from leguminous plants, and it has been reported to relieve various nervous system disorders and exert anti-allergic as well as anti-inflammatory effects. In this study, we demonstrated that MA inhibited proliferation, arrested cell cycle and induced apoptosis in nasopharyngeal carcinoma CNE1 and CNE2 cells in vitro and in vivo. The expression of the related proteins associated with these processes were consistent with the above effects. Moreover, transcriptome sequencing and subsequent Western blot experiments revealed that inhibition of the MAPK/Ras pathway may be responsible to the anti-tumor effect of MA on NPC cells. Therefore, the effects of MA and an activator of this pathway, tertiary butylhydroquinone (TBHQ), alone or combination, were investigated. The results showed TBHQ neutralized the inhibitory effects of MA. These data suggest that MA exerts its anti-tumor effect by inhibiting the MAPK/Ras signaling pathway and it has the potential to become a treatment for patients with NPC.
Humans ; Nasopharyngeal Carcinoma/pathology* ; Cell Line, Tumor ; Cell Proliferation ; Apoptosis ; Signal Transduction ; Nasopharyngeal Neoplasms/pathology*

Objective:To investigate the volume management of intermittent veno-venous hemofiltration (IVVH) guided by critical care ultrasound in the treatment of acute kidney injury (AKI) in patients with heart failure (HF).Methods:A total of 216 patients with HF and AKI treated with IVVH in the coronary care unit (CCU) of the Third Central Hospital of Tianjin from April 2019 to June 2022 were selected as the study subjects, the patients were randomly divided into conventional guidance group (107 cases) and ultrasound guidance group (109 cases). According to the recovery of renal function, IVVH was performed 12 hours every day or 12 hours every other day. The conventional guidance group selected the conventional method to formulate IVVH prescription, and the ultrasound guidance group used critical care ultrasound to adjust the treatment parameters of IVVH on the basis of the conventional guidance group. Respiratory variation index (RVI) of inferior vena cava (IVC), right left ventricular end-diastolic transverse area ratio, early diastolic peak mitral flow velocity/mitral annulus velocity peak (E/E'), aortic flow velocity time integral (VTI), cardiac output (CO), bilateral lung ultrasound B-line range, bilateral renal interlobar arteries resistance index (RI) were recorded before and 3, 6, 9 hours after each treatment. The net dehydration rate was adjusted in real time according to the comprehensive results. Urine volume, serum creatinine (SCr), estimated glomerular filtration rate (eGFR), blood B-type brain natriuretic peptide (BNP), β 2-microglobulin (β 2-MG) and cystatin C (Cys C) levels of patients in both groups were monitored before and 3, 7 and 10 days after initial treatment, and renal function recovery and clinical prognostic indexes of patients in both groups were recorded. Results:The dehydration rate of the ultrasound guidance group was slow at the beginning of IVVH, and gradually increased after 6 hours, and the overall dehydration rate was significantly slower than that of the conventional guidance group. In the ultrasound guidance group using critical care ultrasound, the RVI gradually increased, the right left ventricular end-diastolic area ratio gradually decreased, the E/E' ratio gradually decreased, and the range of B-line of bilateral lungs gradually decreased, RI of bilateral renal interlobar arteries decreased. At 3, 7 and 10 days after the first IVVH, renal function related indexes in both groups were significantly improved compared with before treatment, and the decline rate of β 2-MG and Cys C in the ultrasound guidance group was faster than that in the conventional guidance group at early (3 days) [β 2-MG (mg/L): 3.69±1.31 vs. 3.99±1.45, Cys C (mg/L): 2.91±0.95 vs. 3.14±0.96, both P < 0.05], urine volume, SCr and eGFR at 7 days were also significantly improved compared with the conventional guidance group [24-hour urine volume (mL): 1 128.23±153.92 vs. 1 015.01±114.18, SCr (μmol/L): 145.86±32.25 vs. 155.64±28.42, eGFR (mL/min): 50.26±11.24 vs. 46.51±10.61, all P < 0.05]. The time of SCr recovery, the time of reaching polyuria, the total time of IVVH treatment, the time of non-invasive mechanical ventilation and the time of living in CCU in the ultrasound guidance group were shorter than those in the conventional guidance group. The incidences of hypotension, long-term RRT, incidence of major cardiovascular adverse event (MACE) and at 28-day mortality were all lower than those in the conventional guidance group. Kaplan-Meier survival curve showed that the 28-day cumulative survival rate in the ultrasound guidance group was significantly lower than that in the conventional guidance group (Log-Rank test: χ 2 = 3.903, P = 0.048). Conclusion:The strategy of IVVH guided by critical care ultrasound in the treatment of HF with AKI has unique advantages.

Objective:To explore the effects of non-suicidal self-injury on suicidal ideation in adolescents with depressive disorder, and the mediating role of rumination and depression between them.Methods:A sample of 397 depressive disorder adolescents were recruited to complete the adolescent non-suicidal self-injury behaviour questionnaire, ruminative responses scale (RRS), self-rating depression scale (SDS), and Beck scale for suicide ideation-Chinese version(BSI-CV). All data processing and analysis were performed using SPSS 23.0.The mediating effect was tested by correlation analysis and Bootstrap analysis.Results:The non-suicidal self-injury score was (29.192±11.281), the rumination score was (65.036±12.284), the depression score was (75.770±11.278), and the suicidal ideation score was (40.681±11.626). Non-suicidal self-injury was significantly and positively correlated with suicidal ideation( r=0.403, P<0.01), rumination and depression( r=0.332, 0.470, both P<0.01). Rumination was significantly and positively correlated with depression and suicidal ideation( r=0.549, 0.181, both P<0.05). Depression was significantly and positively correlated with suicidal ideation( r=0.313, P<0.01). The direct effect value of non-suicidal self-injury on suicidal ideation was 0.341(95% CI=0.238-0.444), the indirect effect of non-suicidal self-injury on suicidal ideation through two pathways, the separate mediating effect value of depression was 0.057(95% CI=0.077-0.114), and the chain mediating effect value of rumination and depression was 0.026(95% CI=0.004-0.057). Conclusion:Non-suicidal self-injury can directly affect suicidal ideation of depressive disorder adolescents and indirectly through rumination and depression.

Objective:To investigate the short-term clinical efficacy of Kamikawa anasto-mosis and jejunal interposed double channel anastomosis in laparoscopic proximal gastrectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 68 patients with esophagogastric junctional tumors and upper gastric tumors who underwent laparoscopic proximal gastrectomy in two medical centers, including 63 cases in the Changzhi People's Hospital Affiliated to Changzhi Medical College and 5 cases in the Heji Hospital Affiliated to Changzhi Medical College, from March 2018 to December 2020 were collected. There were 57 males and 11 females, aged 62(range, 39?78)years. Of 68 patients, 35 patients undergoing Kamikawa anastomosis in laparoscopic proximal gastrectomy were allocated into Kamikawa group, and 33 patients under-going jejunal interposed double channel anastomosis in laparoscopic proximal gastrectomy were allocated into double channel group. Observation indicators: (1) intraoperative situations; (2) post-operative situations; (3) follow-up. The patients were followed up by outpatient examinations and telephone interview to detect the postoperative score of chew-wun wu special symptoms, post-operative reflux anastomotic esophagitis and anastomotic stenosis up to December 2021. Measure-ment data with normal distri-bution were represented as Mean±SD, and comparison between groups was performed by the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted by Mann-Whitney U test. Comparison of ordinal data was performed by nonparametric rank sum test. Count data were expressed as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability method. Results:(1) Intraoperative situations. All the 68 patients successfully under-went laparoscopic proximal gastrectomy combined with D 1+ lymph node dissection. The operation time and volume of intraoperative blood loss of the Kamikawa group were (5.15±0.31)hours and (89±11)mL, versus (4.21±0.11)hours and (142±20)mL of the double channel group, respectively, showing significant differences between the two groups ( t=2.81, ?2.34, P<0.05). The digestive tract reconstruction time and the number of lymph node dissection were (1.95±0.13)hours and 30.4±2.4 of the Kamikawa group, versus (1.69±0.76)hours and 28.0±2.4 of the double channel group, respectively, showing no significant difference between the two groups ( t=1.79, 0.73, P>0.05). (2) Postoperative situations. The time to postoperative first flatus, duration of drainage tube placement, duration of postoperative hospital stay were (3.03±0.12)days, (5.46±0.22)days, (13.00±0.50)days of the Kamikawa group, versus (4.42±0.21)days, (9.97±0.76)days, (16.46±0.92)days of the double channel group, showing significant differences in the above indicators between the two groups ( t=?5.80,?5.58, 3.40, P<0.05). Cases with or without drainage tube placement were 32 and 3 of the Kamikawa group, versus 33 and 0 of the double channel group, respectively, showing no significant difference between the two groups ( P>0.05). Cases with grade 1, grade 2, grade 3, grade 4 complica-tions of Clavien-Dindo classification were 31, 0, 4, 0 of the Kamikawa group, versus 27, 3, 1, 2 of the double channel group, respectively, showing a significant difference between the two groups ( Z=?6.28, P<0.05). Postoperative anastomotic stenous, reflux symptoms, anastomotic fistula, pancreatic fistula, pulmonary infection were found in 4, 2, 0, 0, 0 case of the Kamikawa group and 0, 1, 3, 1, 2 cases of the double channel group, respectively. There was no significant difference in the above indicators between the two groups ( P>0.05). There was no complication of incisional infection, abdominal hemorrhage, lymphatic fistula or gastroparesis in either group. Of the 4 patients with perioperative anastomotic stenosis in the Kamikawa group, 2 cases were improved after once gastroscopic balloon dilatation, 2 cases were improved after 4 times of gastro-scopic balloon dilatation. (3) Follow-up. All the 68 patients were followed up at postoperative 3, 6, 12 months. The scores of chew-wun wu special symptoms scale at postopertaive 12 months of the Kamikawa group and double channel group were 16.8±0.7 and 14.6±0.7, respectively, showing a significant difference between the two groups ( t=2.20, P<0.05). There were 2 cases of grade B reflux esophagitis and 1 case of grade B reflux esophagitis, respectively, showing no significant difference between the two groups ( P>0.05). There was no anastomotic stenosis occurred in either group. Conclusions:Laparos-copic proximal gastrectomy with Kamikawa anastomosis or jejunal interposed double channel anastomosis is safe and feasible for esophagogastric junction tumors and upper gastric tumors. The Kamikawa anastomosis has less volume of intraoperative blood loss, shorter time to postoperative first flatus, duration of drainage tube placement and postoperative hospital stay, higher quality of postoperative lfe.