The therapeutic effects of Yueju Pills on depression and cardiovascular diseases have been widely recognized. Previous studies have shown that the drug can significantly improve depressive-like behaviors induced by chronic unpredictable mild stress(CUMS) combined with atherosclerosis(AS). Given the complex pathogenesis of psychocardiac diseases, this study integrated metabolomics and network pharmacology to systematically elucidate the mechanism of Yueju Pills in alleviating depressive symptoms in psychocardiac diseases. The results demonstrate that, after Yueju Pill intervention, the levels of 9 abnormal metabolites in the hippocampus restore to normal ranges, primarily involving key pathways or signaling pathways, including the cyclic adenosine monophosphate(cAMP), mammalian target of rapamycin(mTOR), glycine/serine/threonine metabolism, and aminoacyl-tRNA biosynthesis. In a high-fat diet-induced CUMS ApoE~(-/-) mouse model, Yueju Pills significantly increases adenosine monophosphate(AMP) levels and decreases L-alanine and D-glyceric acid levels in the hippocampus. In conclusion, Yueju Pills exert antidepressant effects by regulating multiple metabolic axes, including glycine/serine/threonine metabolism and the cAMP, mTOR signaling pathways. Network pharmacology predictions reveal that the treatment of CUMS combined with AS by its core active components may be realized through modulating pathways concerning neuroinflammation and synaptic plasticity, including serine/threonine-protein kinase 1(AKT1), mitogen-activated protein kinase 1(MAPK1), and prostaglandin-endoperoxide synthase 2(PTGS2). This study provides a theoretical reference for the clinical application of Yueju Pills in alleviating the depressive symptoms of psychocardiac diseases.
Animals ; Network Pharmacology ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Metabolomics ; Male ; Depression/genetics* ; Humans ; Hippocampus/drug effects* ; Mice, Inbred C57BL ; Signal Transduction/drug effects*

Objective:To prepare the chitin/hyaluronic acid/collagen hydrogel loaded with mouse adipose-derived stem cells and to explore its effects on wound healing of full-thickness skin defects in rats.Methods:The research was an experimental research. Chitin nanofibers were prepared by acid hydrolysis and alkaline extraction method, and then mixed with hyaluronic acid and collagen to prepare chitin/hyaluronic acid/collagen hydrogels (hereinafter referred to as hydrogels). Besides, the hydrogels loaded with mouse adipose-derived stem cells were prepared. Thirty male 12-week-old guinea pigs were divided into negative control group, positive control group, and hydrogel group according to the random number table, with 10 guinea pigs in each group. Ethanol, 4-aminobenzoic acid ethyl ester, or the aforementioned prepared hydrogels without cells were topically applied on both sides of back of guinea pigs respectively for induced contact and stimulated contact, and skin edema and erythema formation were observed at 24 and 48 h after stimulated contact. Adipose-derived stem cells from mice were divided into normal control group cultured routinely and hydrogel group cultured with the aforementioned prepared hydrogels without cells. After 3 d of culture, protein expressions of platelet-derived growth factor-D (PDGF-D), insulin-like growth factor-Ⅰ (IGF-Ⅰ), and transforming growth factor β 1 (TGF-β 1) were detected by Western blotting ( n=3). Eight male 8-week-old Sprague-Dawley rats were taken and a circular full-thickness skin defect wound was created on each side of the back. The wounds were divided into blank control group without any treatment and hydrogel group with the aforementioned prepared hydrogels loaded with adipose-derived stem cells applied. Wound healing was observed at 0 (immediately), 2, 4, 8, and 10 d after injury, and the wound healing rate was calculated at 2, 4, 8, and 10 d after injury. Wound tissue samples at 10 d after injury were collected, the new tissue formation was observed by hematoxylin-eosin staining; the concentrations of interleukin-1α (IL-1α), IL-6, IL-4, and IL-10 were detected by enzyme-linked immunosorbent assay method; the expressions of CD16 and CD206 positive cells were observed by immunohistochemical staining and the percentages of positive cells were calculated. The sample numbers in animal experiment were all 8. Results:At 24 h after stimulated contact, no skin edema was observed in the three groups of guinea pigs, and only mild skin erythema was observed in 7 guinea pigs in positive control group. At 48 h after stimulated contact, skin erythema was observed in 8 guinea pigs and skin edema was observed in 4 guinea pigs in positive control group, while no obvious skin erythema or edema was observed in guinea pigs in the other two groups. After 3 d of culture, the protein expression levels of PDGF-D, IGF-I, and TGF-β 1 in adipose-derived stem cells in hydrogel group were significantly higher than those in normal control group (with t values of 12.91, 11.83, and 7.92, respectively, P<0.05). From 0 to 10 d after injury, the wound areas in both groups gradually decreased, and the wounds in hydrogel group were almost completely healed at 10 d after injury. At 4, 8, and 10 d after injury, the wound healing rates in hydrogel group were (38±4)%, (54±5)%, and (69±6)%, respectively, which were significantly higher than (21±6)%, (29±7)%, and (31±7)% in blank control group (with t values of 3.82, 3.97, and 4.05, respectively, Pvalues all <0.05). At 10 d after injury, compared with those in blank control group, the epidermis in wound in hydrogel group was more intact, and there were increases in hair follicles, blood vessels, and other skin appendages. At 10 d after injury, the concentrations of IL-1α and IL-6 in wound tissue in hydrogel group were significantly lower than those in blank control group (with tvalues of 8.21 and 7.99, respectively, P<0.05), while the concentrations of IL-4 and IL-10 were significantly higher than those in blank control group (with tvalues of 6.57 and 9.03, respectively, P<0.05). The percentage of CD16 positive cells in wound tissue in hydrogel group was significantly lower than that in blank control group ( t=8.02, P<0.05), while the percentage of CD206 positive cells was significantly higher than that in blank control group ( t=7.21, P<0.05). Conclusions:The hydrogel loaded with mouse adipose-derived stem cells is non-allergenic, can promote the secretion of growth factors in adipose-derived stem cells, promote the polarization of macrophages to M2 phenotype in wound tissue in rats with full-thickness skin defects, and alleviate inflammatory reaction, thereby promoting wound healing.

Objective:To explore the application value and treatment effects of multiple free anterolateral perforator flaps of calf for reconstruction of multiple digital wounds in single hand.Methods:From August 2020 to March 2022, 12 patients with soft tissue defects in 35 digits were treated in Department of Hand Surgery, Suzhou Ruihua Orthopaedic Hospital. Ten patients were male and 2 were female, aged 25 to 58 years old. Of the patients, 1 had soft tissue defects in 5 digits, 3 in 4 digits, 2 in 3 digits and 6 in 2 digits. The size of defects was from 1.2 cm ×1.2 cm to 7.0 cm×3.5 cm after debridement. The vascular perforators discovered from intraoperative explorations were found originating from the superficial peroneal artery in 24 flaps, from the peroneal artery in 7 flaps and from the anterior tibial artery in 4 flaps. During surgery, the perforator artery and accompanying veins of the flaps were anastomosed with the proper digital artery and palmar or dorsal subcutaneous veins in the recipient site, respectively. The size of the flaps was from 1.5 cm×1.5 cm to 7.5 cm×4.0 cm. No nerve was affected in the surgery. The wound at donor sites in the calf was sutured directly. Regular postoperative follow-ups were conducted at outpatient clinics. The comprehensive evaluation scale of flap was used to assess the conditions of the donor and recipient sites.Results:In this study, all 35 soft tissue defects of digits in 12 patients were reconstructed by the anterolateral perforator flaps of calf. All the 35 flaps survived after surgery, with a 100% of survival rate. The patients were instructed to carry out early functional training after surgery. Follow-up lasted 6 to 24 months, with an average of 11 months. Twenty-five flaps were found in slightly swollen, and further flap thinning surgery were carried out 3 months after the primary surgery, while the rest of the flaps had good appearance and texture. At 6 months after surgery, all flaps recovered a partial deep and shallow sensory and sense of touch. All wound at donor sites in calf had one-stage healing without dysfunction. The comprehensive evaluation scale was excellent in 28 flaps and good in 7 flaps. The excellent and good rate was 100%.Conclusion:It is an effective method to use multiple free anterolateral perforator flaps of calf to reconstruct multiple digit defects in single hand. The flaps can be conveniently harvested and the multiple digital defects in single hand can be reconstructed in primary surgery with small damages to the donor sites and together with satisfactory clinical outcomes.

Objective: To describe the current status and trends in the treatment of patent ductus arteriosus (PDA) among very preterm infants (VPI) admitted to the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) from 2019 to 2021, and to compare the differences in PDA treatment among these units. Methods: This was a cross-sectional study based on the CHNN VPI cohort, all of 22 525 VPI (gestational age<32 weeks) admitted to 79 tertiary NICU within 3 days of age from 2019 to 2021 were included. The overall PDA treatment rates were calculated, as well as the rates of infants with different gestational ages (≤26, 27-28, 29-31 weeks), and pharmacological and surgical treatments were described. PDA was defined as those diagnosed by echocardiography during hospitalization. The PDA treatment rate was defined as the number of VPI who had received medication treatment and (or) surgical ligation of PDA divided by the number of all VPI. Logistic regression was used to investigate the changes in PDA treatment rates over the 3 years and the differences between gestational age groups. A multivariate Logistic regression model was constructed to compute the standardized ratio (SR) of PDA treatment across different units, to compare the rates after adjusting for population characteristics. Results: A total of 22 525 VPI were included in the study, with a gestational age of 30.0 (28.6, 31.0) weeks and birth weight of 1 310 (1 100, 1 540) g; 56.0% (12 615) of them were male. PDA was diagnosed by echocardiography in 49.7% (11 186/22 525) of all VPI, and the overall PDA treatment rate was 16.8% (3 795/22 525). Of 3 762 VPI who received medication treatment, the main first-line medication used was ibuprofen (93.4% (3 515/3 762)) and the postnatal day of first medication treatment was 6 (4, 10) days of age; 59.3% (2 231/3 762) of the VPI had been weaned from invasive respiratory support during the first medication treatment, and 82.2% (3 092/3 762) of the infants received only one course of medication treatment. A total of 143 VPI underwent surgery, which was conducted on 32 (22, 46) days of age. Over the 3 years from 2019 to 2021, there was no significant change in the PDA treatment rate in these VPI (P=0.650). The PDA treatment rate decreased with increasing gestational age (P<0.001). The PDA treatment rates for VPI with gestational age ≤26, 27-28, and 29-31 weeks were 39.6% (688/1 737), 25.9% (1 319/5 098), and 11.4% (1 788/15 690), respectively. There were 61 units having a total number of VPI≥100 cases, and their rates of PDA treatment were 0 (0/116)-47.4% (376/793). After adjusting for population characteristics, the range of standardized ratios for PDA treatment in the 61 units was 0 (95%CI 0-0.3) to 3.4 (95%CI 3.1-3.8). Conclusions: From 2019 to 2021, compared to the peers in developed countries, VPI in CHNN NICU had a different PDA treatment rate; specifically, the VPI with small birth gestational age had a lower treatment rate, while the VPI with large birth gestational age had a higher rate. There are significant differences in PDA treatment rates among different units.
Infant ; Infant, Newborn ; Male ; Humans ; Female ; Ductus Arteriosus, Patent/drug therapy* ; Infant, Premature ; Cross-Sectional Studies ; Ibuprofen/therapeutic use* ; Infant, Very Low Birth Weight ; Persistent Fetal Circulation Syndrome ; Infant, Premature, Diseases/therapy*

Objective: To investigate the potential value of 18F-fluorodeoxyglucose (FDG) PET/CT in predicting the survival of patients with primary tracheal malignant tumors. Materials and Methods: An analysis of FDG PET/CT findings in 37 primary tracheal malignant tumor patients with a median follow-up period of 43.2 months (range, 10.8–143.2 months) was performed. Cox proportional hazards regression analyses were used to assess the associations between quantitative 18F-FDG PET/CT parameters, other clinic-pathological factors, and overall survival (OS). A risk prognosis model was established according to the independent prognostic factors identified on multivariate analysis. A survival curve determined by the Kaplan-Meier method was used to assess whether the prognosis prediction model could effectively stratify patients with different risks factors. Results: The median survival time of the 37 patients with tracheal tumors was 38.0 months, with a 95% confidence interval of 10.8 to 65.2 months. The 3-year, 5-year and 10-year survival rate were 54.1%, 43.2%, and 16.2%, respectively. The metabolic tumor volume (MTV), total lesion glycolysis (TLG), maximum standardized uptake value, age, pathological type, extension categories, and lymph node stage were included in multivariate analyses. Multivariate analysis showed MTV (p = 0.011), TLG (p = 0.020), pathological type (p = 0.037), and extension categories (p = 0.038) were independent prognostic factors for OS. Additionally, assessment of the survival curve using the Kaplan-Meier method showed that our prognosis prediction model can effectively stratify patients with different risks factors (p < 0.001). Conclusion This study shows that 18F-FDG PET/CT can predict the survival of patients with primary tracheal malignant tumors. Patients with an MTV > 5.19, a TLG > 16.94 on PET/CT scans, squamous cell carcinoma, and non-E1 were more likely to have a reduced OS.

Adolescent ; Adult ; Beijing/epidemiology* ; Contact Tracing ; Female ; Humans ; Male ; Prevalence ; Tuberculosis/transmission* ; Universities ; Young Adult

Background: With the publication of Sepsis-3 definition, epidemiological data based on Sepsis-3 definition from middle-income countries including China are scarce, which prohibits understanding of the disease burden of this newly defined syndrome in these settings. The purpose of this study was to describe incidence and outcome of Sepsis-3 in Yuetan sub-district of Beijing and to estimate the incidence rate of Sepsis-3 in China. Methods: The medical records of all adult residents hospitalized from July 1, 2012 to June 30, 2014 in Yuetan sub-district of Beijing were reviewed. Patients with sepsis-3 and severe sepsis/septic shock were identified. The incidence rates and mortality rate of sepsis-3 and sepsis/septic shock were calculated, incidence rates and in-hospital mortality rates were normalized to the population distribution in the 2010 National Census. Population incidence rate and case fatality rate between sexes were compared with the Z test, as the data conformed to Poisson distribution. Results: Of the 21,191 hospitalized patients, 935 patients were diagnosed with Sepsis-3, and 498 cases met severe sepsis/septic shock criteria. The crude annual incidence rate of Sepsis-3 in Yuetan sub-district was 363 cases per 100,000 population, corresponding to standardized incidence rates of 236 cases per 100,000 population per year, respectively. The overall case fatality rate of Sepsis-3 was 32.0%, the crude population mortality rates of Sepsis-3 was 116 cases per 100,000 population per year, the standardized mortality rate was 67 cases per 100,000 population per year, corresponding to a speculative extrapolation of 700,437 deaths in China. The incidence rate and mortality rate of Sepsis-3 were significantly higher in males, elderly people, and patients with more comorbidities. The 62.1% of patients with Sepsis-3 had community-acquired infections, compared with 75.3% of infected patients without Sepsis-3 (P < 0.001). The most common infection in patients with Sepsis-3 was lower respiratory tract infection. When compared with patients with Sepsis-3, patients diagnosed as severe sepsis/septic shock were more likely to have higher case fatality rate (53.4% vs. 32.0%, P < 0.001) Conclusions: This study found the standardized incidence rate of 236 cases per 100,000 person-year for Sepsis-3, which was more common in males and elderly population. This corresponded to about 2.5 million new cases of Sepsis-3 per year, resulting in more than 700,000 deaths in China. Clinical trial registration NCT02285257, https://clinicaltrials.gov/ct2/show/record/NCT02285257.

Objective: The clinical characteristics and outcomes of patients with chronic myeloid leukemia (CML) who had discontinued tyrosine kinase inhibitors (TKI) therapy were analyzed retrospectively. Methods: Clinical data of 109 cases of chronic CML patients who had discontinued TKI therapy in seven centers were retrospectively analyzed from June 1, 2005 to March 1, 2018. 91 cases with complete clinical data were enrolled in this study. We aimed to observe the status of patients with treatment free remission (TFR) after TKI therapy discontinuation and its prognostic factors. Results: 38 of 91 patients lost MMR after a median follow-up of 9 months and the estimated TFR was 52.6%. 31 of 38 patients who met the definition of molecular relapse resumed TKI treatment immediately and regained the major molecular response (MMR) with a median time of 3 months (range, 1-12 months). No significant difference was found in median course of imatinib therapy between the TFR group and the relapse. Similarly, duration to MMR, age and gender also showed no difference between the two groups. The longer duration of MMR maintenance (more than 24 months), the lower relapse rate was observed (P=0.027). Conclusion: TKI might be safely discontinued in part of CML patients.
China ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Protein Kinase Inhibitors/therapeutic use* ; Protein-Tyrosine Kinases ; Retrospective Studies ; Treatment Outcome

BACKGROUNDCatheter-directed thrombolysis (CDT) has been a mainstay in treating deep venous thrombosis (DVT). However, the optimal dosage of a thrombolytic agent is still controversial. The goal of this study was to evaluate the safety and efficacy of low dosage urokinase with CDT for DVT.

METHODSA retrospective analysis was performed using data from a total of 427 patients with DVT treated with CDT in our single center between July 2009 and December 2012. Early efficacy of thrombolysis was assessed with a thrombus score based on daily venography. The therapeutic safety was evaluated by adverse events. A venography or duplex ultrasound was performed to assess the outcome at 6 months, 1 year and 2 years postoperatively.

RESULTSThe mean total dose of 3.34 (standard deviation [SD] 1.38) million units of urokinase was administered during a mean of 5.18 (SD 2.28) days. Prior to discharge, Grade III (complete lysis) was achieved in 154 (36%) patients; Grade II (50-99% lysis) in 222 (52%); and Grade I (50% lysis) in 51 (12%). The major complications included one intracranial hemorrhage, one hematochezia, five gross hematuria, and one pulmonary embolism. Moreover, no death occurred in the study.

CONCLUSIONSTreatment of low-dose catheter-directed thrombosis is an efficacious and safe therapeutic approach in patients with DVT offering good long-term outcomes and minimal complications.

Adolescent ; Adult ; Aged ; Drug Administration Schedule ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Urokinase-Type Plasminogen Activator ; administration & dosage ; adverse effects ; therapeutic use ; Venous Thrombosis ; drug therapy ; Young Adult