Hemorrhagic shock (HS) is one of the leading causes of death among young adults worldwide. Multiple organ dysfunction in HS is caused by an imbalance between tissue oxygen supply and demand, which is closely related to the poor prognosis of patient. Mitochondrial dysfunction is one of the key mechanisms contributing to multiple organ dysfunction in HS, while mitochondrial quality control regulates mitochondrial function through a series of processes, including mitochondrial biogenesis, mitochondrial dynamics, mitophagy, mitochondrial-derived vesicles, and mitochondrial protein homeostasis. Modulating mitochondrial quality control can improve organ dysfunction. This review aims to summarize the effects of mitochondrial dysfunction on organ function in HS and discuss the potential mechanisms of mitochondrial quality control, providing insights into the injury mechanisms underlying HS and guiding clinical management.

Objective:To evaluate the role of G-protein coupled receptor 37 (GPR37) in cognitive dysfunction in a mouse model of neuropathic pain.Methods:SPF-grade healthy male C57BL/6 mice and GPR37 knockout (GPR37-KO) mice, aged 3 months, with a body weight of approximately 20 g, were divided into 4 groups ( n=6 each) using a random number table method: control group (Con group), neuropathic pain group (NPP group), GPR37-KO+ control group (GPR37-KO Con group) and GPR37-KO+ neuropathic pain group (GPR37-KO NPP group). The mouse model of neuropathic pain was established by ligation of the sciatic nerve. The thermal paw withdrawal latency (TWL) and mechanical paw withdrawal threshold (MWT) were measured at 7 days after surgery. The open field test and Morris water maze test were performed at 28 days after surgery. The mice were subsequently sacrificed, and the medial prefrontal cortex (mPFC) was obtained for determination of the level of phosphorylated calcium/calmodulin-dependent protein kinase Ⅱ(p-CAMKⅡ) and expression of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD-95). Results:Compared to Con group, no significant changes were found in the parameters in GPR37-KO Con group ( P>0.05), and TWL was significantly shortened, MWT was decreased, the time the animal spent in central area was prolonged and the platform-crossing times were increased in the open field test, and the escape latency was prolonged and platform-crossing times were decreased in the Morris water maze test, and the expression of p-CAMKⅡ, BDNF and PSD-95 in the mPFC was down-regulated in NPP group ( P<0.05). Compared with NPP group, TWL was significantly shortened, MWT was decreased, the time the animal spent in central area was prolonged and the platform-crossing times were increased in the open field test, and the escape latency was prolonged and platform-crossing times were decreased in the Morris water maze test, and the expression of p-CAMKⅡ, BDNF and PSD-95 in the mPFC was down-regulated in GPR37-KO NPP group ( P<0.05). Conclusions:GPR37 is involved in the development of cognitive dysfunction in mice with neuropathic pain, and the mechanism may be related to its modulation of synaptic plasticity.

BACKGROUND: Colorectal carcinogenesis and progression are related to the gut microbiota and the tumor immune microenvironment. Our previous clinical trial demonstrated that berberine (BBR) hydrochloride might reduce the recurrence and canceration of colorectal adenoma (CRA). The present study aimed to further explore the mechanism of BBR in preventing colorectal cancer (CRC). METHODS: We performed metagenomics sequencing on fecal specimens obtained from the BBR intervention trial, and the differential bacteria before and after medication were validated using quantitative polymerase chain reaction. We further performed ApcMin/+ animal intervention tests, RNA sequencing, flow cytometry, immunohistochemistry, and enzyme-linked immunosorbent assays. RESULTS: The abundance of fecal Veillonella parvula ( V . parvula ) decreased significantly after BBR administration ( P = 0.0016) and increased through the development from CRA to CRC. Patients with CRC with a higher V. parvula abundance had worse tumor staging and a higher lymph node metastasis rate. The intestinal immune pathway of Immunoglobulin A production was activated, and the expression of TNFSF13B (Tumor necrosis factor superfamily 13b, encoding B lymphocyte stimulator [BLyS]), the representative gene of this pathway, and the genes encoding its receptors (interleukin-10 and transforming growth factor beta) were significantly upregulated. Animal experiments revealed that V. parvula promoted colorectal carcinogenesis and increased BLyS levels, while BBR reversed this effect. CONCLUSION: BBR might inhibit V. parvula and further weaken the immunomodulatory effect of B cells induced by V. parvula , thereby blocking the development of colorectal tumors. TRIAL REGISTRAION ClinicalTrials.gov, No. NCT02226185.
Animals ; Humans ; Berberine/therapeutic use* ; Carcinogenesis ; Veillonella ; Colorectal Neoplasms/genetics* ; Tumor Microenvironment

Objective:To investigate the effect of problem-oriented nursing intervention in the self-management rehabilitation of patients with coronary heart disease after percutaneous coronary intervention (PCI).Methods:A total of 128 patients with coronary heart disease undergoing PCI operation in Changzhou Second People′s Hospital from January 2019 to January 2021 were selected and randomly divided into the observation group and the control group with 64 cases in each group. The control group was given routine self-management intervention, and the observation group was given problem-oriented self-management intervention. After 6 months of intervention, the indicators of self-management ability, cardiac function, and quality of life were compared between the two groups.Results:After 6 months of intervention, the observation group actually completed 58 cases, and the control group actually completed 62 cases. Before the intervention, there were no significant differences between the two groups in the scores of coronary self-management ability scale, cardiac function index and Seattle Angina Questionnaire ( P>0.05). Six months after intervention, the scores of disease knowledge management, symptom management, first aid management, daily life management, bad addiction management, treatment compliance, and self-management ability in the observation group were 16.34 ± 2.36, 13.36 ± 2.42, 12.26 ± 2.23, 17.45 ± 2.74, 16.52 ± 2.45, 12.16 ± 2.15, 103.54 ± 14.32, which were significant higher than those of in the control group, 14.32 ± 2.45, 12.45 ± 2.23, 10.75 ± 2.32, 16.05 ± 2.45, 15.24 ± 2.53, 10.36 ± 2.24, 94.09 ± 13.36 ( t=2.14-4.59, all P<0.05). After six months of intervention, the left ventricular end-systolic diameter (LVESD) and the left ventricular end-diastolic diameter(LVEDD) were (34.39 ± 6.75) mm and (52.60 ± 6.31) mm, which were significant lower than those of the control group, (38.56 ± 6.52) mm and (55.79 ± 5.74) mm ( t=3.52 and 2.90, both P<0.05). Left ventricular ejection fraction (LVEF) and left ventricular short-axis shortening rate (FS) in the observation group after 6 months intervention were (44.25 ± 3.65)% and (23.86 ± 2.41)%, which were significant higher than those of in the control group, (39.24 ± 3.52)% and (22.26 ± 2.51)%( t=7.65 and 3.56, both P<0.05). Six months after the intervention, the scores of the degree of body limitation, angina pectoris, stable angina pectoris attack degree, treatment satisfaction, disease cognition degree, quality of life score in the observation group were 73.09 ± 8.13, 68.21 ± 10.15, 74.10 ± 4.45, 79.36 ± 8.21, 76.53 ± 9.43, 72.26 ± 9.12, which were significant higher than those of in the control group, 64.15 ± 8.11, 59.38 ± 10.23, 63.51 ± 5.23, 62.45 ± 8.16, 67.68 ± 9.20, 63.44 ± 8.65 ( t=4.74-11.91, all P<0.05). Conclusion:Problem-oriented nursing intervention is helpful to promote the development of self-management ability of patients with coronary heart disease after PCI, promote the recovery of postoperative cardiac function, and improve the quality of life of patients.

Objective:To explore the optimum time of ambulation of atrial fibrillation patients after radiofrequency ablation, to provide basis for patients' early postoperative rehabilitation.Methods:By convenient sampling method, a total of 120 patients with atrial fibrillation after radiofrequency ablation were collected at Yanghu Branch and City Branch of Changzhou Second People's Hospital from January 2020 to May 2021. They were divided into the early group, middle group and late group according to the random number table method, each group were 40 cases. All patients received routine postoperative intervention, the time of ambulation were 4, 6 and 12 h after operation in the early group, middle group and late group, respectively. The complication rate within 24 h after operation was compared among the three groups, and the comfort level of the three groups at 24, 48 and 72 h after operation was evaluated with Comfort Status Scale (GCQ).Results:Finally, 111 patients were included, including 37 in the early group, 38 in the middle group and 36 in the late group. There was no significant difference in the incidence of bleeding or hematoma, urinary retention, lumbago within 24 h after operation among the three groups ( P>0.05). The incidence of postural hypotension within 24 h after operation in the early group was 2.7% (1/37), which was lower than 21.1% (7/38) and 25.0% (9/36) in the middle and late groups, with a statistically significant difference ( χ2=4.86, 7.67, both P<0.05). At 48 and 72 h after operation, the scores of physiological dimension, psychological dimension and the total score of GCQ in the early group were (20.68 ± 3.07), (22.54 ± 3.35), (81.68 ± 6.11) and (22.54 ± 3.73), (24.38 ± 2.49), (84.92 ± 6.37), higher than those in the middle group (19.16 ± 2.19), (21.32 ± 2.27), (78.24 ± 5.58), (20.93 ± 2.85), (22.32 ± 2.04), (81.66 ± 6.56), and those in the late group (18.44 ± 1.50) (21.31 ± 1.99), (78.06 ± 4.32), (20.89 ± 2.25), (21.58 ± 1.86), (80.28 ± 6.44), the differences were statistically significant ( t values were 2.19-4.15, all P<0.05). Conclusions:Ambulation at 4 h after operation does not increase peripheral vascular complications, but can reduce the incidence of postural hypotension and improve the comfort of patients with atrial fibrillation after radiofrequency ablation.

OBJECTIVE: To investigate the effect and mechanism of artesunate (ARTS) combined with cytarabine(Ara-C) and/or daunorubicin (DNR) on the proliferation and apoptosis of MV4-11 human mixed-lineage leukemia rearranged（MLL-r） acute myeloid leukemia (AML) cell line. METHODS: CCK-8 assay was used to detect the proliferation effect of individual or in combination of ARTS, DNR, Ara-C on MV4-11 cells. The IC₅₀ of ARTS, DNR and Ara-C was calculated separately. The cell apoptosis and expression of receptors DR4 and DR5 were detected by flow cytometry. Western blot was used to detect the expression of Caspase-3 and Caspase-9 in each groups. RESULTS: The inhibition effect of ARTS, Ara-C and DNR on the proliferation of MV4-11 were all dose-dependently (r=0.99, 0.90 and 0.97, respectively). The IC₅₀ of ARTS, Ara-C and DNR on MV4-11 for 48 hours were 0.31 μg/ml, 1.43 μmol/L and 22.47 nmol/L, respectively. At the dose of ARTS 0.3 μg/ml， Ara-C 1.0 μmol/L and DNR 15 nmol/L, the proliferation rate for 48 hours of the tri-combination treatment was significantly lower than that of the bi-combination treatment, while both were significantly lower than that of the individual treatment (all P＜0.05). In terms of bi-combination treatment, the cells proliferation rate for 48 hours of the ARTS+Ara-C group was significantly lower than that of the ARTS+DNR group, while both were significantly lower than that of the Ara-C+DNR group (all P＜0.05). The cooperativity index (CI) of bi- and tri-combination treatment were all less than 1. After 48 hours of drug action, the cell apoptosis rate of the ARTS+DNR+Ara-C group was significantly higher than that of the Ara-C+DNR group, while both were significantly higher than that of the ARTS+DNR group (all P＜0.05). Meanwhile, the was no statistical difference between the cells apoptotic rate of the ARTS+DNR+Ara-C group and the ARTS+Ara-C group (P>0.05). The expression of DR4 and DR5 also showed no difference between control group and drug group. Compared with the DNR+Ara-C group, the expressions of Caspase-3 were significantly down-regulated in both the ARTS+DNR+Ara-C group and the ARTS+Ara-C group (all P＜0.05). The down-regulation of Caspase-3 expression was the most significantly in the combination group of three drugs, while the Caspase-9 expressions in different groups showed no apparent change. CONCLUSION The in vitro study showed that tri-combination of ARTS+Ara-C+DNR and bi-combination of ARTS+Ara-C could inhibit the proliferation and promote apoptosis of MV4-11 cell line. The inhibition effect of these two combinations were significantly superior to that of the traditional Ara-C+DNR treatment. The mechanism underlying this finding may be identified by the down regulation of Caspase-3, while no altered expression was observed of Caspase-9, DR4 and DR5.
Humans ; Cytarabine/pharmacology* ; Daunorubicin/pharmacology* ; Caspase 3 ; Caspase 9 ; Artesunate/pharmacology* ; Leukemia, Myeloid, Acute ; Apoptosis ; Cell Line

OBJECTIVE: To verrify the anti-tumor efficacy and toxicity between juglone (Jug) and Jug-loaded PLGA nanoparticles (Jug-PLGA-NPs). METHODS: Jug-PLGA-NPs were prepared by ultrasonic emulsification. The anti-tumor activity of Jug (2, 3, 4 µg/mL) and Jug-PLGA-NPs (Jug: 2, 3, 4 µg/mL) in vitro was measured by MTT assay and cell apoptosis analysis. The distribution, anti-tumor effect and biological safety in vivo was evaluated on A375 nude mice. RESULTS: With the advantage of good penetration and targeting properties, Jug-PLGA-NPs significantly inhibited proliferation and migration of melanoma cells both in vitro and in vivo (P<0.05 or P<0.01) with acceptable biocompatibility. CONCLUSIONS Jug can inhibit the growth of melanoma but is highly toxic. With the advantage of sustained release, tumor targeting, anti-tumor activity and acceptable biological safety, Jug-PLGA-NPs provide a new pharmaceutical form for future application of Jug.
Animals ; Cell Line, Tumor ; Delayed-Action Preparations/therapeutic use* ; Drug Carriers/therapeutic use* ; Melanoma/pathology* ; Mice ; Mice, Nude ; Nanoparticles ; Naphthoquinones ; Particle Size ; Polylactic Acid-Polyglycolic Acid Copolymer/therapeutic use*

Immune checkpoint inhibitor ( ICI) activates the host' s anti-tumor immune response by blocking negative regulatory immune signals. A series of clinical trials showed that ICI could effectively induce tumor regression in a subset of advanced cancer patients. Anti-angiogenesis drugs commonly used to block tumor angiogenesis can inhibit the growth of tumors, but they cannot improve the survival of patients with limitations in application such as drug resistance. Tumor immune response is closely related to angiogenesis. In turn, tumor angiogenesis highly depends on immunosuppressive microenvironment. Recent studies have indicated that ICI resistance could be alleviated by combination therapy with anti-angiogenesis treatment, and the efficacy of combination therapy was superior to that of monotherapy. The reciprocal regulation between tumor vascular normalization and immune reprogramming forms a reinforcing loop that reconditions the tumor immune microenvironment to induce durable antitumor immunity. This review clarifies the latest understanding of ICI combined anti-angiogenesis therapy and provides ideas for subsequent research.

BACKGROUND: Chronic urticaria (CU) is a common skin disease, which has a negative effect on quality of life. Current treatments do not fully control the symptoms of urticaria for many CU patients, thus effective and safe treatments for CU are still needed. OBJECTIVE: This review aims to evaluate the effectiveness and safety of cupping therapy in patients with CU. SEARCH STRATEGY: The search strategy looked for the presence of related keywords, such as "chronic urticaria" and "cupping therapy," in the title and abstract of research articles indexed in major databases. Randomized controlled trials (RCTs) were selected after querying nine electronic databases from their inception to May 2019 with the above search terms. INCLUSION CRITERIA: RCTs were included if they recruited patients with CU who were intervened with dry or wet cupping. Publications could be written in Chinese or English. DATA EXTRACTION AND ANALYSIS: Data were extracted, and the studies were assessed for the quality of their methodological design and risk of bias. Meta-analyses of the RCT data were conducted to assess the total effective rate of the treatment as the primary outcome. Skin disease quality of life index score, recurrence rate, and adverse events were assessed as secondary outcomes. Subgroup analyses were conducted based on different interventions. RESULTS: Thirteen comparisons from 12 RCTs involving 842 participants were included. There were no significant differences between wet cupping and medications in total effective rate (n = 372; risk ratio [RR] = 1.10, 95% confidence interval [CI] 0.97 to 1.25; P = 0.14) or recurrence rate (n = 240; RR = 0.56, 95% CI 0.23 to 1.36; P = 0.20). Cupping therapy, in combination with antihistamine treatment was more efficacious than antihistamines alone, with a greater total effective rate (n = 342; RR = 1.18, 95% CI 1.01 to 1.39; P = 0.03) and lower recurrence rate (n = 342; RR = 0.52, 95% CI 0.32 to 0.84; P = 0.007). Cupping therapy combined with acupuncture was more effective than acupuncture alone (n = 156; RR = 1.25, 95% CI 1.07 to 1.46; P = 0.006). No serious adverse events were reported. CONCLUSION: Wet cupping may be as effective as treatment with antihistamines. When cupping therapy is used as an adjuvant therapy to antihistamines or acupuncture, it may enhance the efficacy. Results drawn from these studies should be interpreted with caution and applied with care to clinical practice, because of the poor quality among the studies that were reviewed. SYSTEMATIC REVIEW REGISTRATION PROSPERO, CRD42019137451.

The tumor contains abundant new vessels, which are unevenly distributed, irregular, and branch-disordered. Angiopoietin (Ang) and tyrosine kinase receptor Tie mediate stable maturation of angiogenesis. Ang1 mainly plays a role in promoting vascular stabilization, and Ang2 is highly expressed in vessels, which makes the structure and function of vessels abnormal. Leaked vessels provide opportunities for invasion and metastasis of circulating tumor cells. Targeting the Ang/Tie axis to correct the abnormal state of vessels and promote its normalization, combined with chemotherapy drugs or immunotherapy, play a synergistic effect against tumors. This article summarizes the role of Ang/Tie axis in tumor angiogenesis and metastasis, and it aims to provide new ideas and strategies for clinical treatment of tumors.