Curcumin relieves oxaliplatin-induced neuropathic pain via reducing inflammation and activating antioxidant response.

Oxaliplatin (OXA) has shown high effectiveness in the treatment of cancers, but its anticancer clinical effects often induce neurotoxicity leading to neuropathic pain. Oxidative damage and NLRP3 inflammasome play important roles in neuropathic pain development. Here, neuropathic pain mouse model was constructed by continuous intraperitoneal injection of OXA. OXA administration induced mechanical pain, spontaneous pain, thermal hyperalgesia and motor disability in mice. The spinal cord tissues of OXA mice exhibited the suppressed antioxidative response, the activated NLRP3 inflammasome mediated inflammatory responses, and the increased GSK-3ß activity. Next, we injected curcumin (CUR) intraperitoneally in OXA mice for seven consecutive days. CUR-treated mice showed increased mechanical pain thresholds, reduced number of spontaneous flinches, increased paw withdrawal latency, and restored latency to fall. While in the spinal cord, CUR treatment inhibited the NLRP3 inflammasome mediated inflammatory response, increased Nrf2/GPX4-mediated antioxidant responses, and decreased mitochondrial oxidative generation. Additionally, CUR combined with GSK-3ß through four covalent bonds and reduced GSK-3ß activity. In conclusion, our findings suggest that CUR treatment inhibits GSK-3ß activation, increases Nrf2 mediated antioxidant responses, inhibits oxidative damage and inflammatory reaction, and alleviates OXA-induced neuropathic pain.

Diagnosis and genetic analysis of a case with glycogen storage disease type V caused by compound heterozygous mutations in the PYGM gene.

Glycogen storage disease type V is an autosomal recessive genetic disorder caused by muscle glycogen phosphorylase (PYGM) deficiency, which is characterized by exercise intolerance, second wind phenomena and high level of serum creatine kinase. In this study, we reported a Chinese young man with glycogen storage disease type V, with lower extremity weakness after exercise, increased creatine kinase, and slight fat infiltration in the posterior group of thigh muscle by magnetic resonance imaging (MRI). The proband had complex heterozygous PYGM disease-causing mutations, including c.308T>C (p.L103P) variant transmitted from the mother and c.260_261delCT (p.S87Ffs*23) from the father, of which the former was a novel PYGM mutation. This study enriched the PYGM pathogenic gene mutation spectrum, contributed to improve clinicians' understanding of glycogen storage disease type V and provided a reference for further genetic study of the disease.

Maternal DCAF2 is crucial for maintenance of genome stability during the first cell cycle in mice.

Precise regulation of DNA replication and genome integrity is crucial for gametogenesis and early embryogenesis. Cullin ring-finger ubiquitin ligase 4 (CRL4) has multiple functions in the maintenance of germ cell survival, oocyte meiotic maturation, and maternal-zygotic transition in mammals. DDB1-cullin-4-associated factor-2 (DCAF2, also known as DTL or CDT2) is an evolutionarily conserved substrate receptor of CRL4. To determine whether DCAF2 is a key CRL4 substrate adaptor in mammalian oocytes, we generated a novel mouse strain that carries a Dcaf2 allele flanked by loxP sequences, and specifically deleted Dcaf2 in oocytes. Dcaf2 knockout in mouse oocytes leads to female infertility. Although Dcaf2-null oocytes were able to develop and mature normally, the embryos derived from them were arrested at one- to two-cell stage, owing to prolonged DNA replication and accumulation of massive DNA damage. These results indicate that DCAF2 is a previously unrecognized maternal factor that safeguards zygotic genome stability. Maternal DCAF2 protein is crucial for prevention of DNA re-replication in the first and unique mitotic cell cycle of the zygote.This article has an associated First Person interview with the first author of the paper.

CRL4DCAF1 is required in activated oocytes for follicle maintenance and ovulation.

In mammals, oocytes within the primordial follicles require a number of essential factors to maintain their survival. However, the survival factors for activated oocytes have been poorly characterized. Recently we reported that damaged DNA binding protein-1 (DDB1), the linker subunit of the cullin ring-finger ubiquitin E3 ligase-4 (CRL4) complex, and its substrate adaptor, DDB1-CUL4 associated factor-1 (DCAF1), were essential for primordial follicle maintenance. In this study we specifically deleted these in the oocytes of growing follicles, to investigate if DDB1 and DCAF1 were also survival factors for activated oocytes. In the ovaries of Ddb1(fl/fl);Zp3-Cre mice, the primordial follicle pool was intact, but awakened oocytes and growing follicles beyond the primary stage were rapidly depleted. In the ovaries of Dcaf1(fl/fl);Pten(fl/fl);Gdf9-Cre and Ddb1(fl/fl);Pten(fl/fl);Gdf9-Cre mice, global primordial follicle activation was stimulated by enhanced PI3K signaling, but the awakened oocytes were rapidly lost due to no CRL4(DCAF1) activity. These mouse models provided original evidence that CRL4(DCAF1) was essential for maintaining oocyte survival, not only those in dormancy at the primordial follicle stage, but also naturally awakened oocytes and those awakened by hyper-activation of PI3K signaling. Interestingly, the oocyte-specific Ddb1 or Dcaf1 knockout mice had ovulation defects even before oocyte exhaustion. CRL4(DCAF1) within oocytes was required for cumulus expansion and ovulation-related somatic gene expression in a cell non-autonomous manner. Granulosa cells that surrounded these Ddb1 or Dcaf1-deleted oocytes exhibited increased rates of apoptosis and showed poor responses to ovulation signals. These results suggested that CRL4 in oocytes also regulated granulosa cell functions in a cell non-autonomous manner.

[Case control study on micro external fixator in treating supracondylar fracture of humerus in children].

OBJECTIVE: To explore clinical effects of micro external fixator for the treatment of supracondylar fracture of humerus in children. METHODS: From October 2017 to December 2018, 20 children with supracondylar fracture of humerus (treatment group) were admitted and treated with micro-external fixation after closed reduction, including 14 males and 6 females, aged from 6 to 14 years old with an average of (7.9±2.4) years old, classified to Gartland Ⅲ. Thirty nine children with supracondylar fracture of humerus were admitted as control group from January 2015 to September 2017, and treated with closed reduction Kirschner wire fixation. Among them, including 24 males and 15 females, aged from 6 to 14 years old with an average of (8.1±1.9) years old, classified to GartlandⅢ. Operation time, times of intraoperative fluoroscopy, and complications between two groups were observed and compared, Mayo scoring system at the latest follow up was used to evaluate clinical effect. RESULTS: Twenty children in treatment group were followed up from 6 to 12 months with an average of (8.0±2.5) months, operation time was(30.10±12.50) min, times of intraoperative fluoroscopy was(10.00±2.50). Fifteen patients got excellent results, 3 good, 2 fair according to Mayo elbow joint scoring. No ulnar nerve injury moderate or severe elbow varus occurred in treatment group. Thirty-nine children in control group were followed up from 5 to 13 months with an average of (9.0±3.1) months, operation time was(45.60±18.90) min, times of intraoperative fluoroscopy was(19.00±5.60). Twenty-three patients got excellent results, 12 good, 3 fair and 1 poor according to Mayo elbow joint scoring. One child occurred ulnar nerve injury and recovered at the final follow-up, 1 child occurred severe cubitus varus and 2 children occurred moderate cubitus varus. There was no statistical difference in clinical effect between two groups (P>0.05). Occurrence rate of moderate and server cubitus varus, operation time and times of intraoperative fluoroscopy in treatment group were better than that of control group(P<0.05). CONCLUSION: Treated with closedreduction and mini external fixator fixed on children humerus condyle fracture could receive the same clinical result as closed as reduction gram needle fixation, which has advantages of shorter operation time, less times of intraoperative fluoroscopy, not esay to damage ulnar nerve during operation, less incidence of moderate and severe cubitus varus deformity after operation, and the permeation was simple.

Bovine colostrum and product intervention associated with relief of childhood infectious diarrhea.

This meta-analysis aimed to investigate the protective effects of bovine colostrum against childhood infectious diarrhea. A systematic search was conducted using PubMed, Cochrane Library databases and clinicaltrial.gov. Among 166 research articles, only five RCTs were included into final analysis. Review manager (version 5.2) was used to pool the effect-size across studies. Sensitivity and risk of bias were estimated accordingly. Under a pooled analysis, bovine colostrum consumption correlated with a significant reduction in stool frequency of infectious diarrhea, by 1.42 times per day (95% CI: -2.70, -0.14). Bovine colostrum intervention also reduced occurrence of diarrhea by 71% (pooled OR = 0.29, 95%CI 0.16, 0.52). The OR of positive detection of pathogen in the stool was 0.29 (95%CI 0.08, 0.71) in bovine colostrum treated group, compared with placebo group. In the sensitivity analysis of studies with low risk of biases, bovine colostrum significantly reduced stool frequency, occurrence of diarrhea and pathogen detection. BC and related products have a significant benefit in reducing the frequency and relieving the symptoms of childhood infectious diarrhea.

A unique bone marrow lymphoma patient presenting with an isolated mass: A case report.

Bone marrow lymphoma with the onset of an isolated mass in the bone marrow is extremely rare. The present case report described a unique case of B cell lymphoblastic lymphoma (LBL) presenting with an isolated mass in the bone marrow cavity, without any organopathy or lymphadenopathy. An isolated mass in bone marrow is a rare primary manifestation of LBL. The patient in the present case report presented with pain in the right elbow, a fever, pancytopenia and splenomegaly. Additionally, no abnormality was determined in the lymph nodes, the bone marrow karyotype or a computed tomography scan of the humerus. Positron emission tomography (PET) examination revealed an increased uptake of 18F-fluorodeoxyglucose in right distal humerus. An isolated mass in the bone marrow cavity was removed by surgery. Pathological findings revealed B cell LBL. The patient received an acute lymphocytic leukemia chemotherapy regimen and achieved complete remission. However, 4 months following the initial diagnosis, the patient succumbed due to a relapse. The present case highlighted the importance of PET examination and biopsy, and the requirement to identify appropriate treatments for LBL. Additionally, it is important to broaden the differential diagnosis when an isolated mass is identified in the bone marrow cavity.

[Emergency closed reduction and percutaneous Kirschner wire fixation for treatment of Gartland type II-III supracondylar fractures of the humerus in children].

OBJECTIVE: To analyze the clinical effect and related risk factors of Gartland type II-III supracondylar fractures of humerus in children in the emergency closed reduction and percutaneous Kirschner wire fixation. METHODS: From January 2008 to June 2013,112 children of Gartland type II to III supracondylar humeral fractures were treated in children in emergency closed reduction and percutaneous K-wire fixation, including 72 males and 40 females with an average age of 6.2 years old ranging from 2 to 11 years old. Among them,74 cases were in Gartland type II fractures,38 cases were in type III; The duration from injury to surgery time was 2.5 to 8 hours (averaged 4.6 hours). Elbow cast was applied after operation with the elbow extended of 100 degrees for 4 to 6 weeks, then the gypsum and Kirschner wires were removed. RESULTS: All patients were follow-up from 6 to 60 months (averaged 12 months). All fractures reached clinical healing. The final follow-up was assessed by Flynn criteria, the result was excellent in 86 cases, good in 23 cases, general in 3 cases, excellent and good rate was 97.3%. Three patients had mild cubitus varus deformity without orthopedic treatment. No pin tract infections, iatrogenic ulnar nerve injury, compartment syndrome, and complications such as Volkmann ischemic contracture occurred. CONCLUSION: Closed reduction and percutaneous Kirschner wire fixation had advantages of exact reduction, firm fixation, fewer complications ,less pain in children undergoing emergency surgery, and.high success rate, so it is a safe and efficient treatment for humeral supracondylar fracture in children.

[Manipulative reduction and percutaneous K-wires fixation for treatment of supracondylar fractures of the humerus in children].

OBJECTIVE: To explore clinical effect of manipulative reduction and percutaneous K-wires fixation in treating supracondylar fractures of the humerus in children. METHODS: From July 2010 to December 2012, clinical data of 52 children with supracondylar fractures of the humerus, which treated with manipulative reduction and percutaneous K-wires fixation, were retrospectively analyzed. Among them, there were 35 males and 17 females with an average age of 6.7 (ranged from 2.5 to 12) years old. All fractures were type Garland II - III fractures, and 51 cases were extension type and 1 case were flexion type. Flynn evaluation standard of elbow performance score were applied to evaluate clinical effects. RESULTS: All patients were followed up from 12 to 18 months with average of 16 months. According to Flynn evaluation standard of elbow performance score, 41 cases obtained excellent result, 8 good and 3 moderate. CONCLUSION: Manipulative reduction and percutaneous K-wires fixation for the treatment of supracondylar fractures of the humerus in children has many advantages, such as minimally invasive, rapid recovery, stable fixation. It could prevent osteofascial compartment syndrome, Volkmann Contracture and cubitus varus.