Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

Objective:To observe the clinical features of eyes in children with methylmalonic acidemia (MMA).Methods:A retrospective clinical case study. From June 2019 to June 2022, 13 children with MMA visited on the Department of Ophthalmology of Henan Children's Hospital were included in the study. The anterior segment and fundus were examined under surface or general anesthesia. Best corrected visual acuity (BCVA) and refraction were performed in 9 cases; fluorescein fundus angiography (FFA) was performed in 3 cases; flash electroretinogram (FERG) was performed in 6 cases; flash visual evoked potential (FVEP) was detected in 6 cases; optical coherence tomography (OCT) was performed in 3 cases.Results:Among the 13 pediatric patients with methylmalonic acidemia, 6 cases were male and 7 cases were female. The average age at first visit was 45 months. All cases suffered from hyperhomocysteinemia; 9 cases were with epilepsy; 2 cases were with infantile spasms; 11 cases were with stunting, 13 cases were with repeated pulmonary infection during growth period; 4 cases were with hydrocephalus; 1 cases was with hypertension and renal insufficiency. Genetic dectection results of 8 cases were recorded, MMACHC:c.609G>A:p.W203* mutation site was found in all cases. One case was accompanied by corneal ulcer. There were 10 cases with nystagmus, 4 cases with macular degeneration, 3 cases with hyperopic refractive error and esotropia. Nine cases underwent BCVA examination, BCVA was light perception-0.6. In OCT, 2 cases of 3 cases showed retinal thinning and photoreceptor cell layer atrophy in the macular area. In FFA, 2 cases of 3 cases showed circular transparent fluorescence in the macular area. Five cases of 6 cases who with FVEP had different degrees of P100 peak time delay and decreased amplitude, and 4 cases of 6 cases with FERG had decrease of a and b wave in light and dark adaptation. Conclusions:The clinical phenotypes of eyes in children with MMA are various and the severity was different; most of them are accompanied by nystagmus, and the fundus lesions are common in the characteristic bovine eye like macular region. Those with macular disease have severe visual impairment.

Objective:To observe any effect of dry needling of myofascial trigger points on substance P and synaptophysin expression in the spinal dorsal horn.Methods:Sixty-four Sprague-Dawley rats were randomly divided into a control group ( n=16) and a model group ( n=48). Myofascial trigger points were induced in the model group by a blunt strike and eccentric running. That group was then randomly divided into a no-treatment group ( n=15), a massage group ( n=16), and a dry needling group (16 rats). The rats in the two treatment groups received 4 weeks of dry needling or Chinese massage. Pressure pain thresholds were recorded before the experiment and after the 4 weeks. The content of substance P and synaptophysin in the spinal dorsal horn were measured using immunoblotting and immunohistochemistry. Results:After the treatment 14 rats (93%) in the model group had trigger points, significantly higher than the 8 rats (50%) in the massage group and the 7 rats (44%) in the dry needling group. After treatment, the average pressure pain thresholds of the no-treatment and massage groups was significantly lower than the control group′s average, while the difference between the dry needling group and the control group was not significant. The average pressure pain threshold had improved significantly in the no-treatment group, the massage group and the dry needling group, and the averages of the massage group and the dry needling group were significantly higher than that of the no-treatment group. The level of substance P was significantly higher in the no-treatment group than in the other three groups and the ratio of substance P to Glyceraldehyde 3-phosphate dehydrogenase (GAPDH)was significantly higher. The substance P: GAPDH ratio of the massage group was significantly higher than that of the control group.Conclusions:Dry needling and massage are effective in relieving myofascial pain, at least in rats. Both can reduce the content of substance P in the spinal dorsal horn.

Osteoarthritis (OA) is a common degenerative disease. Its most significant pathological change is destruction of articular cartilage and the main clinical symptoms are pain and dysfunction of joints. Recent studies have shown that the expression of non-coding RNA (ncRNA) in chondrocytes can abnormally up-regulate or down-regulate and alter the activities of chondrocytes like their proliferation, migration and apoptosis, thus leading to the occurrence and development of osteoarthritis. Exosomes are extracellular vesicles with a diameter of 40-100 nm, which are secreted in intercellular fluid, act as medium of intercellular communication. They protect ncRNA, protein, lipid and other bioactive materials from enzymatic degradation by encapsulating them and transferring to sibling chondrocytes, due to their good tissue permeability. They can also improve communication between cells and regulate the activities of chondrocytes. Thus, exosomes behave like gene carriers. The ncRNA carried by exosomes can supplement or adsorb the abnormal ncRNA in chondrocytes, so as to regulate the activity of chondrocytes, and is therefore considered as a possible candidate with capabilities to repair cartilages. In this study we reviewed existing literatures related to the roles and effects of exosome miRNA, lncRNA and circRNA on osteoarthritis. We also reviewed the pathogenesis of exosome ncRNA in osteoarthritis.

Osteosarcoma, the most common primary bone tumor in children and adolescents, is characterized by high malignancy, rapid progression and high metastatic potential. However, no significant progress has been made in treating osteosarcoma recently. The prognosis of osteosarcoma is usually unsatisfied. One of the main reasons is that we cannot be able to identify the Achilles heel of osteosarcoma. A growing number of evidence suggests that different types of RNA play various roles in the development of osteosarcoma. The competing endogenous RNA (ceRNA) is a newly emerging theory, which can propose messenger RNA (mRNA), long non-coding RNA (lncRNA), pseudogene and other different transcripts. Therefore, it can play a role in the regulation of microRNA (miRNA) through competition. In the latest researches, it is shown that the interaction of these transcripts play an important role in the occurrence and development of osteosarcoma by mediating biological processes such as proliferation, apoptosis, metastasis and chemotherapy resistance of osteosarcoma cells. In addition, these different types of transcripts may provide new biomarkers and potential therapeutic targets for osteosarcoma. The present studies review the development of ceRNA hypothesis, summarizes existing knowledge system of ceRNA, and develop a systematic review of the role of different types of ceRNA in the pathogenesis and biological function of osteosarcoma. This review could lay the foundation for the basic and clinical study of osteosarcoma and promote the early diagnosis and treatment effects of osteosarcoma.

Some primary bone tumors are prone to hematogenous metastasis and after that, the therapeutic effect is not that good and prognosis is poor. Circulating tumor cells (CTC) shed from the tumor cells of primary or metastatic focus and then enter into blood circulation. CTC may appear in the early stage of the tumor, which can implant in distant organs to form metastatic sites and self-implant in the primary sites leading to the tumor recurrence; CTC are closely related with the prognosis of patients with tumors. In most primary bone tumors, CTC are heterogeneous compared with primary tumor cells. Studying CTC from various aspects can provide a basis for the early diagnosis and treatment of primary bone tumors. This review summarizes the current researches of CTC in common primary bone tumors, and expects the future of research direction and application practice in clinic.

Objective:To investigate the correlation between UGT1A1 polymorphisms and the irinotecan plus S-1 regimen-induced toxicities in Chinese advanced esophageal squamous cell carcinoma (ESCC) patients.Methods:A total of 46 recurrent or metastatic ESCC patients selected from ESWN 01 trial were randomly assigned to irinotecan plus S-1 group [intravenous infusion of irinotecan (160 mg/m 2) on day 1 and oral S-1 (80-120 mg) on days 1-10, repeated every 14 days]. Peripheral venous blood at baseline was collected and genomic DNA was extracted. The genetic polymorphisms of UGT1A1*6 and UGT1A1*28 were analyzed by polymerase chain reaction (PCR) amplification. Irinotecan plus S-1 regimen-induced toxicities of patients with different UGT1A1 polymorphisms were observed. The correlation between UGT1A1 polymorphisms and the adverse effects was analyzed. Results:Among the 46 patients, the numbers of UGT1A1*6 wild type genotype (GG), mutant heterozygote (GA) and mutant homozygote (AA) were 30, 15 and 1, while those with UGT1A1*28 wild type genotype (TA6/6), mutant heterozygote (TA6/7) and mutant homozygote (TA7/7) were 36, 8 and 2, respectively. Only one patient with UGT1A1*6 AA genotype occurred grade 3 diarrhea, while one of the 2 patients with UGT1A1*28 TA7/7 genotype occurred grade 4 diarrhea. No neutropenia was observed in the patient with UGT1A1*6 AA genotype, however, both of the two patients with UGT1A1*28 TA7/7 genotype occurred grade 3-4 neutropenia. Patients with UGT1A1*28 genetic polymorphism (TA 6/7 or TA7/7) had a higher response rate compared with wild-type TA6/6 carriers. (55.6% versus 26.5%).Conclusions:The homozygous genotype of UGT1A1*6 AA and UGT1A1*28 TA7/7 are rare (<5%) in Chinese ESCC population. Not all homozygous AA and TA7/7 carriers occur severe dose limited toxicities (DLT) when treated with irinotecan (160 mg/m 2) plus S-1 regimen for 2 weeks. However, it′s still necessary torigorously observe the occurrence of severe diarrhea and neutropenia in patients with UGT1A1*6 AA and UGT1A1*28 TA7/7 and adjust the dose timely.

Objective:To investigate the correlation between UGT1A1 polymorphisms and the irinotecan plus S-1 regimen-induced toxicities in Chinese advanced esophageal squamous cell carcinoma (ESCC) patients.Methods:A total of 46 recurrent or metastatic ESCC patients selected from ESWN 01 trial were randomly assigned to irinotecan plus S-1 group [intravenous infusion of irinotecan (160 mg/m 2) on day 1 and oral S-1 (80-120 mg) on days 1-10, repeated every 14 days]. Peripheral venous blood at baseline was collected and genomic DNA was extracted. The genetic polymorphisms of UGT1A1*6 and UGT1A1*28 were analyzed by polymerase chain reaction (PCR) amplification. Irinotecan plus S-1 regimen-induced toxicities of patients with different UGT1A1 polymorphisms were observed. The correlation between UGT1A1 polymorphisms and the adverse effects was analyzed. Results:Among the 46 patients, the numbers of UGT1A1*6 wild type genotype (GG), mutant heterozygote (GA) and mutant homozygote (AA) were 30, 15 and 1, while those with UGT1A1*28 wild type genotype (TA6/6), mutant heterozygote (TA6/7) and mutant homozygote (TA7/7) were 36, 8 and 2, respectively. Only one patient with UGT1A1*6 AA genotype occurred grade 3 diarrhea, while one of the 2 patients with UGT1A1*28 TA7/7 genotype occurred grade 4 diarrhea. No neutropenia was observed in the patient with UGT1A1*6 AA genotype, however, both of the two patients with UGT1A1*28 TA7/7 genotype occurred grade 3-4 neutropenia. Patients with UGT1A1*28 genetic polymorphism (TA 6/7 or TA7/7) had a higher response rate compared with wild-type TA6/6 carriers. (55.6% versus 26.5%).Conclusions:The homozygous genotype of UGT1A1*6 AA and UGT1A1*28 TA7/7 are rare (<5%) in Chinese ESCC population. Not all homozygous AA and TA7/7 carriers occur severe dose limited toxicities (DLT) when treated with irinotecan (160 mg/m 2) plus S-1 regimen for 2 weeks. However, it′s still necessary torigorously observe the occurrence of severe diarrhea and neutropenia in patients with UGT1A1*6 AA and UGT1A1*28 TA7/7 and adjust the dose timely.

Cancer stem cells (CSCs) are a group of tumor cells with the potential for self-replication, multicellular differentiation, and therapeutic resistance—factors which contribute to tumor recurrence, distant metastasis, and the failure of tumor treatment. Mitochondrial homeostasis plays a key role in stemness maintenance and differentiation regulation of CSCs. Mitophagy or selective autophagy of mitochondria, is an important regulatory mechanism for the maintenance of mitochondrial homeostasis. However, the role of mitophagy in CSCs is controversial. Considering that mitophagy regulates mitochondrial quality control, it was originally thought to positively regulate tumor suppression and maintain intracellular homeostasis. However, in recent years, mitophagy has been reported to be involved in reducing oxidative stress damage of tumor cells and promoting tumor progression. Further research on the mechanism of mitophagy regulation can reveal new therapeutic targets for tumor treatment. In this review, we have focused on the role of mitophagy in stemness maintenance, metabolic transformation, and therapeutic resistance of CSCs.

Objective To evaluate the clinical effect of mini-plate internal fixation via anterior elbow approach in treating coronoid process fractures.Methods A retrospective case series study was conducted on the clinical data of 43 cases of ulnar coronoid process fractures treated from December 2014 to December 2016.There were 29 males and 14 females,with an average age of 32.4 years (range,24-64 years).Twenty-four cases were injured on the right,and 19 on the left.There were 18 cases of simple coronoid process fractures,23 combined with ipsilateral capitulum radius fractures,and two combined with ipsilateral ulna olecranon fractures.According to the O'Driscoll classification,there were four cases of type Ⅰ,3 type Ⅱa,9 type Ⅱb,17 type Ⅱc,6 type Ⅲa,and 4 type Ⅲb.The elbow flexion and extension range was 40°-90°[(64 ± 18)°],and the rotation range 60°-130°[(83 ± 15)°].All the patients underwent mini-plate internal fixation via anterior elbow approach.The operation time,intraoperative blood loss,wound healing,fracture healing,and postoperative complications were recorded.Function of elbow joint was evaluated by Mayo elbow performance score (MEPS).Results All patients were followed up for 12-24 months (mean,15.7 months).The average operation time was 52 minutes (range,36-86 minutes).The average blood loss was 20 ml (range,10-50 ml).At the last follow-up,all were seen incision healing by first intention and clinical fracture healing.The index finger,and middle finger palmaris numbness occurred in one patient after surgery,and the patient recovered at 2 months of follow up.The elbow flexion and extension range was 86°-145° [(117 ± 114) °],and the rotation range of 114°-155° [(132 ± 17) °],showing significant difference in comparison with the preoperative measure (P ＜ 0.05).According to the MEPS one year after operation,14 cases were evaluated excellent,27 good,and four fair,with an excellent and good rate of 91％.Conclusion The mini-plate internal fixation via the anterior elbow approach is effective in treating ulnar coronoid process fractures,for the operation is simple,allows full exposure,reduction,or reconstruction under direct vision,and effectively restores the function of the elbow joint.