Glaucoma is a multifactorial degenerative optic neuropathy, and its irreversible and blinding pathological characteristics mainly come from the damage to the optic nerve, namely glaucomatous optic neuropathy(GON). The difficulty in the treatment of GON lies in the early intervention, and currently there is no optic neuroprotective drug for the treatment of all types of GON. The death of retinal ganglion cells(RGCs)is the core pathological change caused by various pathogenic mechanisms of GON. Recent studies have found that the widespread second messenger cyclic adenosine 3', 5' -monophosphate(cAMP)and its downstream effector protein kinase A(PKA)signal cascade play an important role in the pathogenesis of GON. It can also inhibit the apoptosis of RGCs and play a protective and therapeutic role in glaucoma. Therefore, this article reviews the role of cAMP/PKA pathway in the pathophysiological development of GON, focusing on its effects on glaucoma intraocular pressure regulation, oxidative stress, neuroinflammation and optic nerve degeneration, in order to find a common central regulatory target for the optic nerve damage caused by different pathological mechanisms of GON and promote the further understanding and clinical treatment of this disease.

Surgical resection and radiotherapy have been commonly applied to the treatment of early- and intermediate-stage Merkel cell carcinoma. In recent years, immunotherapy based on immunogenic characteristics of Merkel cell carcinoma has been proved to be effective in the treatment of advanced Merkel cell carcinoma. This review focuses on advances in the treatment of Merkel cell carcinoma, and provides a reference for its clinical diagnosis and treatment.

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) have recently been identified to be closely related to the occurrence and development of atherosclerosis (AS). A growing body of evidence has suggested Chinese medicine takes unique advantages in preventing and treating AS. In this review, the related research progress of AS and LOX-1 has been summarized. And the anti-AS effects of 10 active components of herbal medicine through LOX-1 regulation have been further reviewed. As a potential biomarker and target for intervention in AS, LOX-1 targeted therapy might provide a promising and novel approach to atherosclerotic prevention and treatment.
Humans ; Atherosclerosis ; Scavenger Receptors, Class E/physiology* ; Biomarkers ; Plant Extracts ; Lipoproteins, LDL

Objective:To investigate the clinical efficacy in one stage reconstruction of composite defects of Achilles tendon and surrounding soft tissues with a flap transfer combined with allogeneic tendon transplantation.Methods:From July 2018 to August 2022, a total of 12 patients, including 9 males and 3 females, with a mean age of 31.5(ranged 8 to 56) years old, had surgery with flap transfer combined with transplantation of allogeneic tendon in one stage reconstruction for compound defects of Achilles tendon and soft tissue at the Department of Orthopaedics of First Affiliated Hospital of Nanchang University. The defects of Achilles tendons ranged from 4.0 to 9.0 cm, and the soft tissue defects sized from 3.0 cm × 4.0 cm to 14.0 cm × 6.0 cm. Of the 12 patients, 6 received transfers of sural neurovascular flaps, 3 with peroneal perforator flaps and 3 with free anterolateral thigh flaps(ALTF). The flaps sized from 4.0 cm × 4.5 cm to 15.0 cm×7.0 cm, and in addition, allogeneic tendon grafts were used to reconstruct the defects of Achilles tendons in all patients. All the flap donor sites were either directly sutured or covered with skin grafts. Follow-up was carried out by visits of outpatient clinic or telephone or WeChat distant interviews. The flap survival and recovery of ankle function and Achilles tendon were observed.Results:During the 3 months to 2 years of follow-up, none of the patient showed obvious immunological rejection against the transplanted allogeneic tendon. All 12 flaps survived well with the colour and texture close to the surrounding skin. No ulceration occurred in both of the donor and recipient sites. There was no re-rupture of the transplanted allogeneic tendon. At the final follow-up, ankle movement was measured at 13.4°±2.6° in dorsal extension and 33.6°±3.2° in plantar flexion. According to American Orthopaedic Foot and Ankle Society (AOFAS) ankle and hind foot function score, a score of 88.7±5.6 was achieved with 7 patients in excellent, 4 in good and 1 was acceptable.Conclusion:In patients with a composite defect of Achilles tendon and surrrounding soft tissue, the application of a flap transfer combined with a homogeneous allograft tendon transplantation in an one stage surgery is a feasible surgical procedure. It can achieve a satisfactory outcome with less trauma and fewer complications.

【Objective】 To investigate the targets and related pathways of Yiqi Jiedu Tongluo Formula (YQJDTLF) in the treatment of liver cirrhosis based on network pharmacology and molecular docking technology, so as to predict its potential mechanism. 【Methods】 Based on the TCMSP database, the effective active ingredients and action targets of YQJDTLF were extracted, and the therapeutic targets of liver cirrhosis were obtained through Drugbank, OMIM, TTD and DisGeNET; the common targets were screened. We constructed a visualization regulatory network diagram of "drug active components-disease targets" with Cytoscape and a protein interaction network diagram (PPI) with the STRING database. Then we screened the core proteins of PPIs with Cytoscape. Finally, we made Gene Ontology (GO) function enrichment analysis and KEGG pathway enrichment analysis of the core targets by using Metascape. Finally the molecular docking was completed. 【Results】 A total of 93 active ingredients and 135 common targets were obtained. The main active compounds included quercetin, baicalein, and stigmasterol. KEGG pathway enrichment analysis revealed 135 pathways involved in cancer signaling pathways (pathways in cancer) and other pathways. Through molecular docking, it was found that the binding activity between key traditional Chinese medicine components and the key targets was good. 【Conclusion】 YQJDTLF has the characteristics of being multi-component, multi-target and multi-pathway, and can play a role in the treatment of liver cirrhosis by regulating related pathways and targets.

Objective:To investigate the effect of transforming growth factor (TGF- β) signal in muscle fiber itself during inflammation/immunity response on intramuscular inflammation. Methods:Sixteen wild C57BL/6 mice (wild group) and sixteen mice with skeletal muscle-specific deficiency of T βRⅡ (knock-out group) between 4-8 weeks of age were selected for this study. Acute muscle injury in mice was induced by injection of myotoxin cardiotoxin (CTX) into gastrocnemius. The differences in intramuscular inflammation were compared between the wild and knock-out groups on 0, 4, 7 and 10 d after CTX injection by observing exudation of mononuclear phagocytes, macrophages, M1 type macrophages, CD4 +T cells and helpers T cells (Th1, 2&17). Two newborn C57BL/6 wild mice and 2 SM TGF- βr2-/- knock-out mice were selected to culture primary myoblasts in vitro which were divided into 2 groups: an interferon group subjected to interferon simulation and a control group subjected to addition of an equal amount of solvent. The differences in expression of IL-6, IL-10, MCP-1, MIP-1α, H-2K b, H2-Ea, Toll-like receptor (TLR)3 and TLR7 were compared between the interferon and control groups, as well as between the wild and knock-out groups. Results:On 4&7 d after CTX injection, the ratios of mononuclear/macrophage (75.73%±3.62%, 45.27%± 2.32%), macrophages (38.67%±2.76%, 24.87%±2.19%), M1 macrophages (43.21%±0.11%, 30.43%±2.19%), CD4 +T cells (20.13%±1.62%, 5.67%±0.32%) in the muscle tissue from the knock-out mice were significantly higher than those from the wild mice (58.52%±2.43%, 29.21%±2.45%; 20.63%±2.32%, 16.23%±1.25%; 24.98%±0.35%, 14.23%±1.69%; 10.70%±0.43%, 2.50%±0.45%), with a majority of Th1&Th17 ( P<0.05). In vitro results showed that the levels of IL-6, MCP-1, MIP-1α, H-2K b, H2-Ea and TLR3 were significantly upregulated in the interferon group compared with the control group and that such upregulation in the nock-out mice was more significant than in the wild mice ( P<0.05). Conclusions:Endogenous TGF- β signal activation plays a role in the functional recovery after muscle trauma, because it is involved in the regulation of immune behavior of muscle fibers, thus affecting intramuscular inflammation and muscle regeneration.

Objective:To analyze the correlation between clinical phenotypes and genotypes in 6 children with primary distal renal tubular acidosis (dRTA).Methods:The clinical data of 6 children confirmed as dRTA in Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science & Technology from November 2017 to August 2019 were collected, and related auxiliary examination was performed to assess their growth and development.The venous whole blood was reserved for Trio whole exome sequencing, and full spectrum genetic disease accurate diagnosis cloud platform was applied to systematic data screening and analysis.The suspected mutations were checked by Sanger sequencing, and then the role of protein was predicted by software.Results:Clinical manifestations, signs and auxiliary examination results of the 6 children accorded with the diagnostic criteria of dRTA, and the prominent characteristics was growth retardation.One case had knee valgus, one had osteoporosis, and the auxiliary examination results showed that both of them had alkaline urine, metabolic acidosis, and hypokalemia.Three children had nephrocalcinosis, and 2 children had nephrolithiasis.The parents of the 6 patients were all normal without phenotypes.Mutations in the SLC4A1 gene were identified in 4 patients, including 1 child with a reported homozygous autosomal recessive missense mutation(c.2102G>A, p.G701D), who had dRTA and hemolytic anemia, and 3 children with the reported de novo heterozygous autosomal dominant missense mutation(c.1766G>A, p.R589H, c.1765C>T, p.R589C), whose age at diagnosis was related to abnormal renal imaging.Compound heterozygous autosomal recessive mutations in the ATPV1B1 gene were identified in 1 patient, and they were novel heterozygous missense mutations (1153C>A, p.P385T and c. 806C>T, p.P269L). A novel homozygous autosomal recessive missense mutation was identified in 1 patient in the ATPV0A4 gene(c.1899C>A, p.Y633X, 208). Conclusions:Mutations in SLC4A1, ATP6V1B1, ATP6V0A4 genes are identified as the main causes of the primary dRTA, and the phenotypes was related to the mutation features and genotypes.Genetic test should be conducted on patients suspected as dRTA for early molecular diagnosis, thereby improving clinical phenotypic screening and individualized treatment.

Hepatocellular carcinoma (HCC) is a common malignant tumor and patients with HCC often have liver cirrhosis, with an extremely high 5-year recurrence rate and poor prognosis even after curative treatment. In recent years, sarcopenia has attracted more and more attention as a poor prognostic factor for various malignant tumors; however, there is still a lack of studies on the association between skeletal muscle index and prognosis of HCC in China. Evidence in foreign countries has shown that sarcopenia may be an a negative prognostic factor for HCC patients. This article reviews the etiology and possible pathogenesis of HCC-related sarcopenia and related intervention measures including nutritional supplementation, appropriate physical exercise, and medication, in order to provide a reference for related studies in China.

Epstein -Barr virus hepatitis is liver inflammation caused by Epstein -Barr virus infection, mainly self -limited hepatitis or mild or moderate liver injury.It often has good prognosis, but it may progress to chronic liver disease, severe hepatitis, and even intrahepatic cholangiocarcinoma.The clinical manifestations and histopathological features of this disease lack specificity , which may lead to missed diagnosis or misdiagnosis, and thus it should be taken seriously by clinicians .This article introduces the mechanism of Epstein -Barr virus infection and reviews the research advances in Epstein -Barr viral hepatitis.

Objective To explore the clinical effect of peroneal artery perforator flap for the treatment of serious heel spoke injuries in children.Methods From July,2014 to September,2017,13 children with severe heel and ankle injuries were treated by peroneal artery perforator flap.There were 9 males and 4 females,with an average age of 6.5 years (ranged from 3 to 11 years).The size of flaps ranged from 10.0 cm×3.0 cm to 14.5 cm×5.0 cm.The donor sites were sutured directly or covered with skin grafting.Regular follow-up was performed to observe the survival status of the flap and the functional recovery of the ankle joint.Results Twelve flaps survived completely.One flap had partial marginal necrosis in the distal portion,which was healed after dressing.Partial inadequate venous return happened in 1 case,which also recovered by the removal of part of the suture.All cases were followed-up for 3 months to 20 months.The appearance,texture,and color of the flaps were similar to the surrounding skin.No ulcer occurred.All case acquired normal gait.Conclusion The peroneal artery perforator flap is a good option for reconstruction of serious heel spoke injuries in children.The flap has consistent blood supply while leaving minimal morbidity at donor site.