Diabetic retinopathy (DR) has long been recognized as a primary microvasculopathy disease.However, more and more studies have proved that diabetic retinal neurodegeneration (DRN) occurs in the early stage of DR, and may precede microvascular disease.Nevertheless, the association between vasculopathy and neuropathy remains unclear.Reduced contrast sensitivity, localized deficits in visual field, electrophysiological changes and thinning of retinal thickness on optical coherence tomography can occur in the early stage of DRN, the main pathological changes for those abnormalities are increased apoptosis of ganglion cells and increased reactivity of glial cells.The imbalance between pro-apoptotic molecules (such as glutamate, angiotensin Ⅱ, etc.) and neuroprotective molecules (such as pigment epithelium-derived factor, somatostatin, etc.), inflammation, and oxidative stress in retinal neurons are important causes of DRN.Strategies for treating neurodegeneration include reducing the production of anti-apoptotic molecules, inhibiting the apoptosis pathway of nerve cells, and using antioxidants and neuroprotective factors.Studies on neurodegeneration have found that early intervention can effectively control the progression of neurodegeneration and prevent the progression of DR in animal models, but there are currently few drugs available for clinical trials.Further research is needed to discover the link between vascular dysfunction and DRN and to evaluate neuroprotective agents for retinal neurodegeneration to develop effective strategies for preventing DR and delaying its progression.This article reviews the clinical detection methods, pathological mechanisms, and intervention strategies of DRN.

Diabetic retinopathy (DR) has long been recognized as a primary microvasculopathy disease.However, more and more studies have proved that diabetic retinal neurodegeneration (DRN) occurs in the early stage of DR, and may precede microvascular disease.Nevertheless, the association between vasculopathy and neuropathy remains unclear.Reduced contrast sensitivity, localized deficits in visual field, electrophysiological changes and thinning of retinal thickness on optical coherence tomography can occur in the early stage of DRN, the main pathological changes for those abnormalities are increased apoptosis of ganglion cells and increased reactivity of glial cells.The imbalance between pro-apoptotic molecules (such as glutamate, angiotensin Ⅱ, etc.) and neuroprotective molecules (such as pigment epithelium-derived factor, somatostatin, etc.), inflammation, and oxidative stress in retinal neurons are important causes of DRN.Strategies for treating neurodegeneration include reducing the production of anti-apoptotic molecules, inhibiting the apoptosis pathway of nerve cells, and using antioxidants and neuroprotective factors.Studies on neurodegeneration have found that early intervention can effectively control the progression of neurodegeneration and prevent the progression of DR in animal models, but there are currently few drugs available for clinical trials.Further research is needed to discover the link between vascular dysfunction and DRN and to evaluate neuroprotective agents for retinal neurodegeneration to develop effective strategies for preventing DR and delaying its progression.This article reviews the clinical detection methods, pathological mechanisms, and intervention strategies of DRN.

Lysine-specific demethylase 1 (LSD1) is the firstly discovered histone demethylase. In recent years, LSD1 has become a hot topic in the study of the development and progression of malignancies, and its expression is closely related to the poor prognosis of malignancies. At present, some studies have showed that LSD1 is strongly related to the proliferation, invasion and metastasis of triple-negative breast cancer (TNBC). However, the specific mechanism is not fully understood. This article summarizes the possible mechanism of the development and progression in LSD1 and TNBC, and reviews the latest progress of LSD1 in the clinical research application of TNBC, so as to provide a reference for drug combination therapy in TNBC patients.

Objective:To detect the cystic fibrosis transmembrane transduction regulator(CFTR)gene mutations and congenital bilateral absence of vas deferens(CBAVD)susceptibility gene mutations in pa-tients with CBAVD,and to explore their association with the risk of CBAVD.Methods:Whole-exome sequencing and Sanger sequencing validation were conducted on the pathogenic genes CFTR,adhesion G protein-coupled receptor G2(ADGRG2),sodium channel epithelial 1 subunit beta(SCNN1B),carbonic anhydrase 12(CA12),and solute carrier family 9 member A3(SLC9A3)in thirteen cases of isolated CBAVD patients.The polymorphic loci,intron and flanking sequences of CFTR gene were amplified by polymerase chain reaction(PCR)followed by Sanger sequencing.Bioinformatics methods were employed for conservative analysis and deleterious prediction of novel susceptibility gene mutations in CBAVD.Ge-netic analysis was performed on the pedigree of one out of thirteen patients with CBAVD to evaluate the risk of inheritance in offspring.Results:Exome sequencing revealed CFTR gene exon mutations in only six of the thirteen CBAVD patients,with six missense mutations c.2684G＞A(p.Ser895Asn),c.4056G＞C(p.Gln1352His),c.2812G＞(p.Val938Leu),c.3068T＞G(p.Ile1023Arg),c.374T＞C(p.Ile125Thr),c.1666A＞G(p.Ile556Val)),and one nonsense mutation(c.1657C＞T(p.Arg553Ter).Among these six patients,two also had the CFTR homozygous p.V470 site,additional-ly,mutations in CFTR gene exon regions were not detected in the remaining seven patients.Within the thirteen CBAVD patients,three carried the homozygous p.V470 polymorphic site,four carried the 5T al-lele,two carried the TG13 allele,and ten carried the c.-966T＞G site.Four CBAVD patients simulta-neously carried 2-3 of the aforementioned CFTR gene mutation sites.Susceptibility gene mutations in CBAVD among the thirteen patients included one ADGRG2 missense mutation c.2312A＞G(p.Asn771Ser),two SLC9A3 missense mutations c.2395T＞C(p.Cys799Arg),c.493G＞A(p.Val165Ile),one SCNN1B missense mutation c.1514G＞A(p.Arg505His),and one CA12 missense mutation c.1061C＞T(p.Ala354Val).Notably,the SLC9A3 gene c.493 G＞A(p.Val165Ile)mutation site was first identi-fied in CBAVD patients.The five mutations exhibited an extremely low population mutation frequency in the gnomAD database,classifying them as rare mutations.Predictions from Mutation Taster and Poly-phen-2 software indicated that the harmfulness level of the SLC9A3 gene c.493G＞A(p.Val165Ile)site and the SCNN1B gene c.1514G＞A(p.Arg505His)site were disease causing and probably damaging.The genetic analysis of one pedigree revealed that the c.1657C＞T(p.Arg553Ter)mutation in the proband was a de novo mutation,as neither the proband's father nor mother carried this mutation.The proband and his spouse conceived a daughter through assisted reproductive technology,and the daughter inherited the proband's pathogenic mutation c.1657C＞T(p.Arg553Ter).Conclusion:CFTR gene mutations remain the leading cause of CBAVD in Chinese patients;however,the distribution and fre-quency of mutations differ from data reported in other domestic and international studies,highlighting the need to expand the CFTR mutation spectrum in Chinese CBAVD patients.The susceptibility genes ADGRG2,SLC9A3,SCNN1B,and CA12 may explain some cases of CBAVD without CFTR mutations.Given the lack of specific clinical manifestations in CBAVD patients,it is recommended that clinicians conduct further physical examinations and consider scrotal or transrectal ultrasound before making a defi-nitive diagnosis.It is advisable to employ CFTR gene mutation testing in preconception genetic screening to reduce the risk of CBAVD and cystic fibrosis in offspring.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

As an important part of tumor microenvironment, neutrophils are poorly understood due to their spatiotemporal heterogeneity in tumorigenesis. Here we defined, at single-cell resolution, CD44-CXCR2- neutrophils as tumor-specific neutrophils (tsNeus) in both mouse and human gastric cancer (GC). We uncovered a Hippo regulon in neutrophils with unique YAP signature genes (e.g., ICAM1, CD14, EGR1) distinct from those identified in epithelial and/or cancer cells. Importantly, knockout of YAP/TAZ in neutrophils impaired their differentiation into CD54+ tsNeus and reduced their antitumor activity, leading to accelerated GC progression. Moreover, the relative amounts of CD54+ tsNeus were found to be negatively associated with GC progression and positively associated with patient survival. Interestingly, GC patients receiving neoadjuvant chemotherapy had increased numbers of CD54+ tsNeus. Furthermore, pharmacologically enhancing YAP activity selectively activated neutrophils to suppress refractory GC, with no significant inflammation-related side effects. Thus, our work characterized tumor-specific neutrophils in GC and revealed an essential role of YAP/TAZ-CD54 axis in tsNeus, opening a new possibility to develop neutrophil-based antitumor therapeutics.
Humans ; Animals ; Mice ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Stomach Neoplasms/pathology* ; Neutrophils/pathology* ; Signal Transduction/genetics* ; YAP-Signaling Proteins ; Tumor Microenvironment ; Hyaluronan Receptors/genetics*

Autologous ozonized blood transfusion(AOBT) is a therapy of re-transfusion of 100-200 mL of autologous blood after shaking and agitation with appropriate amount of oxygen-ozone in vitro. The oxidation of blood through the strong oxidation of ozone can enhance the non-specific immune response of the body, regulate the internal environment and promote health. This therapy has been increasingly applied in clinical practice, while no unified standard for the operation process in terms of ozone concentration, treatment frequency and treatment course had been established. This operation process of AOBT is primarily explored in order to standardize the operation process and ensure its safety and efficacy.

Objective: To investigate the correlation between calcaneal bone mineral density and bone mineral, fat and muscle content in adolescents. Methods: A total of 368 adolescents who received health examination in Hainan People’s Hospital were selected as the study subject. Calcaneal bone mineral density, bone mineral content, fat content and muscle content of adolescents were measured. Bone mineral density and body composition of adolescents of different ages and sexes were compared. The correlation between calcaneal bone mineral density and bone mineral content, fat and muscle content were analyzed. Results: The BUA, muscle mass and bone mineral content of boys were significantly higher than those of girls, and the fat content of boys was significantly lower than that of girls, the differences were of statistical significance(t=13.51, 10.65, 4.52, -7.55, P<0.05). Calcaneal bone mineral density in adolescents was positively correlated with BMI, bone mineral content and muscle mass(r=0.39, 0.42, 0.69, P<0.05). There were significant differences in BUA, BMI, muscle mass and bone mineral content among boys of different ages(F=7.95, 8.63, 6.96, 5.01, P<0.05). There were significant differences in BUA, fat, muscle and bone mineral contents among girls of different age groups(F=8.65, 10.33, 7.96, 4.87, P<0.05). There was no significant correlation between BUA value of calcaneus and BMI and muscle mass in adolescents aged 12, 13-year old(P>0.05), while BUA value of calcaneus in adolescents aged 14-year old, 15-year old and 16-year old was positively correlated with BMI and muscle mass(P<0.05). Conclusion Calcaneal bone mineral density in adolescents is closely related to bone mineral and muscle content, but not to fat content.

Objective To explore the efficacy of middle and high (mid-high) flow intracranial-external vascular bypass in treatment of complex intracranial aneurysms and selection of grafts. Methods The clinical data of 79 patients with complicated intracranial aneurysms treated by mid-high flow extracranial-intracranial bypass in our hospital from August 2010 to October 2017 were collected retrospectively. The grafts were radial artery (n=21), saphenous vein of the calf segment (n=29) or thigh saphenous vein segment (n=29). The efficacy was determined based on Glasgow outcome scale (GOS) scores at discharge and modified Rankin scale (mRS) scores at follow-up, and the differences of occlusion in different types of grafts were analyzed. Results CTA showed patency of the grafts in all patients one d after surgery. There were 6 patients having vascular occlusion: 2 patients (the grafts at saphenous vein of the calf segment ) were occluded 3 and 4 d after surgery, without symptom; 2 patients (the grafts at the radial artery), with decreased limb muscle strength, were occluded 5 and 25 d after procedure; 2 patients ( the grafts at the saphenous veins of the calf segment) were occluded 6 months after procedure without any symptom. There were 4 patients developed cerebral ischemia after operation: one had cerebral infarction and three had vasospasm. GOS scores at discharge and mRS scores at follow-up showed that 78 patients had improved symptoms and good prognosis; one patient showed no improvement in symptoms and plant survival. Conclusion Mid-high flow extracranial-intracranial bypass for treatment of complex intracranial aneurysms is effective; the graft should be individually selected based on preoperative assessment results.

Objective To evaluate the value of hysteroscopy in elder women with abnormal uterine bleeding (AUB) and asymptomatic postmenopausal women with a thickened endometrium.Methods Fifty-three cases in the AUB group and seventy-eight cases in the endometrial hyperplasia group underwent hysteroscopy examination and hysteroscopy-guided biopsy,then the hysteroscopic and histopathological results were compared between the two groups.Results Of the 131 cases,the normal endometrium accounted for 29.8％ (n=39),endometrial polyp for 49.6％ (n=65),submucous myomas for 4.6％ (n=6),hyperplasia endometrii for 6.1％(n=8) and endometrial carcinoma for 9.9％ (n=13).Both the AUB group and theendometrial hyperplasia group had 8 cases of endometrial carcinoma (15.1％,6.4％,respectively).For the diagnosis of normal endometrium with hysteroscopy,the sensitivity,specificity,positive predictive value (PPV) and negative predictive value (NPV) were 88％,97％,94％ and 95％,respectively,in the AUB group,versus 82％,95％,86％ and 93％,respectively,in the endometrial hyperplasia group.For the endometrial polyps,hysteroscopy showed a sensitivity,specificity,PPV and NPV of 100％,79％,74％,100％,respectively,in the AUB group and 98％,88％,92％,97％,respectively,in the endometrial hyperplasia group.For the endometrial cancer,hysteroscopy had a sensitivity,specificity,PPV and NPV of 75％,100％,100％ and 96％,respectively,in the AUB group;while in the endometrial hyperplasia group,the sensitivity was 80％,the specificity and PPV were 100％,and the NPV was 99％.Conclusions In elder females,hysteroscopy allows for an accurate diagnosis in endometrial disease,and hysteroscopically directed sampling is mandatory,even if the uterine cavity appears normal at hysteroscopy,to rule out endometrial neoplasms.