Hepatic encephalopathy is a difficult and critical disease with rapid progression and limited treatment methods in the field of liver disease， and it is urgently needed to make breakthroughs in its pathogenesis. Selection of appropriate prevention and treatment strategies is of great importance in delaying disease progression and reducing the incidence and mortality rates. This article reviews the theory of “turbid toxin pathogenesis” and related prevention and treatment strategies for hepatic encephalopathy in traditional Chinese medicine/Zhuang medicine， proposes a new theory of “turbid toxin pathogenesis”， analyzes the scientific connotations of “turbid”， “toxin”， and the theory of “turbid toxin pathogenesis”， and constructs the “four-step” prevention and treatment strategies for hepatic encephalopathy， thereby establishing the new clinical prevention and treatment regimen for hepatic encephalopathy represented by “four prescriptions and two techniques” and clarifying the effect mechanism and biological basis of core prescriptions and techniques in the prevention and treatment of hepatic encephalopathy， in order to provide a reference for the prevention and treatment of hepatic encephalopathy.

Objective:To observe the efficacy and safety of subretinal injection of Aflibercept for the treatment of refractory or recurrent polypoidal choroidal vasculopathy (PCV).Methods:A prospective clinical research. From January to June 2022, 18 patients of 18 eyes with PCV diagnosed in The Affiliated Eye Hospital of Nanchang University were included in the study. All patients underwent best corrected visual acuity (BCVA), indocyanine green angiography and optical coherence tomography (OCT). The BCVA examination was performed using the international standard visual acuity chart, which was converted to logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. The large choroidal vessel thickness (LVCT), central retinal thickness (CRT), sub-foveal choroidal thickness (SFCT) and retinal pigment epithelium detachment (PED) height were measured by enhanced depth imaging technique of OCT. The choroidal vascular index (CVI) was calculated. There were 18 patients of 18 eyes, 11 males of 11 eyes and 7 females of 7 eyes. The age was (64.22±3.86) years old. The disease duration was (5.22±1.80) years. The patient had received intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs for (7.72±1.36) times. The logMAR BCVA of the affected eyes was 1.28±0.25. The SFCT, CRT, LVCT, PED height were (436.56±9.80), (432.44±44.29), (283.78±27.10), (342.44±50.18) μm, respectively, and CVI was 0.65±0.01. All eyes were treated with a single subretinal injection of 40 mg/ml Aflibercept 0.05 ml (including Aflibercept 2.0 mg). According to the results of OCT and BCVA after treatment, the lesions were divided into active type and static type. The active lesions were treated with intravitreal injection of Aflibercept at the same dose as before. Quiescent lesions were followed up. Examinations were performed 1-3, 6, 9 and 12 months after treatment using the same equipment and methods before treatment. The BCVA, LVCT, CRT, SFCT, PED height, CVI, interretinal or subretinal fluid, lesion regression rate, injection times, and complications during and after treatment were observed. The BCVA, SFCT, CRT, LVCT, PED height and CVI before and after treatment were compared by repeated measures analysis of variance.Results:Eighteen eyes received subretinal and/or intravitreal injection of Aflibercept (1.61±0.85) times (1-4 times). At the last follow-up, the polypoid lesions regressed in 4 eyes and PED disappeared in 1 eye. Compared with before treatment, BCVA ( F=50.298) gradually increased, CRT ( F=25.220), PED height ( F=144.16), SFCT ( F=69.77), LVCT ( F=136.69), CVI ( F=72.70) gradually decreased after treatment. The differences were statistically significant ( P<0.001). Macular hole occurred in 1 eye after treatment, and the hole closed spontaneously 3 months after treatment. No serious complications such as retinal tear, retinal detachment, endophthalmitis and vitreous hemorrhage occurred during and after treatment. Conclusion:Subretinal injection of Aflibercept is safe and effective in the treatment of refractory PCV.

Objective:To observe the efficacy and safety of vitrectomy combined with subretinal injection of alteplase (tPA) and intravitreal injection of Conbercept in the treatment of large area submacular hemorrhage (SMH) secondary to polypoidal choroidal vasculopathy (PCV).Methods:A retrospective clinical study. From January to September 2021, 32 eyes of 32 patients with massive SMH secondary to PCV diagnosed in the Affiliated Eye Hospital of Nanchang University were included in the study. Large SMH was defined as hemorrhage diameter ≥4 optic disc diameter (DD). There were 32 patients (32 eyes), 20 males and 12 females. The mean age was (72.36±8.62) years. All patients had unilateral disease.The duration from onset of symptoms to treatment was (7.21±3.36) days. All patients underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT) examination. BCVA examination was performed using the international standard visual acuity chart, which was converted to the logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. The central macular thickness (CMT) was measured by spectral domain-OCT. The average size of SMH was (6.82±1.53) DD. The logMAR BCVA 1.73±0.44; CMT was (727.96±236.40) μm. All patients were treated with 23G pars plana vitrectomy combined with subretinal injection of tPA and intravitreal injection of Conbercept. At 1, 3, 6 and 12 months after treatment, the same equipment and methods were used for relevant examinations before treatment. The changes of BCVA and CMT, the clearance rate of macular hemorrhage, and the complications during and after surgery were observed. BCVA and CMT before and after treatment were compared by repeated measures analysis of variance.Results:Compared with before treatment, BCVA gradually increased at 1, 3, 6 and 12 months after treatment, and the differences were statistically significant ( F=77.402, P<0.001). There was no significant difference in BCVA between any two groups at different time points after treatment ( P>0.05). Correlation analysis showed that BCVA at 12 months after treatment was negatively correlated with the course of disease ( r=-0.053, P=0.774). One week after treatment, macular hemorrhage was completely cleared in 30 eyes (93.75%, 30/32). The CMT was (458.56±246.21), (356.18±261.46), (345.82±212.38) and (334.64±165.54) μm at 1, 3, 6 and 12 months after treatment, respectively. Compared with before treatment, CMT decreased gradually after treatment, and the difference was statistically significant ( F=112.480, P<0.001). There were statistically significant differences in different follow-up time before and after treatment ( P<0.001). The number of treatments combined with Conbercept during and after surgery was (4.2±1.8) times. At the last follow-up, there was no recurrence of SMH, retinal interlamellar effusion and other complications. Conclusion:Subretinal injection of tPA combined with intravitreal injection of Conbercept is safe and effective in the treatment of large SMH secondary to PCV, and it can significantly improve the visual acuity of patients.

Originating but free from chromosomal DNA, extrachromosomal circular DNAs (eccDNAs) are organized in circular form and have long been found in unicellular and multicellular eukaryotes. Their biogenesis and function are poorly understood as they are characterized by sequence homology with linear DNA, for which few detection methods are available. Recent advances in high-throughput sequencing technologies have revealed that eccDNAs play crucial roles in tumor formation, evolution, and drug resistance as well as aging, genomic diversity, and other biological processes, bringing it back to the research hotspot. Several mechanisms of eccDNA formation have been proposed, including the breakage-fusion-bridge (BFB) and translocation-deletion-amplification models. Gynecologic tumors and disorders of embryonic and fetal development are major threats to human reproductive health. The roles of eccDNAs in these pathological processes have been partially elucidated since the first discovery of eccDNA in pig sperm and the double minutes in ovarian cancer ascites. The present review summarized the research history, biogenesis, and currently available detection and analytical methods for eccDNAs and clarified their functions in gynecologic tumors and reproduction. We also proposed the application of eccDNAs as drug targets and liquid biopsy markers for prenatal diagnosis and the early detection, prognosis, and treatment of gynecologic tumors. This review lays theoretical foundations for future investigations into the complex regulatory networks of eccDNAs in vital physiological and pathological processes.
Male ; Female ; Animals ; Humans ; Swine ; DNA, Circular/genetics* ; Genital Neoplasms, Female ; Semen ; DNA ; Reproduction

In recent years,the morbidity and mortality of hepatocellular carcinoma(HCC)have been increasing worldwide,and the treatment strategies for HCC are still insufficient,which highlights the importance of exploring the pathogenesis and progression of HCC.Transient receptor potential(TRP)pathway is an important non-selective cation pathway,which is closely related to inflammatory response and sensory conduction.At present,a number of studies have shown that TRP pathway is also involved in the occurrence and development of HCC,inducing HCC invasion and migration.However,the overall potential mechanism and possible signal transduction pathways of TRP pathway in HCC remain unclear.Therefore,this article discusses the abnormal expression of TRP pathway in HCC,and reviews the key biological events of TRP pathway involved in the formation and progression of HCC,such as chronic liver inflammation-fibrosis progression,HCC cell proliferation,migration,apoptosis and HCC stem cell generation,and looks forward to its application prospect in HCC treatment.The aim is to better un-derstand the significance of TRP pathway in HCC,help to find new therapeutic targets and effective drugs,and open up a new situation for future clinical treatment.

Objective:To study the feasibility and efficacy of pericranial flaps for the repairs of large anterior skull base defects.Methods:The average length of the pericranial flaps needed for skull base repair was determined with computed tomography measurements in 20 adults and anatomical dissections in 5 cadaver specimen. A series of patients who underwent endoscopic skull base surgeries and subsequent reconstructions with pericranial flaps at the Department of Otolaryngology Head and Neck Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People′s Hospital from 2016 to 2022 were retrospectively reviewed. There were 19 males and 6 females, aged from 11 to 59 years, including 13 cases of cerebrospinal fluid (CSF) rhinorrhea (12 traumatic) and 12 cases of sinonasal skull base tumors. Descriptive statistical methods were used.Results:The mean areas of anterior skull base, sellar, and clival defects were 16.13, 14.03 and 13.12 cm 2, respectively, and the mean pericranial flap lengths were (18.77±3.44)mm, (133.99±5.08)mm, (181.76±6.31)mm, respectively. Among sinonasal skull base neoplasms, the pathologies included olfactory neuroblastoma ( n=6), squamous cell carcinoma ( n=3), chondrosarcoma ( n=1), osteosarcoma ( n=1), and invasive schwannoma ( n=1), in whom 8 patients underwent adjuvant radiotherapy after surgery. One patient (7.7%) had acoustic neuroma-related CSF leak before radiotherapy. All 25 patients successfully underwent skull base reconstruction without complications such as CSF leak, intracranial infection, forehead wrinkles disappearance, or scalp necrosis. All flaps survived well with no CSF leaks within the follow-up period of 2-4 years. Conclusion:Pericranial flap is a safe choice for large anterior skull base defects following resection of sinonasal skull base neoplasms and complex traumatic CSF leaks when endonasal flaps are not available.

At present, there is still a big gap between China and developed countries in the field of high-end medical devices, and the ability of independent innovation needs to be improved. In order to comprehensively cultivate innovative talents in the field of medical devices and promote the development of the field of medical devices, the biomedical engineering major of Chongqing Medical University has put forward a "Trinity" innovative talent training system in the field of medical devices, including the teaching of theoretical knowledge, the improvement of practical skills and the guarantee of the innovation system, and established a four stage curriculum system framework of "Perception-Understanding-Enlightenment-Challenge" to form a characteristic course with ultrasonic treatment equipment as the main line. After three years of practice, the results of this training mode show that the innovative ability, professional connotation construction quality and employment postgraduate entrance examination rate of our college students have been steadily improved. The exploration of this talent training mode has reference significance for the cultivation of innovative talents in the field of medical devices in higher medical colleges and universities in China.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) signal pathway is a classical pathway of STING activation, and in recent years, its role in stimulating innate immunity has gradually attracted wide attention. Besides, cGAS can recognize and combine endogenous or exogenous DNA, then catalyze ATP and GTP to synthesize cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), subsequently activate STING signal to promote type I interferon and inflammatory factors, finally induce natural and adaptive immunity. Existing studies have indicated that cGAS-STING signal pathway plays an important role in infections, inflammations and tumors, especially in high-grade gliomas with poor clinical treatment efficacy. Here, we briefly summarize the cGAS-STING signal pathway and its mechanism in brain tumors to provide new ideas for exploring therapeutic targets and drugs for brain tumors.

As an essential trace element in living organisms, copper is actively involved in normal physiological processes in various systems and is maintained at low level to achieve copper homeostasis. Copper homeostasis, once being disrupted, would induce cell death, and this new form of cell death is known as copper death. In recent years, copper death has been increasingly recognized as an important factor mediating the onset and progression of central nervous system (CNS) diseases. Therefore, we review the pathogenic mechanism of copper death in CNS diseases, as well as its therapeutic strategies so as to deepen the understanding of researchers.

Objective:To observe the changes of retinal blood flow density and thickness in the macular region of eyes with high myopia (HM) combined with peripapillary intrachoroidal cavitation (PICC).Methods:A cross-sectional study. From March 2019 to May 2021, 65 patients (65 eyes) diagnosed as PICC (HM+PICC group) in Eye Hospital, China Academy of Chinese Medical Sciences, sex-and age-matched 69 HM patients of 69 eyes (HM group) and 65 healthy people of 65 eyes (control group) were enrolled in this study. The optical coherence tomography angiography was used to scan macular areas in 3 mm×3 mm, and measure the macular fovea and optic disc on superior, inferior, nasal, temporal superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel density in the foveal and parafoveal region, and macular retinal ganglion cell complex (mGCC) thickness, full retinal thickness. One-way analysis of variance were used to test the difference of the index values among three groups, and then two groups were compared with Bonferroni test. A paired t-test was used to test the difference of the macular vessel density and thickness between the superior and inferior hemifield in three groups. Pearson partial regression analysis was used to calculate the correlations between them at same sites. Results:PICC was located most frequently at the inferior temporal disc border, followed by the inferior nasal region, superior temporal region, and superior nasal region in the HM+PICC group on 57(87.7%, 57/65), 25(38.5%, 25/65), 3(4.6%, 3/65) and 1(1.5%, 1/65 ) eye. There were significant differences in the global and regional full retinal thickness, mGCC thickness, SCP and DCP vessel density among 3 groups ( F=29.097, 51.929, 16.253, 6.135; P<0.001). The macular SCP and DCP vessel density except in the fovea, all regional macular full retinal thickness and mGCC thickness in the HM+PICC group were significantly lower than those in the normal group ( P<0.05). Compared to the HM group, the HM+PICC group had lower all regional mGCC thickness and SCP vessel density, as well as full retinal thickness in the inferior hemifield and DCP vessel density in the foveal region ( P<0.05). Macular vessel density and thickness in the inferior hemifield were significantly lower than those in the superior hemifield ( t=6.356, 11.693, 6.212, 2.936; P<0.01). Pearson partial regression analysis showed the SCP vessel density was positively correlated with corresponding mGCC thickness and full retinal thickness ( r=0.584, 0.534, 0.592, 0.496, 0.485, 0.517; P<0.001). However, there was no significant correlation between the DCP vascular density and mGCC thickness ( P>0.05), and only a weak positive correlation between the DCP vascular density and the full retinal thickness in the inferior hemifield ( r=0.319, P=0.014). However, no association with average and superior full retinal thickness ( r=0.066, 0.002, 0.125, 0.184, 0.016, 0.319; P>0.05). Conclusion:The macular SCP vessel density, mGCC thickness and the full retinal thickness in the inferior hemifield in PICC eyes are lower than those in the HM eyes, especially the mGCC thickness and SCP vessel density in the inferior hemifield, and there is a strong positive correlation between them.