This paper discusses the pathogenesis and treatment strategies of skin cancer based on the theory of "spleen deficiency-sweat pore obstruction-toxin accumulation". It is believed that although the disease is located in the skin and body hair， it is not only the localized disorder but closely related to the imbalance of qi and blood of zang-fu （脏腑） organs. The core of the disease is the synergistic disorder of spleen， sweat pore， and skin and body hair. The disease progression follows a dynamic evolution from spleen deficiency with loss of nourishment， initial closure of sweat pore to binding of dampness and stasis with obstruction of sweat pore， and then to cancer toxin consolidation with damage to sweat pore. Based on this， three principles of building earth， opening sweat pore and attacking toxin are established. The method of fortifying spleen and raising the clear aims to consolidate the root and restore validity， with commonly used prescriptions including modifications of Buzhong Yiqi Decoction （补中益气汤）， Liujunzi Decoction （六君子汤） and Guipi Decoction （归脾汤）. The method of opening sweat pores with acrid-moistening medicinals is suggested when dredging and unblocking the sweat pore， commonly using acrid and warm dispersing medicinals， supplemented with herbs that nourish fluids and moisten dryness. The method of clearing heat and removing toxin is to break cancer toxin directly， and modifications of prescriptions such as Wuwei Xiaodu Beverage （五味消毒饮）， Xiaolei Pills （消瘰丸） and Xihuang Pills （犀黄丸） are commonly used. These approaches provide valuable ideas for the prevention and treatment of skin cancer with traditional Chinese medicine.

This paper discusses the pathogenesis and treatment strategies of skin cancer based on the theory of "spleen deficiency-sweat pore obstruction-toxin accumulation". It is believed that although the disease is located in the skin and body hair， it is not only the localized disorder but closely related to the imbalance of qi and blood of zang-fu （脏腑） organs. The core of the disease is the synergistic disorder of spleen， sweat pore， and skin and body hair. The disease progression follows a dynamic evolution from spleen deficiency with loss of nourishment， initial closure of sweat pore to binding of dampness and stasis with obstruction of sweat pore， and then to cancer toxin consolidation with damage to sweat pore. Based on this， three principles of building earth， opening sweat pore and attacking toxin are established. The method of fortifying spleen and raising the clear aims to consolidate the root and restore validity， with commonly used prescriptions including modifications of Buzhong Yiqi Decoction （补中益气汤）， Liujunzi Decoction （六君子汤） and Guipi Decoction （归脾汤）. The method of opening sweat pores with acrid-moistening medicinals is suggested when dredging and unblocking the sweat pore， commonly using acrid and warm dispersing medicinals， supplemented with herbs that nourish fluids and moisten dryness. The method of clearing heat and removing toxin is to break cancer toxin directly， and modifications of prescriptions such as Wuwei Xiaodu Beverage （五味消毒饮）， Xiaolei Pills （消瘰丸） and Xihuang Pills （犀黄丸） are commonly used. These approaches provide valuable ideas for the prevention and treatment of skin cancer with traditional Chinese medicine.

The excessive accumulation of advanced glycosylation end products(AGEs), the end products of non-enzymatic glycosylation reactions, can be involved in the pathological processes of various ocular diseases through mechanisms such as oxidative stress, inflammatory responses and apoptosis. In this paper, we systematically reviewed the key role of AGEs in diabetic keratopathy, cataract, glaucoma, age-related macular degeneration(ARMD)and diabetic retinopathy(DR). It was found that AGEs activate signalling pathways such as NADPH oxidase, MAPK and NF-κB by binding to the receptor RAGE, leading to reactive oxygen species(ROS)generation, release of inflammatory factors, and vascular endothelial dysfunction, which in turn induces delayed corneal healing, cross-linking of lens proteins, optic nerve degeneration, formation of choroidal neovascularisation(CNV), and blood-retinal barrier(BRB)disruption. For example, in diabetic keratopathy, AGEs delay wound healing via the ROS/NLRP3 inflammatory vesicle axis; in cataract, ascorbic acid-mediated cross-linking of lens proteins due to AGEs directly impairs lens transparency; and in DR, AGEs exacerbate microvascular damage by regulating vasucular endothelial growth factor(VEGF)expression and pericyte apoptosis. In addition, this article discusses the advances and limitations of AGEs detection techniques, such as the potential application of lens AGEscan fluorescence assay in screening for diabetic complications, and the need to develop tissue-specific assays for aqueous humour and vitreous. For therapeutic strategies, the research directions of inhibiting AGEs production, blocking RAGE signalling pathway and developing anti-glycosylation drugs are proposed to emphasise their clinical value in delaying disease progression. This review not only integrates the molecular mechanisms and clinical associations of AGEs in ocular diseases, but also provides a theoretical basis for targeted interventions, which is of great significance in exploring novel diagnostic and therapeutic strategies.

In response to the clinical needs of cancer treatment and rehabilitation, Professor Lin Hongsheng proposed the Wuzhi Wuyang (five treatments and rehabilitation) concept on the basis of years of clinical experience and the Guben Qingyuan (consolidate the foundation and clear the source) theory. Wuzhi Wuyang emphasizes the importance of treatment and rehabilitation and aims to provide personalized and stage-specific treatment and rehabilitation plans by integrating the advantages of traditional Chinese medicine (TCM) and modern medicine to achieve comprehensive life-cycle management for patients with cancer. The proposal of Wuzhi Wuyang has provided new ideas and methods for the treatment, prevention, and rehabilitation of cancer, along with valuable references for clinical practice and academic research. This article summarizes the connotation of Wuzhi Wuyang and its application in the comprehensive management of cancer prevention and treatment with TCM.

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

Objective To investigate the effects of SAC/VAL on myocardial fibrosis and miR-21 expression in rats induced by AAC.Methods A total of 72 SPF SD male rats were randomly di-vided into sham operation group,AAC group,low-and high-dose SAC/VAL groups,high-dose SAC/VAL+agomiR-NC group,and high-dose SAC/VAL+miR-21 agomiR group,with 12 rats in each group.Echocardiography was used to test cardiac function.HE staining and Masson staining were applied to observe the pathological changes in myocardial tissues and myocardial tissue fi-brosis,respectively.Immunohistochemical assay was employed to detect the expression of α-SMA and COL-l in myocardial tissue.Real-time fluorescence quantitative polymerase chain reaction was conducted to detect miR-21 level.Results Compared with the sham operation group,the AAC group had thicker and broken myocardial fibers in disordered arrangement,hypertrophic myocar-dial cells with condensed and deeply stained nuclei,and extensive infiltration of inflammatory cells,and obvious myocardial fibrosis,increased LVEDD and LVESD values,and up-regulated miR-21,α-SMA and COL-1 expression,but decreased LVEF and LVFS levels(P＜0.05).Low-and high-dose SAC/VAL treatment resulted in well-arranged less broken myocardial fibers in uniform distribution,relatively normal myocardial cells,less inflammatory cell infiltration,and reduced severity of myocardial fibers,lower LVEDD and LVESD values,decreased miR-21,α-SMA and COL-1 levels,but increased LVEF and LVFS levels when compared to the AAC group(P＜0.05).When compared to the high dose SAC/VAL+agomiR NC group,the high-dose SAC/VAL+miR-21 agomiR group had disorderly-arranged myocardial fiber with thickening and breakage,aberrant myocardial cells,obvious infiltration of inflammatory cells,and intensified my-ocardial fibrosis,higher LVEDD and LVESD values and miR-21,α-SMA and COL-1 expression levels,and lower LVEF and LVFS levels[7.11±0.45 mm vs 6.05±0.38 mm,P＜0.05;5.58±0.35 mm vs 4.01±0.28 mm,P＜0.05;2.57±0.14 vs 0.98±0.10,P＜0.05;0.62±0.06 A vs 0.41±0.04 A,P＜0.05;0.79±0.08 A vs 0.53±0.05 A,P＜0.05;(58.26±2.61)％vs(80.24±2.87)％,P＜0.05;(24.52±1.03)％vs(33.72±1.25)％,P＜0.05].Conclusion SAC/VAL inhibits AAC-induced myocardial fibrosis in rats,which is related to its regulation of miR-21 expression.

Objective To investigate the effects of SAC/VAL on myocardial fibrosis and miR-21 expression in rats induced by AAC.Methods A total of 72 SPF SD male rats were randomly di-vided into sham operation group,AAC group,low-and high-dose SAC/VAL groups,high-dose SAC/VAL+agomiR-NC group,and high-dose SAC/VAL+miR-21 agomiR group,with 12 rats in each group.Echocardiography was used to test cardiac function.HE staining and Masson staining were applied to observe the pathological changes in myocardial tissues and myocardial tissue fi-brosis,respectively.Immunohistochemical assay was employed to detect the expression of α-SMA and COL-l in myocardial tissue.Real-time fluorescence quantitative polymerase chain reaction was conducted to detect miR-21 level.Results Compared with the sham operation group,the AAC group had thicker and broken myocardial fibers in disordered arrangement,hypertrophic myocar-dial cells with condensed and deeply stained nuclei,and extensive infiltration of inflammatory cells,and obvious myocardial fibrosis,increased LVEDD and LVESD values,and up-regulated miR-21,α-SMA and COL-1 expression,but decreased LVEF and LVFS levels(P＜0.05).Low-and high-dose SAC/VAL treatment resulted in well-arranged less broken myocardial fibers in uniform distribution,relatively normal myocardial cells,less inflammatory cell infiltration,and reduced severity of myocardial fibers,lower LVEDD and LVESD values,decreased miR-21,α-SMA and COL-1 levels,but increased LVEF and LVFS levels when compared to the AAC group(P＜0.05).When compared to the high dose SAC/VAL+agomiR NC group,the high-dose SAC/VAL+miR-21 agomiR group had disorderly-arranged myocardial fiber with thickening and breakage,aberrant myocardial cells,obvious infiltration of inflammatory cells,and intensified my-ocardial fibrosis,higher LVEDD and LVESD values and miR-21,α-SMA and COL-1 expression levels,and lower LVEF and LVFS levels[7.11±0.45 mm vs 6.05±0.38 mm,P＜0.05;5.58±0.35 mm vs 4.01±0.28 mm,P＜0.05;2.57±0.14 vs 0.98±0.10,P＜0.05;0.62±0.06 A vs 0.41±0.04 A,P＜0.05;0.79±0.08 A vs 0.53±0.05 A,P＜0.05;(58.26±2.61)％vs(80.24±2.87)％,P＜0.05;(24.52±1.03)％vs(33.72±1.25)％,P＜0.05].Conclusion SAC/VAL inhibits AAC-induced myocardial fibrosis in rats,which is related to its regulation of miR-21 expression.

[摘 要] 目的：采用基于中国人群单核苷酸多态性位点开发的同源重组缺陷（HRD）检测工具评估云南地区卵巢癌患者的HRD状态和BRCA1/2基因突变频率并探讨其临床意义。方法：共纳入2021年1月至2023年5月间在云南省肿瘤医院收治的卵巢癌患者248例，HRD状态采用基因组瘢痕评分法（GSS）（主要依据拷贝数的长度、类型、位置及基因组断片）或HRD评分法（杂合性缺失、端粒等位基因失衡及大片段移位等基因组不稳定事件的总和）进行评估，当组织样本的GSS≥50分或HRD评分≥42分者或检测到有害的BRCA1/2基因突变时HRD被定义为阳性。分析患者HRD状态与临床病理特征的关系。结果：248名卵巢癌患者中70.97%的患者HRD呈阳性，其中BRCA1/2基因突变率为30.65%。Ⅲ~Ⅵ期、高级别浆液腺癌的卵巢癌患者具有更高的HRD阳性率（均P<0.01），HRD评分更高的患者其合并其他基因突变的频率也越高（P<0.05）。HRD状态与卵巢癌的病理类型、临床分期和其他基因突变均有关联（均P<0.01）。结论：云南地区卵巢癌患者HRD阳性率较高，HRD阳性的卵巢癌患者可以从聚ADP核糖聚合酶（PARP）抑制剂治疗中获得更大的收益。

Objective:To construct breast cancer organoid culture system and conduct histological characterization and preliminary radiobiological characteristics study.Methods:Different molecular types of breast cancer cell lines and patient-derived tumor cells were cultured in vitro to form breast cancer organoids and characterize their tissue structure. In addition, Ki-67, ER, PR and Her2 markers were evaluated by immunohistochemical staining. Breast cancer organoids were irradiated with 4 Gy and 8 Gy. The numbe and diameter changes of breast cancer organoids at 0, 24, 48 and 96 h after irradiation were observed to evaluate the irradiation-induced damage to the organoids. Results:Breast cancer cell lines and patient-derived tissues formed organoid structures at 6 d. HE staining showed the microstructures, and the expression profile of markers was spatially heterogeneous. The expression patterns of markers were similar between patient-derived organoids and original tumor tissues. Irradiation of MCF-7 breast cancer organoids led to growth arrested, and some of the formed organoids collapsed and the proliferating trend gradually recovered from 48 h to 96 h. MDA-MB-231 breast tumor organoids showed radioresistance, growth arrested, but the structures remained intact, the recovery trend was still not observed at 96 h. The tissue-derived organoids from triple-negative patients also showed radiation tolerance. After irradiation, the organoids continued to grow without significant structural changes, whereas the growth trend was significantly smaller than that in the non-irradiated group.Conclusions:Breast cancer organoids formed by in vitro culture of breast cancer cells from different sources and different molecular types have microstructure and heterogeneity, which can reflect the expression of source tissue markers and show different radioresistance. Organoids derived from triple-negative breast cancer are more resistant to irradiation.

Objective:To analyze the clinical features and surgical outcomes of petrous bone cholesteatomas (PBCs).Methods:Data from 39 PBCs patients treated in the Department of Otorhinolaryngology, Xijing Hospital from September 2011 to December 2017 were reviewed retrospectively, including 23 males, 16 femals, aged 12-71 years old, with the median age of 37. Clinical classifications, surgical methods, facial and hearing function, and intraoperative and postoperative complications were made summary analysis.Results:In this study, five patients were congenital PBCs and 34 patients were acquired PBCs. The common clinical symptoms were hearing loss (100%, 39/39), ear discharge/pus (89.7%, 35/39) and facial paralysis (46.2%, 18/39). According to Sanna′s classification, 14 cases were supralabyrinthine, including three cases underwent transcochlear (TC) approach, six cases underwent transotic (TO) approach and five underwent translabyrinthine (TL) approach. 10 cases were infralabyrinthine, including eight cases underwent subtotal petrosectomy, one case underwent TO approach and one underwent TL approach.10 cases were massive, including seven cases underwent TC approach, three cases underwent TO approach. Five cases were infralabyrinthine-apical, including two cases underwent TC approach, two cases underwent TO approach, and one case underwent endoscope assisted infratemporal fossa type B. The degree of facial nerve (FN) dysfunction from high to low was massive (6/10), supralabyrinthine (8/14), infralabyrinthine-apical (2/5) and infralabyrinthine (2/10). 19 cases involved in facial nerve operation, three cases underwent FN decompression, four cases underwent FN rerouting, four cases underwent nerve grafting, and one case underwent facial-hypoglossal anastomosis. Preoperative FN involvement in 18 cases, and the FN function was improved in 14 cases after surgery. The improved rate of postoperative FN function was 77.8%. The bone conducted hearing retained 50.0% (14/28) postoperatively. Five cases with cerebrospinal fluid leak were managed by inserting free muscle plugs and cavity obliteration. Two cases with the cholesteatomas matrix involved the sigmoid sinus and the jugular bulb, and occlusion of the sigmoid sinus was performed. Postoperatively, two patients presented with synkinesis. The patients were followed up for 40 to 115 months, and there was no recurrence.Conclusions:There are no specific clinical manifestations for PBCs, thus, it is difficult in early diagnosis and treatment. According to Sanna′s classification, preoperative FN and hearing function, the best surgical approach should be selected with minimal recurrences and perioperative morbidity.