Pulmonary lymphangioleiomyomatosis is a rare disease characterized by the abnormal proliferation of pulmonary lymphatic smooth muscle cells. It is common in women and often accompanied by recurrent pneumothorax, chylothorax and progressive dyspnea, imaging characterized by diffuse cystic lesions in both lungs. Pulmonary lymphangioleiomyomatosis progresses aggressively and has a very poor prognosis, with a lack of effective medical treatment options in the advanced stages. Lung transplantation is a safe and effective method for the treatment of advanced pulmonary lymphangioleiomyomatosis, which may significantly improve the survival rate and quality of life of patients. The median survival period after surgery can reach 12 years. This article reviews the pathogenesis, diagnosis, treatment of pulmonary lymphangioleiomyomatosis, and the current status and existing problems of lung transplantation in pulmonary lymphangioleiomyomatosis, aiming to provide a reference for the clinical treatment and subsequent research of pulmonary lymphangioleiomyomatosis.

Objective To identify the characteristics of complementary and alternative therapies for cancer patients and investigate the effect on symptom clusters in cancer patients,in order to provide references in management of the symptom clusters.Methods A scoping review was conducted to search nine databases,namely PubMed,Cochrane Library,Web of Science,Embase,PsycINFO,CINAHL,CNKI,Wanfang Data,and VIP,for literatures published between January 2016 and January 2024.Results Twenty articles focusing on complementary and alternative therapies were included.Four themes were identified from the retrieved articles:cancer research subjects,characteristics of complementary alternative therapies,type of symptom cluster and effectiveness of complementary alternative therapies.Specifically,the cancer research subjects in relation to symptom cluster management included those of breast cancer,advanced cancer and the cancer under radio or chemotherapy.The most commonly used types of complementary and alternative therapies in managing the symptom clusters were exercise therapies,cognitive-behavioural interventions,traditional Chinese medicine therapies,multidisciplinary collaborative models and specific interventions.Interventions for symptom clusters predominantly targeted fatigue,mental status,pain,and gastrointestinal symptoms.Conclusion The interventions for symptom clusters in complementary and alternative therapies vary across different types of complementary and alternative therapies,so as the effectiveness.Some of the complementary and alternative therapies have unidentified effects and further investigations are required.The complementary and alternative therapies currently that have been used in managing the symptom clusters were found to have shortcomings.Further studies should focus on sentinel and core symptoms of symptom clusters and emphasize the development of standardised and individualised intervention plans based on symptom management theories,hence to improve the management of symptom clusters in cancer patients.

ObjectiveTo investigate the effects of licoflavone A on the proliferation and glycolysis of gastric cancer cells in the hypoxic environment. MethodHuman gastric cancer AGS cells were classified into five groups： Normoxia， hypoxia， and low-， medium-， and high-dose （25， 50， 100 μmol·L^-1， respectively） licoflavone A. The cells in other groups except the normoxia group were cultured in the environment with 5% O₂ for 48 h. The cell counting kit-8 （CCK-8） and colony formation assay were employed to examine the proliferation of AGS cells. Cell migration was detected by the scratch assay. The protein and mRNA levels of hypoxia-inducible factor 1-alpha （HIF-1α）， glucose transporter 1 （GLUT1）， lactate dehydrogenase A （LDHA）， pyruvate kinase M2 （PKM2）， and hexokinase Ⅱ （HK2） in AGS cells were measured by Western blotting and real-time quantitative polymerase chain reaction （Real-time PCR）， respectively. The corresponding kits were used to determine glucose uptake and HK activity. ResultThe CCK-8 results showed that compared with the hypoxia group， the high- and medium-dose licoflavone A groups showed decreased proliferation rate of AGS cells at the time point of 24 h （P<0.01） and all the licoflavone A groups demonstrated decreased proliferation rate at the time point of 48 h （P<0.01）. Compared with the normoxia group， the hypoxia group showed increased number of clone formation of AGS cells （P<0.01）， which was decreased after the treatment with licoflavone A at high， medium， and low doses （P<0.01）. Compared with the normoxia group， the hypoxia group showed increased migration of AGS cells （P<0.01）， which was attenuated by the high， medium， and low doses of licoflavone A （P<0.01）. Compared with the normoxia group， the hypoxia group showed up-regulated mRNA levels of GLUT1， LDHA， PKM2， and HK2 （P<0.05， P<0.01）. Compared with those in the hypoxia group， the mRNA levels of GLUT1， LDHA， PKM2， and HK2 in the high-dose licoflavone A group， GLUT1， LDHA， and HK2 in the medium-dose licoflavone A group， and HK2 in the low-dose licoflavone A group were down-regulated （P<0.05， P<0.01）. The protein levels of HIF-1α， GLUT1， LDHA， PKM2， and HK2 in the hypoxia group were higher than those in the normoxia group （P<0.05， P<0.01）. Compared with those in the hypoxia group， the protein levels of HIF-1α， GLUT1， LDHA， PKM2， and HK2 in the high-dose licoflavone A group and HK2 in the medium- and low-dose licoflavone A groups were down-regulated （P<0.05， P<0.01）. The glucose uptake and HK activity were elevated in the hypoxia group compared with those in the normoxia group （P<0.01）. Compared with the hypoxia group， high-dose licoflavone A decreased the glucose uptake and HK activity， and medium-dose licoflavone A decreased the HK activity （P<0.01）. ConclusionLicoflavone A inhibits the proliferation of AGS cells under hypoxic conditions by regulating glycolysis in gastric cancer.

Objective:Exploring the dilemmas faced by adolescents with type 1 diabetes mellitus in self-management during the transition to adult healthcare, to inform healthcare professionals in the delivery of transitional care interventions.Methods:Using descriptive qualitative research methods, in-depth interviews were conducted from August to December 2023 to adolescents with type 1 diabetes mellitus (selected by objective sampling) who met the inclusion and exclusion criteria in the Department of Endocrinology of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine and the Shenzhen Children′s Hospital, and the data were analysed inductively using directed content analysis.Results:A total of 12 adolescents with type 1 diabetes mellitus were included for interview, 6 males and 6 females, aged 12-18 years. The self-management dilemmas for adolescents with type 1 diabetes in the transition to adult healthcare can be summarised into 4 themes and 10 sub-themes: disease management dilemmas (weak awareness of disease management, insufficient disease-related knowledge and competence, low adherence to disease management, and restriction of daily activities), role adaptation difficulties (lack of perceived transition to the healthcare role, difficulty in transitioning to the family role, and maladaptation to the social role), negative emotions Inadequate social support system (lack of school support, limited accessibility of social organisations, insufficient socio-economic support).Conclusions:Adolescents with type 1 diabetes mellitus face multiple dilemmas in disease self-management during the transition to adult healthcare, and healthcare professionals should pay attention to transition self-management education, improve patients′ awareness of transition self-management and their ability to participate in it, formulate a transition preparation plan, build an emotional support network, and improve the social security system, so as to help juvenile patients with type 1 diabetes master the method of self-management and make a successful transition to adulthood.

Objective:To conduct a scoping review on self-transcendence in cancer patients, analyze and summarize the current status of self-transcendence in cancer patients, so as to provide a reference for its future development in cancer.Methods:The relevant research was systematically searched on China National Knowledge Infrastructure, WanFang Data, VIP, PubMed, Web of Science, Embase, Cochrane Library, and CINAHL, with a search period from database establishment to September 5, 2023. The included literature was summarized and analyzed.Results:A total of 43 articles were included, consisting of 16 cross-sectional surveys, 8 qualitative studies, and 19 intervention studies. Five aspects were elaborated and summarized, namely theoretical evolution and development, evaluation tools, current situation and influencing factors, implementation approaches, and intervention program characteristics.Conclusions:The research on self-transcendence in cancer patients is in the ascendant. In the future, it is necessary to strengthen the development of self-transcendence assessment tools for cancer patients, adopt various research methods to comprehensively understand the changes in self-transcendence level and psychological experience of cancer patients, and improve the scientific and rigorous nature of self-transcendence intervention program for cancer patients.

Mycobacterium neoaurum has the ability to produce steroidal intermediates known as 22-hydroxy-23, 24-bisnorchol-4-en-3-one (BA) upon the knockout of the genes for either the hydroxyacyl-CoA dehydrogenase (Hsd4A) or acyl-CoA thiolase (FadA5). In a previous study, we discovered a novel metabolite in the fermentation products when the fadA5 gene was deleted. This research aims to elucidate the metabolic pathway of this metabolite through structural identification, homologous sequence analysis of the fadA5 gene, phylogenetic tree analysis of M. neoaurum HGMS2, and gene knockout. Our findings revealed that the metabolite is a C23 metabolic intermediate, named 24-norchol-4-ene-3, 22-dione (designated as 3-OPD). It is formed when a thioesterase (TE) catalyzes the formation of a β-ketonic acid by removing CoA from the side chain of 3, 22-dioxo-25, 26-bisnorchol-4-ene-24-oyl CoA (22-O-BNC-CoA), followed by spontaneously undergoing decarboxylation. These results have the potential to contribute to the development of novel steroid intermediates.
Mycobacterium/metabolism* ; Phylogeny ; Steroids/metabolism* ; Metabolic Networks and Pathways ; Sterols/metabolism*

ObjectiveTo observe the effect of Huangqi Baihe granules on the hypoxia-inducible factor 1α （HIF-1α）/nuclear factor-κB （NF-κB）/NOD-like receptor hot protein domain related protein 3 （NLRP3） signaling pathway in a rat model of high altitude hypoxia. MethodSixty male SPF SD rats were randomly divided into blank group， model group， dexamethasone group （5 mg·kg^-1）， and high， middle， and low-dose groups of Huangqi Baihe granules （4.1， 2.05， 1.025 g·kg^-1）. Among them， each Chinese medicine group was administrated orally for continuously 14 d， once a day， and the dexamethasone group was injected intraperitoneally for continuously 3 d as the positive control group. On the 15^th d， the model group， dexamethasone group， and high， middle， and low dose groups of Huangqi Baihe granules were exposed to the simulated high altitude， low pressure， and low oxygen environment in the animal low-pressure simulation cabin， and the exposure lasted for 3 d. Blood was collected from the abdominal aorta and serum was separated， and the brain tissue was taken after being killed. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in brain tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect the content of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） in rat serum. Western blot was used to detect HIF-1α， NLRP3， phosphorylated nuclear factor-κB （p-NF-κB）， NF-κB， desquamation D （GSDMD）， and cysteine aspartate-specitis protein-1（Caspase-1） in rats of each group. The mRNA expression levels of HIF-1α， NLRP3， NF-κB p65， GSDMD， and Caspase-1 were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultThe results of HE staining showed that as compared with the normal group， the pathological sections of brain tissues in the model group showed that pyramidal cells were loosely arranged and distributed in disorder， with different sizes. Compared with the model group， the pathological changes in pyramidal cells in the dexamethasone group and high and middle-dose groups of Huangqi Baihe granules were reduced. The results of ELISA showed that as compared with the normal group， the content of TNF-α， IL-6， and IL-1β in the serum of rats in the model group was significantly higher （P<0.01）. Compared with the model group， the content of TNF-α， IL-6， and IL-1β in the serum of rats in the dexamethasone group and high and middle-dose groups of Huangqi Baihe granules decreased significantly （P<0.05， P<0.01）. The results of Western blot showed that as compared with the normal group， the relative protein expression levels of HIF-1α， NLRP3， p-NF-κB p65， GSDMD， and Caspase-1 in the brain tissue of the model group were significantly higher （P<0.01）. As compared with the model group， the relative expressions of HIF-1α， NLRP3， p-NF-κB p65， GSDMD， and Caspase-1 in the brain tissue of rats in the dexamethasone group and the high-dose group of Huangqi Baihe granules were significantly decreased （P<0.05， P<0.01）. The relative protein expression levels of HIF-1α， NLRP3， p-NF-κB p65， and Caspase-1 in the brain tissue of rats in the middle-dose group of Huangqi Baihe granules decreased significantly （P<0.01）， and the relative protein expression of HIF-1α in the brain tissue of rats in the low-dose group of Huangqi Baihe granules was reduced （P<0.05）. The Real-time PCR analysis showed that as compared with the normal group， the mRNA expression levels of HIF-1α， NLRP3， NF-κB p65， GSDMD， and Caspase-1 in the brain tissue of the model group were significantly increased （P<0.01）. As compared with the model group， the mRNA expression levels of HIF-1α， NLRP3， NF-κB p65， GSDMD， and Caspase-1 in the brain tissue of rats in the dexamethasone group were significantly decreased （P<0.01）. The mRNA expression levels of HIF-1α， NF-κB p65， GSDMD， and Caspase-1 in the brain tissue of rats in the high-dose group of Huangqi Baihe granules decreased significantly （P<0.01）. The mRNA expression levels of HIF-1α， NLRP3， and Caspase-1in the brain tissue of rats in the middle-dose group of Huangqi granules decreased （P<0.05， P<0.01）. ConclusionThe protective effect of Huangqi Baihe granules on acute brain injury in low-pressure hypoxic rats may be related to the HIF-1α/NF-κB/NLRP3 signaling pathway.

Steroids are a class of medicines with important physiological and pharmacological effects. In pharmaceutical industry, steroidal intermediates are mainly prepared through Mycobacteria transformation, and then modified chemically or enzymatically into advanced steroidal compounds. Compared with the "diosgenin-dienolone" route, Mycobacteria transformation has the advantages of abundant raw materials, cost-effective, short reaction route, high yield and environmental friendliness. Based on genomics and metabolomics, the key enzymes in the phytosterol degradation pathway of Mycobacteria and their catalytic mechanisms are further revealed, which makes it possible for Mycobacteria to be used as chassis cells. This review summarizes the progress in the discovery of steroid-converting enzymes from different species, the modification of Mycobacteria genes and the overexpression of heterologous genes, and the optimization and modification of Mycobacteria as chassis cells.
Mycobacterium/metabolism* ; Steroids/metabolism* ; Phytosterols/metabolism* ; Genomics

OBJECTIVE: To establish the finite element model of varus-type ankle arthritis and to implement the finite element mechanical analysis of different correction models for tibial anterior surface angle (TAS) in supramalleolar osteotomy. METHODS: A female patient with left varus-type ankle arthritis (Takakura stage Ⅱ, TAS 78°) was taken as the study object. Based on the CT data, the three-dimensional model of varus-type ankle arthritis (TAS 78°) and different TAS correction models [normal (TAS 89°), 5° valgus (TAS 94°), and 10° valgus (TAS 99°)] were created by software Mimics 21.0, Geomagic Wrap 2021, Solidworks 2017, and Workbench 17.0. The 290 N vertical downward force was applied to the upper surface of the tibia and 60 N vertical downward force to the upper surface of the fibula. Von Mises stress distribution and stress peak were calculated. RESULTS: The finite element model of normal TAS was basically consistent with biomechanics of the foot. According to biomechanical analysis, the maximum stress of the varus model appeared in the medial tibiotalar joint surface and the medial part of the top tibiotalar joint surface. The stress distribution of talofibular joint surface and the lateral part of the top tibiotalar joint surface were uniform. In the normal model, the stress distributions of the talofibular joint surface and the tibiotalar joint surface were uniform, and no obvious stress concentration was observed. The maximum stress in the 5° valgus model appeared at the posterior part of the talofibular joint surface and the lateral part of the top tibiotalar joint surface. The stress distribution of medial tibiotalar joint surface was uniform. The maximum stress of the 10° valgus model appeared at the posterior part of the talofibular joint surface and the lateral part of the top tibiotalar joint surface. The stress on the medial tibiotalar joint surface increased. CONCLUSION With the increase of valgus, the stress of ankle joint gradually shift outwards, and the stress concentration tends to appear. There was no obvious obstruction of fibula with 10° TAS correction. However, when TAS correction exceeds 10° and continues to increase, the obstruction effect of fibula becomes increasingly significant.
Humans ; Female ; Tibia/surgery* ; Finite Element Analysis ; Ankle ; Arthritis ; Fibula/surgery* ; Ankle Joint/surgery*

Objective:To analyze the correlation between the posterior malleolus fracture and fixation and the rotational stability of the ankle and to explore the surgical indications for posterior malleolus fracture aiming to provide the theories for the diagnosis and treatment of disorder.Methods:Twenty fresh frozen cadaver specimens were selected. Further, the extent of the tibial insertion of the posterior inferior tibiofibular ligament (PITFL) and inferior transverse tibiofibular ligament (ITTFL) complex was dissected and measured. Based on the tibial insertion of the ligament complex, the model for the supination-external rotation degree 3 ankle fracture with a posterior malleolar fragment and syndesmosis diastasis was created. Moreover, the area threshold of the posterior tibial insertion of posterior malleolus fracture was biomechanically assessed. The difference of the antirotating ability of the ankle-stiffness between simple posterior malleolus fixation and simple syndesmotic fixation was analyzed statistically.Results:The PITFL and ITTFL were presented in all specimens with relatively broad in PITFL tibial insertion. The PITFL was attached to the posterolateral tibia. The distance between the highest point of the tibial insertion and the articular line was 45.2±5.6 mm, while the ITTFL was attached to the posterior distal tibia. The distance between the highest point of the tibial insertion and the articular line was 5.5±1.0 mm. The width of the tibial insertion of the PITFL and ITTFL complex decreased as the distance from the joint line increased. Biomechanical analysis showed that the threshold of posterior area of posterior malleolus fracture was 1/4S. The stiffnesses of posterior malleolus fixation and syndesmosis stabilization were 0.264±0.080 N·m/° and 0.164 ± 0.061 N·m/°, respectively. The percentage of stiffness restored by posterior ankle fixation was 60.9%±10.2%, which was greater than that by syndesmosis stabilization 37.5%±7.9% ( t=17.09, P<0.001) . Conclusion:The surgical technique for posterior malleolus fracture should consider restoration of the axial and rotational stability of the ankle simultaneously. Posterior malleolus fracture fixation is recommended when the syndesmosis is unstable with the area ratio of posterior tibial insertion of posterior malleolus fracture greater than or equal to 1/4. Syndesmotic fixation is proposed to restore and maintain the rotational stability of the ankle when the syndesmosis is unstable with the area ratio less than 1/4. Regardless of the area ratio, the surgical indications for stable syndesmosis depend on the impact of the posterior malleolus fracture on the axial stability of tibiotalar joint, on the involved articular surface area and on the displacement degree of posterior malleolus fragment.