The tumor microenvironment is a crucial factor in tumor occurrence and progression. The hypoxic microenvironment is widely present in tumor tissue and is a key endogenous factor accelerating tumor deterioration. The "blood stasis toxin" theory, as an emerging perspective in tumor research, is regarded as the unique "soil" in tumor progression from the perspective of traditional Chinese medicine(TCM) due to its dynamic evolution mechanism, which closely resembles the formation of the hypoxic microenvironment. Scientifically integrating TCM theories with the biological characteristics of tumors and exploring precise syndrome differentiation and treatment strategies are key to achieving comprehensive tumor prevention and control. This article focused on the hypoxic microenvironment of the tumor, elucidating its formation mechanisms and evolutionary processes and carefully analyzing the internal relationship between the "blood stasis toxin" theory and the hypoxic microenvironment. Additionally, it explored the interaction among blood stasis, toxic pathogens, and hypoxic environment and proposed micro-level prevention and treatment strategies targeting the hypoxic microenvironment based on the "blood stasis toxin" theory, aiming to provide TCM-based theoretical support and therapeutic approaches for precise regulation of the hypoxic microenvironment.
Humans ; Tumor Microenvironment/drug effects* ; Neoplasms/therapy* ; Animals ; Medicine, Chinese Traditional ; Disease Progression ; Drugs, Chinese Herbal

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disease caused by abnormal expression of glycosylphosphatidylinositol (GPI) on the cell membrane due to mutations in the phosphatidylinositol glycan class A(PIGA) gene. It is commonly characterized by intravascular hemolysis, repeated thrombosis, and bone marrow failure, as well as multiple systemic involvement symptoms such as renal dysfunction, pulmonary hypertension, swallowing difficulties, chest pain, abdominal pain, and erectile dysfunction. Due to the rarity of PNH and its strong heterogeneity in clinical manifestations, multidisciplinary collaboration is often required for diagnosis and treatment. Peking Union Medical College Hospital, relying on the rare disease diagnosis and treatment platform, has invited multidisciplinary clinical experts to form a unified opinion on the diagnosis and treatment of PNH, and formulated the Expert Consensus of Multidisciplinary Diagnosis and Treatment for Paroxysmal Nocturnal Hemoglobinuria (2024), with the hope of promoting the standardization of PNH diagnosis and treatment.

The disorder of group 3 innate lymphoid cells(ILC3)subgroup,such as the predominance of NCR-ILC3 but the deple-tion of NCR+ILC3,is unfavorable to damaged intestinal barrier repair,which leads to the prolongations and obstinacy of ulcerative colitis(UC).Our previous studies had shown that luteolin promoted NCRILC3 differentitating into NCR+ILC3 to improving the de-pletion of NCR+ILC3 in UC mice,while the mechanism is unclear.This article aimed to explore the underlying mechanism of luteolin enhancing the proportion NCR+ILC3.UC mice model was established with 2％DSS and Notch signaling was blocked,then luteolin was used to intervene.The results showed that the effect of luteolin on ameliorating disease symptoms in UC mice,including inhibit-ing the weight loss,reducing the pathological damage of colon mucosa,etc.,was diminished with blocking Notch signaling pathway.In addition,luteolin increased the proportion of NCR+ILC3,NCR+MNK3 and IL-22+ILC3,decreased intestinal permeability,pro-moted mucin secretion,and promoted ZO-1 and Occludin expression,the above effect of luteolin was neutralized by Notch inhibitor LY-411575.Luteolin activated the abnormally blocked Notch signaling pathway in UC mice.And molecular docking predicted the af-finity of luteolin for RBPJ to be-7.5 kcal·mol-1 in mouse,respectively;the affinity of luteolin for Notchl and RBPJ was respectively scored to be-6.4 kcal·mol-1 and-7.7 kcal·mol-1 homo sapiens.These results proved that luteolin is positive for enhancing the propor-tion of NCR+ILC3 via Notch signaling,and it provides a basis for targeting NCR+ILC3 for restoring intestinal barrier function to alle-viating ulcerative colitis.

This study systematically reviewed the literature on the prevention and treatment of colorectal cancer(CRC) with traditional Chinese medicine(TCM), aiming to present a more intuitive and concise overview of existing evidence. Four major Chinese databases, including CNKI, Wanfang, VIP, and SinoMed, were searched for randomized controlled trial(RCT) on TCM treatment of CRC. The retrieval period was from database inception to August 1, 2023. The evidence was presented using a combination of text and charts. A total of 1 778 RCTs were included, and the overall publication volume showed an upward trend. The quality of the RCT was generally low, with sample sizes concentrated between 60 and 100 cases. The intervention durations were mainly 4, 8, and 12 weeks. Keywords primarily focused on advanced CRC, postoperative CRC, immune function, and gastrointestinal function. Clinical complications were often caused by surgery or chemotherapy, including intestinal obstruction, peripheral neuropathy, diarrhea, and anxiety and depression. There were various intervention measures, including TCM decoctions, TCM injections, Chinese medicine nursing, Chinese patent medicines, and acupuncture. Among them, TCM decoctions(excluding self-made prescriptions) included Shenling Baizhu Powder(32 articles, 1.80%) and Sijunzi Decoction(22 articles, 1.24%). TCM injections included Fufang Kushen Injection(54 articles, 3.04%) and Aidi Injection(46 articles, 2.59%). Chinese patent medicines included Cinobufacin Capsules(16 articles, 0.90%) and Fufang Banmao Capsules(10 articles, 0.56%). The outcome indicators were divided into 13 domains, including recent efficacy, quality of life, safety events, and TCM syndrome/symptom scores. The existing outcome indicators mostly followed the western medicine evaluation system, with complex types and no unified standards, lacking outcome indicators or scales with TCM characteristics, and relatively insufficient attention to long-term efficacy, anxiety, and depression. Future research should optimize clinical study designs, build a core index set and clinical evaluation system with TCM characteristics, and produce more high-level evidence to support the safety and effectiveness of TCM in preventing and treating CRC.
Humans ; Colorectal Neoplasms/therapy* ; Randomized Controlled Trials as Topic ; Drugs, Chinese Herbal/administration & dosage* ; Medicine, Chinese Traditional

Objective:To analyze the trend of late-diagnosis of HIV-infected men who have sex with men (MSM) before and after the AIDS Conquering Project in Guangxi Zhuang Autonomous Region (Guangxi) and its influencing factors, in order to find out the population groups that need priority intervention at the present stage.Methods:The HIV-infected MSM in Guangxi from 2005-2021 were selected from the National Integrated HIV/AIDS Control and Prevention Data System. The Joinpoint 4.9.1.0 software was used to test the time trend of late-diagnosis and non-late-diagnosis cases, and logistic regression was applied to analyze the factors influencing the proportion of late-diagnosis at each stage.Results:From 2005 to 2021, 5 764 HIV-infected MSM were reported in Guangxi from 2005 to 2021, with an overall late-diagnosis of 28.45% (1 640 cases). Under the 2015 baseline data as the boundary, the proportion of late-diagnosis cases showed a trend of sharp decline followed by stabilization from 2005 to 2015, average annual percent change= -6.90% ( P<0.001). The effect of factors such as resident population, occupation as a farmer or worker, and sample originating from medical consultation on late-diagnosis changed considerably before and after the implementation of the project, and the factors influencing late-diagnosis at this stage were age, resident population, occupation as a farmer, worker or student. The factors influencing late-diagnosis at this stage are age, resident population, and occupation as a farmer, worker and a student. Conclusions:The proportion of late diagnosis cases of HIV-infected MSM in Guangxi decreased significantly before and after the project. However, late-diagnosis should not be neglected and precise prevention and control should be carried out for the resident population, farmers, workers or students.

Recent studies revealed the relationship among homologous recombination repair (HRR), androgen receptor (AR), and poly(adenosine diphosphate-ribose) polymerase (PARP); however, the synergy between anti-androgen enzalutamide (ENZ) and PARP inhibitor olaparib (OLA) remains unclear. Here, we showed that the synergistic effect of ENZ and OLA significantly reduced proliferation and induced apoptosis in AR-positive prostate cancer cell lines. Next-generation sequencing followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed the significant effects of ENZ plus OLA on nonhomologous end joining (NHEJ) and apoptosis pathways. ENZ combined with OLA synergistically inhibited the NHEJ pathway by repressing DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and X-ray repair cross complementing 4 (XRCC4). Moreover, our data showed that ENZ could enhance the response of prostate cancer cells to the combination therapy by reversing the anti-apoptotic effect of OLA through the downregulation of anti-apoptotic gene insulin-like growth factor 1 receptor ( IGF1R ) and the upregulation of pro-apoptotic gene death-associated protein kinase 1 ( DAPK1 ). Collectively, our results suggested that ENZ combined with OLA can promote prostate cancer cell apoptosis by multiple pathways other than inducing HRR defects, providing evidence for the combined use of ENZ and OLA in prostate cancer regardless of HRR gene mutation status.
Male ; Humans ; Prostatic Neoplasms, Castration-Resistant/genetics* ; Drug Resistance, Neoplasm/genetics* ; Cell Line, Tumor ; Receptors, Androgen/genetics* ; Nitriles ; Apoptosis

Objective To investigate the effects of semen brassicae albae on the proliferation and apoptosis of rheumatoid arthritis(RA)synoviocytes,and to analyze the related mechanisms.Methods Logarithmic RA fibroblastic synovial cells(RA-FLS)were randomly divided into blank group,experimental-L,M,H groups and positive control group.Blank group did not make any treatment.Experimental-L,M,H groups were cultured using DMEM medium containing 20,40,80 μg·mL-1 of semen brassicae albae extract,respectively.Positive control group was cultured at DMEM medium containing 5 mg·L-1 of Tripterygium glycosides.Five groups were cultured for 48 h.The survival rates of RA-FLS cells were detected by CCK-8 method,the apoptosis rates of RA-FLS cells were detected by Annexin V-FITC/PI double staining method,and the expression levels of proliferation and apoptosis-related proteins were detected by Western blotting.Results The cell survival rates of experimental-M,-H groups,blank group and positive control group were(71.35±10.86)％,(58.56±17.92)％,(99.12±0.38)％and(56.21±15.11)％;the apoptosis rates were(28.98±4.35)％,(39.12±5.85)％,(8.96±1.36)％and(41.21±6.01)％;the expression levels of PCNA protein were 0.87±0.13,0.50±0.08,1.30±0.19 and 0.49±0.09;the expression levels of Bel-2 protein were 1.20±0.14,1.35±0.19,0.45±0.06 and 1.31±0.21;the expression levels of Bax protein were 0.65±0.09,0.27±0.04,1.14±0.15 and 0.29±0.06,respectively.Compared with blank group,the differences of above indexes of experimental-M,-H groups and positive control group were statistically significant(all P＜0.05).Conclusion Semen brassicae albae can inhibit the proliferation of RA-FLS cells and induce cell apoptosis,and its mechanism may be related to regulating the expression of proliferation and apoptosis related proteins.

Objective: To investigate the origin of infection and risk factors of a case with SARS-CoV-2 infection associated with overseas countries in the Ningbo-Zhoushan Port, Zhejiang Province, so as to provide the evidence for improving the COVID-19 control measures at ports. Methods: Ningbo Center for Disease Control and Prevention ( CDC ) and Beilun CDC conducted case finding and epidemiological surveys immediately after being informed. The general information, history of vaccination and the travel during the latest 14 days were collected from the positive case, and all close contacts were tracked. Saliva samples were collected for SARS-CoV-2 nucleic acid testing and whole-genome sequencing, and the sequencing results were aligned with the GISAID's EpiCoV database. The origin of infection and transmission route of the positive case was investigated. Results: A case was identified positive for SARS-CoV-2 nucleic acid during company M's routine screening in the Ningbo-Zhoushan Port on August 10, 2021, and was confirmed positive for SARS-CoV-2 nucleic acid by Beilun CDC and Ningbo CDC on August 11. Whole-genome sequencing showed SARS-CoV-2 B.1.617.2 ( Delta ) variant, which shared the highest homology with the virus sequence uploaded by Russia on June, 2021 ( Russia/MOW-RII-MH27356S/2021 ). The case was a bundling worker for overseas container ships, and reported communicated with foreign boatmen and contacted materials without protected interventions on the SINOKOR AKITA Container Ship between August 4 and 5, 2021. This ship anchored at Vladivostok, Russia from July 27 to 29, anchored at Ningbo Harbor on August 4, and departed on August 5. Then, 11 boatmen from this ship were tested positive for SARS-CoV-2 nucleic acid on August 8. One asymptomatic case was reported in this epidemic; 254 close contacts and 617 secondary close contacts were identified, and all were tested negative for SARS-CoV-2 nucleic acid. No new cases with SARS-CoV-2 infections were detected until August 25, 2021, and the emergency response was therefore terminated. Conclusions The infection was a sporadic COVID-19 epidemic associated with overseas countries, which was caused by Delta variant infection through contacts with foreign boatmen or materials by a bundling worker in Ningbo-Zhoushan Port; fortunately, no epidemic spread occurred. Intensified closed-loop management and increased frequency of SARS-CoV-2 nucleic acid test among high-risk populations, and improving the precision and rapid emergency treatment of COVID-19 epidemics are required for the containment of COVID-19 at ports.

Objective: The scientific community knows little about the long-term influence of coronavirus disease 2019 (COVID-19) on olfactory dysfunction (OD). With the COVID-19 pandemic ongoing worldwide, the risk of imported cases remains high. In China, it is necessary to understand OD in imported cases. Methods: A prospective follow-up design was adopted. A total of 11 self-reported patients with COVID-19 and OD from Xi'an No. 8 Hospital were followed between August 19, 2021, and December 12, 2021. Demographics, clinical characteristics, laboratory and radiological findings, and treatment outcomes were analyzed at admission. We surveyed the patients via telephone for recurrence and sequelae at the 1-, 6-, and 12-month follow-up. Results: Eleven patients with OD were enrolled; of these, 54.5% (6/11) had hyposmia and 45.5% (5/11) had anosmia. 63.6% (7/11) reported OD before or on the day of admission as their initial symptom; of these, 42.9% (3/7) described OD as the only symptom. All patients in the study received combined treatment with traditional Chinese medicine and Western medicine, and 72.7% (8/11) had partially or fully recovered at discharge. In terms of OD recovery at the 12-month follow-up, 45.5% (5/11) reported at least one sequela, 81.8% (9/11) had recovered completely, 18.2% (2/11) had recovered partially, and there were no recurrent cases. Conclusions Our data revealed that OD frequently presented as the initial or even the only symptom among imported cases. Most OD improvements occurred in the first 2 weeks after onset, and patients with COVID-19 and OD had favorable treatment outcomes during long-term follow-up. A better understanding of the pathogenesis and appropriate treatment of OD is needed to guide clinicians in the care of these patients.
COVID-19/complications* ; Follow-Up Studies ; Humans ; Olfaction Disorders/etiology* ; Pandemics ; Prospective Studies ; SARS-CoV-2

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome