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

Cinnabar(HgS) was widely used in ancient times for medicinal purposes, religious rituals, and pigments. A group of bright red powdery clumps was excavated from Mawangdui Tomb No.3 of the Han Dynasty. Early studies considered the clumps as evidence of cinnabar's medicinal use during the Qin-Han period. This study employed a range of archaeometric techniques, including extended-depth-of-field stereo imaging, micro-CT, scanning electron microscopy-energy dispersive spectroscopy, Raman spectroscopy, and Fourier transform infrared spectrometry FTIR, to systematically analyze the material composition and structural characteristics of these remains. The results revealed that the cinnabar particles were granular, finely ground, and tightly bound to silk matrix, with no detectable excipients typically associated with medicinal formulations. Micro-CT imaging indicated a well-preserved textile structure, with clear signs of sedimentary accumulation and mechanical damage. Based on historical and archaeological studies, this study suggested that these remains were more likely degraded accumulations of cinnabar-colored silk textiles rather than medicinal cinnabar. By clarifying the diversity of ancient cinnabar applications and preservation states, this study provides new insights for the archaeological identification of mineral medicinal materials and contributes to the standardized study of Chinese medicinal materials and understanding of the historical use of cinnabar.
History, Ancient ; China ; Humans ; Medicine, Chinese Traditional/history* ; Archaeology ; Drugs, Chinese Herbal/history* ; Spectroscopy, Fourier Transform Infrared ; Spectrum Analysis, Raman ; Mercury Compounds

OBJECTIVE: To evaluate the efficacy and safety of DCAG (decitabine, cytarabine, anthracyclines, and granulocyte colony-stimulating factor) regimen in the treatment of patients with relapsed/refractory (R/R) acute myeloid leukemia (AML). METHODS: The clinical data of 64 R/R AML patients received treatment at Chinese PLA General Hospital from January 1st, 2012 to December 31st, 2022 were retrospectively analyzed. Primary endpoints included efficacy measured by overall response rate (ORR) and safety. Secondary endpoints included overall survival (OS), event-free survival (EFS) and duration of response (DOR). The patients were followed from enrollment until death, or the end of last follow-up (June 1st, 2023), whichever occurred first. RESULTS: Sixty-four patients who failed prior therapy were enrolled and completed 1 cycle, and 26 and 5 patients completed 2 and 3 cycles, respectively. Objective response rate was 67.2% ［39: complete remission (CR)/CR with incomplete hematologic recovery (CRi), 4: partial remission (PR)］. With a median follow-up of 62.0 months (1.0-120.9), the median overall survival (OS) was 23.3 and event-free survival was 10.6 months. The median OS was 51.7 months (3.4-100.0) in responders (CR/CRi/PR) while it was 8.4 months (6.1-10.7) in nonresponders ( P <0.001). Grade 3-4 hematologic toxicities were observed in all patients. Four patients died from rapid disease progression within 8 weeks after chemotherapy. CONCLUSION The DCAG regimen represents a feasible and effective treatment for R/R AML.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Cytarabine/administration & dosage* ; Granulocyte Colony-Stimulating Factor/administration & dosage* ; Retrospective Studies ; Male ; Female ; Decitabine ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anthracyclines/administration & dosage* ; Middle Aged ; Adult ; Treatment Outcome ; Aged ; Recurrence

Objective To investigate the role of magnesium ion(Mg2+)in cisplatin-induced acute kidney injury(Cis-AKI)in kidney organoids and HK-2 cells,as well as the potential mechanism.Methods Initially,we utilized human-derived induced pluripotent stem cells(iPSCs)to construct kidney organoids,and then built a Cis-AKI model based on kidney organoids.HE staining was used to observe the structure of kidney organoids,and immunofluorescence staining was used to observe the localization of markers and the expression of cleaved caspase-3.qRT-PCR was conducted to detect mRNA levels of tubular and glomerular markers,as well as inflammatory factors.Subsequently,the kidney organoids were randomly divided into control group,cisplatin group(Cis group),and Mg2+pretreatment group(Cis+Mg2+group).CCK-8 and ATP content assays were employed to evaluate the cell viability of renal tubular epithelial cells.TUNEL staining was performed to detect the apoptosis of renal tubular epithelial cells.Western blot was utilized to detect the expression of apoptosis-associated proteins(Bcl-2,Bax,cleaved caspase-3)and organic cation transporter 2(OCT2).Immunofluorescence was used to detect the localization and expression of OCT2.Results On the 10th day,the tubular structure in kidney organoids was visible,with abundant expression of renal markers.Treatment with 10 μmol/L cisplatin resulted in structural damage to kidney organoids,significantly increased expression of cleaved caspase-3 and mRNA levels of inflammatory factors,and significantly decreased ATP content.Compared with the Cis group,the Cis+Mg2+group showed increased ATP content in kidney organoids,reduced number of TUNEL-positive cells,significantly decreased expression of apoptosis-associated proteins,and significantly decreased expression of OCT2.However,there was no significant improvement in HK-2 cell viability,the number of TUNEL-positive cells,or apoptosis-associated proteins in the Cis+Mg2+group,and HK-2 cells did not express OCT2.Conclusion Kidney organoid is an ideal in vitro model to study the pathogenesis and treatment of Cis-AKI.Mg2+pretreatment can significantly reduce the damage of kidney organoids induced by cisplatin,and the mechanism may be related to the downregulation of OCT2.

The advantages of fluorescence detection of uric acid were introduced compared to the traditional detection methods.The preparation process,detection principle and performance of organic,inorganic and organic-inorganic hybrid fluorescent probes were reviewed.The advantages and disadvantages of kinds of fluorescent probes were analyzed when used for uric acid detection,and the futural directions were pointed out for related research.[Chinese Medical Equipment Journal,2024,45(6):93-104]

Objective This study aimed to investigate the effect and underlying mechanism of Fructus lycii in improving exercise fatigue.Methods A network pharmacological approach was used to explore potential mechanisms of action of Fructus lycii. Skeletal muscle C2C12 cells and immunofluorescence were employed to verify the effect and mechanism of the representative components in Fructus lycii predicted by network pharmacological analysis.Results Six potential active components, namely quercetin, β-sitosterol, stigmasterol, 7-O-methylluteolin-6-C-beta-glucoside_qt, atropine, and glycitein, were identified to have potency in improving exercise fatigue via multiple pathways, such as the PI3K-Akt, neuroactive ligand-receptor interaction, IL-17, TNF, and MAPK signaling pathways. The immunofluorescence results indicated that quercetin, a significant active component in Fructus lycii, increased the mean staining area of 2-NBDG, TMRM, and MitoTracker, and decreased the area of CellRox compared to the control. Furthermore, the protein expression levels of p-38 MAPK, p-MAPK, p-JNK, p-PI3K, and p-AKT markedly increased after quercetin treatment.Conclusion Fructus lycii might alleviate exercise fatigue through multiple components and pathways. Among these, quercetin appears to improve exercise fatigue by enhancing energy metabolism and reducing oxidative stress. The PI3K-AKT and MAPK signaling pathways also appear to play a role in this process.

AIM To establish an HPLC method for the simultaneous content determination of gallic acid,protocatechuic acid,morroniside,loganin,sweroside,paeoniflorin,hypericin,astragalin,salvianolic acid B,salvianolic acid A,epimedin C and icariin in Bushen Huoxue Sanjie Capsules.METHODS The analysis was performed on a 30℃thermostatic Agilent 5 TC-C18 column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 240 nm.RESULTS Twelve constituents showed good linear relationships within their own ranges(r≥0.999 8),whose average recoveries were 97.11%-101.14%with the RSDs of 0.60%-2.65%.CONCLUSION This simple,accurate and reproducible method can be used for the quality control of Bushen Huoxue Sanjie Capsules.

Objective:To determine the prevalence and risk factors of constipation in Hangzhou urban areas by analyzing data from a recent epidemiological survey.Methods:From August 2022 to June 2023, a cross-sectional survey was conducted on 43 communities on eight streets in suburbs of Hangzhou, including Wangjiang, Sijiqing, Puyan, Changhe, Ziyang, Xiaoshanchengxiang, Zhuantang, and Banshan. Written questionnaires were filled out face to face by community doctors. The prevalence of constipation was investigated using a combination of the Bristol stool typing method and the Rome IV criteria. The risk factors for constipation were analyzed using multivariate logistic regression analysis.Results:The study cohort comprised 10,479 participants, 5551 of whom were male (53.0%) and 4928 female (47.0%). The overall prevalence of constipation was 10.6% (1107/10,479). The prevalence was 11.0% (613/5551) for male and 10.0% (494/4928) for female participants; this difference is not statistically significant ( P>0.05).There were no significant differences in the prevalence of constipation between different categories of body mass index ( P>0.05). The prevalence of constipation was highest in individuals aged 70 years and above, accounting for 15.4% (264/1717) of all cases. There were significant differences in the prevalence of constipation between different occupations, marital statuses, and educational levels ( P<0.001). Patients with hypertension or diabetes mellitus had a higher prevalence of constipation than those without these conditions, those who had been taking long-term medication had a higher prevalence of constipation than those who did not, parents of children with constipation had a higher prevalence of constipation than those with children who did not have constipation, and there were other significant differences in various variables ( P<0.001). Multivariate logistic regression analysis of modifiable factors revealed that eating less fruit (OR=1.284, 95%CI: 1.061–1.553, P=0.010), liking spicy and salty food (OR=1.234, 95%CI: 1.039–1.466, P=0.016), sleeping for too long (OR=1.644, 95%CI: 1.260–2.144, P<0.001), irregular sleep patterns (OR=1.370, 95%CI: 1.127–1.665, P=0.002) and minimal exercise (OR=1.388, 95% CI: 1.168–1.649, P<0.001) were all risk factors for constipation; whereas mix diets (OR=0.709,95%CI:0.608–0.826, P<0.001), meat diets (OR=0.604,95%CI: 0.495–0.736, P<0.001), moderate alcohol consumption (OR=0.659, 95% CI: 0.534–0.812, P<0.001), less or no drinking (OR=0.523, 95% CI: 0.428–0.638, P<0.001), and non-smoking (OR=0.819, 95%CI:0.674–0.995, P<0.001) protected against constipation. We found no association between dietary preferences and the risk of constipation (refined grains: OR=1.147, 95%CI:0.944–1.393, P=0.167; no specific preference: OR=0.935, 95%CI:0.783–1.117, P=0.459). The rate of agreement between self-evaluation of constipation by the respondents and objective criteria was higher for negatives (95.8%) than for positives (38.0%). Conclusion:The prevalence of constipation is relatively high in the urban population of Hangzhou. A good lifestyle and diet can significantly reduce its incidence. There should be more emphasis on preventive education, promotion of prevention of constipation, and advocacy for a healthy lifestyle.

OBJECTIVE: To analyze the characteristics and prognosis of acute leukemia(AL) with SET-NUP214 fusion gene. METHODS: The clinical data of 17 patients over 14 years old newly diagnosed with SET-NUP214 positive AL admitted in Institute of Hematology and Blood Diseases Hospital from August 2017 to May 2021 were analyzed retrospectively. RESULTS: Among the 17 SET-NUP214 positive patients, 13 cases were diagnosed as T-ALL (ETP 3 cases, Pro-T-ALL 6 cases, Pre-T-ALL 3 cases, Medullary-T-ALL 1 case), AML 3 cases (2 cases M5, 1 case M0) and ALAL 1 case. Thirteen patients presented extramedullary infiltration at initial diagnosis. All 17 patients received treatment, and a total of 16 cases achieved complete remission (CR), including 12 cases in patients with T-ALL. The total median OS and RFS time were 23 (3-50) months and 21 (0-48) months, respectively. Eleven patients received allogeneic hematopoietic stem cell transplantation(allo-HSCT), with median OS time of 37.5 (5-50) months and median RFS time of 29.5 (5-48) months. The median OS time of 6 patients in chemotherapy-only group was 10.5 (3-41) months, and median RFS time of 6.5 (3-39) months. The OS and RFS of patients with transplantation group were better than those of chemotherapy-only group (P=0.038). Among the 4 patients who relapsed or refractory after allo-HSCT, the SET-NUP214 fusion gene did not turn negative before transplantation. While, in the group of 7 patients who have not relapsed after allo-HSCT till now, the SET-NUP214 fusion gene expression of 5 patients turned negative before transplantation and other 2 of them were still positive. CONCLUSION The fusion site of SET-NUP214 fusion gene is relatively fixed in AL patients, often accompanied by extramedullary infiltration. The chemotherapy effect of this disease is poor, and allo-HSCT may improve its prognosis.
Humans ; Adolescent ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Retrospective Studies ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation ; Acute Disease ; Prognosis ; Leukemia-Lymphoma, Adult T-Cell/therapy* ; Nuclear Pore Complex Proteins

OBJECTIVE To systematically evaluate the safety of paroxetine in the treatment of pregnant patients with depression in the second and third trimesters of pregnancy， and provide reference for rational clinical use of it. METHODS Retrieved from Cochrane Library， PubMed， Embase， VIP， CNKI， Wanfang database and SinoMed database， by manual search， randomized controlled studies or observational studies were collected on depression patients who were given paroxetine vs. selective serotonin reuptake inhibitor （SSRI） in the second and third trimesters of pregnancy during the inception to Aug. 2022. Methodological qualities of the included studies were assessed by Cochrane Handbook 5.1.0 or Newcastle-Ottawa Scale （NOS）. Meta-analysis was performed with RevMan 5.4.1 software. RESULTS Finally， 9 observational studies were included， and all included studies were of high quality in NOS scale. Meta-analysis was performed on 8 cohort studies. Meta-analysis showed that the total incidence of adverse pregnancy outcomes of mothers and infants [RR＝0.99， 95%CI（0.89，1.10），P＝0.87]， total incidence of maternal adverse pregnancy outcomes [RR＝0.98， 95%CI （0.87，1.10）， P＝0.69] and premature birth [RR＝0.89， 95%CI （0.43， 1.83）， P＝0.75] in the second and third trimesters of pregnancy were lower than that with other SSRI， without statistical significance. The incidence of neonatal complications with paroxetine in the second and third trimesters of pregnancy was higher than that with other SSRI， but the difference was not statistically significant [RR＝1.02， 95%CI （0.82，1.29）， P＝0.84]. One study reported that the incidence of neonatal pulmonary hypertension in paroxetine group was higher than that in other SSRI group （0.4% vs. 0.3%）. CONCLUSIONS The safety of peroxetine in the second and third trimesters of pregnancy is comparable with that of other SSRI， but it is necessary to be alert to the occurrence of neonatal pulmonary hypertension.