ObjectiveTo characterize the changes in the overall chemical profile and key index components during nine-time repeating steaming and sun-drying processing of Rhei Radix et Rhizoma， and to reveal the change law of its material basis. MethodsHigh performance liquid chromatography（HPLC） was used to analyze the changes in the overall chemical profile of Rhei Radix et Rhizoma decoction pieces， and the contents of 15 main active components such as chrysophanol-8-O-β-D-glucoside， chrysophanol and gallic acid in the process of nine-time repeating steaming and sun-drying were determined. Combined with chemometrics， the contents and quantity ratio relationships of the glycosides， aglycones and tannins during the processing of Rhei Radix et Rhizoma were analyzed， and the partial least squares-discriminant analysis（PLS-DA） and cluster analysis of the main components in different steaming times were conducted， the statistically significant differential markers were selected with the variable importance in the projection（VIP） value>1. ResultsIn the nine-time repeating steaming and sun-drying process of Rhei Radix et Rhizoma， there were certain regularity in the number and peak area of characteristic peaks and the steaming and sun-drying times， the anthraquinone glycosides and aglycones could be roughly divided into three stages， including rapid change stage， fluctuation change stage and stable stage， and the total amount of tannins showed a decreasing trend. However， the ratios between the three components mentioned above tended to stabilize after five rounds of steaming and sun-drying. The results of PLS-DA and cluster heatmap showed that the content of each component in Rhei Radix et Rhizoma fluctuated greatly during the 1-4 steaming and sun-drying processes， while the content of each component was relatively close during the 5-9 steaming and sun-drying processes. After screening， it was found that chrysophanol， emodin， chrysophanol-8-O-β-D-glucoside， rhein， physcion and emodin-8-O-β-D-glucoside could be used as the index components for distinguishing the processed products of Rhei Radix et Rhizoma with different steaming and sun-drying times. ConclusionThe changes in the properties and efficacy of Rhei Radix et Rhizoma caused by the processing of nine-time repeating steaming and sun-drying are due to the changes in the composition and ratio of various glycosides and complex tannins in this herb， which is also the key to the formation of its characteristic of "purgation with supplement". This study can provide a basis for the research on the processing mechanism of Rhei Radix et Rhizoma and the establishment of processing specifications.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

OBJECTIVES: To assess the efficacy and safety of Tiaozhou Ziyin (TZZY) recipe for treatment of premature ovarian insufficiency (POI) and explore the possible mechanisms. METHODS: We used bioinformatics analyses and network pharmacology to identify the main active ingredients in TZZY recipe and their core targets, which were verified by Western blotting. We tested the efficacy and safety of the recipe in 60 POI patients, who were randomized into control group (n=30) with Femoston treatment and TZZY group (n=30) with additional TZZY recipe treatment for 3 menstrual cycles. RESULTS: The core active ingredients of TZZY recipe included kaempferol, β-sitosterol, luteolin, and quercetin. The core targets included SRC, TP53, STAT3, PIK3CA, and MAPK3, which were involved in positive regulation of cell movement and protein phosphorylation, the cancer pathways and the PI3K-Akt signaling pathway. Molecular docking showed that the core active ingredients had good binding ability with the core targets. In female rat models of POI, TZZY recipe treatment significantly up-regulated ovarian expressions of p-PI3K and p-Akt proteins. In the clinical trial, treatment with Femoston and Femoston plus TZZY recipe both significantly increased E₂ levels and reduced FSH and LH levels and Kupperman scores of the patients, and the combined treatment produced significantly stronger effects. Both treatments increased the number of antral follicles of the patients, but the combined treatment also significantly increased the levels of AMH. CONCLUSIONS The therapeutic mechanism of TZZY recipe for POI involves multiple active ingredients, multiple therapeutic targets and multiple pathways, and activating the PI3K /Akt pathway is one of its main mechanisms of action, to improve ovarian reserve function, alleviate clinical symptoms, and enhance clinical efficacy in POI patients.
Female ; Primary Ovarian Insufficiency/drug therapy* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Rats ; Molecular Docking Simulation ; Signal Transduction ; Sitosterols/therapeutic use* ; Kaempferols/therapeutic use*

The Internet has become an important carrier of medical information.Good electronic health literacy can enhance the public’s ability to obtain correct medical and health information with the help of electronic resources,which is helpful for the public to use health information to prevent diseases,avoid drug abuse,reduce the waste of medical resources and strengthen the self-management of chronic diseases.The improvement of electronic health literacy is of great value to the healthy development of citizens’ health literacy and healthy behavior.In view of the late start and slow development in the field of electronic health literacy in China,by combing the theoretical and practical research experience of electronic health literacy outside the region and combining with the COVID-19,this paper put forward new thinking on electronic health literacy in China,in order to provide useful reference for improving electronic health literacy of Chinese citizens,realizing self-care,self-management and disease prevention.

BACKGROUND:In recent years,the demand for in vitro maturation of immature oocytes has increased.Oocyte maturation is affected by many factors,among which the selection of medium is particularly important,and there is currently no unified plan. OBJECTIVE:To compare the in vitro maturation of germinal vesicle stage oocytes with different maturation media and to investigate its effects on oocyte quality and developmental potential. METHODS:Germinal vesicle oocytes were matured in G-1TM PLUS medium,CZB medium and M16 medium,and mature oocytes in vivo were used as control group to compare in vitro fertilization and early embryo development among various groups.The immunofluorescence method was used to evaluate mitochondrial function in mature oocytes of each group.Calcium oscillation was detected by confocal microscopy real-time imaging system. RESULTS AND CONCLUSION:(1)There was no significant difference in the first polar body ejection rate among the three groups(P>0.05).(2)The rate of in vitro fertilization was higher in the G-1TM PLUS group(52.86±11.24)%than that in the M16 group(37.76±6.70)%and the CZB group(30.62±5.51)%.The blastocyst rate was lower in the CZB group(36.23±6.63)%than that in the control group(78.16±4.17)%,G-1TM PLUS group(55.75±7.63)%and M16 group(53.36±6.33)%.(3)Compared with the control group,the length-to-width ratio of the spindle in the CZB group increased(P<0.005).(4)The mitochondrial function of the CZB group was worse than that of the control group,G-1TM PLUS group and M16 group,and abnormal mitochondrial agglutination occurred in the CZB group.(5)The frequency of calcium oscillations in the CZB and M16 groups was significantly higher than that in the G1 and control groups.In conclusion,during in vitro maturation of mouse oocytes,in vitro maturation rate was not significantly different among G-1TM PLUS,CZB and M16 media,but the G-1TM PLUS medium had a higher rate of fertilization and blastocyst formation.

Objective To investigate the equivalent conversion of head injury criterion(HIC)under anterior-posterior(AP)and lateral-medial(LM)craniocerebral impact for mild craniocerebral injury in rats using motor evoked potential(MEP)and β-amyloid precursor protein(β-APP)immunohistochemistry(IHC).Methods Sixty healthy adult male SD rats were randomly divided into 0 m control group,0.5 m-AP and 0.5 m-LM injury groups,and 1 m-AP and 1 m-LM injury groups(12 rats in each group).The control group did not undergo any impact injury experiment.After the impact injury experiment,the injury and control groups were subjected to excessive anesthesia to produce β-APP immunohistochemical stained slices,and the percentage of positive area and integral optical density(IOD)in the brainstem pyramidal tract area of the slices were determined.The MEP groups were divided in the same manner as the IHC groups and the MEP amplitudes of the MEP and control groups were measured after the impact injury experiment.Results With an increase in the degree of injury,the decrease in MEP amplitude,percentage of positive areas,and IOD in the injury groups significantly increased.When the degree of injury was low,the sensitivity of IHC was higher than that of MEP.When the degree of injury was the same,the HIC in the LM direction was lower than that in the AP direction.When the HIC was the same,the degree of injury in the LM direction was greater than that in the AP direction.Conclusions The joint evaluation of MEP and β-APP can provide experimental references for the study of HIC equivalent conversion in AP-LM craniocerebral impact injury.

Objective:To investigate the effect of iron deficiency on the prognosis of elderly patients with ejection fraction preserved heart failure (HFpEF).Methods:The clinical data of old patients (>75 years) with HFpEF from November 2021 to May 2023 in General Hospital of Eastern Theater of the Chinese People′s Liberation Army were retrospectively analyzed. The patients were divided into iron deficiency group (65 cases) and non-iron deficiency group (90 cases) according to serum ferritin (SF) and transferrin saturation (TSAT) at admission. The first hematological indexes and echocardiogram examination results after admission were compared between two groups. The patients were followed up until November 2023, the poor prognosis was recorded. The correlation between iron deficiency, iron metabolism indexes and poor prognosis in elderly patients with HFpEF was analyzed by Spearman correlation analysis. The Kaplan-Meier survival curve was drawn to analyze the effect of iron deficiency on the cumulative survival in elderly patients with HFpEF.Results:There were no statistical difference in triglyceride, total cholesterol, low density lipoprotein cholesterol, C-reactive protein, hemoglobin and echocardiogram indexes between the two groups ( P>0.05). The N-terminal pro-brain natriuretic peptide (NT-proBNP), creatinine, procalcitonin (PCT) and interleukin-6 (IL-6) in iron deficiency group were significantly higher than those in non-iron deficiency group: 427.23 (281.00, 736.90) pmol/L vs. 313.50 (182.47, 363.25) pmol/L, (167.93 ± 51.22) μmol/L vs. (121.71 ± 11.99) μmol/L, 0.12 (0.05, 0.22) μg/L vs. 0.07 (0.04, 0.16) μg/L and 25.60 (8.38, 47.01) ng/L vs. 10.15 (4.75, 19.89) ng/L, the SF, serum iron (SI) and TSAT were significantly lower than those in non-iron deficiency group: 75.40 (42.30, 198.00) μg/L vs. 207.00 (281.00, 736.90) μg/L, (6.49 ± 2.66) μmol/L vs. (12.75 ± 4.24) μmol/L and (16.65 ± 6.26)% vs. (33.78 ± 11.16)%, and there were statistical differences ( P<0.01 or <0.05). The patients were followed up for (12.06 ± 7.58) months, the all-cause mortality, cardiovascular mortality, readmission rate and heart failure readmission rate in iron deficiency group were significantly higher than those in non-iron deficiency group: 40.0% (26/65) vs. 20.0% (18/90), 18.5% (12/65) vs. 4.4% (4/90), 90.8% (59/65) vs. 70.0% (63/90) and 66.2% (43/65) vs. 17.8% (16/90), and there were statistical differences ( P<0.01). Spearman correlation analysis result showed that the iron deficiency was positive correlation with all-cause death, cardiovascular death, readmission and heart failure readmission in elderly patients with HFpEF ( P<0.01); the SI and TSAT were negative correlation with all-cause death, cardiovascular death, readmission and heart failure readmission ( P<0.01 or <0.05); and the SF was not correlation with the indexes ( P>0.05). Kaplan-Meier survival analysis result showed that the risk of all-cause death was significantly increased in elderly HFpEF patients with iron deficiency, and the cumulative survival rate was significantly reduced (log-rank χ2 = 6.48, P<0.05). Conclusions:The elderly HFpEF patients with iron deficiency have poor prognosis with high mortality and readmission rate.

Objective To summarize the clinical characteristics of patients with occupational melanosis. Methods Diagnostic data of 69 patients with occupational melanosis was analyzed using retrospective analysis. Results The main occupational hazards for the 69 patients with occupational melanosis were coal tar, petroleum and its fractionated products, pigments and dyes and their intermediates, rubber additives and rubber products. The median length of occupational exposure and disease latency were 8.0 and 6.0 years, respectively, with a highly positive correlation between them (Spearman correlation coefficients=0.962, P<0.01). Skin lesions were mainly found on exposed areas such as the face-to-neck and limbs, prevalence of 94.2% and 75.4% respectively. And 78.3% of patients had skin lesion on more than two sites. The lesions were mostly in the form of irregular flakes (59.4%), with a gray-black color (44.9%). About 43.5% of patients experienced skin itching. Complete blood count, liver function, and kidney function were all within normal ranges. Skin biopsy results showed that epidermal hyperkeratosis, thinning of the spinous layer, liquefaction degeneration of basal cells, increased superficial dermal melanocytes, and infiltration of lymphocytes, histiocytes, and melanocytes around the blood vessels. Reflectance confocal microscopy (RCM) detection showed focal liquefaction degeneration of basal cells in the lesions, with a significant infiltration of melanocytes and inflammatory cells in the dermal papillae and superficial layers. Conclusion The primary target organ of occupational melanocytes is the skin, and no damage to other organs was identified thus far. Results from skin biopsies and RCM examinations can be used for differential diagnosis.

The Internet has become an important carrier of medical information.Good electronic health literacy can enhance the public’s ability to obtain correct medical and health information with the help of electronic resources,which is helpful for the public to use health information to prevent diseases,avoid drug abuse,reduce the waste of medical resources and strengthen the self-management of chronic diseases.The improvement of electronic health literacy is of great value to the healthy development of citizens’ health literacy and healthy behavior.In view of the late start and slow development in the field of electronic health literacy in China,by combing the theoretical and practical research experience of electronic health literacy outside the region and combining with the COVID-19,this paper put forward new thinking on electronic health literacy in China,in order to provide useful reference for improving electronic health literacy of Chinese citizens,realizing self-care,self-management and disease prevention.

Objective:To determine whether the neutrophil-lymphocyte-ratio (NLR) a inflammatory factor can predict tumor response to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer.Methods:Between 2014 and 2019, 205 locally advanced rectal cancer patients underwent CRT before curative surgery. After propensity score matching, 148 patients (74 matched pairs) were enrolled in this study. The hematological parameters were collected and their relationship with tumor response was investigated.Results:After propensity score matching, NLR before CRT in good response group were significantly lower than that in poor response group(2.2±1.0 vs. 2.4±1.2, Z=-2.465, P<0.05), while there was no significant difference in all hematological characteristics between two groups after CRT. The cutoff values of pre-CRT NLR was 3.88 after receiver operating characteristic analysis(AUC=0.618, 95% CI: 0.528-0.708). Multivariate analysis model indicated that pre-CRT NLR≥3.88 was the predictor of poor tumor response ( OR=5.826, 95% CI: 1.299-26.132, P<0.05). Conclusion:The increased NLR before CRT can be regarded as a hematological factor for poor tumor response in locally advanced rectal cancer.