Simmering method is one of the traditional processing methods of Chinese materia medica， which has been documented in the herbal literature and medical books of the past dynasties and has a great variety， but at present， there are not many specific varieties of Chinese materia medica involved， and there are few related researches. By reviewing the ancient and modern related information， the authors have organized and analyzed the historical evolution， processing purpose， modern representative Chinese materia medica（processing technology， quality evaluation， pharmacological research） of simmering method. After sorting out， it was found that the simmering method was widely used in ancient times， which was first seen in Huashi Zhongzangjing of the Eastern Han dynasty， and was enriched and developed through the Tang， Song， Jin， Yuan， Ming and Qing dynasties， and entered its heyday in Ming and Qing dynasties along with the economic prosperity and development of the Ming dynasty， involving as many as 159 varieties of Chinese materia medica， and gradually perfecting the processing theory of the simmering method. However， the number of varieties that still use the simmering method in modern times significantly decreased. The main purposes of using simmering method in modern Chinese materia medica are to reduce adverse reactions， moderate medicinal properties， enhance therapeutic effects， remove non-medicinal parts， and facilitate further processing， etc. This paper combed the key information of simmering methods for Chinese materia medica from ancient to modern times， which can provide a literature basis for the clinical application and modern research of simmered products of Chinese materia medica.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

BACKGROUND:At present,the biological functions and molecular changes of bone marrow mesenchymal stem cells in the tumor microenvironment of acute myeloid leukemia are still unclear. OBJECTIVE:To explore the changes in the biological function of bone marrow mesenchymal stem cells in acute myeloid leukemia and the role of acute myeloid leukemia conditioned medium by bioinformatics and experiment. METHODS:Differential genes were screened from GEO data sets,and enrichment analysis was performed.The protein-protein interaction network was constructed and the Hub gene was obtained.Bone marrow mesenchymal stem cells from patients with acute myeloid leukemia and healthy donors were cultured.Bone marrow mesenchymal stem cells from healthy donors were treated with acute myeloid leukemia conditioned culture solution.Each group was subjected to the adipogenic differentiation,osteogenic differentiation,staining of β-galactosidase,detection of the cell cycle,and validation of Hub genes. RESULTS AND CONCLUSION:(1)Gene expression data of bone marrow mesenchymal stem cells from acute myeloid leukemia patients and healthy donors were obtained from GSE84881,and 184 up-regulated genes and 140 down-regulated genes were screened.(2)The biological functions of enrichment mainly include cell cycle,adipocyte differentiation,cell metabolism,and MYC pathway.According to the Degree algorithm,10 up-regulated Hub genes and 10 down-regulated Hub genes were selected.(3)The cell in vitro experiment found that:compared with the control group,the surface antigen of acute myeloid leukemia mesenchymal stem cells did not change,but it showed enhanced lipid differentiation ability,weakened osteogenic differentiation ability,increased β-galactosidase positive cell number,altered cell morphology,arrested cell cycle,increased LGALS3 expression,and decreased MYC expression.Mesenchymal stem cells from healthy donors showed similar changes after being cultured in acute myeloid leukemia conditioned medium.(4)The results show that biological function of mesenchymal stem cells is altered in the acute myeloid leukemia microenvironment,which provides new insights into the interaction between mesenchymal stem cells and tumor cells.

[Objective] To investigate the functional differences and potential effects of chromatin spatial structure in patients with normal karyotype and complex karyotype multiple myeloma. [Methods] High-throughput chromosome conformational capture (Hi-C) analysis was performed on plasma cells of 1 case with 1q21 complex karyotype and 1 case with normal karyotype multiple myeloma, and the differences in three-dimensional genome structure between the two patients were analyzed, and the transcriptome characteristics of plasma cells were combined to investigate the differential features through gene functional enrichment. [Results] A/B switch occurred in 36% of the chromatin compartments in two cases, and 1 041 genes in patient with complex karyotype had B/A switch. About 3 500 topological association domains (TADs) were identified in each sample, and there was no significant difference. The number of loops identified in complex karyotype sample was 1 069, which was 1/6 of the normal sample, and there were significant differences in the number of three different types of loops, which to some extent reflected the loss of genome stability. Transcriptome analysis showed significant differences in expression profiles between the two patients, and a total of 6 150 differentially expressed genes (3 303 up-regulated genes and 2 847 down-regulated genes) were identified. [Conclusion] Compared with patient with normal karyotype, patient with 1q21 complex karyotype multiple myeloma exhibit significant changes in the spatial structure of plasma cell chromatin at different levels, which leads to changes in gene expression and activation of pathways related to cancer progression.

Objective:To investigate the effect of vitamin D supplementation on weight loss efficacy and insulin resistance (IR) in obese patients.Methods:It was a randomized controlled trial. A total of 190 obese patients with vitamin D deficiency were selected from the obesity clinic of Tianjin Union Medical Center from March to December in 2023. The patients were divided into control group (95 cases) and vitamin D group (95 cases) according to random number table. The control group was given energy-limited high-protein diet combined with moderate intensity exercise, and the vitamin D group was supplemented with vitamin D on the basis of the control group, 14 000 U/week for 24 weeks. A total of 25 dropped out of the study from the two groups for various reasons. Finally, 79 cases in the control group and 86 cases in the vitamin D group were included in the analysis. Independent sample t test and rank sum test were used to compare serum 25 hydroxyvitamin D [25 (OH) D] level, body weight, body mass index, fat mass, visceral fat area, fasting blood glucose, fasting insulin and glycated hemoglobin (HbA 1c) between the two groups at baseline and after intervention. Homeostasis model insulin resistance index (HOMA-IR) was used to evaluate the degree of insulin resistance (IR), and the effects of vitamin D supplementation on weight loss efficiency and IR in those patients were analyzed. Results:There was no significant differences in serum 25(OH)D level between the two groups before intervention ( P>0.05); the serum 25(OH)D level in the vitamin D group was significantly higher than that in the control group after intervention [(30.90±7.55) vs (16.00±4.34) μg/L] ( t=-15.35, P<0.001). The body weight, body mass index, fat mass, visceral fat area, fasting blood glucose, fasting insulin, HbA 1c, and HOMA-IR were all significantly lower after the intervention than those before the intervention in both groups [control group: (93.32±13.47) vs (98.95±14.31) kg, (33.74±5.09) vs (35.80±5.52) kg/m 2, (39.77±11.87) vs (44.12±12.79) kg, (183.76±40.95) vs (204.01±32.18) m 2, 5.00 (4.55, 5.67) vs 5.24 (4.68, 6.42) mmol/L, 16.78 (13.94, 24.30) vs 22.56 (15.95, 31.2) mU/L, 5.55%±0.53% vs 6.05%±0.99%, 4.11 (3.14, 5.57) vs 5.51 (3.61, 8.49); vitamin D group: (88.14±17.66) vs (104.43±22.02) kg, (31.02±5.10) vs (36.66±5.98) kg/m 2, (35.51±12.87) vs (46.67±13.33) kg, (166.50±49.50) vs (213.64±40.14) m 2, 4.70 (4.35, 5.07) vs 5.17 (4.77, 6.30) mmol/L, 13.18 (9.87, 18.84) vs 21.67 (15.78. 32.74) mU/L, 5.43%±0.48% vs 6.21%±1.22%, 2.88 (1.99, 4.21) vs 5.19 (3.82, 9.27)], and the body weight, body mass index, adiposity, visceral fat area, fasting blood glucose, fasting insulin, and HOMA-IR were all significantly lower in vitamin D group than those in the control group [(88.14±17.66) vs (93.32±13.47) kg, (31.02±5.10) vs (33.74±5.09) kg/m 2, (35.51±12.87) vs (39.77±11.87) kg, (166.50±49.50) vs (183.76±40.95) m 2, 4.70 (4.35, 5.07) vs 5.00 (4.55, 5.67) mmol/L, 13.18 (9.87, 18.84) vs 16.78 (13.94, 24.30) mU/L, and 2.88 (1.99, 4.21) vs 4.11 (3.14, 5.57), respectivley] (all P<0.05). The IR remission rate was significantly higher in the vitamin D group than that in the control group after the intervention (37.3% vs 15.3%) ( χ2=8.071, P=0.002). Conclusion:Supplementation of vitamin D on the basis of energy-limited high-protein diet combined with moderate intensity exercise can significantly improve the efficacy of weight loss and IR in obese patients with vitamin D deficiency.

Objective To explore the expression and clinical value of serum calprotectin and toll like receptor 2(TLR2)with type 2 diabetic kidney disease(DKD).Method According to the levels of UACR,90 T2DM patients treated in our hospital from January 2019 to January 2022 were divided into normal albuminuria group(Con,UACR<30 mg/g),microalbuminuria group(Micro,UACR 30～300 mg/g),and macroalbuminuria group(Macro,UACR>300 mg/g),30 cases per group.Result The levels of BMI,HbAlc,calprotectin,TLR2,and NLRP3 increased sequentially from Con,Micro to Macro groups(P<0.05),while eGFR in the Macro group was lower than that in the Con or Micro groups(P<0.05).Pearson correlation analysis showed that serum calprotectin was positively correlated with BMI,WC,SBP,FPG,HbAlc,TC,TG,Scr,UACR(P<0.05 or P<0.01),and negatively correlated with eGFR(P<0.01);NLRP3 is positively correlated with BMI,WC,SBP,FPG,HbAlc,TC,TG,Scr,SUA,and UACR(P<0.01),and negatively correlated with eGFR(P<0.01);TLR2 was positively correlated with BMI,WC,SBP,FPG,HbAlc,TC,TG,Scr and UACR(P<0.05 or P<0.01),and negatively correlated with eGFR(P<0.01).Multiple linear regression analysis showed that FPG,HbAlc,TC,Scr,calprotectin,and TLR2 were the influencing factors of UACR.Receiver operating characteristic(ROC)curve analysis showed that the area under the curve for diagnosing DKD with serum calprotectin and TLR2 was 0.883 and 0.961,with sensitivities of 73.33%and 96.67%,and specificity of 100.00%and 83.33%.Conclusion Serum calprotectin and TLR2 are closely related to the occurrence and development of DKD.The diagnostic value of TLR2 for DKD is superior to serum calprotectin.

Under the background of scientific and technological innovation in the new era, ethical review of traditional Chinese medicine (TCM) is facing new opportunities and challenges. Focusing on how to maintain integrity and innovation in the ethical review work of TCM clinical research in TCM medical institutions, starting from the characteristics of innovation and inheritance of TCM clinical research, this paper discussed the construction of the ethical review system of TCM clinical research, key elements of attention, shortcomings and deficiencies, training and communication, etc. It is also proposed that the joint construction of a Chinese characteristic scientific and technological ethics governance system should consider the unique requirements of modern technological means for the ethical review of scientific and technological projects such as dialectical treatment, re-evaluation of prescription projects, and expansion of indications in clinical research of TCM; innovate the form of review and strengthen the process management of ethical review; scientifically, objectively and impartially evaluate the scientific nature and social value of clinical research projects in TCM; pay attention to the toxic side effects of TCM, especially compound preparations. So as to further improve the procedural norms and quality of ethical review of clinical research of TCM, protect the legitimate rights and interests and safety of subjects, and promote the development of medicine in China.

Objective:To construct a new model for assessing insulin resistance(IR) in newly diagnosed type 2 diabetic patients by combining anthropometry parameters and biochemical parameters.Methods:A total of 677 newly diagnosed type 2 diabetic patients were included in this study. Clinical data, biochemical indicators, and body composition measurements were collected, and a predictive model was constructed using logistic regression analysis.Results:The IR prediction model was constructed based on five indicators: triglycerides(TG), fasting plasma glucose(FPG), visceral fat area(VFA), alanine aminotransferase(ALT), and uric acid(UA). The formula for the new predictive model was as follows: y=-17.765+ 1.389×ln VFA+ 1.045×ln UA+ 0.91×ln ALT+ 2.167×ln FPG+ 0.805×ln TG. The receiver operating characteristic curve(ROC) area under the curve(AUC) for the model was 0.82, with an optimal cutoff value of 1.67, sensitivity of 0.80, and specificity of 0.71. The AUC values for the triglyceride glucose(TyG) index, lipid accumulation product(LAP), and triglyceride/high-density lipoprotein cholesterol ratio(THR) were 0.75, 0.75, and 0.70, respectively. The corresponding sensitivities were 0.66, 0.84, and 0.71, and the specificities were 0.71, 0.59, and 0.60. The optimal cutoff values were 1.81, 30.31, and 1.14, respectively. Conclusion:The new model constructed using TG, FPG, VFA, ALT, and UA as indicators showed high predictive value and can serve as a new model for assessing IR in newly diagnosed type 2 diabetic patients.

Objective:To investigate the relationship between telomere length of bone marrow mononuclear cells and prognosis of patients with acute myeloid leukemia (AML) who received allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:Telomere length of bone marrow mononuclear cells before transplantation, after transplantation and before donor mobilization as well as information related to follow-up of 33 AML patients who received allo-HSCT in the Affiliated Hospital of Guizhou Medical University between June 2020 and June 2021 were retrospectively analyzed. Telomere length was detected by using telomeric terminal restriction fragment (TRF) method. Telomere length was compared among patients with different prognoses. The recurrence within 1 year was treated as the gold standard and receiver operating characteristic (ROC) curve was used to analyze the effect of telomere length before transplantation or before donor mobilization in the judgement of the recurrence within 1 year after transplantation. The patients were stratified according to the optimal threshold value of telomere length for patients or donors, and Kaplan-Meier method was used to compare the progression-free survival (PFS) of patients with different stratification, and log-rank test was performed.Results:The median age of 33 patients was 34 years (14-61 years), and there were 17 males and 16 females; 31 patients were initially diagnosed with AML, 1 patient transferred from myelodysplastic syndrome (MDS) to AML, and 1 patient transferred from chronic granulocytic leukemia (CML) to AML; 14 received identical sibling transplantation and 19 received haploidentical sibling transplantation. The median age of the donors was 30 years (20-65 years), including 24 males and 9 females. Telomere length of bone marrow mononuclear cells before mobilization in 33 donors was longer than that in patients before transplantation (33 cases) and at +30 d after transplantation (31 cases) [(6.67±0.31) kb, (6.40±0.33) kb, (6.48±0.33) kb, respectively; all P < 0.05], and the difference between patients before and at +30 d after transplantation was not statistically significant ( t = 0.89, P = 0.378), and the telomere length of bone marrow mononuclear cells in 11 patients +180 d after transplantation was (6.66±0.18) kb. The incidence of acute graft-versus-host disease (aGVHD) after transplantation was 45.5% (15/33), the incidence of infection with clear imaging and pathogenic basis was 39.4% (13/33), the mortality rate within 1 year after transplantation was 3.0% (1/33), and the recurrence rate within 1 year after transplantation was 15.2% (5/33). There were no statistically significant differences in telomere length of donor pre-mobilization bone marrow mononuclear cells between the groups with and without aGVHD and between the infected and non-infected groups (all P > 0.05).Compared with patients who had not relapsed within 1 year after transplantation, telomere length of donor pre-mobilization bone marrow mononuclear cells was shorter in patients who relapsed within 1 year after transplantation [(6.39±0.19) kb vs. (6.72±0.30) kb, t = -3.23, P = 0.011], telomere length was longer in patients before transplantation [(6.75±0.16) kb vs. (6.35±0.36) kb, t = 4.17, P = 0.001]. ROC curve analysis showed that the optimal threshold values for telomere length of pre-transplantation and donor pre-mobilization bone marrow mononuclear cells were 6.48 and 6.42 kb, respectively for patients who relapsed within 1 year after transplantation. PFS in patients with pre-transplantation bone marrow mononuclear cells telomere length < 6.48 kb was better than that in patients with telomere length ≥ 6.48 kb ( P = 0.003); PFS in patients with pre-mobilization bone marrow mononuclear cells telomere length>6.42 kb was better than that in patients with telomere length ≤ 6.42 kb ( P < 0.001). Conclusions:In allo-HSCT for AML, patients have an increased risk of relapse within 1 year after transplantation when their pre-transplantation bone marrow mononuclear cells telomere length is long and the donor bone marrow mononuclear cells telomere length is short.

Objective:To explore the application of Tongdu Tiaoshen acupuncture in patients with hemiplegia after stroke.Methods:Randomized controlled trial. A total of 70 patients who met the inclusion criteria for post-stroke hemiplegia in our hospital from January 2020 to December 2021 were divided into two groups, with 35 cases in each group, according to the random number table. The control group was given conventional treatment combined with rehabilitation exercise therapy, and the observation group was given Tongdu Tiaoshen acupuncture on the basis of the above, and both groups were treated continuously for 1 month. Compare of the two groups Fugl-Meyer Assessment (FMA), Modified Ashworth Scale (MAS), National Institutes of Health Stroke Scale (NIHSS), Activity of Daily Living (ADL) score; Brunnstrom stage method was used to assess the patient's motor ability, and Holden walking function grade was used to assess the patient's walking ability. The activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time(TT), and serum fibrinogen (FIB), D-dimer (D-D), plasminogen activator inhibitor 1 (PAI-1) levels were observed by ELISA. Adverse events were recorded and clinical efficacy was evaluated.Results:The total effective rates of the observation group and the control group were 97.14% (34/35) and 77.14% (27/35), respectively, and the difference between the two groups was statistically significant ( χ2=6.25, P=0.012). After treatment, the scores of FMA and ADL in the observation group were significantly higher than those in the control group ( t values were 9.23 and 9.54, respectively, P<0.01), the MAS and NIHSS scores were significantly lower than those in the control group ( t values were 10.23 and 11.97, respectively, P<0.01). After treatment, the distribution of patients in Brunnstrom stage Ⅴ and Ⅵand Holden functional walking stage Ⅳ and Ⅴ in the observation group was significantly higher than those in the control group ( χ2 values were 11.96 and 11.27, respectively, P<0.05). After treatment, APTT, PT and TT in the observation group were significantly longer than those in the control group ( t values were 10.37, 13.57 and 6.54, respectively, P<0.01); serum FIB, D-D and PAI-1 levels were significantly lower than those in the control group ( t values were 12.85, 11.94 and 27.39, respectively, P<0.01). No adverse reactions occurred in both groups. Conclusion:The treatment of post-stroke hemiplegia with Tongdu Tiaoshen acupuncture can improve the effect of clinical treatment and the ability of daily life, neurological function, limb function, movement and walking ability, and stabilize the clotting state.