Iodine accumulation represents a differentiation marker of thyroid cancer (TC) and a cornerstone of benefits from 131I therapy. However, dedifferentiation phenotypes occur in nearly 70% of recurrent or metastatic TCs driven by oncogenic mutations such as B-Raf proto-oncogene, serine/threonine kinase (BRAF), telomerase reverse transcriptase (TERT) promoters, and tumor proten p53 (TP53). Beyond genetic alterations, epigenetics, autophagy, tumor microenvironment and other pathways are also involved in the dedifferentiation of TC and the tolerance to 131I therapy. Targeting the above-mentioned pathways has potential to improve the malignant phenotype of TC and restore sensitivity to 131I therapy, which is of great clinical significance. Based on the relevant mechanisms of dedifferentiation, this paper elaborates on the progress of preclinical experiments and clinical studies related to differentiation therapies of TC.

Objective: To explore the effects of porcine acellular dermal matrix (ADM) combined with human epidermal stem cells (ESCs) on wound healing of full-thickness skin defect in nude mice. Methods: The morphology of porcine ADM was analyzed by photograph of digital camera, the cell residues in porcine ADM were observed by hematoxylin-eosin (HE) staining, the surface structure of porcine ADM was observed by scanning electron microscope, the secondary structure of porcine ADM was analyzed by infrared spectrometer, the porcine ADM particle size was analyzed by dynamic light scattering particle size analyzer, and the porcine ADM potential was analyzed by nano-particle size potentiometer. The morphology of porcine ADM was observed by inverted fluorescence microscope when it was placed in culture medium for 30 min, 1 d, and 5 d (n=2). The porcine ADM was divided into 5 min group, 10 min group, 20 min group, 30 min group, 60 min group, and 120 min group according to the random number table (the same grouping method below) in static state at normal temperature for the corresponding time to calculate the water absorption by weighing method (n=3). Swiss white mouse embryonic fibroblasts (Fbs) were divided into blank control group (culture medium only), and 50.0 g/L ADM extract group, 37.5 g/L ADM extract group, 25.0 g/L ADM extract group, 12.5 g/L ADM extract group, and 6.5 g/L ADM extract group which were added with the corresponding final concentrations of ADM extract respectively. At post culture hour (PCH) 24, 48, and 72, the cell survival rate was detected by cell counting kit 8 and the cytotoxicity was graded (n=5). The erythrocytes of a 6-week-old male Sprague-Dawley male rat were divided into normal saline group, ultra-pure water group, and 5 mg/mL ADM extract group, 10 mg/mL ADM extract group, and 15 mg/mL ADM extract group which were treated with the corresponding final concentrations of porcine ADM extract respectively. After reaction for 3 h, the absorbance value of hemoglobin was detected by microplate reader to represent the blood compatibility of porcine ADM (n=3). ESCs were isolated and cultured from the discarded prepuce of a 6-year-old healthy boy who was treated in the Department of Urology of the First Affiliated Hospital of Army Medical University (the Third Military Medical University) in July 2020, and then identified by flow cytometry. The porcine ADM particles of composite ESC (hereinafter referred to as ESC/ADM) were constructed by mixed culture. After 3 days of culture, the composite effect of ESC/ADM was observed by HE staining and laser scanning confocal microscope. Thirty-six 7-8-week-old male non-thymic nude mice were divided into phosphate buffer solution (PBS) alone group, ADM alone group, ESC alone group, and ESC/ADM group, with 9 mice in each group, and the wound model of full-thickness skin defect was established. Immediately after injury, the wounds were treated with the corresponding reagents at one time. On post injury day (PID) 1, 7, 11, and 15, the wound healing was observed and the wound healing rate was counted (n=3). On PID 7, the epithelialization of wounds was observed by HE staining and the length of un-epithelialized wound was measured (with this and the following sample numbers of 4). On PID 11, the dermal area and collagen deposition of wounds were observed by Masson staining and the dermal area of wound section was calculated, the number of cells expressing CD49f, a specific marker of ESC, was calculated with immunofluorescence staining, the mRNA expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in ESC after wound transplantation was detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction. Data were statistically analyzed with independent sample t test, one-way analysis of variance, analysis of variance for repeated measurement, and least significant difference t test. Results: The porcine ADM was white particles and composed of reticular structure, with no cells inside, disordered structure, and rough surface. The absorption peak of porcine ADM appeared at the wave numbers of 1 659, 1 549, and 1 239 cm^-1, respectively. The main particle size distribution of porcine ADM in solution was 500 to 700 nm, with negative charge on the surface. The morphology of porcine ADM in static state at 30 min and on 1 and 5 d was relatively stable. The water absorption of porcine ADM remained relatively high level in static state from 30 min to 120 min. The cytotoxicity of mouse embryonic Fbs in 6.5 g/L ADM extract group, 12.5 g/L ADM extract group, and 25.0 g/L ADM extract group was grade 1 at PCH 24, and the cytotoxicity of the other groups was 0 grade at each time point. After reaction for 3 h, the absorbance value of hemoglobin of erythrocytes in ultra-pure water group was significantly higher than the values in normal saline group and 15 mg/mL ADM extract group (with t values of 8.14 and 7.96, respectively, P<0.01). After 3 days of culture, the cells of the fourth passage showed pebble-like morphology, with low expression of CD71 and high expression of CD49f, which were identified as ESCs. There was ESC attachment and growth on porcine ADM particles. On PID 1, the wound sizes of nude mice were almost the same in PBS alone group, ADM alone group, ESC alone group, and ESC/ADM group. On PID 7, 11, and 15, the wound contraction of nude mice in each group was observed, especially in ADM alone group, ESC alone group, and ESC/ADM group. On PID 7, the wound healing rates of nude mice in ESC alone group and ESC/ADM group were significantly higher than the rate in PBS alone group (with t values of 2.83 and 4.72 respectively, P<0.05 or P<0.01). On PID 11, the wound healing rate of nude mice in ESC/ADM group was significantly higher than that in PBS alone group (t=4.86, P<0.01). On PID 15, the wound healing rates of nude mice in ADM alone group, ESC alone group, and ESC/ADM group were significantly higher than the rate in PBS alone group (with t values of 2.71, 2.90, and 3.23 respectively, P<0.05). On PID 7, the length of un-epithelialized wound of nude mice in ADM alone group, ESC alone group, and ESC/ADM group was (816±85), (635±66), and (163±32) μm, respectively, which were significantly shorter than (1 199±43) μm in PBS alone group (with t values of 5.69, 10.19, and 27.54 respectively, P<0.01). On PID 11, the dermal areas of wound section of nude mice in ADM alone group, ESC alone group, and ESC/ADM group were significantly larger than the area in PBS alone group (with t values of 27.14, 5.29, and 15.90 respectively, P<0.01); the collagen production of nude mice in ADM alone group and ESC/ADM group was more obvious than that in PBS alone group, and the collagen production of nude mice in ESC alone group and PBS alone group was similar. On PID 11, in the wounds of nude mice in ESC alone group and ESC/ADM group, the cells with positive expression of CD49f were respectively 135±7 and 185±15, and the mRNA expressions of GAPDH were positive; while there were no expressions of CD49f nor mRNA of GAPDH in the wounds of nude mice in PBS alone group and ADM alone group. Conclusions: ESC/ADM particles can promote the wound healing of full-thickness skin defects in nude mice, which may be related to the improved survival rate of ESCs after transplantation and the promotion of dermal structure rearrangement and angiogenesis by ADM.
Acellular Dermis ; Animals ; Fibroblasts ; Humans ; Male ; Mice ; Mice, Nude ; Rats ; Rats, Sprague-Dawley ; Stem Cells ; Swine ; Wound Healing

Objective    To quest the risk factors of poor prognoses in children with tetralogy of Fallot (TOF) during perioperative period and evaluate its clinical application values. Methods    A retrospective analysis of the clinical data of 119 children who underwent one-stage correction of TOF in Guangdong Provincial People's Hospital from September 2016 to January 2019. The cohort includes 75 males and 44 females, with ages ranging from 3.2-137.1 (13.2±1.4) months and weights ranging from 4.6-21.0 (8.3±0.2) kg. Perioperative poor prognosis was defined as duration of mechanically assisted ventilation >48 h or secondary intubation, vasoactive-inotropic score (VIS) within 48 h >40, postoperative length of stay >14 d, and the occurrence of the major adverse events. Major adverse events were defined as early death, malignant arrhythmia, low cardiac output syndrome, non-fatal cardiac arrest, postoperative reintervention, diaphragm paralysis, and other clinical complications. Univariate and multivariate logistic analyses were used to analyze the correlation between risk factors and poor prognoses. Results    There was 1 perioperative death, and 9 with major adverse events. Variables selected by Least Absolute Shrinkage and Selection Operator (LASSO) included 2 preoperative variables (McGoon index, aortic root diameter index) and 4 intra-operative variables [left-right direction of bicuspid pulmonary valve, total length of right ventricular outflow tract (RVOT) incision index, pulmonary valve with commissurotomy, and minimum temperature in cardiopulmonary bypass (CPB)]. Univariate and multivariate logistic analyses were used to the above factors, respectively. The variables with statistical significance (P≤0.05) were McGoon index, aortic root diameter index, left-right direction of bicuspid pulmonary valve, and minimum temperature in CPB. A nomogram was established based on the above factors, and the results showed that the left-right direction of bicuspid pulmonary valve was more risky than the tricuspid pulmonary valve and the anterior-posterior direction of bicuspid pulmonary valve. The lower the McGoon index, the higher aortic root diameter, and the lower temperature in CPB, the higher risk of poor prognostic events in children with TOF. Conclusion    The left-right direction of the pulmonary bicuspid valve has a higher risk of poor prognosis than the tricuspid pulmonary valve and the anterior-posterior direction of bicuspid pulmonary valve. With the smaller McGoon index and the larger aortic root diameter, the risk of poor prognoses in children with TOF is higher. The temperature in CPB being lower than medium-low temperature obviously relates to the high incidence of poor prognostic events, which can be used as an auxiliary reference standard for decision-making in pediatric TOF surgery in the future.

Objective To examine whether polymorphisms of histone deacetylase( HDACs) and environment factors can be implicated in type 2 diabetes mellitus ( T2DM) ，and to provide evidence for the prevention and treatment of T2DM． Methods In 2017，T2DM patients and controls were selected from 17 villages in Huadu District，Guangzhou． According the Diagnostic criteria for T2DM，the case group of T2DM was matched with control group from the population diagnosed as normal by gender，age no more than 5 years old，and from the same natural village． Conditional logistic regression model was used to analyze the effect of gene and environment and their interaction on T2DM． Results The average age of 499 cases group were ( 61．53±13．08) years old，and the average age of 499 controls group were ( 61．48±13．09) years old． There were no statistic difference between two groups． Furthermore，the two groups were gender－balanced too． In conditional logistic regression model，we found that glycerin trilau- rate ( TG) abnormalities ( OR= 2．410，95% CI: 1．755－3．310，P＜0．001) and cholesterol total ( TC) ab- normalities ( OR= 1．436，95% CI: 1．046－1．972，P = 0．025) were risk factors for T2DM． The subjects carries rs72792338 TC+TT genotype ( OR= 0．526，95% CI: 0．349－0．793，P= 0．002) had lower the risk to develop T2DM． Conclusions Abnormal TG and TC are risk factors for T2DM． Rs72792338 TT and TC genotype carryings decrease the risk of T2DM．

OBJECTIVE: To observe clinical effect of heat-sensitive moxibustion on coronavirus disease 2019 (COVID-19) and to discusses the effective moxibustion treatment program. METHODS: A total of 42 patients with COVID-19 (general type) were treated with heat-sensitive moxibustion at the acupoint area of Shenque (CV 8) and Tianshu (ST 25). The treatment was conducted under the standards of heat-sensitive moxibustion manipulation, which were "locating acupoint by feeling, moxibustion by differentiate sensation, dosage varies individually, ending after sufficient dosage". The incidence of after first heat-sensitive moxibustion, the reduction of negative emotions, the improvement of chest distress and impaired appetite, and the active acceptance rate of moxibustion before and after treatment were observed. RESULTS: ① The rate of heat-sensitive moxibustion for 20 min、40 min、1 h were respectively 52.4% (22/42), 90.5% (38/42), 100.0% (42/42). ② The incidences of feeling relaxed and comfortable immediately after the first, second, and third heat-sensitive moxibustion were 61.9% (26/42), 73.8% (31/42), and 92.9% (39/42), which were higher than 42.9% (18/42) before heat-sensitive moxibustion treatment (<0.05). ③ The incidences of chest distress after the first, second, and third heat-sensitive moxibustion were 23.8% (10/42), 16.7% (7/42), and 9.5% (4/42), which were lower than 50.0% (21/42) before heat-sensitive moxibustion treatment (<0.05); the incidences of impaired appetite after the first, second, and third heat-sensitive moxibustion were 26.2% (11/42), 19.0% (8/42), 9.5% (4/42), which were lower than 57.1% (24/42) before heat-sensitive moxibustion treatment (<0.05). ④ After the first treatment, the active acceptance rate of patients for heat-sensitive moxibustion was 100.0% (42/42), which was higher than 11.9% (5/42) before heat-sensitive moxibustion (<0.05). CONCLUSION The heat-sensitive moxibustion can effectively reduce the negative emotions and improve the symptoms of chest distress and impaired appetite with COVID-19. It is generally accepted by patients, and worthy of popularization and application in clinical treatment.
Acupuncture Points ; Betacoronavirus ; Coronavirus Infections ; therapy ; Hot Temperature ; Humans ; Moxibustion ; Pandemics ; Pneumonia, Viral ; therapy

Background:Studies on the association between spicy food intake and cancer risk have reported inconsistent results. We quantitatively assessed this association by conducting a meta-analysis based on evidence from case-control studies.

Methods:PubMed, EMBASE, and the Cochrane Library were searched for eligible publications. Combined odds ratios (OR s) with their 95% confidence interval (CI) were calculated using a random- or fixed-effects model. The methodological quality of the included articles was assessed using the Newcastle-Ottawa scale (NOS). All data were analyzed using STATA 11.0 software (version 11.0; StataCorp., College Station, TX, USA). Subgroup analyses were also performed with stratification by region, sex, number of cases, cancer subtype, source of the control group, and NOS score.

Results:A total 39 studies from 28 articles fulfilled the inclusion criteria for the meta-analysis (7884 patients with cancer and 10,142 controls). Comparison of the highest versus lowest exposure category in each study revealed a significant OR of 1.76 (95% CI = 1.35-2.29) in spite of significant heterogeneity (P < 0.001). In the subgroup analyses, this positive correlation was still found for gastric cancer, different regions, different numbers of cases, different sources of the control group, and high-quality articles (NOS score of ≥ 7). However, no statistically significant association was observed for women, esophageal cancer, gallbladder cancer, or low-quality articles (NOS score of <7). No evidence of publication bias was found.

Conclusions:Evidence from case-control studies suggested that a higher level of spicy food intake may be associated with an increased incidence of cancer despite significant heterogeneity. More studies are warranted to clarify our understanding of the association between high spicy food intake and the risk of cancer.

Various chromatographic techniques, including silica gel column chromatography, Sephadex LH-20, preparative thin-layer chromatography, and preparative HPLC, were employed to isolate the chemical constituents from callus cultures of Dysosma versipellis. Structures of the compounds were elucidated based on UV, IR, MS and NMR spectroscopic data analysis. Totally, seven flavonoid glycosides were isolated from the 95% ethanol extract of the callus cultures and identified as kaempferol-3-O-[6″-(3″'-methoxy)-malonyl]-β-D-glucopyranoside(1), kaempferol-3-O-(6″-O-acetyl)-β-D-glucopyranoside(2), kaempferide-3-O-β-D-glucopyranoside(3), kaempferol-3-O-β-D-glucopyranoside(4), isoquercitrin(5), quercetin-4'-O-β-D-glucopyranoside(6) and kaempferol-3-(6″-malonyl)-β-D-glucopyranoside(7), respectively.All these compounds were isolated from callus cultures of D. versipellis for the first time.Compounds 1, 2, 3, 6 and 7 were firstly obtained from plant materials of D. versipellis, and compound 1 was a new compound.

Objective To evaluate the effects of beraprost sodium com-bined with losartan potassium on kidney function and microalbuminuria index of patients with early diabetic nephropathy .Methods A total of 68 cases of patients with early diabetic nephropathy were divided into the trial group ( n=34 ) and control group ( n=34 ) .The patients of control group were treated with conventional symptomatic treatment and beraprost sodium 40 μg, tid.On the basis of control group , the patients of trial group were treated with losartan potassium 50 mg, qd.The treatment for patients of two groups all lasted for 12 weeks.The changes in renal func-tion ( serum creatinine , blood urea nitrogen , homocysteine , cystatin C levels ) , and microalbuminuria index (β2 microglobulin , urine mi-croalbumin , urinary microalbumin /urine creatinine , 24 h urinary albu-min excretion rate ) and blood pressure , blood glucose and glycosylated hemoglobin of the two groups before and after the treatment were ob-served.Results In the terms of urea nitrogen , homocysteine , cystatin C,β2 microglobulin, urine microalbumin, urinary microalbumin /urine creatinine , 24 h urinary albumin excretion rate , the patients of twogroups all significantly decreased than before treatment (P <0.05), and in the terms of homocysteine , cystatin C, mi-croalbuminuria index , the patients of the trial group got more significant decline ( P <0.05 ) , but in the terms of serum creatinine, urea nitrogen, there was no significant difference between the two groups (P>0.05).The blood pressure of two groups significantly decreased after treatment , but blood glucose and glycosylated hemoglobin of two groups all got no significant difference than those of before treatment ( P>0.05 ) .There was no serious adverse drug reactions in the two groups, including coughing , elevated serum potassium and so on .Conclusion The beraprost sodium com-bined with losartan potassium can protect the kidney endothelial cells and improve kidney function of patients with early diabetic nephropathy , effectively reduce urinary protein and slow the progression of disease with high safety .

OBJECTIVETo analyze retrospectively the therapeutic efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for chronic myelomonocytic leukemia (CMML).

METHODSThe engraftment, graft versus host disease (GVHD), infection, relapse, and survival of 13 CMML patients received allo-HSCT were observed. The clinical outcome of allo-HSCT for CMML was analyzed.

RESULTSThirteen (10 males and 3 females) CMML patients with a median age of 38 years old received allo-HSCT including 4 from HLA-matched unrelated donors, 6 from HLA-matched sibling donors and 3 from haploidentical related donors. All 13 patients achieved engraftment, and the median time of neutrophil engraftment and platelet engraftment were 12 (11-18) days and 15 (10-55) days respectively, acute GVHD occurred in 8 patients. After the median follow-up of 13 (6-29) months, the overall survival, disease free survival and relapse were 53.8%, 53.8%, 7.7%, respectively.

CONCLUSIONAllo-HSCT can improve the survival of patients with CMML, and is a effective method for treatment of CMML.

Adult ; Disease-Free Survival ; Female ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myelomonocytic, Chronic ; Male ; Retrospective Studies ; Siblings ; Tissue Donors ; Transplantation, Homologous

OBJECTIVETo observe the effect of Compound Shenhua Tablet (, SHT) on the sodium-potassium- exchanging adenosinetriphosphatase (Na(+)-K(+)-ATPase) in the renal tubular epithelial cells of rats with acute ischemic reperfusion and to investigate the mechanisms underlying the effects of SHT on renal ischemic reperfusion injury (RIRI).

METHODSFifty male Wistar rats were randomly divided into the sham surgery group, model group, astragaloside group [150 mg/(kg·d)], SHT low-dose group [1.5 g/(kg·d)] and SHT high-dose group [3.0 g/(kg·d)], with 10 rats in each group. After 1 week of continuous intragastric drug administration, surgery was performed to establish the model. At either 24 or 72 h after the surgery, 5 rats in each group were sacrificed, blood biochemistry, renal pathology, immunoblot and immunohistochemical examinations were performed, and double immunofluorescence staining was observed under a laser confocal microscope.

RESULTSCompared with the sham surgery group, the serum creatinine (SCr) and blood urea nitrogen (BUN) levels were significantly increased, Na(+)-K(+)-ATPase protein level was decreased, and kidney injury molecule-1 (KIM-1) protein level was increased in the model group after the surgery (P<0.01 or P<0.05). Compared with the model group, the SCr, BUN, pathological scores, Na(+)-K(+)-ATPase, and the KIM-1 protein level of the three treatment groups were significantly improved at 72 h after the surgery (P<0.05 or P<0.01). And the SCr, BUN of the SHT low- and high-dose groups, and the pathological scores of the SHT high-dose group were significantly lower than those of the astragaloside group (P<0.05). The localizations of Na(+)-K(+)-ATPase and megalin of the model group were disrupted, with the distribution areas overlapping with each other and alternately arranged. The severity of the disruption was slightly milder in three treatment groups compared with that of the model group. The results of immunofluorescence staining showed that the SHT high-dose group had a superior effect as compared with the astragaloside group and the SHT low-dose group.

CONCLUSIONSThe SHT effectively alleviated RIRI caused by ischemic reperfusion, promoted the recovery of the polarity of renal tubular epithelial cells, and protected the renal tubules. The therapeutic effects of SHT were superior to those of astragaloside as a single agent.

Acute Disease ; Animals ; Blood Urea Nitrogen ; Cell Adhesion Molecules ; metabolism ; Chromatography, Liquid ; Creatinine ; blood ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Fluorescent Antibody Technique ; Immunoblotting ; Kidney Function Tests ; Kidney Tubules ; blood supply ; drug effects ; enzymology ; pathology ; Low Density Lipoprotein Receptor-Related Protein-2 ; metabolism ; Male ; Rats ; Rats, Wistar ; Reperfusion Injury ; drug therapy ; enzymology ; pathology ; Saponins ; analysis ; Sodium-Potassium-Exchanging ATPase ; metabolism ; Staining and Labeling ; Tablets