OBJECTIVE To explore the effect of Jinkui shenqi pill and its potential mechanism on diabetic nephropathy-related osteoporosis （DNOP） in rats. METHODS The rats were randomly divided into blank control group， control group， model group， Jingui shenqi pill low-， medium- and high-dose groups （0.62， 1.24， 2.48 g/kg）， and positive control group （denosumab 3 mg/ kg）， with 12 cases in each group. Except for the blank control group and the control group， models of DNOP were constructed in the remaining groups by high-glucose and high-fat forage， 3% fructose solution for feeding+intraperitoneal injection of streptozotocin solution. At 2 d after successful molding， Jingui shenqi pill low-， medium- and high-dose groups， and positive control group were given intragastric administration or subcutaneous injection of the corresponding drugs， once a day， for consecutive 8 weeks. After the last administration， bone mineral density （BMD） and serum bone metabolism-related indexes [osteocalcin （OC）， calcium， phosphorus， alkaline phosphatase （ALP）， tartrate-resistant acid phosphatase （TRAP）] were detected. The pathological changes of right femoral tissues were observed， and the expressions of receptor activator of NF-κB ligand （RANKL）/receptor activator of NF-κB （RANK）/osteoprotegerin （OPG） pathway-related mRNAs and proteins in left femoral tissues were detected. RESULTS Compared with the blank control group and the control group， there was rupture of bone trabecula and severe structural damage in the model group， and tissue space was obvious. BMD and ALP activities， mRNA and protein expressions of OPG were significantly decreased or down-regulated， while the levels of OC， calcium and phosphorus， TRAP activity， mRNA and protein expressions of RANKL and RANK were significantly increased or up-regulated （P＜0.05）. Compared with the model group， the number of bone trabeculae was increased in all Jingui shenqi pill groups， and the arrangement of bone trabeculae was more regular and dense. The above indexes generally were improved in a certain dose-dependent manner （P＜0.05）. CONCLUSIONS Jingui shenqi pill can promote osteogenesis and regulate the balance of bone metabolism in DNOP rats， which may be related to down-regulating the expressions of RANKL and RANK， and up-regulating the expression of OPG.

Objective:To explore the effect of early eschar dermabrasion combined with antimicrobial soft silicone foam dressing (hereinafter referred to as foam dressing) in treating the deep partial-thickness burn wounds in children.Methods:This study was a randomized controlled trial. From June 2021 to December 2022, 78 pediatric patients with deep partial-thickness burns who met the inclusion criteria were admitted to the Department of Burns in Guiyang Steel Plant Employees Hospital. According to the random number table, the pediatric patients were divided into two groups, with 38 cases left in combined treatment group (with 20 males and 18 females, aged 26.00 (16.75, 39.75) months) and 39 cases in foam dressing group (with 21 males and 18 females, aged 19.00 (14.00, 31.00) months) after the exclusion of one dropped-out child in follow-up. The pediatric patients in combined treatment group underwent eschar dermabrasion of the wound within 48 hours after injury, the wound was covered with foam dressing after operation, and the dressing was replaced once every 7 days; for the pediatric patients in foam dressing group, the wound was sterilized within 48 hours after injury and covered with foam dressing, and the dressing was replaced once every 2 to 3 days. After the wound healing, the children in both groups were routinely applied with silicone gel twice a day for 3 weeks before started wearing elastic sleeves for more than 18 hours a day, and continuously for over than 6 months. The degree of pain during dressing change was evaluated using the children's pain behavior inventory FLACC. The adverse reactions during the treatment period, number of dressing changes, and wound healing time were observed and recorded. Six months after wound healing, the Vancouver scar scale (VSS) was used to evaluate the condition of the wound scar.Results:When changing dressing, the FLACC score for pain of pediatric patients in combined treatment group was 3.5 (2.0, 5.0), which was significantly lower than 6.0 (5.0, 8.0) in foam dressing group ( Z=-5.40, P<0.05). During the treatment period, no adverse reactions such as wound edema, fluid accumulation, or peripheral skin rash allergies occurred in any pediatric patient in both groups. The number of dressing changes of pediatric patients in combined treatment group was 3 (3, 4) times, which was significantly less than 8 (7, 10) times in foam dressing group ( Z=-7.58, P<0.05). The wound healing time of pediatric patients in combined treatment group was (19±5) days, which was significantly shorter than (25±6) days in foam dressing group ( t=-4.48, P<0.05). Six months after wound healing, the VSS score for scar of pediatric patients in combined treatment group was 5 (2, 8), which was significantly lower than 7 (5, 10) in foam dressing group ( Z=-3.05, P<0.05). Conclusions:Compared with using foam dressings alone, early eschar dermabrasion combined with foam dressings can reduce the number of dressing changes, alleviate the pain during dressing changes, and shorten the wound healing time in treating children with deep partial-thickness burns, and effectively alleviate scar hyperplasia by combining with anti-scar treatment post burns.

Aim To investigate whether SIRT6 overexpression inhibits angiotensin Ⅱ(Ang Ⅱ)-induced cardio-myocyte apoptosis by activating adenosine 5'-monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2/heme oxygenase-1(AMPK/Nrf2/HO-1)signaling pathway.Methods The experiment was divided into 4 groups:control group,AngⅡ group,Ang Ⅱ+SIRT6 group,Ang Ⅱ+empty vector(EV)group.The mRNA level of SIRT6 was detected by RT-PCR.The cell activity was measured by MTT assay.The cell apoptosis was analyzed by flow cy-tometry.SIRT6,cardiomyocyte apoptosis related proteins(Bax,cleaved Caspase-3,Bcl-2),DNA damage related pro-teins(γ-H2AX,p-ATM),AMPK/Nrf2/HO-1 signaling pathway related proteins(p-AMPK,Nrf2,HO-1)were measured by Western blot.The reactive oxygen species(ROS)content was determined by DCFH-DA staining.The changes of the above indexes among the groups were observed.Results Compared with control group,the mRNA and protein ex-pression levels of SIRT6 and cell activity were significantly decreased in Ang Ⅱ group.Apoptosis rate,the expressions of Bax,cleaved Caspase-3 were increased,and the expression of Bcl-2 was decreased.The expressions of γ-H2AX and p-ATM were increased,and the expressions of p-AMPK,Nrf2,HO-1 were decreased.The activity of ROS was increased(P＜0.01).Compared with Ang Ⅱ+EV group,the expression of SIRT6 and cell activity were significantly increased in Ang Ⅱ+SIRT6 group.Apoptosis rate,the expressions of Bax and cleaved Caspase-3 were decreased,and the expression of Bcl-2 was increased.The expressions of γ-H2AX and p-ATM were decreased,the expressions of p-AMPK,Nrf2,HO-1 were increased.The activity of ROS was decreased(P＜0.01).Conclusion SIRT6 overexpression inhibits Ang Ⅱ-induced cardiomyocyte apoptosis through activation of AMPK/Nrf2/HO-1 signaling pathway.

Objective:To construct a microfluidic organ-on-a-chip and evaluate its capability in simulating subchondral bone remodeling during the progression of osteoarthritis.Methods:The chip′s main body was designed based on the microfluidic technology and cell co-culture technique. MC3T3-E1 cells were cultured adherently within the cell seeding micro-chamber, with the culture medium perfused at a flow rate of 0.5 ml/min at the bottom of the micro-chamber. Evaluation metrics were as follows: (1) Assessment of the microfluidic organ-on-a-chip: The growth culture medium was perfused and simulation experiments were conducted to test the concentration differences and equilibrium times of the fluid inside and at the bottom of the cell seeding micro-chamber at various time points; live-dead staining was performed to observe the biocompatibility of cells cultured continuously for 3 days and 7 days at a set flow rate, which was divided into 3-day and 7-day groups. (2) Osteogenic potential of the microfluidic organ-on-a-chip: The osteogenic induction medium was perfused, and ALP staining and PCR were performed to compare the number of the black alkaline phosphatase (ALP)-positive cells and the expression levels of osteogenesis-related marker genes including osteoblast-specific transcription factor 2 (RUNX2), type I collagen (COL1A1), bone morphogenetic protein-2 (BMP-2), and osteocalcin (OCN) under static, 3-day and 7-day perfusion conditions, which was divided into static non-induced, static-induced and perfusion-induced groups. (3) Characterization of morphology and size, and biocompatibility of extracellular vesicles (EVs) of three osteoblast subtypes: Three different subtypes of osteoblasts were obtained [endothelial-type osteoblasts (EnOB)-EVs, stromal-type osteoblasts (StOB)-EVs and mineralizing-type osteoblasts (MinOB)-EVs]. Their morphology and size were obtained through transmission electron microscopy and particle size analysis. Growth medium containing EVs of three different cell subtypes was perfused, and cell proliferation/apoptosis assay was performed to compare the biocompatibility of the addition of different EVs concentrations (1, 1.25, 2.5, and 5 μg/ml) for 24 hours, which was categorized into the EnOB-EVs group, StOB-EVs group and MinOB-EVs group. (4) Osteogenic effect of EVs from three subtypes of osteoblasts: Osteogenic induction media containing EVs from three different osteoblast subtypes were perfused for 3 days, and ALP staining and PCR were performed to compare the number of black ALP-positive cells and the expression levels of osteogenesis-related marker genes including RUNX2, COL1A1, BMP-2, and OCN, which was divided into non-EVs group, EnOB-EVs group, StOB-EVs group and MinOB-EVs group.Results:(1) Evaluation of the microfluidic organ-on-a-chip: Simulation results showed that the concentration in the top layer of the upper chamber reached more than 95% of that in the lower chamber and that the concentration in the bottom layer was about 96.5% of that in the lower chamber after 12 hours of continuous perfusion, reaching an equilibrium state of the concentration difference between the upper and lower chambers. The results of live-dead staining showed that the chip was biocompatible at a flow rate of 0.5 ml/min, and the cell survival rate at 3 and 7 days of perfusion was (99.48±0.12)% and (97.07±1.05)% ( P<0.01). (2) ALP staining results showed that at 3 days, the perfusion-induced group showed the highest number of black ALP-positive cells, followed by the static-induced group, and the least in the static non-induced group. At 7 days, the static-induced group had the highest number of black ALP-positive cells, followed by the perfusion-induced group, and the least in the static non-induced group. PCR results indicated that at 3 days, the expression levels of RUNX2, COL1A1, BMP-2, and OCN were 1.00±0.03, 1.00±0.12, 1.00±0.01, and 1.00±0.02 respectively in the static non-induced group; 1.80±0.04, 4.05±0.37, 9.80±1.94, and 4.38±0.89 respectively in the static-induced group, and 2.45±0.23, 5.48±0.42, 91.50±4.56, and 10.82±4.96 respectively in the perfusion-induced group ( P<0.01). At 7 days, the expression levels of RUNX2 was 1.00±0.01 in the static non-induced group, 1.46±0.46 in the static-induced group, and 1.11±0.08 in the perfusion-induced group ( P>0.05); the expression levels of COL1A1, BMP-2, and OCN were 1.00±0.03, 1.00±0.13, and 1.00±0.09 respectively in the static non-induced group, 9.38±0.25, 14.27±4.35, and 84.01±4.02 respectviely in the static-induced group, and 2.39±0.08, 133.64±8.87, and 86.64±8.36 respectively in the perfusion-induced group ( P<0.01). When comparing the static non-induced, static-induced, and perfusion-induced groups at both 3 and 7 days, the perfusion-induced group demonstrated the strongest osteogenic capability. (3) Characterization of morphology and size and biocompatibility of EVs from three osteoblast subtypes: Under the transmission electron microscope, EVs from EnOB-EVs, StOB-EVs, and MinOB-EVs all exhibited a typical saucer-shaped morphology. The particle sizes of EnOB-EVs, StOB-EVs, and MinOB-EVs were (91.3±14.7)nm, (106.0±16.0)nm, and (68.1±10.7)nm, respectively. Cell proliferation/apoptosis assay results indicated that the optimal administration concentration of EnOB-EVs, StOB-EVs, and MinOB-EVs was all 1.25 μg/mL. (4) Validation of osteogenic effect of the microfluidic organ-on-a-chip on three types of EVs: ALP staining results showed that the non-EVs group had the fewest black ALP-positive cells, followed by the EnOB-EVs group, then the StOB-EVs group, and the MinOB-EVs group had the most. PCR results showed that the expression levels of RUNX2, COL1A1, BMP-2, and OCN were 1.00±0.01, 1.00±0.03, 1.00±0.02, and 1.00±0.02 respectively in the non-EVs group, 1.95±0.11, 6.78±2.04, 7.99±0.57, and 6.93±3.83 repectively in the EnOB-EVs group, 0.79±0.12, 5.68±1.53, 12.59±3.15, and 25.59±0.95 respectively in the StOB-EVs group, and 0.68±0.10, 4.36±0.69, 18.75±3.21, and 34.74±3.98 repectively in the MinOB-EVs group ( P<0.01). Compared with the non-EVs group, EnOB-EVs group, StOB-EVs group, and MinOB-EVs group, the MinOB-EVs group showed the most significant osteogenic effect. Conclusions:The microfluidic organ-on-a-chip constructed using microfluidic technology and cell co-culture techniques is capable of maintaining the normal growth of MC3T3-E1 cells, enhancing their proliferation and osteogenic induction differentiation. EVs released by osteoblasts at different stages possess osteogenic effects and can accelerate the bone sclerosis in the remodeling of subchondral bone during the progression of osteoarthritis.

Purpose: The aim of this study was to assess carotid stiffening in a pre-hypertensive (PHT) population using ultrafast pulse wave velocity (ufPWV). Methods: This study retrospectively enrolled 626 individuals who underwent clinical interviews, serum tests, and assessments of the systolic blood pressure (SBP), diastolic blood pressure (DBP), carotid intima-media thickness (cIMT), pulse wave velocity-beginning of systole (PWV-BS), and pulse wave velocity-end of systole (PWV-ES) between January 2017 and December 2021. The patients were divided into three groups according to their blood pressure (BP)—normal BP (NBP): SBP <130 mmHg and DBP <80 mmHg (n=215); PHT: 130 mmHg≤SBP<140 mmHg and/or 80 mmHg≤DBP<90 mmHg (n=119); hypertensive (HT): SBP ≥140 mmHg and/or DBP ≥90 mmHg (n=292). Correlation analyses and comparisons were performed among the groups and in the cIMT subgroups (cIMT ≥0.050 cm and <0.050 cm). Results: cIMT and PWV-ES significantly differed among the BP groups (P<0.05). The BP groups had similar PWV-BS when cIMT <0.050 cm or cIMT ≥0.050 cm (all P>0.05). However, the NBP group had a notably lower PWV-ES than the PHT (P<0.001 and P=0.024) and HT (all P<0.001) groups in both cIMT categories, while the PWV-ES in the PHT group were not significantly lower than in the HT group (all P>0.05). Conclusion Carotid morphological and biomechanical properties in the PHT group differed from those in the NBP group. ufPWV could be used for an early evaluation of carotid stiffening linked to pre-hypertension.

Metabolic reprogramming, a newly recognized trait of tumor biology, is an intensively studied prospect for oncology medicines. For numerous tumors and cancer cell subpopulations, oxidative phosphorylation (OXPHOS) is essential for their biosynthetic and bioenergetic functions. Cancer cells with mutations in isocitrate dehydrogenase 1 (IDH1) exhibit differentiation arrest, epigenetic and transcriptional reprogramming, and sensitivity to mitochondrial OXPHOS inhibitors. In this study, we report that berberine, which is widely used in China to treat intestinal infections, acted solely at the mitochondrial electron transport chain (ETC) complex I, and that its association with IDH1 mutant inhibitor (IDH1^mi) AG-120 decreased mitochondrial activity and enhanced antileukemic effect in vitro andin vivo. Our study gives a scientific rationale for the therapy of IDH1 mutant acute myeloid leukemia (AML) patients using combinatory mitochondrial targeted medicines, particularly those who are resistant to or relapsing from IDH1^mi.
Humans ; Oxidative Phosphorylation ; Berberine ; Electron Transport ; Mitochondria ; Leukemia, Myeloid, Acute ; Isocitrate Dehydrogenase

Objective:To analyze the registration characteristics and reporting quality of Taijiquan-related clinical trials.Methods:A database search of the China Clinical Trials Registry (ChiCTR) and ClinicalTrials.gov was performed by computer to collect basic information, study content, interventions, and other registration information of Taijiquan-related clinical trials from inception to June 30, 2022. The WHO TRDS was used to evaluate the registration quality of clinical trials.Results:Totally 381 Taijiquan-related clinical trials were incorporated, of which 241 (63.25%) were prospective registration and 140 (36.75%) were retrospective registration. The quantity of Taijiquan-related clinical trial registrations generally showed an increasing trend, reaching a peak in 2020 (14.70%). The number of clinical trials registered in Shanghai accounted for the most (9.97%). The largest contributor to the registered trials was Fujian University of Traditional Chinese Medicine (4.46%). 55.12% of registered studies were funded by hospitals and universities. The registered studies were most focused on cognitive impairment. 74.54% of the studies adopted randomized parallel controls, and the sample size was mainly between 20 and 200 (80.31%), and the age of the subjects was concentrated above 39 years (53.28%). The average report completion rate of WHO TRDS items was 86.90%.Conclusions:Presently, the development trend of clinical trials related to Taijiquan is relatively promising. However, imbalances exist in some aspects, for instance distribution of registration areas and institutions, funding allocation, and population of subjects. The description of some registration items is missing or not comprehensive, so corresponding measures are required to improve the quality of clinical trial design and to optimize registration details.

Objective:To investigate the effect of homogeneous management combined with staged teaching on physicians receiving standardized training of hepatobiliary surgery.Methods:A total of 46 physicians who received standardized training in Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, from January to March 2020 were selected as control group and were given conventional teaching, and 50 physicians who received standardized training from April to June 2020 were selected as observation group and were given homogeneous management combined with staged teaching. The two groups were compared in terms of professional level, clinical ability, and the degree of satisfaction with teaching before and after teaching. SPSS 24.0 was used to perform the independent samples t-test, the paired t-test, the chi-square test, and the rank sum test. Results:After teaching, both groups had significant increases in the scores of theoretical examination and operation skill examination, and compared with the control group, the observation group had significantly higher scores of theoretical examination (94.57±3.28 vs. 90.32±2.12) and operation skill examination (94.37±4.18 vs. 91.25±3.46). After teaching, both groups had significant increases in the scores of clinical consultation, physical examination, humanistic concern, clinical diagnosis, communication ability, organizational ability, and overall evaluation, and the observation group had significantly higher scores of the above seven aspects than the control group (6.98±0.94/6.45±0.14/6.95±0.88/6.65±0.93/6.53±0.26/6.84±0.92/6.58±0.35 vs. 6.13±0.31/6.21±0.76/6.21±0.42/6.18±0.35/6.32±0.61/6.33±0.24/6.25±0.71). The observation group had a significantly higher overall satisfaction rate than the control group [94.00% (47/50) vs. 78.26% (36/46)].Conclusion:In the standardized training and teaching of hepatobiliary surgery, homogeneous management combined with staged teaching can improve the professional level and clinical ability of physicians and enhance the degree of satisfaction with teaching.

Objective:To evaluate the relationship between hemoglobin(Hb) level and the risk of diabetic retinopathy(DR) in patients with type 2 diabetes mellitus(T2DM).Methods:This study was a prospective cohort study. A total of 1 730 T2DM patients without DR, who received regular management at the Li′s Clinic in Taiwan, China starting from 2002, were selected as the study population. All patients underwent annual dilated fundus examination by professional ophthalmologists. General patient information and laboratory results were collected and analyzed. Based on the occurrence of DR during patient follow-up, patients were divided into the DR group and the non-DR(NDR) group. The impact of Hb levels on DR was explored using a generalized linear mixed model, and the relationship between Hb levels and DR was studied using Cox proportional hazards regression model.Results:After an average follow-up of 9.79 years, 481 patients with DR were detected. Compared with NDR group, DR group displayed a longer course of diabetes, higher rates of cataract, insulin use, and anemia, and higher systolic blood pressure, HbA 1C, and UACR as well as lower Hb. The results of the generalized linear mixed model showed a negative correlation between Hb and the occurrence of DR( β=-0.015, P<0.001). The Cox proportional hazards regression model showed that, after adjusting for confounding variables and based on quartiles of average Hb levels during follow-up, the risk of developing DR increased by 56.9% in the Q1 group(Hb≤127 g/L) compared to the Q4 group(Hb≥142 g/L). The cumulative risk plot showed that, after adjusting for confounding variables, the Q1 group had the highest cumulative risk of developing DR, and the difference was statistically significant( P<0.05). Conclusion:Hb was negatively correlated with DR, and the lower Hb levels were associated with the occurrence of DR, independent of other influencing factors.

Single-cell or low-input multi-omics techniques have revolutionized the study of pre-implantation embryo development.However,the single-cell or low-input proteomic research in this field is rela-tively underdeveloped because of the higher threshold of the starting material for mammalian embryo samples and the lack of hypersensitive proteome technology.In this study,a comprehensive solution of ultrasensitive proteome technology(CS-UPT)was developed for single-cell or low-input mouse oocyte/embryo samples.The deep coverage and high-throughput routes significantly reduced the starting material and were selected by investigators based on their demands.Using the deep coverage route,we provided the first large-scale snapshot of the very early stage of mouse maternal-to-zygotic transition,including almost 5,500 protein groups from 20 mouse oocytes or zygotes for each sample.Moreover,significant protein regulatory networks centered on transcription factors and kinases between the MII oocyte and 1-cell embryo provided rich insights into minor zygotic genome activation.