ObjectiveTo explore the target of Erzhiwan in reducing myocardial injury in ovariectomized mice through non-targeted myocardial metabolomics combined with experimental verification. MethodsOvariectomized mouse model was selected， 40 female C57BL/6 mice were randomly divided into sham operation group， model group， estrogen group（estradiol valerate， 1.3×10^-4 g·kg^-1）， Erzhiwan low and high dose groups（3.12， 9.36 g·kg^-1）， with 8 mice in each group. Each administration group was given the corresponding dose of Erzhiwan by gavage， and the sham operation group and model group were given equal volume of distilled water by gavage for 12 weeks. Echocardiography was used to detect cardiac function， hematoxylin-eosin（HE） staining was used to observe myocardial morphological changes， and enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of estrogen， N-terminal pro-brain natriuretic peptide（NT-proBNP）， hypersensitive troponin T（hs-TnT）， total cholesterol（TC）， triglyceride（TG）， low density lipoprotein cholesterol（LDL-C）， high density lipoprotein cholesterol（HDL-C）， interleukin（IL）-1β， IL-18 and tumor necrosis factor-α（TNF-α）. The non-targeted metabolomics of mouse myocardium were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）， and the differential metabolites and corresponding metabolic pathways were obtained. The mRNA expression levels of phosphatidylinositol 3-kinase（PI3K） and protein kinase B（Akt） in mouse myocardial tissues were detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the protein expression levels of PI3K， Akt， phosphorylated（p）-Akt were detected by Western blot. ResultsCompared with the sham operation group， the model group showed abnormal cardiac function， increased myocardial fiber space， cardiomyocyte atrophy， sarcoplasmic aggregation， and occasional dissolution or rupture of muscle fiber， the level of estrogen in the serum was decreased， the levels of NT-proBNP， hs-TnT， IL-1β， IL-18， TNF-α， TG， TC and LDL-C were increased， and the level of HDL-C was decreased（P<0.01）. Compared with the model group， Erzhiwan could increase the level of estrogen， improve the abnormal cardiac function， reduce the pathological injury of myocardial tissue， decrease the levels of myocardial injury markers（NT-proBNP， hs-TnT） and inflammatory factors（IL-1β， IL-18， TNF-α）， decrease the levels of TG， TC， LDL-C， and increased the level of HDL-C（P<0.01）. The results of non-targeted myocardial metabolomics showed that 31 of the 162 differential metabolites between the model group and sham operation group were significantly adjusted after administration of Erzhiwan， which were mainly glycerol phospholipid metabolites. Pathway enrichment results showed that Erzhiwan mainly affected glycerophospholipid metabolic pathway， PI3K-Akt pathway， cyclic guanosine monophosphate（cGMP）-protein kinase G（PKG） pathway and other metabolic pathways. Compared with the sham operation group， the levels of phosphatidylcholine（PC， 11 types） and phosphatidylethanolamine（PE， 5 types） in mouse myocardial tissue of the model group were increased（P<0.05， P<0.01）， and the mRNA and protein expressions of PI3K and p-Akt were decreased（P<0.05， P<0.01）. Compared with the model group， the levels of PC（11 types） and PE（5 types） were decreased（P<0.05， P<0.01） in myocardial tissue of Erzhiwan group， the mRNA and protein expressions of PI3K and p-Akt were elevated（P<0.01）. ConclusionErzhiwan can alleviate the pathological injury of myocardium in ovariectomized mice， improve the abnormal cardiac function， improve lipid metabolism disorder， and reduce the levels of myocardial injury markers and inflammatory factors， which involves a number of signaling and metabolic pathways in the heart， among which glycerophospholipid metabolism pathway and PI3K/Akt pathway may have key roles.

BACKGROUND: Approximately 40% of individuals with diabetes worldwide are at risk of developing diabetic kidney disease (DKD), which is not only the leading cause of kidney failure, but also significantly increases the risk of cardiovascular disease, causing significant societal health and financial burdens. This study aimed to describe the burden of DKD and explore its cross-country epidemiological status, predict development trends, and assess its risk factors and sociodemographic transitions. METHODS: Based on the Global Burden of Diseases (GBD) Study 2021, data on DKD due to type 1 diabetes (DKD-T1DM) and type 2 diabetes (DKD-T2DM) were analyzed by sex, age, year, and location. Numbers and age-standardized rates were used to compare the disease burden between DKD-T1DM and DKD-T2DM among locations. Decomposition analysis was used to assess the potential drivers. Locally weighted scatter plot smoothing and Frontier analysis were used to estimate sociodemographic transitions of DKD disability-adjusted life years (DALYs). RESULTS: The DALYs due to DKD increased markedly from 1990 to 2021, with a 74.0% (from 2,227,518 to 3,875,628) and 173.6% (from 4,122,919 to 11,278,935) increase for DKD-T1DM and DKD-T2DM, respectively. In 2030, the estimated DALYs for DKD-T1DM surpassed 4.4 million, with that of DKD-T2DM exceeding 14.6 million. Notably, middle-sociodemographic index (SDI) quintile was responsible for the most significant DALYs. Decomposition analysis revealed that population growth and aging were major drivers for the increased DKD DALYs in most regions. Interestingly, the most pronounced effect of positive DALYs change from 1990 to 2021 was presented in high-SDI quintile, while in low-SDI quintile, DALYs for DKD-T1DM and DKD-T2DM presented a decreasing trend over the past years. Frontiers analysis revealed that there was a negative association between SDI quintiles and age-standardized DALY rates (ASDRs) in DKD-T1DM and DKD-T2DM. Countries with middle-SDI shouldered disproportionately high DKD burden. Kidney dysfunction (nearly 100.0% for DKD-T1DM and DKD-T2DM), high fasting plasma glucose (70.8% for DKD-T1DM and 87.4% for DKD-T2DM), and non-optimal temperatures (low and high, 5.0% for DKD-T1DM and 5.1% for DKD-T2DM) were common risk factors for age-standardized DALYs in T1DM-DKD and T2DM-DKD. There were other specific risk factors for DKD-T2DM such as high body mass index (38.2%), high systolic blood pressure (10.2%), dietary risks (17.8%), low physical activity (6.2%), lead exposure (1.2%), and other environmental risks. CONCLUSIONS DKD markedly increased and varied significantly across regions, contributing to a substantial disease burden, especially in middle-SDI countries. The rise in DKD is primarily driven by population growth, aging, and key risk factors such as high fasting plasma glucose and kidney dysfunction, with projections suggesting continued escalation of the burden by 2030.
Humans ; Global Burden of Disease ; Risk Factors ; Male ; Female ; Disability-Adjusted Life Years ; Diabetic Nephropathies/epidemiology* ; Middle Aged ; Diabetes Mellitus, Type 2/epidemiology* ; Adult ; Diabetes Mellitus, Type 1/complications* ; Aged ; Adolescent ; Young Adult ; Quality-Adjusted Life Years

OBJECTIVE: To explore the effectiveness of primary interventional revascularization combined with secondary perforator composite flap in the treatment of peripheral arterial disease (PAD) accompanied by soft tissue defects around the ankle. METHODS: Between January 2022 and January 2025, 12 patients with PAD and soft tissue defects around the ankle were admitted. Among them, there were 9 males and 3 females; their ages ranged from 52 to 82 years, with an average of 68.9 years. The causes of injury included 4 cases of traffic accident, 5 cases of falls, 1 case of falling from height, 1 case of foreign body puncture injury, and 1 case of electric shock injury. The infection duration ranged from 1 month to 35 years, with a median duration of 3.5 months. The wound size ranged from 5.5 cm×3.0 cm to 15.0 cm×9.0 cm. The ankle-brachial index (ABI) was 0.32±0.12. The visual analogue scale (VAS) score for pain was 3.3±0.5. Preoperative vascular stenosis assessment was performed in all patients, with primary intervention to dredge large and medium-sized arteries, followed by secondary repair of the wound using a perforator composite flap. The flap size ranged from 6.5 cm×4.0 cm to 16.0 cm×10.0 cm. The donor sites were sutured directly or repaired with skin grafts. After two stages of treatment, the effectiveness was evaluated by measuring ABI, observing flap survival and wound healing, assessing VAS scores, and American Orthopedic Foot and Ankle Society (AOFAS) scores. RESULTS: All 12 cases completed two stages of treatment; all patients were followed up after the second-stage treatment, with a follow-up period ranging from 7 to 28 months, with an average of 16.8 months. After the first-stage treatment, the skin temperature around the ankle was significantly higher than that before treatment, and the ABI increased to 0.71±0.07, with a significant difference ( t=9.918, P<0.001). After the second-stage treatment, the blisters on the distal end of the skin flap occurred in 3 cases. The flaps survived and the wounds healed, with a healing time ranging from 10 to 14 days (mean, 11.8 days). The incisions at the donor site healed by first intention, and the skin grafts survived. The VAS score was 0.5±0.5 at 3 weeks, which was significantly lower than that before treatment ( t=13.675, P<0.001). No infection recurrence occurred during follow-up. At 6 months after the second-stage treatment, the AOFAS score of the ankle joint ranged from 92 to 97, with an average of 94.7, all reaching excellent. CONCLUSION Interventional revascularization combined with perforator composite flap for staged treatment of PAD with ankle soft tissue defects can obtain good effectiveness, by unclogging the main blood vessels, improving lower limb blood supply, and improving the survival rate of the skin flap.
Humans ; Male ; Female ; Middle Aged ; Aged ; Peripheral Arterial Disease/surgery* ; Soft Tissue Injuries/surgery* ; Perforator Flap/blood supply* ; Plastic Surgery Procedures/methods* ; Aged, 80 and over ; Ankle/blood supply* ; Treatment Outcome ; Ankle Brachial Index ; Skin Transplantation/methods*

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Objective To evaluate the efficacy and safety of modified pelvic floor reconstruction in non-nerve-sparing robot-assisted radical prostatectomy (NNS RARP) for improving postoperative urinary control. Methods A retrospective analysis was conducted on the clinical data of 79 prostate cancer patients who underwent NNS RARP at Tangdu Hospital during Jan.2020 and Dec.2023, including 29 in the reconstruction group, and 50 in the non-reconstruction group. The baseline characteristics including age, body mass index, prostate-specific antigen (PSA) level, clinical stage, prostate volume, and biopsy Gleason score, and perioperative indexes including operation time, intraoperative blood loss, catheter indwelling time, complication rate, and positive rate of surgical margins were compared between the two groups. Additionally, urinary continence function was assessed before operation and 1,3,6, and 12 months after operation using the international consultation on incontinence questionnaire-short form (ICIQ-SF) and the incontinence quality of life questionnaire score (I-QoL). Results No statistically significant differences were observed in the baseline characteristics between the two groups (P>0.05). The operation time was significantly longer in the reconstruction group than in the non-reconstruction group [ (110.24±15.08) min vs. (101.80±9.89) min, P=0.010]. There were no significant differences in intraoperative blood loss, catheter indwelling time, complication rate, and positive rate of surgical margins between the two groups (P>0.05). The reconstruction group demonstrated significantly lower ICIQ-SF scores at 1 month [ (10.17±2.16) vs. (11.56±1.66), P=0.002],3 months [ (7.62±1.29) vs. (9.52±1.80), P<0.001], and 6 months postoperatively [ (4.93±1.22) vs. (6.18± 1.67), P=0.001]compared to the non-reconstruction group (adjusted P<0.0125). Conversely, the I-QoL scores were significantly higher in the reconstruction group at 1 month [ (73.32±10.30) vs. (63.88±9.55), P<0.001]and 3 months postoperatively [ (78.91±4.82) vs. (75.66±5.17), P=0.007] (adjusted P<0.0125). However, no significant differences were found in ICIQ-SF or I-QoL scores between the two groups preoperatively and 12 months postoperatively (adjusted P>0.0125). Conclusion The application of modified pelvic floor reconstruction technique in NNS RARP is safe and feasible. Although it slightly prolongs the operation time, it does not increase surgical risks; instead, it effectively promotes early recovery of postoperative urinary continence, thereby significantly enhancing patients'quality of life.

Objective: To analyze the results of national external quality assessment (EQA) for transfusion compatibility test from 2018 to 2023, with the aim of providing references for improving laboratory testing quality and ensuring the safety of clinical blood transfusion. Methods: Three EQA programs were conducted annually, each distributing 22 quality assessment samples. Participating transfusion laboratories were required to complete testing within specified deadlines and to submit results along with documentation of testing methodologies, reagents, and equipment used. National Center for Clinical Laboratories (NCCL) conducted statistical analysis of laboratory results, evaluated testing outcomes and related circumstances, and provided feedback to participating laboratories. EQA data from transfusion laboratories across China from 2018 to 2023 were collected and systematically analyzed. Results: From 2018 to 2023, the qualification rates for all five items (ABO forward typing, ABO reverse typing, Rh blood group typing, antibody screening, and cross-matching) were 67.59%, 77.11%, 77.38%, 72.78%, 79.96%, and 85.16%, respectively. The mean qualification rates for ABO forward typing, ABO reverse typing, RhD blood group typing, antibody screening, and cross-matching over the past six years were 96.25%±0.59%, 90.45%±4.52%, 96.05%±0.71%, 90.88%±2.86%, and 88.34%±3.48%, respectively. The qualification rates in 2019, 2020, 2022, and 2023 all showed a stable trend of "blood stations>tertiary hospitals>secondary hospitals". The mean qualification rate of laboratories in secondary hospitals from 2018 to 2023 was significantly lower than those of laboratories in tertiary hospitals and blood stations (P<0.05), while no significant difference was observed between laboratories in tertiary hospitals and blood stations (P>0.05). The micro column agglutination method was the most widely used in all five tests. In the four test items, namely ABO forward typing, ABO reverse typing, antibody screening, and cross-matching, there was a statistically significant difference in the qualification rate of micro column agglutination method compared to other methods (P<0.05). There was a statistical difference in the qualification rate between manual and automated detection using micro column agglutination method in the cross-matching tests (P<0.05), whereas no significant difference was noted for the other test items (P>0.05). Conclusion: From 2018 to 2023, the number of laboratories participating in EQA activities has been increasing year by year, and the qualification rate has shown an overall upward trend. The type of laboratory is a key factor affecting the qualification rate, and the testing capabilities of some laboratories still need to be improved. The micro column agglutination method is widely used in transfusion compatibility tests. The established EQA program effectively monitors quality issues in laboratories, drives continuous improvement, and ensures sustained enhancement of testing standards to safeguard clinical blood safety.

Objective To investigate the effect of esketamine on depression and improvement of postoperative cognitive function in patients with major depressive disorder treated by electroconvulsive therapy(ECT).Methods A total of 115 patients with major depressive disorder,37 males and 78 fe-males,aged≥12 years,BMI 18-30 kg/m2,ASA physical status Ⅰ or Ⅱ were selected to receive ECT.The patients were randomly divided into two groups using a random number table:the esketamine group(group E,n=56)and the control group(group C,n=59).Group E received esketamine,propofol,and succincholine during anesthesia induction,and group C received propofol and succincholine during an-esthesia induction.ECT indicators(including EEG twitch time,twitch time,stimulus intensity,and twitch energy index)were recorded during each ECT session.Montreal cognitive assessment(MoCA)and Mini-mental state examination(MMSE)were used to evaluate cognitive function at baseline and after ECT treat-ment.Hamilton depression(HAMD)scale was used to score depression.The occurrence of headache,nau-sea,vomiting,dizziness,delirium,and other adverse reactions were recorded.Results Compared with group C,the EEG convulsion time in group E was significantly prolonged(P＜0.05),the incidence of Mo-CA score decreased by≥1 point and MMSE score decreased by≥1 point in group E after the end of ECT treatment was significantly reduced(P＜0.05),the incidence of nausea,vomiting,and dizziness were sig-nificantly decreased(P＜0.05).Conclusion Using esketamine in ECT for the treatment of major depres-sive disorder can improve cognitive function after ECT.

Objective:To evaluate the clinical efficacy of Professor Ding Zhiguo's internal and external combined treatment of Hashimoto's disease, and to explore its mechanism.Methods:Prospective cohort study. A total of 85 patients of professor Ding Zhiguo from Sun Simmiao Hospital of Beijing University of Chinese Medicine and Dongzhimen Hospital of Beijing University of Chinese Medicine from August 2022 to March 2023 were selected and divided into control group (43 cases) and drug group (42 cases) by random number table method. Another 20 healthy volunteers were recruited for health control observation. The control group was given iodine restricted diet, the drug group was treated with Qinggan Sanjie Xiaoying Prescription combined with Liqi Sanjie Xiaoying Ointment, and the healthy control group was not treated with any intervention. Both drug group and control group were observed continuously for 4 weeks. TCM syndrome scores were performed before and after treatment. Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) were used to assess the degree of anxiety and depression, Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality, and fatigue severity Scale (FSS) was used to assess the degree of fatigue. Lower limb lymphedema self-sensory symptoms assessment questionnaire was used to evaluate the symptoms of lower limb lymphedema. The serum levels of thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) were measured by automatic electrochemiluminescence immunoassay, and the reduction rate was calculated. The levels of serum Akt, ERK and protein kinase C (PKC) were detected by ELISA. The thyroid volume was calculated and the anterior and posterior diameter of the isthmus was recorded. The clinical efficacy and safety were evaluated.Results:The total effective rate was 71.43% (30/42) in the drug group and 27.91% (12/43) in the control group, with statistical significance ( χ2=16.10, P<0.01). The serum TPOAb [137.95 (141.44) IU/ml vs. 153.40 (154.93) IU/ml, Z=-4.37] and TGAb [182.00 (238.52) IU/ml vs. 190.50 (257.55) IU/ml, Z=-2.13] levels in the drug group were lower after treatment ( P<0.01 or P<0.05), and the decrease rate of TPOAb [15.62 (21.90)% vs. -6.42 (32.89)%, Z=-4.12] and TGAb [5.25 (20.49)% vs. -0.72 (17.67)%, Z=-2.67] were higher than that in the control group ( P<0.01). The thyroid volume [11.37 (6.48) cm 3vs. 12.89 (6.63) cm 3, Z=-2.95] and isthmus thickness [0.27 (0.14) cm vs. 0.28 (0.15) cm, Z=-2.18] in the drug group were reduced after treatment compared with that before treatment ( P<0.05). TCM syndrome scores (6.10±1.38 vs. 14.42±7.35, t=-7.29), HAMA (5.21±1.32 vs. 9.28±2.25, Z=-7.02), HAMD (8.28±3.17 vs. 10.42±5.28, t=-2.26), PSQI (6.00±2.16 vs. 9.47±3.08, t=-6.01), FSS (34.71±5.51 vs. 38.23±8.35, t=-2.30), lower limb lymphedema self-induced symptom evaluation questionnaire scores (4.95±2.56 vs. 7.86±3.07, t=-4.74) after treatment were lower than before treatment and lower than control group ( P<0.001 or P<0.05).The serum levels of Akt [52.28 (17.72) μmol/L vs. 44.38 (2.75) μmol/L],ERK [2 843.43 (607.90) ng/L vs. 2 648.25 (290.74) ng/L],PKC [8.87 (3.10) pmol/L vs. 7.88 (1.25) pmol/L] in drug group were higher than those in the healthy control group before treatment ( P<0.05), the levels of Akt [37.37 (7.90) μmol/L vs. 44.38 (2.75) μmol/L], ERK [2 432.74 (402.56) ng/L vs. 2 648.25 (290.74) ng/L] in drug group were lower than those in the healthy group after treatment ( P<0.05). After treatment, the levels of Akt [37.37 (7.90) μmol/L vs. 52.28 (17.72) μmol/L, 49.56 (9.12) μmol/L], ERK [2 432.74 (402.56) ng/L vs. 2 843.43 (607.90) ng/L, 3 021.76 (360.22) ng/L], PKC [7.37 (1.84) pmol/L vs. 8.87 (3.10) pmol/L, 10.00 (2.42) pmol/L] in drug group were lower than before treatment and lower than control group ( P<0.01). There were no adverse events during treatment in both groups. Conclusion:The internal and external treatment of Hashimoto's disease by Professor Ding Zhiguo can effectively reduce the level of thyroid antibody titer, reduce the thyroid swelling and isthmus thickness, improve the clinical symptoms of patients with Hashimoto's disease, and may play a therapeutic role by interfering with MAPK signaling pathway.

OBJECTIVE To systematically evaluate the effects of C3435T polymorphism in ABCB1 gene on lipid-lowering efficacy of statins. METHODS Retrieved from PubMed， Web of Science， the Cochrane Library， CNKI and VIP， the cohort studies on the use of statins were collected from the inception to November 1， 2023. After literature screening， data extraction and quality evaluation， meta-analysis was performed by using RevMan 5.4 software. RESULTS A total of 11 literature involving 1 575 patients were included. The results showed that under the dominant genetic model， the reduction of low-density lipoprotein cholesterol （LDL-C） [MD＝－1.87， 95%CI （－3.62， －0.13）， P＝0.04]， total cholesterol （TC） [MD＝－1.42， 95%CI （－2.80， －0.04）， P＝0.04] in patients with CT+TT genotype was significantly higher than CC genotype. There was no significant difference in the increase of high-density lipoprotein cholesterol （HDL-C） [MD＝－0.65， 95%CI （－2.48， 1.18）， P＝0.49] or the decrease of triglyceride （TG） [MD＝－0.05， 95%CI （－2.94， 2.84）， P＝0.97] between patients with CT+TT genotype and CC genotype. Under the recessive genetic model， the reduction of TC [MD＝2.26， 95%CI （0.97， 3.56）， P＝0.000 6] and the increase of HDL-C [MD＝2.38， 95%CI （0.42， 4.35）， P＝0.02] in patients with TT genotype were significantly higher than CC+ CT genotype. There was no significant difference in the reduction of LDL-C [MD＝1.53， 95%CI （－0.10， 3.15）， P＝0.07] or TG [MD＝0.06， 95%CI （－2.98， 3.10）， P＝0.97] between CC+CT genotype and TT genotype. Under the additive genetic model， the reduction of TC [MD＝2.98， 95%CI （1.27， 4.69）， P＝0.000 6] and LDL-C [MD＝2.84， 95%CI （0.67， 5.01）， P＝0.01] in patients with TT genotype were significantly higher than CC genotype. There was no significant difference in the increase of HDL-C [MD＝2.40， 95%CI （－0.17， 4.97）， P＝0.07] or the decrease of TG [MD＝0.97， 95%CI 　　 （－2.93， 4.87）， P＝0.63] between patients with TT genotype and CC genotype. CONCLUSIONS The reduction of LDL-C and TC in patients with dyslipidemia treated with statins may be related to the heterozygous and homozygous mutation of C3435T in ABCB1 gene， and the reduction of LDL-C and TC in patients with CT or TT genotype is more obvious， compared with patients with CC genotype. The elevation of HDL-C may be related to homozygous mutation， and the effect of HDL-C elevation may be more obvious in patients with TT genotype， compared with CC+CT genotype. However， the change of TG may not be related to the C3435T polymorphism in ABCB1 gene.