ObjectiveTo observe the effect of Yangxin Tongmai Formula （养心通脉方） by midnight-noon ebb-flow administration method for rat models of premature coronary heart disease （PCHD） with blood stasis syndrome， and to explore the possible mechanism of action from the perspective of DNA methylation differential gene expression. MethodsThere were 3 SD rats in each of the blank group， model group and Yangxin Tongmai Formula group， and the rats in the model group and Yangxin Tongmai Formula group were fed with high-fat chow plus vitamin D3 by gavage plus isoproterenol hydrochloride by subcutaneous injection to construct rat models of PCHD with blood stasis syndrome. After successful modelling， rats in Yangxin Tongmai Formula group were gavaged with 18 g/（kg‧d） of Yangxin Tongmai Formula， and rats in blank group and the model group were gavaged with 4 ml/（kg‧d） of 0.9% NaCl solution， and serum samples of rats in each group were collected for DNA methylation sequencing after 3 weeks to screen for the relevant DNA methylation differentiation genes. In addition， rats with successful modelling of PCHD with blood stasis were randomly divided into model group， Yangxin Tongmai Formula with midnight-noon ebb-flow administration method group ［18 g/（kg‧d） of Yangxin Tongmai Formula was gavaged twice in the heart channel period （12：00） and pericardium channel period （20：00）］， the Yangxin Tongmai Formula control group ［18 g/（kg‧d） of Yangxin Tongmai Formula was gavaged twice at 8：00 and 18：00］ and the Atorvastatin Calcium group ［atorvastatin calcium tablets solution 1.8 mg/（kg‧d） at the same intervention time as that in Yangxin Tongmai Formula control group］， and set up a blank group of 8 rats in each group. The model group and blank group were gavaged with 0.9% NaCl solution 4 ml/（kg‧d） for the same time as the Yangxin Tongmai Formula control group. After 3 weeks of gavage， the blood lipids ［including total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）］ levels of rats in each group were detected； the HE staining of myocardial tissues and thoracic aorta was used to observe the pathomorphological changes； the levels of serum inflammation indexes ［tumour necrosis factor alpha （TNF-alpha）， lipopolysaccharide （LPS）， and interleukin 10 （IL-10）］ were detected； immunoprecipitation-realtime fluorescence quantitative PCR was used to detect the relative expression of cardiac tissue screening differential genes. ResultsThe genes screened for differentially methylated regions were calmodulin 2 （Calm2）， calcium voltage-gated channel subunit α1s （Cacna1s）， and phospholipase Cβ1 （Plcb1）. Compared with the blank group， rats in the model group showed elevated levels of TC， LDL， TNF-α and LPS， and decreased levels of HDL and IL-10 （P＜0.05 or P＜0.01）； HE staining showed obvious swelling of myocardial fibres， accompanied by a large number of inflammatory cell infiltration， and thickening of the inner wall of the aortic vessels with internal wall damage， which was visible as a large number of lipid cholesterol crystals and obvious inflammatory cell infiltration. Compared with the model group， the TC， LDL， TNF-α and LPS contents of rats in the Yangxin Tongmai Formula with midnight-noon ebb-flow administration method group， the Yangxin Tongmai Formula control group， and the atorvastatin calcium group all reduced， and the contents of HDL and IL-10 all elevated （P＜0.05）， with the improvement of myocardial tissue damage and the reduction of inflammatory infiltration， and the improvement of the damage of the inner lining of the thoracic aorta and the reduction of lipid infiltration. Compared with Yangxin Tongmai Formula control group， LDL， TNF-α and LPS contents reduced， and IL-10 contents increased in the midnight-noon ebb-flow administration method group （P＜0.05）. Compared with the model group， the relative expression of Calm2 and Plcb1 genes decreased and the relative expression of Cacna1s gene increased in Yangxin Tongmai Formula control group and the midnight-noon ebb-flow administration method group （P＜0.05）； compared with the Yangxin Tongmai Formula control group， the relative expression of Calm2 gene decreased and the relative expression of Cacna1s gene increased in the midnight-noon ebb-flow administration method group （P＜0.05）. ConclusionThe intervention of Yangxin Tongmai Formula in the heart channel period （12：00） and pericardium channel period （20：00） was more effective in improving the blood lipid level， inhibiting inflammation， and improving myocardial tissue damage in rats of PCHD with blood stasis syndrome， and Calm2 and Cacna1s genes may be the key targets of Yangxin Tongmai Formula in intervening the blood stasis syndrome of PCHD.

OBJECTIVE: To compare the effectiveness of single-stage vascularized lymph node transfer (VLNT) combined with lymphaticovenular anastomosis (LVA) and liposuction (LS) (3L) versus LVA combined with LS (2L) for the treatment of moderate-to-late stage upper limb lymphedema following breast cancer surgery. METHODS: A retrospective analysis was conducted on the clinical data of 16 patients with moderate-to-late stage upper limb lymphedema after breast cancer surgery, treated between June 2022 and June 2024, who met the selection criteria. Patients were divided into 3L group (n=7) and 2L group (n=9) based on the surgical approach. There was no significant difference (P>0.05) in baseline data between the groups, including age, body mass index, duration of edema, volume of liposuction, International Society of Lymphology (ISL) stage, preoperative affected limb volume, preoperative circumferences of the affected limb at 12 levels (from 4 cm distal to the wrist to 42 cm proximal to the wrist), preoperative Lymphoedema Quality of Life (LYMQoL) score, and frequency of cellulitis episodes. The 2L group underwent LS on the upper arm and proximal forearm and LVA on the middle and distal forearm. The 3L group received additional VLNT in the axilla, with the groin serving as the donor site. Outcomes were assessed included the change in affected limb volume at 12 months postoperatively, and comparisons of limb circumferences, LYMQoL score, and frequency of cellulitis episodes between preoperative and 12-month postoperative. Ultrasound evaluation was performed at 12 months in the 3L group to assess lymph node viability. RESULTS: Both groups were followed up 12-20 months, with an average of 15.13 months. There was no significant difference in the follow-up time between the groups (t=-1.115, P=0.284). All surgical incisions healed by first intention. No adverse events, such as flap infection or necrosis, occurred in the 3L group. At 12 months after operation, ultrasound confirmed good viability of the transferred lymph nodes in the 3L group. Palpation revealed significant improvement in skin fibrosis and improved skin softness in both groups. Affected limb volume significantly decreased in both groups postoperatively (P<0.05). The reduction in limb volume significantly greater in the 3L group compared to the 2L group (P<0.05). Circumferences at all 12 measured levels significantly decreased in both groups compared to preoperative values (P<0.05). The reduction in circumference at all 12 levels was better in the 3L group than in the 2L group, with significant differences observed at 7 levels (8, 12, 16, 30, 34, 38, and 42 cm) proximal to the wrist (P<0.05). Both groups showed significant improvement in the frequency of cellulitis episodes and LYMQoL scores postoperatively (P<0.05). While the improvement in LYMQoL scores at 12 months did not differ significantly between groups (P>0.05), the reduction in cellulitis episodes was significantly greater in the 3L group compared to the 2L group (P<0.05). CONCLUSION The combination of VLNT+LVA+LS provides more durable and comprehensive outcomes for moderate-to-late stage upper limb lymphedema after breast cancer surgery compared to LVA+LS, offering an improved therapeutic solution for patients.
Humans ; Female ; Lipectomy/methods* ; Retrospective Studies ; Anastomosis, Surgical/methods* ; Lymphedema/etiology* ; Middle Aged ; Upper Extremity/surgery* ; Breast Neoplasms/surgery* ; Lymph Nodes/blood supply* ; Adult ; Lymphatic Vessels/surgery* ; Iliac Artery/surgery* ; Postoperative Complications/surgery* ; Perforator Flap/blood supply* ; Treatment Outcome ; Mastectomy/adverse effects* ; Quality of Life ; Aged

Virus-induced senescence (VIS) is a significant biological phenomenon, which is associated with declining immune function, accelerating aging process and causing aging-related diseases. A variety of common viruses, including RNA viruses (such as SARS-CoV-2), DNA viruses (such as herpesviruses and hepatitis B virus), and prions can cause VIS in host cells. The primary mechanisms include abnormal activation of the cGAS-STING signaling pathway, DNA damage response, and potential correlations with the integrated stress response due to intracellular phase separation. Viral infection and cellular senescence influence each other: cellular senescence serves as a defense to restrict viral replication and transmission, while some viruses exploit cellular senescence to enhance their infectivity and replication. Understanding the mechanisms of VIS is conducive to the development of therapeutic strategies for viral infections and promotion of healthy aging. However, there is lack of research on therapeutic targets and drug development in this field so far. Although senolytics may be effective for anti-senescent cells therapy, their efficacy for VIS needs evidence from further clinical trials. This article reviews the research progress on the connection between viral infection and cellular senescence, to provide insights for the prevention and treatment of aging related diseases.
Humans ; Cellular Senescence/physiology* ; Virus Diseases/physiopathology* ; Signal Transduction ; Nucleotidyltransferases/metabolism* ; DNA Damage ; Virus Replication ; COVID-19 ; Membrane Proteins/metabolism* ; SARS-CoV-2

Objective To observe the protective and anti-inflammatory effects of Emodin and Geniposide compatibility on the intestinal mucosal barrier function damage in rats with systemic inflammatory response syndrome(SIRS).Methods Male Sprague-Dawley(SD)rats aged 6-8 weeks were randomly divided into normal control group,model group,Emodin group,Geniposide group,Emodin and Geniposide compatibility group(compatibility group),and Ulinastatin group.The SIRS model in rats was established by abdominal injection of yeast polysaccharide.The Emodin,Geniposide,Ulinastatin,and compatibility groups received administration immediately and 12 hours after the injection of yeast polysaccharide.After 24 hours of modeling,the contents of D-lactate(D-LA),diamine oxidase(DAO),endotoxin(ET),tumor necrosis factor-α(TNF-α),interleukins(IL-1β,IL-6,IL-10)in the serum of each group were measured;The small intestine was taken for histopathological examination,and the positive protein expression levels of nuclear factor-κB p65(NF-κB p65)and Toll-like receptor 4(TLR-4)in the small intestine tissue were determined by immuno histochemistry.Results Compared with the normal control group,the levels of D-LA,DAO,ET,TNF-α,IL-1β,IL-6 and IL-10 in the serum of the model group were significantly increased[D-LA(μmol/L):99.11±11.93 vs.36.94±1.92,DAO(U/L):5 018.80±759.00 vs.2 253.23±372.40,ET(μg/L):0.36±0.04 vs.0.15±0.02,TNF-α(ng/L):66.61±20.88 vs.9.47±0.78,IL-1β(ng/L):63.73±7.64 vs.25.86±5.90,IL-6(ng/L):392.00±56.47 vs.111.17±36.22,IL-10(ng/L):41.90±8.12 vs.19.75±1.54,all P<0.05],histopathological observations showed that the small intestine mucosa was significantly swollen,the arrangement of mucosal epithelial cells was disordered,and there was cell shedding,increased infiltration of inflammatory cells in the intestinal mucosa,decreased goblet cells,loose and congested lamina propria;the positive protein expression of TLR-4 and NF-κB in the small intestine tissue was enhanced[TLR-4 positive protein expression(A value):0.59±0.08 vs.0.27±0.04,NF-κB positive protein expression(A value):0.65±0.07 vs.0.30±0.06,both P<0.05].Compared with the model group,the levels of D-LA,DAO,and ET in the serum of the Emodin group,Geniposide group,Ulinastatin group,and compatibility group were significantly decreased[D-LA(μmol/L):67.49±8.32,69.08±6.76,69.17±5.63,58.16±7.12 vs.99.11±11.93,DAO(U/L):3 659.38±563.90,3 713.29±354.70,3 575.30±444.4,3 087.01±227.50 vs.5 018.80±759.0,ET(μg/L):0.27±0.04,0.24±0.03,0.23±0.03,0.20±0.02 vs.0.36±0.04,all P<0.05],and the contents of pro-inflammatory factors TNF-α,IL-1β,and IL-6 were significantly decreased[TNF-α(ng/L):44.34±10.63,39.23±11.74,35.80±11.49,28.74±9.56 vs.66.61±20.88,IL-1β(ng/L):50.30±8.22,46.74±5.10,48.25±5.16,40.84±5.02 vs.63.73±7.64,IL-6(ng/L):299.27±50.65,263.98±37.62,281.84±63.24,216.72±38.90 vs.392.00±56.47,all P<0.05].The levels of serum anti-inflammatory factor IL-10 were significantly increased(ng/L:92.63±32.83,87.34±30.79,71.66±16.82,133.70±39.40 vs.41.90±8.12,all P<0.05).The pathological changes in the intestinal tissue of the Emodin group,Geniposide group,compatibility group,and Ulinastatin group were reduced,and the positive expressions of NF-κB p65 and TLR-4 proteins in the small intestine tissue were significantly decreased[TLR-4 positive protein expression(A value):0.49±0.03,0.47±0.08,0.36±0.08,0.42±0.06 vs.0.59±0.08,NF-κB p65 positive protein expression(A value):0.50±0.06,0.49±0.07,0.42±0.06,0.46±0.09 vs.0.65±0.07,all P<0.05].Compared with the Emodin group and Geniposide group,the serum D-LA,DAO,ET,TNF-α,IL-1β,and IL-6 in the compatibility group were significantly decreased,the serum IL-10 level was significantly increased,the pathological changes in the intestinal tissue were reduced,and the expression levels of NF-κB p65 and TLR-4 in the small intestine tissue were significantly decreased(all P<0.05).Conclusions Emodin and Geniposide can help relieve SIRS induced by yeast polysaccharide,and their effect is related to protecting the intestinal mucosal barrier and inhibiting the inflammatory response.When combined,they exhibit a synergistic effect.

Humans ; Autistic Disorder ; China/epidemiology* ; Cohort Studies ; Autism Spectrum Disorder/genetics* ; Asian People

Objective:To analyze clinical phenotypes and pathogenic mutations of a patient with classic tuberous sclerosis complex.Methods:Clinical data was collected from a patient with classic tuberous sclerosis complex. Next-generation sequencing was performed to screen pathogenic gene variants, and Sanger sequencing to verify the mutations. Minigene plasmids were constructed and transfected into the human renal epithelial cell line 293T, and RNA was extracted for transcriptional analysis.Results:The patient clinically presented with recurrent epileptic seizures, facial angiofibroma, periungual fibroma, pulmonary lymphangioleiomyomatosis, renal angiomyolipoma and multiple osteosclerosis. Next-generation sequencing revealed a suspected pathogenic variant in the TSC2 gene in the patient. Sanger sequencing identified a heterozygous mutation c.336_336+15delGGTAAGGCCCAGGGCG in exon 4 of the TSC2 gene in the patient, but not in his parents or 100 unrelated healthy controls. Moreover, this mutation had not been previously reported. The minigene experiment showed changed mRNA sequence of the TSC2 gene in this patient with loss of the authentic splice site in exon 4 and insertion of a 74-bp intron, which shifted the splice site 90 bp downstream (r.336delins336+16_336+90) .Conclusion:The novel heterozygous mutation c.336_336+15delGGTAAGGCCCAGGGCG in exon 4 of the TSC2 gene can lead to aberrant splicing, and may contribute to tuberous sclerosis complex in this patient.

Objective:To investigate the clinical effect of the anterolateral thigh perforator chimeric flap in the treatment of the wound of diabetic foot ulcer (DFU) .Methods:From January, 2018 to December, 2019, 14 cases wound of DFU of type II diabetic were treated by anterolateral thigh chimeric perforator flap. The patients were 10 males and 4 females, at 49 to 58 years old. Of the 14 patients, 10 with simple peripheral neuropathy, 4 with peripheral neuropathy complicated with vascular disease, and none with single vascular disease. With strict control of patients' blood glucose, antibiotics blended bone cement was applied or filled onto grade 2 or higher grade Wagner's DFU after debridement. In addition, the anterolateral thigh chimeric perforator flap was transferred 2 to 3 weeks later. The size of flap was 8 cm×3 cm-27 cm×7 cm. Regular followed-up were made after surgery.Results:Thirteen flaps survived in one stage after surgery. The other 1 flap had venous vascular crisis, and survived completely after active exploration. The patients were followed-up for 6-12 months. All the flaps survived well in good shape and texture. The donor and recipient areas healed well. The functional recoveries of the DF were satisfactory.Conclusion:Application of anterolateral thigh perforator chimeric flap in repair of the refractory wound of DF achieves a good clinical outcome and effectively improves the life quality of patients.

Objective    To analyze the results and diagnostic value of postoperative chylous test of pleural effusion and to verify the clinicopathological factors affecting the results of chylous test. Methods    The clinical data of 265 consecutive patients undergoing selective surgery at the Department of Thoracic Surgery, Shangjin Nanfu Hospital between May and August 2020 were retrospectively analyzed, including 106 males and 159 females with an average age of 53.0±12.2 years. According to the results of the chylous test on the operation day and postoperative first and second days, the patients were divided into two subgroups, including a positive group and a negative group, and the clinical data of the two groups were compared. Sensitivity and specificity of the chylous test were calculated. The influencing factors for chylous test were analyzed by multiple logistic regression analysis. Results    The positive rate of chylous test was 91.7%, 95.8% and 87.9% on the operation day and postoperative first and second days, respectively. There was no statistical difference in age, sex, surgical type, surgical approach, surgical site, surgical time, degree of lymph node dissection, treatment of thoracic duct, 24 hours pleural fluid drainage or 24 hours protein and fat food intake between the positive group and the negative group (P>0.05). The diagnostic sensitivity and specificity of the chylous experiment were 100.0%and 4.0%, respectively. Multiple logistic regression analysis showed that the surgical site (left/right chest) might be an influencing factor for the results of the chylous test (P=0.043, OR=0.458, 95%CI 0.216-0.974). Conclusion    The positive rate of chylous test of pleural effusion after thoracic surgery is very high. The chylous test produces a high misdiagnosis rate of chylothorax. The surgical site (left/right chest) may be an influencing factor for chylous test. The positive result of chylous test is not recommended as the direct diagnostic basis for postoperative chylothorax and guidance of the subsequent treatment.

Objective To analyze histopathological and clinical features of dermatofibroma,and to explore the relationship between them.Methods Clinical and histopathological data were collected from 150 patients with histopathologically confirmed dermatofibroma in Department of Pathology,Shanghai Skin Disease Hospital from September 2017 to August 2018,and analyzed retrospectively.Results Among the 150 patients,65 were males,and 85 were females.Their age was 42 ± 13.8 years,and the course of disease ranged from 3 months to 30 years.Some of the patients had concomitant symptoms,mainly manifesting as itching,some had spontaneous pain and mild tenderness,and 18 patients had a history of injury,insect bite or infection at lesion sites.Skin lesions mainly occurred on the extremities (107 cases,71.3％),and most were solitary (105 cases,70％).Before pathological examinations,102 cases were clinically diagnosed as dermatofibroma,16 as epidermoid cyst,13 as pigmented nevus,3 as keloid,12 as skin mass,1 as malignant melanoma,1 as xanthogranuloma,1 as prurigo nodularis,and 1 as neurofibroma.Among 169 hematoxylin and eosin (HE)-stained sections,25 (14.8％) appeared to be consistent with aneurysmal dermatofibroma,66 (39.1％)with cellular dermatofibroma,36 (21.3％) with sclerosing dermatofibroma,and 22 (13.0％)with epithelioid dermatofibroma.Coexistence of two or more subtypes could be seen in 12 sections.There were also a few new variants,such as dermatofibroma with hyperplastic sweat duct (1 case),deep dermatofibroma (3 cases),dermatofibroma with epithelioid cells intermingled with hyperplastic collagen (1 case).The duration of aneurysmal dermatofibroma varied from 7 months to 30 years,and most manifested as skin masses on the lower extremities.A relatively short course of disease was observed in patients with cellular dermatofibroma,who often visited a hospital several months after the onset,and cellular dermatofibroma was commonly observed on the extremities and frequently accompanied with itching and pain.The duration of sclerosing or atrophic dermatofibroma was usually long for years or decades,and it commonly occurred on the upper limbs without concomitant symptoms.Epithelioid dermatofibroma of varied durations had various clinical manifestations,frequently occurred on the lower limbs without concomitant symptoms.Conclusions The clinical and pathological manifestations of dermatofibroma are diverse.Different dermatofibroma lesions can share similar typical histopathological manifestations,and atypical pathological features can interfere with the diagnosis of dermatofibroma.

Oxidative stress and cardiomyocyte apoptosis are involved in the pathogenesis of doxorubicin (DOX)-induced cardiotoxicity. Matrine is well-known for its powerful anti-oxidant and anti-apoptotic capacities. Our present study aimed to investigate the effect of matrine on DOX-induced cardiotoxicity and try to unearth the underlying mechanisms. Mice were exposed with DOX to generate DOX-induced cardiotoxicity or normal saline as control. H9C2 cells were used to verify the effect of matrine . DOX injection triggered increased generation of reactive oxygen species (ROS) and excessive cardiomyocyte apoptosis, which were significantly mitigated by matrine. Mechanistically, we found that matrine ameliorated DOX-induced uncoupling protein 2 (UCP2) downregulation, and UCP2 inhibition by genipin could blunt the protective effect of matrine on DOX-induced oxidative stress and cardiomyocyte apoptosis. Besides, 5'-AMP-activated protein kinase 2 () deficiency inhibited matrine-mediated UCP2 preservation and abolished the beneficial effect of matrine in mice. Besides, we observed that matrine incubation alleviated DOX-induced H9C2 cells apoptosis and oxidative stress level activating AMPK/UCP2, which were blunted by either AMPK or UCP2 inhibition with genetic or pharmacological methods. Matrine attenuated oxidative stress and cardiomyocyte apoptosis in DOX-induced cardiotoxicity maintaining AMPK/UCP2 pathway, and it might be a promising therapeutic agent for the treatment of DOX-induced cardiotoxicity.