ObjectiveTo observe the efficacy of Huoxue Jiedu Formulas （活血解毒方药， HJF） as an adjunctive treatement for patients with binding of stasis and toxin syndrome during the vulnerable period after acute myocardial infarction （AMI） percutaneous coronary intervention （PCI） surgery， and to explore its potential mechanism from the perspective of serum neutrophil extracellular traps （NETs）. MethodsA total of 129 patients with binding of stasis and toxin syndrome within 6 months after PCI for AMI were enrolled and divided into a treatment group （65 cases） and a control group （64 cases） based on patients' willingness to take Chinese herbal medicine. The control group received standard western medical therapy alone， while the treatment group additionally received HJF， one dose daily. Both groups were treated for four weeks. Before and after treatment， TCM syndrome scores were assessed. Seattle angina questionnaire （SAQ） was used to record angina stability and frequency scores， while the short form-36 health survey （SF-36） was employed to assess quality of life across eight dimensions， including physical functioning， role-physical， bodily pain， general health， vitality， social functioning， role-emotional， and mental health. The Pittsburgh sleep quality index （PSQI） was used to evaluate sleep quality， and the patient health questionnaire-15 （PHQ-15） was used to assess psychosomatic symptoms； Duke activity status index （DASI） was used to measure daily physical activity. Serum levels of neutrophil extracellular traps （NET） markers including myeloperoxidase-DNA （MPO-DNA）， neutrophil elastase-DNA （NE-DNA）， and citrullinated histone H3 （CitH3） were measured in 20 patients from the treatment group. ResultsAfter treatment， TCM syndrome score， PSQI score and PHQ-15 score in both groups significantly decreased， while DASI score， angina stability and frequency scores， and all eight dimensions of the SF-36 scale significantly increased （P＜0.05）. Compared to the control group， the treatment group had significantly lower TCM syndrome scores and significantly higher DASI， angina stability and frequency scores （P＜0.05）， as well as higher scores in the SF-36 dimensions of physical functioning， role-physical， social functioning， bodily pain， and vitality （P＜0.05）. After treatment， serum levels of MPO-DNA， CitH3， and NE-DNA in the treatment group were significantly reduced （P＜0.05）. ConclusionHJF combined with conventional therapy can significantly improve angina symptoms， TCM syndrome scores， and psychosomatic conditions in patients with binding of stasis and toxin syndrome during the vulnerable period after AMI. It also enhances quality of life， sleep quality， and daily physical activity. The underlying mechanism may be associated with the inhibition of serum NETs level.

Objective:To evaluate the short-term outcomes of all-inside endoscopic running locked stitch technique for acute Achilles tendon ruptures.Methods:This is a retrospective case series study. Forty-eight cases with acute Achilles tendon rupture were treated with the all-inside endoscopic running locked stitch technique from April 2020 to March 2022 at Department of Orthopaedics, General Hospital of Central Theater Command. There were 44 males and 4 females, aged (34.8±7.4) years (range: 24 to 50 years). Body mass index was (21.2±2.4)kg/m 2 (range: 18 to 26 kg/m 2); There were 29 cases (60.4%) on the left side and 19 cases (39.6%) on the right side. Under endoscopic control, the proximal tendon stumps were stitched with the running locked method using a semi-automatic flexible suture passer. The threads of the high-strength suture were grasped through the paratenon sub-space and then fixed into calcaneal insertion with a knotless anchor. MRI of Achilles tendon was performed to observe the regeneration of Achilles tendon during follow-up. Surgical time and complications were assessed. Achilles tendon total rupture score (ATRS), Achilles tendon resting angle, and heel rise height were utilized to evaluate final clinical outcomes. The differences of bilateral limbs were compared using the paired sample t test. Results:The follow-up time was (24.1±3.5)months (range:18 to 32 months). Appropriate tendon regeneration was observed on MRI at 12 months after operation. The median ATRS score ( M(IQR)) was 95.0 (4.7) points. Furthermore, there was no significant difference between the injured and contralateral side in the Achilles tendon resting angle ((17.1±2.4)° vs. (17.4±2.6)°, t=1.92, P=0.062) and heel rise height ((14.2±1.7)cm vs. (14.4±1.5)cm, t=1.71, P=0.094). No nerve injury, infection, deep vein thrombosis and re-rupture was encountered. Sports activity resumed six months postoperative in 46 patients. One patient had a slight anchor cut-out, due to an addition injury, which was removed after 5 months. Conclusions:All-inside endoscopic running locked stitch technique for acute Achilles tendon ruptures shows promising results. It provides stable connection of the tendon stumps with a low risk of complications.

Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Objective:To explore the genetic etiology of a child with primary hypertrophic osteoarthropathy(PHO).Methods:A child who was admitted to Zhongnan Hospital of Wuhan University on July 27, 2021 was selected as the study subject. Genomic DNA was extracted from peripheral blood samples of the child and his parents and subjected to whole exome sequencing. Suspected splicing variant was verified by Sanger sequencing of family members. In vitro function was validated through a minigene assay, whilst the suspected exonic deletion was validated by long-fragment PCR. This study was approved by the Children′s Hospital Affiliated to Zhengzhou University (Ethics No. 2023-K-011). Results:Whole exome sequencing revealed that the child has harbored compound heterozygous variants of HPGD gene, including a heterozygous deletion (Exon 3 del) derived from his father and a splicing variant (c.421+ 1G>T) derived from his mother. Long-fragment PCR verified that the child and his father had both harbored a 7 565 bp heterozygous deletion (c.218-1304_324+ 6156del), whilst the minigene assay proved that the splicing variant has resulted in skipping of exon 4. Conclusion:The heterozygous c. 218-1304_324+ 6156del deletion and the c. 421+ 1G>T splicing variant of the HPGD gene probably underlay the pathogenesis in this child. Above finding has enriched the mutational spectrum of the HPGD gene and provided a basis for genetic counseling and prenatal diagnosis for this family.

Objective:To evaluate the short-term outcomes of all-inside endoscopic running locked stitch technique for acute Achilles tendon ruptures.Methods:This is a retrospective case series study. Forty-eight cases with acute Achilles tendon rupture were treated with the all-inside endoscopic running locked stitch technique from April 2020 to March 2022 at Department of Orthopaedics, General Hospital of Central Theater Command. There were 44 males and 4 females, aged (34.8±7.4) years (range: 24 to 50 years). Body mass index was (21.2±2.4)kg/m 2 (range: 18 to 26 kg/m 2); There were 29 cases (60.4%) on the left side and 19 cases (39.6%) on the right side. Under endoscopic control, the proximal tendon stumps were stitched with the running locked method using a semi-automatic flexible suture passer. The threads of the high-strength suture were grasped through the paratenon sub-space and then fixed into calcaneal insertion with a knotless anchor. MRI of Achilles tendon was performed to observe the regeneration of Achilles tendon during follow-up. Surgical time and complications were assessed. Achilles tendon total rupture score (ATRS), Achilles tendon resting angle, and heel rise height were utilized to evaluate final clinical outcomes. The differences of bilateral limbs were compared using the paired sample t test. Results:The follow-up time was (24.1±3.5)months (range:18 to 32 months). Appropriate tendon regeneration was observed on MRI at 12 months after operation. The median ATRS score ( M(IQR)) was 95.0 (4.7) points. Furthermore, there was no significant difference between the injured and contralateral side in the Achilles tendon resting angle ((17.1±2.4)° vs. (17.4±2.6)°, t=1.92, P=0.062) and heel rise height ((14.2±1.7)cm vs. (14.4±1.5)cm, t=1.71, P=0.094). No nerve injury, infection, deep vein thrombosis and re-rupture was encountered. Sports activity resumed six months postoperative in 46 patients. One patient had a slight anchor cut-out, due to an addition injury, which was removed after 5 months. Conclusions:All-inside endoscopic running locked stitch technique for acute Achilles tendon ruptures shows promising results. It provides stable connection of the tendon stumps with a low risk of complications.

Cognitive dysfunction refers to dysfunction of individual perception,memory,understanding,learning,creation and other dysfunctions caused by abnormal brain function and structure.Based on the fact that the spleen can't regulate transportation and transformation,govern blood and send up essential substance,combined with the microbiota-gut-brain axis,this article discussed the etiology and pathogenesis of intestinal flora imbalance affecting cognitive dysfunction in TCM.It was proposed that the spleen in TCM and intestinal flora are connected in physiology and pathology:the spleen regulates spirit and governs cognition,when the spleen fails to function normally that it can't dominate transportation and transformation,govern blood and send up essential substance will cause that the brain spirit can not be nourished;intestinal flora is closely related to the spleen in TCM,and affects brain function through the nervous system,endocrine,immune and metabolic mechanisms.This article can provide explore new ideas for the clinical research and treatment of cognitive dysfunction of traditional Chinese and Western medicine.

Coronary heart disease (CHD) is a kind of cardiovascular diseases originated from atherosclerosis (AS), and chronic inflammation is one of the pathological characteristics. The peripheral blood leukocytes, especially mononuclear cells, play an important role in the AS processes. Recently, in a series of Epigenome-Wide Association Studies (EWAS), multiple DNA differential methylation sites in peripheral blood cells were found to be statistically associated with CHD, which suggested that these DNA differential methylation sites might serve as new risk factors for CHD. The recognition of the variant of DNA methylation as a common epigenetic nucleic acid modification in the occurrence and development of CHD, is ongoing. DNA methylation has the potential to become warning biomarkers, which might provide new ideas and evidences for mechanistic studies of CHD.

Metastasis accounts for 90% of breast cancer deaths, where the lethality could be attributed to the poor drug accumulation at the metastatic loci. The tolerance to chemotherapy induced by breast cancer stem cells (BCSCs) and their particular redox microenvironment further aggravate the therapeutic dilemma. To be specific, therapy-resistant BCSCs can differentiate into heterogeneous tumor cells constantly, and simultaneously dynamic maintenance of redox homeostasis promote tumor cells to retro-differentiate into stem-like state in response to cytotoxic chemotherapy. Herein, we develop a specifically-designed biomimic platform employing neutrophil membrane as shell to inherit a neutrophil-like tumor-targeting capability, and anchored chemotherapeutic and BCSCs-differentiating reagents with nitroimidazole (NI) to yield two hypoxia-responsive prodrugs, which could be encapsulated into a polymeric nitroimidazole core. The platform can actively target the lung metastasis sites of triple negative breast cancer (TNBC), and release the escorted drugs upon being triggered by the hypoxia microenvironment. During the responsiveness, the differentiating agent could promote transferring BCSCs into non-BCSCs, and simultaneously the nitroimidazole moieties conjugated on the polymer and prodrugs could modulate the tumor microenvironment by depleting nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) and amplifying intracellular oxidative stress to prevent tumor cells retro-differentiation into BCSCs. In combination, the BCSCs differentiation and tumor microenvironment modulation synergistically could enhance the chemotherapeutic cytotoxicity, and remarkably suppress tumor growth and lung metastasis. Hopefully, this work can provide a new insight in to comprehensively treat TNBC and lung metastasis using a versatile platform.

Objective:To investigate the effects of ectodysplasin-A1 (EDA1) on the proliferation and cell cycle of ameloblast-like epithelial cells (LS8 cells).Methods:Wild EDA1 plasmid pCR3-Flag-EDA1-W (wild group), syndrome mutant EDA1 plasmid pCR3-Flag-EDA1-H252L (mutant group) and empty vector plasmid pCR3-Flag (control group) were transfected into LS8 cells. Cell proliferation was detected by methyl thiazolyl tetrazolium (MTT) assay and cell cycle was detected by flow cytometry. All tests were repeated three times.Results:Compared with the control group (0.105±0.032), the proliferation activity of the wild group (0.201±0.009) was significantly higher after 72 h ( P<0.05). Compared with the control group (0.168±0.054) and the mutant group (0.194±0.059), the proliferation activity of the wild group (0.386±0.066) was significantly higher after 96 h ( P<0.05). There was no significant difference between the mutant group and the control group at all time points ( P>0.05). In the G 0/G 1 phase, compared with the control group (65.4%±2.1%) and the mutant group (66.6%±3.1%), the cell distribution ratio of the wild group (51.2%±1.1%) was significantly lower ( P<0.01). In the S phase, compared with the control group (23.1%±2.0%) and the mutant group (21.9%±1.8%), the cell distribution ratio of the wild type group (37.3%±2.4%) was significantly higher ( P<0.01). There was no significant difference in cell cycle distribution between the mutant group and the control group ( P<0.05). Conclusions:Wild EDA1 promotes the proliferation of LS8 cells and the transformation from G 0/G 1 to S phase. The syndrome mutant EDA1 (EDA1-H252L) loses its function of regulating the cell proliferation and cell cycle of LS8 cells.

OBJECTIVE:To investigate the effects of hydrophilic polymers on the stability of self-microemulsifying drug deliv-ery systems (SMEDDS). METHODS:Taking felodipine (FDP) as model drug,the content of FDP was determined by HPLC method. The effects of pure water,0.5% Kollidon VA64,HPMC E5,HPMC K100LV,HPMC K4M,PVP K30 solution,while 0.1%,0.5% and 1.0% HPMC E5 and Kollidon VA64 on residual content of dissolved FDP were determined in SMEDDS. RE-SULTS:The residual contents of dissolved FDP in SMEDDS placed in Kollidon VA64,HPMC E5,HPMC K100LV,PVP K30, HPMC K4M and pure water for 1 h were 92.7%,63.6%,50.2%,46.2%,36.0%and 24.0%,respectively. The order of maintain-ing the supersaturation state was Kollidon VA64>HPMC E5>HPMC K100LV>PVP K30>HPMC K4M>pure water. The residu-al contents of dissolved FDP in SMEDDS placed in 0.1%,0.5%,1% Kollidon VA64 and HPMC E5 and pure water for 1 h were 93.2%,95.1%,96.0% and 48.4%,62.1%,75.1%. CONCLUSIONS:Kollidon VA64 and HPMC E5 can significantly inhibit drug release in SMEDDS and be used as stabilizer of SMEDDS,wherein Kollidon VA64 was better.