ObjectiveTo investigate the therapeutic effects and mechanism of decoctions from four kinds of processed products of Aconiti Radix Lateralis Praeparata（ARLP） in deficiency-cold syndrome. MethodsA total of 36 SD rats were randomly divided into the control group， model group， Shengfupian（SFP） group， Paofuzi（PFZ） group， Heishunpian（HSP） group and Paofupian（PFP） group with 6 rats in each group. Except for the control group， rats in other groups were administered hydrocortisone sodium succinate via intramuscular injection to induce a cold deficiency syndrome model. After 14 consecutive days， each ARLP decoction pieces was administered via continuous gastric lavage at a dose of 12 g·kg^-1·d^-1 for 7 d， while the control and model groups received an equivalent volume of physiological saline. After the end of administration， body weight， spleen weight and thymus weight were measured for calculating the spleen and thymus indexes. Hematoxylin-eosin（HE） staining was used to observe the pathological morphology of adrenal tissue. The fully automatic biochemistry analyzer was used to measure the total cholesterol（TC）， triglyceride（TG）， lactic dehydrogenase（LDH） and lactate（LAC） levels in serum. Enzyme-linked immunosorbent assay（ELISA） was employed to measure the contents of 17-hydroxycorticosteroid（17-OHCS）， cortisol（CORT）， triiodothyronine（T₃）， thyroxine（T₄）， thyrotropin（TSH）， immunoglobulin（Ig） M， IgG， cyclic adenosine monophosphate（cAMP） and cyclic guanosine monophosphate（cGMP）. Western blot was used to measure the protein expression levels of protein kinase A（PKA）， cAMP response element-binding protein（CREB）， silent information regulator 1（Sirt1） and peroxisome proliferator-activated receptor γ coactivator-1α（PGC-1α）. And high performance liquid chromatography（HPLC） was used to determine the content of major alkaloids， followed by Pearson correlation analysis with pharmacodynamic indicators. ResultsAfter modeling， compare with the control group， the model rats exhibited symptoms such as lethargy and loose stools， mild abnormalities were observed in adrenal tissue structure， and both spleen and thymus indices were significantly reduced（P<0.01）. Thyroid， adrenal and immune system functions were suppressed， with decreased serum cAMP level and significantly elevated cGMP level（P<0.01）. Compared with the model group， the adrenal injury by hydrocortisone sodium succinate were repaired and the spleen index were increased significantly in all four ARLP groups（P<0.05， P<0.01）. The thymus index in SFP and PFZ groups were increased significantly（P<0.05）. The contents of T₃， TSH， 17-OHCS and CORT were increased significantly in SFP and PFZ groups（P<0.05）. In addition， the content of IgG in SFP， PFZ and PFP groups were increased significantly（P<0.01）， while the content of IgM in PFZ and HSP groups were also increased significantly（P<0.05）. Regarding the cyclic nucleotide system， PFZ significantly elevated cAMP level while reducing cGMP level（P<0.05）， exhibiting the most pronounced effect among the four decoction pieces. For energy metabolism indicators， PFZ significantly improved abnormal markers including TC， TG， LDH， and LAC（P<0.05）. HSP showed marked improvement effects on TG， LDH， and LAC（P<0.05）. Both PFZ and SFP significantly elevated the expression levels of PKA， CREB， Sirt1， and PGC-1α proteins（P<0.01）. Additionally， the diester alkaloids in ARLP showed a strong positive correlation with TG， IgG， and CORT， a strong negative correlation with LAC， a moderate positive correlation with T₄， and moderate negative correlations with cAMP and spleen index. Monomeric alkaloids showed strong positive correlations with TG and IgG， strong negative correlations with LAC， moderate positive correlations with CORT and T₄， and moderate negative correlations with cAMP and spleen index. However， the content of water-soluble alkaloids showed strong positive correlations with TC， LDH， 17-OHCS， T₃， TSH， and thymus index， moderate positive correlations with cAMP， CORT， T₄， and spleen index， and moderate negative correlation with cGMP. ConclusionAmong different processed ARLP decoction pieces， PFZ processed according to ZHANG Zhongjing's method exhibits the most potent warming and cold-dispelling effects. Its pharmacological actions are mediated through regulating the thyroid， adrenal， immune， cyclic nucleotide systems， and material-energy metabolism pathways. Among these， water-soluble alkaloids show strong or moderate correlations with more indicators of deficiency-cold syndrome and exhibit the highest content in PFZ. Therefore， PFZ processed according to ZHANG Zhongjing's method may exert its warming and cold-dispelling effects through water-soluble alkaloids.

Kui was first recorded in The Rites of Zhou and is the earliest domesticated wild vegetable in China. In the Qi Min Yao Shu, Kui was called “the master of all vegetables” and has a long history of application in China. As a medicine, Kuizi was first recorded in Shen Nong’s Herbal Classic, which has a history of more than 2 000 years of medicinal use and a long history of clinical application. By researching the ancient and modern herbal literature, the first herbs texts of Kui were examined, various recorded texts, confused products and the history of the original medicinal use were clarified. It was concluded that the ancient herbal texts recorded the base plant of Kui as Malva verticillata L. belonging to family Malvaceae, which provided scientific basis for the development and utilization of Kui.

Objective To investigate the clinical efficacy of minimally invasive mitral valvuloplasty (MVP) in the treatment of infective endocarditis (IE) with mitral regurgitation (MR). Methods A retrospective analysis was conducted on the clinical data of patients who underwent MVP for IE with MR at the Department of Cardiovascular Surgery in Zhongshan Hospital, Fudan University from 2016 to 2020. Patients were divided into two groups based on the surgical incision: those with a right mini-thoracotomy were classified as a minimally invasive surgery (MIS) group, and those with a median sternotomy (MS) were classified as an MS group. All patients had isolated mitral valve involvement. Perioperative data were analyzed, and mid- to long-term outcomes were compared between the two groups. Results A total of 86 patients were included, with 40 in the MIS group [22 males and 18 females, with a mean age of (39.78±15.36) years ranging from 14 to 75 years] and 46 in the MS group [27 males and 19 females, with a mean age of (49.94±16.13) years ranging from 14 to 71 years]. The patients in the MIS group were relatively younger (P=0.004) with better preoperative cardiac function (P=0.004). There was no statistical difference in preoperative fever, gender, or comorbidities between the two groups (P>0.05). The MIS group had shorter postoperative ventilation times, less postoperative 24-hour drainage, less blood transfusion, and shorter total hospital stays compared to the MS group (P＜0.05). There was no statistical difference in cardiopulmonary bypass times or ICU stays between the two groups (P>0.05). The perioperative complication rates and mortality rates were not significantly different between the two groups (P>0.05). Follow-up was conducted for 11-92 months, with a mean duration of (49±19) months and an overall follow-up rate of 91.9%. During the follow-up, 3 patients in each group required reoperation for mitral valve issues, with no statistical difference in incidence (7.5% vs. 6.5%, P=0.691). There were no warfarin-related complications, recurrences, or deaths in either group during follow-up. Multivariate regression analysis identified age, preoperative cardiac function, and surgeon experience as influencing factors for the choice of surgical approach. Conclusion Minimally invasive MVP for IE with MR is relatively safe in the perioperative period and shows significant efficacy, with clear mid- to long-term outcomes. It is recommended for younger patients with better preoperative cardiac function and when performed by surgeons with extensive experience in mitral valvuloplasty.

BACKGROUND:Wogonin is a flavonoid extracted from the root of Scutellaria baicalensis.Previous studies have shown that baicalein has protective effects against cerebral ischemia-reperfusion injury,and can also reduce blood sugar and complications in diabetic mice,but its role and mechanism in diabetic cerebral infarction remain unclear. OBJECTIVE:To explore the effect of wogonin on nerve injury in rats with diabetic cerebral infarction and its mechanism. METHODS:Sprague-Dawley rats were randomly divided into six groups:control group,model group,low-dose wogonin group,medium-dose wogonin group,high-dose wogonin group,and high-dose wogonin+Ras homolog gene family member A(RhoA)activator group.Except for the control group,the other rats were established with diabetes and cerebral ischemia models using intraperitoneal injection of streptozotocin and middle cerebral artery occlusion.Low,medium-and high-dose wogonin groups were intragastrically given 10,20,40 mg/kg wogonin,respectively;high-dose wogonin+RhoA activator group was intragastrically given 40 mg/kg wogonin and intraperitoneally injected 10 mg/kg lysophosphatidic acid;control group and model group were given the same amount of normal saline once a day for 7 consecutive days.Rats in each group were evaluated for neurological deficits and their blood glucose levels were measured after the last dose.TTC staining was applied to detect the volume of cerebral infarction.Hematoxylin-eosin staining was applied to observe pathological changes in brain tissue.ELISA kit was applied to detect tumor necrosis factor-α,interleukin-6,malondialdehyde,and superoxide dismutase levels in brain tissue.Western blot was applied to detect the protein expression of RhoA and Rho-associated protein kinase(ROCK)2 in brain tissue. RESULTS AND CONCLUSION:Compared with the control group,the neuronal structure of rats in the model group was severely damaged,with cell necrosis and degeneration,the neurological deficit score,blood glucose level,and infarct volume were significantly elevated(P<0.05),the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue were significantly increased(P<0.05),and the superoxide dismutase level was decreased(P<0.05).Compared with the model group,the low-,medium-,and high-dose wogonin groups showed improved neuronal damage,reduced cell degeneration and necrosis,a significant reduction in neurological deficit score,blood glucose level,infarct volume,and the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue,and an increase in the superoxide dismutase level(P<0.05).Compared with the high-dose wogonin group,the high-dose wogonin+RhoA activator group significantly weakened the improvement in the above indexes of rats with diabetic cerebral infarction(P<0.05).To conclude,wogonin can improve the blood glucose level in rats with diabetic cerebral infarction,reduce cerebral infarction and nerve injury,and its mechanism may be related to the inhibition of RhoA/ROCK signaling pathway.

ObjectiveTo investigate the effects of artemisinin （ART） on histopathological damage and salivary secretion in the submandibular gland （SMG） of mice with Sjögren's syndrome （SS） model，and on the expression of aquaporin 5 （AQP5） in SMG cells. MethodsThe NOD/Ltj mice were used as a model of SS and randomly divided into the SS model group，the ART group，and the hydroxychloroquine sulfate （HCQ） group，with six mice per group. Another 6 female BALB/c mice at the same week were selected as the control group. Mice in the ART group was fed with the ART solution daily in the dosage of 50 mg·kg^-1，and mice in the HCQ group was given with the HCQ solution （1 300 mg·kg^-1）. Mice in the SS model and control groups were given saline daily. The treatment lasted for 8 weeks. The 24-hour average water intake，salivary flow rate，SMG pathology scores of mice in each group were measured，as well as the expression levels of AQP5 protein and gene in the SMG tissues. ResultsCompared with the control group，the 24-hour average water intake of mice in the model group was significantly increased （P<0.01），and the saliva flow rate was significantly decreased （P<0.01）. Compared to the SS model group，the 24-hour average water intake of mice in the ART and HCQ groups was significantly reduced （P<0.01），and the salivary flow rate was significantly increased in the ART group（P<0.01），comparisons between groups showed that the ART was superior to the HCQ in reducing water intake and improving saliva flow rate in SS model mice （P<0.05）. The HE staining results showed that，compared with the normal group，the number of lymphocyte infiltration foci in SMG tissue in the model group increased，and the pathological score increased （P<0.01）. Compared to the SS model group，after the intervention of the ART and HCQ，the number of lymphocytic infiltration foci in the SMG tissue decreased，the area of the lymphocytic infiltration foci was reduced，and the pathology score of the SMG tissues was lowered in the ART group（P<0.01）. However，there was no difference in pathological scores between the ART and HCQ groups . The results of IHC，Western blot，and Real-time PCR showed that，compared with the normal group，the expression levels of AQP5 protein and gene in SMG tissue in the model group significantly decreased （P<0.05）. Comparing with the SS model group，the ART and HCQ groups could significantly up-regulated the expression levels of AQP5 protein and mRNA in the SMG tissue，and the treatment effect was better than that of HCQ. ConclusionART was able to ameliorate SMG structural damage and salivary secretion function in SS model mice，and its mechanism of action may be related to the up-regulation of AQP5 protein and gene expression levels in SMG cells.

Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

Objective: This study aimed to explore the correlation between balance function and core muscle activation in patients with adolescent idiopathic scoliosis (AIS), compared to healthy individuals. Methods: A total of 24 AIS patients and 25 healthy controls were recruited. The limits of stability (LOS) test were conducted to assess balance function, while surface electromyography was used to measure the activity of core muscles, including the internal oblique, external oblique, and multifidus. Diaphragm thickness was measured using ultrasound during different postural tasks. Center of pressure (COP) displacement and trunk inclination distance were also recorded during the LOS test. Results: AIS patients showed significantly greater activation of superficial core muscles, such as the internal and external oblique muscles, compared to the control group (p < 0.05). Diaphragm activation was lower in AIS patients during balance tasks (p < 0.01). Although no significant difference was observed in COP displacement between the groups, trunk inclination was significantly greater in the AIS group during certain tasks (p < 0.05). Conclusion These findings suggest distinct postural control patterns in AIS patients, highlighting the importance of targeted interventions to improve balance and core muscle function in this population.

Objective To investigate the mechanism of long non-coding RNA(LncRNA)FUT8-AS1 on diabetic ischemia-reperfusion injury by regulating growth differentiation factor 15(GDF15).Methods Male SD rats were randomly divided into Sham group,cerebral ischemia-reperfusion injury(MCAO/R)group,diabetic cerebral ischemia-reperfusion injury(DM-MCAO/R)group,DM-MCAO/R+sh NC group,and DM-MCAO/R+sh FUT8-AS1 group.TTC staining was used to assess the size of cerebral infarction.Tunel staining was selected to evaluate the apoptosis of neurons in brain tissue.Nissl staining was used to assess the number of neurons in brain tissue.The expression of LncRNA FUT8-AS1,GDF15 mRNA in Willis arterial loop and internal carotid artery tissues were detected by qRT-PCR.The expression of α-SMA,eNOS,p-eNOS,GDF15 protein in Willis arterial loop and internal carotid artery was detected by Western blot.The rat brain microvascular endothelial cells were divided into control(Con)group,OGD/R group,HG-OGD/R group,HG-OGD/R+sh NC group,HG-OGD/R+sh FUT8-AS1 group,HG-OGD/R+sh FUT8-AS1+oe NC group,and HG-OGD/R+sh FUT8-AS1+oe GDF15 group.MTT assay was used to detect cell viability.Lactate dehydrogenase(LDH)assay was used to detect cell damage.The expression ofα-smooth muscle actin(α-SMA),endothelial nitric oxide synthase(eNOS),p-eNOS protein was detected by Western blot.Results Compared with the Sham group,the percentage of cerebral infarction,the number of Tunel-positive cells,the FUT8-AS1 and mRNA expression of GDF15 and the expression of GDF-15 protein increased(P<0.05),and the expression of α-SMA,eNOS,p-eNOS proteins decreased in the MCAO/R group(P<0.05),and the number of neurons in the hippocampus decreased,the morphology was shrunk,and the color was dark in the MCAO/R group.Compared with the MCAO/R group,the percentage of cerebral infarction,the number of Tunel-positive cells,the FUT8-AS1 and mRNA expression of GDF15 and the expression of GDF-15 protein increased(P<0.05),and the expression of α-SMA,eNOS,p-eNOS proteins decreased in the DM-MCAO/R group(P<0.05),and the number of neurons in the hippocampus decreased in the DM-MCAO/R group.Compared with the DM-MCAO/R+sh NC group,the percentage of cerebral infarction,the number of Tunel-positive cells,the FUT8-AS1 and mRNA expression of GDF15 and the expression of GDF-15 protein decreased(P<0.05),and the expression of α-SMA,eNOS,p-eNOS proteins increased in the DM-MCAO/R+sh FUT8-AS1 group(P<0.05),and the number of neurons in the hippocampus increased in the DM-MCAO/R+sh FUT8-AS1 group.Compared with the Con group,the LDH release,FUT8-AS1 expression,GDF15 mRNA and protein expression increased(P<0.05),and the cell activity,α-SMA,eNOS,and p-eNOS protein expressions decreased in the OGD/R group(P<0.05).Compared with the OGD/R group,the LDH release,FUT8-AS1 expression,GDF15 mRNA and protein expression increased(P<0.05),and the cell activity,α-SMA,eNOS,and p-eNOS protein expressions decreased in the HG-OGD/R group(P<0.05).Compared with the HG-OGD/R+sh NC group,the LDH release,FUT8-AS1 expression,GDF15 mRNA and protein expression decreased(P<0.05),and the cell activity,α-SMA,eNOS,and p-eNOS protein expressions increased in the HG-OGD/R+sh FUT8-AS1 group(P<0.05).Compared with the HG-OGD/R+sh NC group,the LDH release,GDF15 mRNA and protein expression increased(P<0.05),and the cell activity decreased in the HG-OGD/R+oe GDF15 group(P<0.05).Compared with the HG-OGD/R+sh FUT8-AS1+oe NC group,the expression of α-SMA,eNOS,p-eNOS proteins decreased in the HG-OGD/R+sh FUT8-AS1+oe GDF15 group(P<0.05).Conclusions LncRNA FUT8-AS1 may exacerbate diabetic cerebral ischemia-reperfusion injury by regulating GDF15.

Aim To investigate the im-munomodulatory effects of Ononin on Th17/Treg bal-ance and inflammatory responses,and to evaluate its neuroinmune regulatory role in ischemic stroke.Methods A Foxp3 promoter-driven luciferase reporter assay was used to assess the effect of Ononin on Foxp3 transcriptional activity.The effect of Ononin on the dif-ferentiation of na?ve CD4+T cells into Th 17 and Treg subsets was evaluated by flow cytometry.A transient middle cerebral artery occlusion(tMCAO)model was established in mice to evaluate the effects of Ononin on infarct size,neurological recovery,body weight resto-ration,and survival rate.Flow cytometry and RT-PCR were conducted to elucidate the immunological mechanisms underlying Ononin's effects.Results On-onin significantly enhanced Foxp3 promoter activity,promoted the differentiation of na?ve CD4+T cells into Treg cells,and suppressed Th17 polarization.In the tMCAO model,Ononin significantly reduced acute in-farct size,improved survival,ameliorated long-term neurological deficits,and increased Treg cell propor-tions in ischemic brain tissue.Conclusions Ononin modulates peripheral and central inflammation by resto-ring the Th17/Treg immune balance,thereby exerting significant immunomodulatory effects.Its therapeutic benefit in ischemic stroke is closely linked to immune balance restoration.

Objective To compare the effects of quadratus lumborum block at the lateral supra-arcuate ligament(QLB-LSAL)versus subcostal transversus abdominis plane block(STAPB)on perioperative analgesia and postoperative inflammation in patients undergoing laparoscopic radical resection of colorectal cancer.Methods In this prospective randomized study,we recruited 102 patients undergoing laparoscopic colorectal cancer surgery between October 2022 and October 2024 under general anesthesia and randomly assigned them to two groups:QLB-LSAL(Group Q,n=51)and STAPB(Group S,n=51).Mean arterial pressure(MAP)and heart rate(HR)were recorded before anesthesia induction(T0),before surgical incision(T1),start of surgery(T2),during pneumoperitoneum establishment(T3),during peritoneal lavage(T4),at the end of surgery(T5),and upon leaving the operating room(T6).Intraoperative remifentanil consumption,time to first patient-controlled analgesia demand,and frequency of effective compression and rescue analgesia were recorded.Visual Analog Scale(VAS)scores at rest and during coughing were assessed at 24,48,and 72 hours postoperatively.Interleukin-6(IL-6)and systemic immune-inflammatory index(SII)at 1 day preoperatively,1,and 3 days postoperatively were recorded.Postoperative recovery indicators and adverse events were also recorded.Results Group Q demonstrated significantly lower MAP and HR compared with Group S from T3 to T6(P<0.05).Group Q had significantly lower intraoperative remifentanil consumption,significantly longer time to first analgesic pump demand,fewer effective pump compres-sion,and lower frequency for rescue analgesia requests(all P<0.05).VAS scores at rest and during coughing in Group Q were significantly lower at 24 h and 48 h postoperatively(P<0.05).As compared with preoperative levels,both IL-6 and SII increased at 1 and 3 days postoperatively,but magnitude of increase in Group Q was smaller than in Group S(P<0.05).In comparison to Group S,Group Q demonstrated significantly earlier ambulation,shorter hospital stay,and fewer adverse events(P<0.05).Conclusion QLB-LSAL is superior to STAPB in enhancing perioperative analgesia,attenuating inflammatory response,and accelerating postoperative rehabilitation in patients undergoing laparoscopic colorectal cancer resection.