BACKGROUND: Recent studies have shown that sodium-glucose cotransporters-2 (SGLT2) inhibitors significantly improve major adverse cardiovascular events in heart failure with preserved ejection fraction (HFpEF) patients, but the exact mechanism is unknown. Ferritinophagy is a special form of selective autophagy that participates in ferroptosis. In this study, we aimed to investigate whether ferritinophagy was activated during the occurrence of HFpEF, and whether canagliflozin (CANA) could inhibite ferritinophagy. METHODS: We reared Dahl salt-sensitive (DSS) rats on a high-salt diet to construct a hypertensive HFpEF model, and simultaneously administered CANA intervention. Then we detected indicators related to ferritinophagy. RESULTS: The expression of nuclear receptor coactivator 4 (NCOA4), as well as microtubule-associated proteins light chain 3 (LC3), Bcl-2 interacting protein 1 (Beclin-1) and p62, were upregulated in HFpEF rats, accompanied by the downregulation of ferritin heavy chain 1 (FTH1), upregulation of mitochondrial iron transporter sideroflexin1 (SFXN1) and increased reactive oxygen species (ROS) production. Above changes were diminished by CANA. CONCLUSION Ferritinophagy is activated in HFpEF rats and then inhibited by CANA, leading to HFpEF benefits. The inhibition of ferritinophagy could provide new prospective targets for the prevention and treatment of HFpEF, and provide new ideas for investigating the mechanism of cardiovascular benefit of SGLT2 inhibitors.

Objective To investigate CBX2 and TIM3 in salivary adenoid cystic carcinoma(SACC)tissue and their relationship with clinical pathological features and prognosis.Methods 80 patients with SACC who underwent surgical treatment in the First Affiliated Hospital of Hebei North University from January 2016 to January 2020 were selected.Immunohistochemistry was used to measure CBX2 and TIM3 in tissues.The relationship between CBX2 and TIM3 in SACC tissue and prognosis was discussed though Kaplan-Meier method.The factors influencing the prognosis of SACC were discussed using multivariate Cox regression.Results The positive rates of CBX2 and TIM3 in SACC tissues were clearly higher than those in normal glandular tissues adjacent to cancer(χ2=11.237,8.229,P<0.05).The CBX2 and TIM3 were associated with nerve invasion and distant metastasis(P<0.05).After a 5-year follow-up,26 cases died and 54 cases survived,with an overall 5-year survival rate of 67.50%(54/80).The death group had higher positive rates of CBX2 and TIM3 in SACC tissues than the survival group(P<0.05).Patients with positive CBX2 and TIM3 in SACC tissues had clearly lower 5-year survival rate than patients with negative CBX2 and TIM3(Log Rank χ2=6.564,5.197,P<0.05).CBX2,TIM3 positivity,nerve invasion,and distant metastasis were risk factors affecting prognosis(P<0.05).Conclusion The positive expression of CBX2 and TIM3 in SACC tissues is closely related to the clinical pathological features and prognosis of patients.

Immunoinflammation mediates the development of hypertensive nephropathy,and aberrant activation of the complement system,an important component of the innate immune system,plays an important role in the development of hypertensive nephropathy.Complement inhibition is expected to be a potential strategy for the treatment of hypertensive nephropathy.In this article,we summarized and reviewed relevant studies on the complement system in the development of hypertensive nephropathy,and complement-targeted drug therapy,aiming to provide new ideas for clinicians on the clinical diagnosis and treatment of hypertensive nephropathy.

Aim Mouse model of myocardial hypertro-phy was established via intraperitoneal injection of iso-proterenol(ISO)in mice.This approach allows for an in-depth investigation into the pharmacological effects and mechanisms of action of emodin,offering novel in-sights and directions for the improvement of myocardial hypertrophy.Methods The mice were randomly di-vided into the following groups:control group(CON),emodin group(EMO),MAPK activator control group(EMO+Ani),model group(ISO),treatment group(ISO+EMO),and activator intervention group(ISO+EMO+Ani).After treatment with emodin and inter-vention with MAPK activator,the heart weight ratio and cardiac size of each group were observed.Hematoxy-lin-eosin(HE)staining was used to observe the patho-logical changes in cardiac tissue,and kits were utilized to measure the levels of GSH,LDH,and MDA in the serum.Western blot was employed to detect the protein expression levels of inflammatory and oxidative factors,as well as p-p38,p-ERK,p38,and ERK in cardiac tis-sue.Results Emodin can significantly inhibit the production of myocardial inflammatory and oxidative factors induced by ISO,thereby effectively alleviating the degree of myocardial hypertrophy and fibrosis.Af-ter the p38/ERK signaling pathway was specifically ac-tivated by farnesol,the improvement effect of emodin on myocardial hypertrophy was weakened.Further comparison revealed that,compared with the myocardi-al hypertrophy pathological model group,the pathologi-cal protein expression levels in the farnesol-treated group showed no significant difference,and were even higher in some indicators.Conclusion Emodin can effectively inhibit the release of inflammatory factors and improve the state of oxidative stress by modulating the p38/ERK signaling pathway,thereby exerting an ameliorative effect on myocardial hypertrophy.

Objective:To explore differences in the efficacy and safety of ruxolitinib in patients with myelofibrosis by age and to identify prognostic factors by analyzing clinical features and characteristics of chromosomes and gene mutations.Methods:This study retrospectively analyzed 188 patients with myelofibrosis who received ruxolitinib in the Department of Hematology, Qilu Hospital, Shandong University from January 1, 2017, to July 1, 2024. According to age at diagnosis, the patients were divided into the middle-aged group (≤55 years), young elderly group (56-65 years), and elderly group (>65 years). Clinical features, the characteristics of chromosomes and gene mutations, and the efficacy and safety of ruxolitinib treatment were compared across the three age groups. Independent factors influencing overall survival were identified through Cox proportional risk regression analysis.Results:Before treatment, the elderly group had more underlying comorbidities, a heavier symptom burden, higher leukocyte count, higher proportion and frequency of JAK2 mutations, and lower proportion of CALR mutations. The incidence of nondriver gene mutations was significantly higher in the young elderly group. After ruxolitinib treatment, the degree of reduction in spleen size did not differ significantly among the three groups. The length of the palpable spleen below the left costal margin reduced by more than 50% from baseline in 50.9% (27/53) of the patients in the middle-aged group, 43.5% (27/62) in the young elderly group, and 45.5% (20/44) in the elderly group ( P=0.720). No significant difference was observed among the three groups in the degree of reduction in Myeloproliferative Neoplasm Symptom Assessment Form (10-item version) score ( P=0.153), with a reduction in total symptom score by more than 50% achieved by 54.0% (27/50), 60.3% (41/68), and 66.7% (34/51) of the patients from the three groups, respectively ( P=0.429). The most common hematological adverse events were anemia and thrombocytopenia, while the most common nonhematological adverse events were electrolyte disturbance, elevated transaminase activity, and pulmonary infection. Multivariate analysis indicated that in ruxolitinib-treated patients with myelofibrosis, poor overall survival was independently predicted by increased age, reduced hemoglobin, percentage of bone marrow blasts ≥ 1%, absence of JAK2 mutations, chromosomal abnormalities, ≥2 high-molecular-risk mutations, and TP53 mutations. Conclusions:Patients with myelofibrosis stratified by age exhibited heterogeneous clinical features and gene mutation profiles but similar efficacy of ruxolitinib treatment and occurrence of adverse events.

ObjectiveThis paper aims to systematically collect and organize ancient and modern clauses and studies containing Xieqingwan， excavate and analyze the key information of Xieqingwan， and provide a reference for facilitating the development of the classic formula Xieqingwan. MethodsThe composition， dosage， decocting methods， usage， and other key information of Xieqingwan in ancient traditional Chinese medicine books were collected and analyzed by means of literature research and metrological methods. The modern clinical application of Xieqingwan was summarized. ResultsA total of 42 pieces of effective data involving 32 ancient traditional Chinese medicine books were collected. Xieqingwan was first recorded in Xiaoer Yaozheng Zhijue. The drug origin of this formula is basically clear in the ancient traditional Chinese medicine books. The modern drug usage and decocting method were as follows： Angelicae Sinensis Radix， Gentianae Radix et Rhizoma， Chuanxiong Rhizoma， Gardenia seeds， Radix et Rhizoma Rhei， Notopterygii Rhizoma et Radix， and Saposhnikoviae Radix were grounded to fine powder， decocted with honey， and finally formed into pills with the size of a chicken head （1.5 g）. It was suggested that half a pill or one pill were taken for one dose with warm Lophatheri decoction and sugar. The indications and clinical application had developed from the recordings in Xiaoer Yaozheng Zhijue and evolved from pediatrics to ophthalmic otolaryngology， neurology， dermatology， digestion， and respiratory diseases. The main pathogenesis of these diseases is heat in the liver meridian and is treated. The effect of Xieqingwan is "clearing away heat and toxicity， removing fire and relaxing the bowels， and dispersing swelling and relieving pain". It is recommended to use the corresponding preparation methods in the 2020 Edition of Pharmacopoeia of the People's Republic of China. Modern clinical studies are centered around the clinical application of Xieqingwan， which is often modified and used in treating Tourette syndrome， herpes， febrile convulsion， sleepwalking， and insomnia. ConclusionThis paper conducts a thorough textual research of the key information of Xieqingwan， induces its historic evolution， and confirms its key information， so as to provide a reference for the future development of Xieqingwan.

Objective To investigate whether ginsenoside Rh1(G-Rh1)can alleviate liver fibrosis induced by a choline-deficient,L-amino acid-defined,high-fat diet(CDAHFD)and to explore its underlying mechanisms.Methods Male C57BL/6J mice were randomly divided into 6 groups(n=8 in each group),including a standard diet group(or the control group),a high-fat diet group(or the CDAHFD group),a silymarin group(given silymarin at 5 mg/kg),a low-dose G-Rh1 group(given G-Rh1at 5 mg/kg),a medium-dose G-Rh1 group(given G-Rh1at 10 mg/kg),and a high-dose G-Rh1 group(given G-Rh1 at 20 mg/kg).The control group was given a standard feed,while the other groups were fed CDAHFD for 7 weeks to establish the mouse model of liver fibrosis.Starting from the first week,the mice in the treatment groups were administered the corresponding drugs by intragastric gavage once daily for 7 weeks in succession.After the administration of the final drug treatment,the body mass and organ mass of the mice in different groups were measured,and the organ index was obtained according.Liver tissues were examined using HE staining,Sirius red staining,and immunohistochemistry(IHC)staining.Western blot was performed to measure α-smooth muscle actin(α-SMA)and transforming growth factor-β1(TGF-β1),two liver fibrosis-related proteins,and fibroblast growth factor 12(FGF-12),a pathway-related protein.The serum biochemical indicators,including aspartate transferase(AST),alanine aminotransferase(ALT),total bilirubin(TBIL),and direct bilirubin(DBIL),were measured.Additionally,RAW246.7 cells were randomly divided into 5 groups,including a control group,a lipopolysaccharide(LPS)group,and 3 G-Rh1 treatment groups.The control group had only RAW246.7 cells in the culture medium.The other groups were given LPS(500 ng/mL),and the 3 treatment groups received G-Rh1 at 10,20,and 40 μmol/L in addition.The supernatants from the 5 groups of RAW246.7 cells were collected and cocultured with HSC-T6 cells for 24 hours to observe and compare the effects of G-Rh1 and LPS on the expression of fibrosis-related proteins,including α-SMA,Col1a1,etc,in HSC-T6 cells and on the expression of fibrotic signaling pathway-related proteins,including fibroblast growth factor 12(FGF-12)and signal transducer and activator of transcription 3(STAT3)/phosphorylated STAT3(p-STAT3),in RAW264.7 cells.Flow cytometry was conducted to analyze the phenotypes of RAW246.7 cells,and ELISA was performed to measure fibrosis-related factors,including monocyte chemoattractant protein-1(MCP-1)and transforming growth factor-β(TGF-β).Results Compared with the control mice,the mice in the CDAHFD group exhibited obvious liver fibrosis.Compared with CDAHFD mice,mice in the G-Rh1 treatment groups all showed alleviation of liver fibrosis of was alleviated to some extent in a dose-dependent manner,and the improvement effect was superior to that of silymarin,a reference drug.G-Rh1 also alleviated CDAHFD-induced body mass loss(P＜0.01),reduced the liver index(P＜0.01),and significantly decreased the serum levels of AST,ALT,DBIL,and TBIL(P＜0.0001).Significant differences in the protein expression ofα-SMA,TGF-β1,and FGF-12 in the liver were observed(P＜0.01).Compared with the LPS group,the LPS+G-Rh,groups exhibited significant differences in the expression of FGF-12 and p-STAT3/STAT3 in RAW246.7 cells,and α-SMA and Col1a1 in HSC-T6 cells(P＜0.001).In the LPS+G-Rh,groups(the 20 μmol/L and 40 μmol/L treatment groups),the conversion ratio of Ly6C-low expressing RAW246.7 cells into Ly6C-high expressing RAW246.7 cells decreased significantly(P＜0.0001),while the secretion of fibrosis-related factors MCP-1 and TGF-β decreased(P＜0.0001),which was consistent with the trend of the activation levels of HSC-T6 cells.Conclusions G-Rh1 can prevent and improve CDAHFD-induced liver fibrosis in mice,potentially through mechanisms involving the reduction of RAW264.7 phenotype transformation mediated by FGF-12 overexpression.

Objective:To investigate the differences in clinical outcomes of septic children with varying serum zinc levels,and to analyze the relationship between reduced serum zinc levels and organ dysfunction as well as 28-day mortality in septic children.Methods:This study conducted a retrospective analysis of clinical data from pediatric patients diagnosed with sepsis or septic shock in the Department of critical care medicine of the children's Hospital of Soochow University between January 2017 and December 2022.Clinical characteristics,organ dysfunction,and prognosis were compared between two groups:children with low serum zinc levels and those with normal zinc levels.Results:The serum zinc level of septic children within 24 hours of admission was 9.60(5.52,13.80)μmol/L,with 50.54%(94/186)of the children exhibiting low serum zinc levels(<10.07 μmol/L).Compared to the normal serum zinc group,the low serum zinc group had a significantly lower Pediatric Critical Illness Score(PCIS)[(78.71±9.35)vs.(85.12±8.51),P=0.005]and higher 28-day mortality(46.80%vs.14.13%,P<0.001).The low serum zinc group also had a higher proportion of invasive mechanical ventilation(64.89%vs.47.82%,P=0.019),renal replacement therapy(15.59%vs.3.26%,P=0.003),and use of vasoactive drugs(56.38%vs.30.43%,P<0.001).The rate of underlying conditions in the low serum zinc group was significantly higher than that in the normal serum zinc group(57.44%vs.36.95%,P=0.005).Additionally,the low serum zinc group had a higher incidence of disseminated intravascular coagulation(DIC),respiratory failure,acute kidney injury,shock,and multiple organ dysfunction syndrome(MODS)compared to the normal serum zinc group(P<0.05).Serum zinc levels had predictive value for 28-day mortality in septic children(AUC=0.813;95%CI:0.725～0.902;P<0.001).A serum zinc level of less than 6.950 μmol/L predicted the death of septic children with a sensitivity of 0.618 and a specificity of 0.902.Conclusion:Sepsis in children is commonly associated with low serum zinc levels,especially in those with underlying conditions such as hematologic and oncologic disorders.Sepsis patients hypozincemia with a higher incidence of DIC,respiratory failure,acute kidney injury,shock,and MODS.A serum zinc level below 6.95 μmol/L serves as a significant predictor of 28-day mortality in children with severe sepsis.

Objective:To observe the effect of acupuncture synchronized exercise therapy on sensory and motor functions of lower limbs in stroke patients,and to provide scientific basis for the optimization of rehabilitation program for stroke patients.Method:Seventy stroke patients hospitalized in the Rehabilitation Department of the Affiliated Hospital of Shan-dong University of Traditional Chinese Medicine from March 2022 to July 2022 were selected and randomly di-vided into synchronous group and control group,35 patients in each group.The patients in the synchronous group received routine exercise therapy and synchronized acupuncture treatment,while the patients in the con-trol group received acupuncture and subsequent exercise therapy continuously.Before and after treatment,the revised Nottingham sensory assessment scale(reNSA),Fugl-Meyer sensory rating scale,Fugl-Meyer motor function assessment(FMA),Berg rating scale,modified Barthel index rating scale(MBI)and modified Ash-worth spasm rating scale(MAS)were used to evaluate the curative effects.Result:After treatment,the scores of reNSA deep sensation,reNSA compound sensation and Fugl sensation in two groups were significantly increased(P<0.05).The scores of deep and shallow sensation in the synchro-nous group were significantly higher than those in the control group,while there was no significant difference between the two groups in the scores of compound sensation and Fugl sensation(P>0.05).After treatment,the FMA-UE score,Berg score and MBI score in the two groups were significantly increased(P<0.05),and the FMA-UE score,Berg score and MBI score of the synchronous group were also significantly higher than those of the control group(P<0.05).The composition of MAS scores in both groups also improved significant-ly after treatment,but there was no significant difference between the two groups before or after treatment(χ2=2.469,P=0.650;χ2=1.651,P=0.648).Conclusion:Acupuncture synchronized exercise therapy can effectively improve the sensory and motor functions of the lower limbs after stroke,and its effect is better than that of exercise therapy and acupuncture sequen-tial therapy.

Objective To observe the effect of acupuncture synchronized with speech training on speech function of patients with post-stroke motor aphasia.Methods Sixty inpatients with post-stroke motor aphasia were selected from the Affiliated Hospital of Shandong Univer-sity of Traditional Chinese Medicine,from January to August,2023.They were randomly divided into control group(n=30)and synchronous group(n=30).Both groups received acupuncture and speech training;the con-trol group received acupuncture in the morning and speech training in the afternoon,while the synchronous group received acupuncture and speech training synchronously,for three weeks.They were assessed with Chi-nese Rehabilitation Research Center Standard Aphasia Examination(CRRCAE),Non-Language-Based Cognitive Assessment(NLCA)and Communication Activities of Daily Living(CADL)before and after treatment.Results The subscores of CRRCAE and NLCA,and score of CADL increased in both groups(|t|>2.081,P<0.05)after treatment,and they were better in the synchronous group than in the control group(|t|>2.680,P<0.05).Conclusion Synchronous mode of acupuncture and speech training is more effective on post-stroke motor aphasia than time-sequence mode.