To summarize Prof. ZHANG Zhiyuan's clinical experience in using large doses of Fuzi （Aconiti Lateralis Radix Praeparata）. The effect of Fuzi is based on its acrid and hot propoerties， warming and invigorating yang qi and running without guard. The application of large doses of Fuzi can be categorized into raw and processed， with common dosage ranging from 30 g to 60 g of raw Fuzi， and 15 g to 30 g， 30 g to 60 g of processed Fuzi. The quantity-effect relationship of the large dose of Fuzi is summarized as 15 g to 30 g of processed Fuzi could warm water， warm yang and eliminate timidity， as the treatment of asthma with deficiency cold phlegm， edema of yang deficiency， and panic and timidity of yang deficiency； 30 g to 60 g of processed Fuzi could tonify fire， warm the meridians and collaterals， assist yang to dispel cold and relieve pain， as the treatment of coldness in the limbs， abdominal pain， pain in the joints of the limbs， and loose stools due to deficient yang qi and exuberant internal yin cold； 30 g to 60 g raw Fuzi could restore yang to save from collapse， as the treatment of yang depletion after profuse sweating and vomiting. At the same time， different dosages of Fuzi were flexibly paired with other medicines， i.e.， 15 g to 30 g of processed Fuzi was paired with Mahuang （Ephedrae Herba） and Xixin （Asari Radix et Rhizoma） to assist yang to dispel coldness， 30 g to 60 g of processed Fuzi was paired with Baizhu （Atractylodis macrocephalae rhizoma） or Wuzhuyu （Euodiae Fructus） to warm yang and dispel dampness， and 30 g to 60 g of raw Fuzi was paired with Shanzhuyu （Corni Fructus） to tonify both yin and yang.

Objective Radiation-induced brain injury (RIBI) is a common complication of radiotherapy for the head and neck tumors, and the current treatment methods are limited. Repetitive transcranial magnetic stimulation (rTMS), as a non-invasive neural regulation technique, has shown great potential in neuroprotection. However, the parameter selection and biological safety of rTMS in the prevention and treatment of RIBI have not been reported. Methods Using a mouse model of RIBI, this study employed three rTMS frequencies (5, 10, and 25 Hz) for intervention. Biochemical and pathological assays were conducted to identify the optimal stimulation parameter. Subsequently, this parameter was used to evaluate the biological safety in normal mice. Results Under the conditions of this experiment, rTMS interventions with all three frequencies could reduce the levels of serum brain injury markers (NSE and S100B) and inflammatory factors in mice (P < 0.001), and alleviate the morphological and structural damage of hippocampal tissue. The 10 Hz rTMS could significantly promote hippocampal neurogenesis in RIBI mice (P < 0.05). Furthermore, 10 Hz rTMS showed no significant effects on the cognitive function and mood of normal mice. The intervention did not significantly change the morphology and structure of the main organs, blood biochemical indicators, and the level of hippocampal neurogenesis in mice. Conclusion The 10 Hz rTMS is optimal for the prevention and treatment of RIBI with high biological safety.

Objective:To investigate the molecular characteristics of obacunone, and to screen and identify potential targets of obacunone against sepsis.Methods:The pharmacological parameters and molecular characteristics of obacunone were analyzed with the aid of the Traditional Chinese Medicine Systems Pharmacology Database Analysis Platform (TCMSP). The potential targets of obacunone against sepsis were screened using SwissTargetPrediction and Drug Repositioning and Adverse Drug Reaction Chemical-Protein Interactome (DRAR-CPI) software, with a Z'-score < -0.5. The anti-sepsis targets of obacunone were selected by Online Mendelian Inheritance in Man (OMIM), Comparative Toxicogenomics Database (CTD) and Therapeutic Target Database (TTD). The anti-sepsis potential target was identified by molecular docking software.Results:The oral bioavailability of obacunone was 81.58% and the drug-likeness was 0.57 indicating that obacunone showed good drug formation. A total of 242 potential targets were screened through SwissTargetPrediction and DRAR-CPI software, 13 targets were directly related to sepsis. Cathepsin G (CTSG), caspase-1 (CASP1), S100 calcium binding protein A9 (S100A9), protein C (inactivator of coagulation factors Ⅴa and Ⅷa, PROC), mitogen-activated protein kinase 1 (MAPK1), glucose-6-phosphate dehydrogenase (G6PD), interleukin-10 (IL-10), migration inhibitory factor (MIF), complement C5a receptor 1 (C5AR1), caspase-3 (CASP3), CXC chemokine receptor 2 (CXCR2), thrombin receptor (F2R), nicotinamide phosphoribosyltransferase (NAMPT) were identified as the potential targets for anti-sepsis of obacunone by molecular docking software, the free binding energies were -32.55, 1.26, -30.00, 300.08, -31.88, -30.29, -21.38, -30.79, 16 777.84, -21.80, 6 443.36, -20.38, -23.47 kJ/mol, respectively.Conclusions:Obacunone can inhibit blood coagulation and improve inflammatory response by regulating PROC and F2R. It regulates MIF, S100A9, G6PD and IL-10 to play a role in immune response. It regulates CTSG, CASP1, MAPK1, C5AR1 and CASP3 to protect sepsis-damaged organs. By regulating CXCR2, it can reduce the excessive migration of neutrophils to the site of inflammation, alleviate tissue damage. By regulating NAMPT, it improves cellular energy status, reduces oxidative stress, and protects cells from damage.

Objective To analyze the very high frequency(VHF)ultrasound features of mixed tumor of the skin(MTS),and to explore the diagnostic value of VHF ultrasound features for MTS.Methods A total of 63 cases of MTS confirmed by surgery and pathology in the Department of Dermatology of Hangzhou Third People's Hospital from January 2019 to March 2024 were selected as observation group,and 63 other benign skin tumors in the same period were used as control group.The VHF ultrasound features of MTS were retrospectively analyzed and summarized,and the diagnostic efficiency of VHF ultrasound features for MTS was evaluated.Results Compared with other benign skin tumors,there were no significant differences in the length diameter,transverse diameter,aspect ratio,presence or absence of calcification,cystic disease,blood flow grade and resistance index between two groups(P＞0.05).However,MTS had a more obvious pseudo-capsule,and most of the internal echoes were not uniform,and the posterior side was accompanied by a enhancing effect,and the blood flow was dominated by marginal blood flow,and the difference between two groups was obvious(P＜0.05).The receiver operating characteristic curve showed that the combination of pseudo capsule,internal echo,marginal flow and peripheral enhancement had the highest diagnostic efficacy,with an area under the curve of 0.772,a sensitivity of 77.8％ ,and a specificity of 71.4％ .Conclusion MTS have specific VHF ultrasound features,which can provide more assistance in the clinical diagnosis of MTS.

Objective To study the effect of hearing loss on language function and the mediating effect of de-pression on hearing loss and language function,to provide a reference for the intervention of language function im-pairment in the elderly.Methods Data of 6 002 older adults ≥65 years old from the Hubei Aging and Memory Co-hort Study(HAMCS)were collected from 2018 to 2022.A multivariate logistic regression model was used to ana-lyze the effect of hearing loss on language function,and a Bootstrap method was used to analyze the mediating effect of depression score on hearing loss on language function.Results Among 6 002 older adults ≥65 years old,1 137(18.94％)had mild hearing loss,264(4.40％)had moderate and severe hearing loss,and 2 611(43.50％)had language function impairment.After controlling for related factors such as age,years of education,marital status,place of residence,physical exercise,intellectual activity,hypertension,coronary heart disease and cerebrovascular disease,multivariate logistic regression analysis showed that the risk of speech function impairment in the elderly with mild hearing loss and moderate to severe hearing loss was 1.33 times(95％CI:1.13～1.56,P=0.001)and 1.77 times(95％CI:1.29～2.42,P＜0.001)respectively.The mediating effect showed that depression played a partial mediating role between hearing loss and language function,and the mediating effect was-0.021(95％CI:-0.027～-0.015,P＜0.001),accounting for 12.96％of the total effects.Conclusion Hearing loss increases the risk of language impairment,and depression playing a partial mediating role between hearing loss and language func-tion in the elderly.

Objective To investigate the changes in the levels of serum high-sensitivity C-reactive protein(hs-CRP)and soluble fms-like tyrosine kinase-1(sFlt-1)in hypertensive disorder of pregnancy(HDP)patients with fetal growth restriction(FGR),and to evaluate their predictive value for FGR.Methods A total of 137 HDP patients admitted to the Obstetrics De-partment of Ganzhou Maternal and Child Health Hospital from December 2021 to May 2023 were selected as the study subjects.According to whether their fetuses had growth restriction,they were divided into the restricted group(n=46)and the non-re-stricted group(n=91).The general information and serum levels of hs-CRP and sFlt-1 were collected and analyzed.Multiple lo-gistic regression analysis was used to identify the influencing factors for fetal growth restriction in HDP patients,and receiver oper-ating characteristic(ROC)curve was plotted to evaluate the predictive value of serum hs-CRP and sFlt-1 levels for fetal growth restriction in HDP patients.Results Univariate analysis showed that the serum levels of folic acid(FA),vitamin B12(VitB12),and placental growth factor(PIGF)in the restricted group were lower than those in the non-restricted group,while the serum lev-els of hs-CRP and sFlt-1 were higher than those in the non-restricted group,with statistically significant differences(P＜0.05).Multivariate analysis showed that serum hs-CRP,sFlt-1,and PIGF levels were independent risk factors for fetal growth restriction in HDP patients.The H-L test of the model showedx2=7.014,P=0.535,indicating a good fit.The area under the ROC curve(AUC)was 0.932,with a 95％CI of 0.889-0.975(P＜0.05),a sensitivity of 93.50％,and a specificity of 89.00％.Conclusion Serum hs-CRP and sFlt-1 levels are upregulated in HDP patients with fetal growth restriction,indicating their good predictive value for the occurrence of fetal growth restriction.

This paper summarized the experience of ZHANG Zhiyuan， a master of traditional Chinese medicine， in treating gastric diseases with Daizheshi （Haematitum）. It is believed that the treatment of gastric diseases should focus on restoring the purification and descent of stomach qi， and Daizheshi， as the essential medicine for directing stomach qi and counterflow downward， is especially suitable. Commonly， Daizheshi is used in combination with herbal medicinals Chaihu （Radix Bupleuri） and Wuzhuyu （Fructus Evodiae） to relieve constraint and direct counterflow downward， with Dahuang （Radix et Rhizoma Rhei） and Gualou （Fructus Trichosanthis） to disperse phlegm and direct qi downward， with Chenxiang （Lignum Aquilariae Resinatum） to regulate qi and unblock the center， and with Renshen （Radix et Rhizoma Ginseng） to open congestion and supplement deficiency. For the syndrome of disharmony between the liver and stomach， the addition of Daizheshi to liver soothing and qi regulating medicinals can lower liver Qi and calm Chong Qi（冲气）， restore the unblock and purge nature of stomach qi. For the syndrome of disharmony between the gallbladder and stomach， adding Daizheshi to the medicinals for gallbladder function promoting and phlegm resolving can direct phlegm turbidity downward， and promote gallbladder fire to reach the stomach， permitting the clear qi of the gallbladder rising naturally.For spleen and stomach disharmony syndrome， adding Daizheshi to the medicinals for spleen fortifying and stomach warming can calm the counterflow and the center， allowing the deficiency can be replenished. For lung and stomach disharmony， the addition of Daizheshi to medicinals for lung moistening and stomach clearing can directing stomach qi downward and harmonizing yin， direct repulsion of hyperactive fire， assist metal to purify qi， bank up earth to generate metal， and help with transformation of body fluids.

Objective To evaluate the nutritional status of elderly inpatients by using the nutritional risk screening table 2002(NRS2002)and the short-form mini-nutritional assessment(MNA-SF),and to eval-uate the applicability of the two tools.Methods The general data were collected from the inpatients aged ≥80 years old by the random sampling method.They were divided into the two age groups:≥90 years old and＜90 years old,and their nutritional status was assessed by using the two nutritional screening tools.Meanwhile,the fasting venous blood nutritional related indicators including albumin(Alb),hemoglobin(Hb),C-reactive protein(CRP),transferrin(TRF),prealbumin(PA)and retinol-binding protein(RBP)levels were detected.Furthermore the results conducted the correlation analysis.Results There were 404 cases(48.56％)of nutri-tional risk in the NRS2002 evaluation.The occurrence rate of nutritional risk in the ≥90 years old group was higher than that in the＜90 years old group(P＜0.01).There were 616 cases(74.04％)of malnutrition/risk of malnutrition in the MNA-SF evaluation.The incidence rate of malnutrition risk in the≥90 years old group was higher than that in the＜90 years old group(P＜0.01).With the serum ALB＜30 g/L as the ref-erence standard,the applicabilities were compared between the two kinds of nutritional screening tools,the re-sults found that the two kinds of nutritional screening tools all were suitable for the nutritional status screen-ing of elderly inpatients.The area under the receiver operating characteristic(ROC)curve(AUC)of the MNA-SF for evaluating the nutritional status in the elderly inpatients was 0.814,the sensitivity and specificity were 75.7％and 87.7％respectively.AUC of ROC in NRS2002 for evaluating the nutritional status in the elderly inpatients was 0.805,the sensitivity and specificity were 88.6％and 62.2％respectively.The correla-tion analysis results of Hb,CRP,PA,RBP and TRF biochemical indexes with MNA-SF score and NRS2002 score showed that NRS2002 score and MNA-SF score were correlated with PA,RBP and TRF.Conclusion The incidence rate of nutritional risk in elderly inpatients is high.Both NRS2002 and MNF-SF nutritional screening tools are suitable for elderly inpatients and have high accuracy.Meanwhile,combining nutrition-related indicators to evaluate the nutritional status of elderly patients can improve the accuracy of nutritional assessment.

Objective:To evaluate the protective effect of foam dressing in preventing intraoperative acquired pressure injury (IAPI), and to provide reference basis for prevention and treatment of IAPI during clinical operation.Methods:The clinical data of 455 surgical patients admitted to Xinhua Hospital Affiliated to Shanghai Jiao Tong University from October 2020 to January 2021 were retrospectively collected. According to whether foam dressing was used at the compression site during operation, the patients were divided into dressing group (101 cases) and control group (354 cases). The two groups were matched with age, body mass index, preoperative Braden and cerebrovascular disease as covariates, and were finally divided into 89 patients in the dressing group and 162 patients in the control group. Logistic regression analysis and stratified analysis were used to comprehensively evaluate the actual effect of foam dressing on the occurrence of IAPI in the surgical patients.Results:Among the 251 patients, there were 14 (15.7%) cases with IAPI in the dressing group and 13 (8.0%) cases in the control group, and the difference was not statistically significant ( χ2=3.41, P>0.05). Among the patients in the prone position, compared to the control group, the dressing group can effectively reduce the risk of IAPI in surgical patients by 77% ( OR=0.23, 95% CI 0.05-0.98, P<0.05). There was no interaction between foam dressing and intraoperative surgical characteristics ( P>0.05). Conclusions:Foam dressing plays a protective role in preventing the occurrence of IAPI in patients undergoing surgery in the prone position. There was no significant protective effect of intraoperative foam dressing in patients with other surgical characteristics.

OBJECTIVE: To explore the mechanism of ursolic acid in treating sepsis using myeloid differentiation protein-2 (MD-2) as the research carrier. METHODS: The affinity of ursolic acid and MD-2 was determined by biofilm interferometry technique, and the bonding mode between ursolic acid and MD-2 was tested with the aid of molecular docking technique. Raw 264.7 cells were cultured in RPMI 1640 medium and subcultured was conducted when the cell density reached 80%-90%. The second-generation cells were used for in the experiment. The effects of 8, 40 and 100 mg/L ursolic acid on cell viability were assessed by methyl thiazolyl tetrazolium (MTT) method. Cells were divided into blank group, lipopolysaccharide (LPS) group (LPS 100 μg/L) and ursolic acid group (100 μg/L LPS treatment after addition of 8, 40 or 100 mg/L ursolic acid). The effect of ursolic acid on the release of cytokines nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukins (IL-6, IL-1β) were evaluated by enzyme-linked immunosorbent assay (ELISA). The influence of ursolic acid on the mRNA expressions of TNF-α, IL-6, IL-1β, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were detected by reverse transcription-polymerase chain reaction (RT-PCR). The implication of ursolic acid on the protein expressions of LPS-Toll-like receptor 4 (TLR4)/MD-2-nuclear factor-κB (NF-κB) pathway were tested by Western blotting. RESULTS: Ursolic acid could bind to the hydrophobic cavity of MD-2 through hydrophobic bond with the amino acid residues of the protein. Therefore, ursolic acid showed high affinity with MD-2 [dissociation constant (KD) = 1.43×10^-4]. The cell viability were decreased slightly, with the concentration of ursolic acid increasing, and the cell viability of 8, 40 and 100 mg/L ursolic acid were 96.01%, 94.32% and 92.12%, respectively, and there was no significant difference compared with the blank group (100%). Compared with the blank group, the cytokine level of the LPS group was significantly increased. The level of cytokines were significantly reduced by the treatment of 8, 40 and 100 mg/L ursolic acid, and the higher the concentration, the more obvious effect [compared between 100 mg/L ursolic acid group and LPS group: IL-1β (μmol/L): 38.018±0.675 vs. 111.324±1.262, IL-6 (μmol/L): 35.052±1.664 vs. 115.255±5.392, TNF-α (μmol/L): 39.078±2.741 vs. 119.035±4.269, NO (μmol/L): 40.885±2.372 vs. 123.405±1.291, all P < 0.01]. Compared with the blank group, the mRNA expressions of TNF-α, IL-6, IL-1β, iNOS and COX-2 in the LPS group were significantly increased, and the protein expressions of MD-2, myeloid differentiation factor 88 (MyD88), phosphorylation NF-κB p65 (p-NF-κB p65) and iNOS in the LPS-TLR4/MD-2-NF-κB pathway were significantly up-regulated. Compared with the LPS group, the mRNA expressions of TNF-α, IL-6, IL-1β, iNOS and COX-2 were significantly reduced by the treatment of 100 mg/L ursolic acid bound with MD-2 protein [TNF-α (2^-ΔΔCt): 4.659±0.821 vs. 8.652±0.787, IL-6 (2^-ΔΔCt): 4.296±0.802 vs. 11.132±1.615, IL-1β (2^-ΔΔCt): 4.482±1.224 vs. 11.758±1.324, iNOS (2^-ΔΔCt): 1.785±0.529 vs. 4.249±0.811, COX-2 (2^-ΔΔCt): 5.591±1.586 vs. 16.953±1.651, all P < 0.01], and the proteins expressions of MD-2, MyD88, p-NF-κB p65 and iNOS in the LPS-TLR4/MD-2-NF-κB pathway were significantly down-regulated (MD-2/β-actin: 0.191±0.038 vs. 0.704±0.049, MyD88/β-actin: 0.470±0.042 vs. 0.875±0.058, p-NF-κB p65/β-actin: 0.178±0.012 vs. 0.571±0.012, iNOS/β-actin: 0.247±0.035 vs. 0.549±0.033, all P < 0.01). However, there was no difference in protein expression of NF-κB p65 among the three groups. CONCLUSIONS Ursolic acid inhibits the release and expression of cytokines and mediators and regulates LPS-TLR4/MD-2-NF-κB signaling pathway by blocking MD-2 protein, and thus plays an anti-sepsis role.
Humans ; Tumor Necrosis Factor-alpha ; Actins ; Cyclooxygenase 2 ; Interleukin-6 ; Lipopolysaccharides ; Lymphocyte Antigen 96 ; Molecular Docking Simulation ; Myeloid Differentiation Factor 88 ; NF-kappa B ; Toll-Like Receptor 4 ; Sepsis ; Cytokines ; Cell Differentiation ; RNA, Messenger