OBJECTIVE To form an expert consensus addressing clinical issues regarding the use of parenteral direct thrombin inhibitors （DTIs） in special populations. METHODS Led by the Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital（the Affiliated Hospital of UESTC）， a multidisciplinary working group was formed comprising experts from multiple fields， including clinical pharmacy， cardiac surgery， obstetrics， pediatrics and evidence-based medicine. Through literature review and the Delphi method， clinical questions regarding the efficacy and safety of parenteral DTIs used in special populations were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” （PICO） framework；systematic searches were conducted in CJFD， PubMed， Embase and other databases. Relevant evidence from randomized controlled trials，cohort studies and systematic reviews were included and synthesized. Evidence quality was assessed using the Grading of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through three rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven clinical questions were ultimately selected （with a consensus rate exceeding 90%）， resulting in the formulation of seven recommendations on the use of parenteral DTIs in special populations， including children， pregnant women， patients with hepatic or renal impairment， patients with mesenteric venous thrombosis， and individuals with thrombophilia. These recommendations clarify the preferred agents， dosing ranges， monitoring parameters， and safety management strategies for parenteral DTIs in these special populations. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in special populations.

To optimize the traditional refining process of Hydrargyrum Chloratum Compositum(HCC) and explore the change law of substances before and after refining, this study applied the hierarchical analysis method(AHP)-entropy weight method, using appearance, yield, and mercuric chloride content as evaluation indexes. The temperature and time of mild and strong fire were examined as single factors, and an L_9(3~4) orthogonal experiment was used to optimize the refining process. An infrared thermal imaging platform was set up to record the temperature changes on the surface of the tank, aiming to establish a standardized operating procedure for the refining process. Elemental changes, physical phase changes, and thermal property changes of the materials before and after refining were analyzed using atomic absorption spectrophotometry(AAS), X-ray diffraction(XRD) and differential scanning calorimetry(DSC). The results showed that the average overall score of the finished product obtained from the optimized HCC refining process(with mild fire temperature of 102 ℃, mild fire refining time of 30 min, strong fire temperature of 178 ℃, and strong fire refining time of 68 min) was 91.59, with an RSD of 0.076%, indicating that the process is stable and feasible. Combined with thermal imaging data and related research results, it was found that, at the strong fire temperature, mercury ions and nitrate ions generated mercuric chloride under the catalysis of other ions. The mercury content of mercurous chloride, mercuric chloride synthesized from nitric acid, HCC, and the pre-refined sample was 84.535%, 72.376%, 70.838%, and 41.334%, respectively. The highest intensity of the(120) diffraction peak for HCC appeared around 20.36°, but the residual fit value was larger. The synthesis of mercuric chloride from HCC and nitric acid showed an exothermic peak at 190-204 ℃, with the peak shape exhibiting a rightward trend. This study optimized the traditional refining process of HCC and analyzed the elemental changes, physical phase changes, and thermal property changes before and after refining. The findings provide experimental data for exploring the changing patterns in the refining process of HCC and its pharmacological value, as well as for standardizing the traditional refining process in clinical practice.
Drugs, Chinese Herbal/chemistry* ; X-Ray Diffraction ; Temperature ; Calorimetry, Differential Scanning ; Mercuric Chloride/chemistry*

Hongsheng Dan, historically referred to as the "surgical sacred medicine", is at risk of losing its refining technology in contemporary times. This study aimed to preserve and innovate this traditional non-heritage refining technology. By utilizing the analytic hierarchy process(AHP) combined with the entropy weight method, this study established the hierarchical structure model of refining process of Hongsheng Dan and conducted a single factor experiment and an L_9(3~4) orthogonal experiment to optimize the refining method of Hongsheng Dan. Additionally, the study employed infrared thermal imaging to monitor temperature variations of Hongsheng Dan during the refining process. The optimized refining parameters for Hongsheng Dan were established as follows: a slow fire temperature of 175 ℃ with a duration of 30 minutes, a strong fire temperature of 270 ℃ with a duration of 60 minutes, and a tail fire temperature of 180 ℃ with a duration of 15 minutes. The stability and feasibility of this optimized process were confirmed through validation tests. The research focused on the material transformation of Hongsheng Dan, starting from the material changes during the refining process of Hongsheng Dan and the synthesis of mercuric oxide from nitric acid. The study investigated elemental transformations, physical phase changes, and alterations in thermal properties. 78.98% of the mercury in Hongsheng Dan and 80.21% of the mercury in mercuric oxide from nitric acid were retained. The diffraction peak intensity of the(011) crystal plane of Hongsheng Dan was highest at approximately 30.07°, indicating that the(011) crystal plane had a preferred crystalline orientation. Furthermore, the temperature range for the alteration in thermal properties during the refining process of Hongsheng Dan was found to be between 80 ℃ and 130 ℃. This research not only optimized the refining technology of Hongsheng Dan but also pioneered the application of infrared thermal imaging to study temperature changes throughout the refining process. By exploring the material transformation patterns of Hongsheng Dan and the synthesis of mercuric oxide from nitric acid, the study provided technical support for the preservation and innovation of Hongsheng Dan.
Drugs, Chinese Herbal/standards* ; Temperature

Objective To investigate the vaccination status and vaccination willingness of novel coronavirus in HIV/AIDS population in Yunnan.Methods From October 2021 to June 2022,a questionnaire survey was conducted among 2180 HIV/AIDS patients in Kunming,Qujing,Yuxi,Zhaotong,Puer,Baoshan,Lincang,Honghe,Wenshan,Xishuangbanna,Dali,Dehong and Nujiang prefectures.The questionnaire included age,sex,education,nationality,education level,vaccination,adverse reactions within 7 days after the vaccination,safety of COVID-19 vaccine,awareness of effectiveness,vaccination willingness and so on.Results Among the subjects,2109 completed 3 injections,accounting for 96.74%,and 71 were not vaccinated,accounting for 3.26% .Within 7 days of inoculation,local adverse reactions occurred in 116 cases,accounting for 5.50%,and systemic adverse reactions occurred in 56 cases,accounting for 2.66% .Injection site pain,fatigue and muscle pain accounted for the highest proportion of adverse symptoms in different sex,age and the Han nationality,while the proportion of minority adverse reactions was very low,and there was no difference among the different sex and age(P>0.05).The main reasons for the reluctance of HIV/AIDS population to be vaccinated were(recommended by doctors)that HIV/AIDS patients could not be vaccinated(67.61%)and may have serious adverse reactions after the vaccination(19.72%).The factors affecting the vaccination were found by logistic regression analysis,whether they were worried about infecting novel coronavirus(OR = 0.121,95% CI = 0.083～0.640,P<0.001)and how much they knew about COVID-19 vaccine(OR = 28.932,95% CI = 15.469～54.115,P<0.001),safety of vaccination(OR = 13.953,95% CI = 4.819～40.404,P<0.001)and belief in the preventive effect of vaccine(OR = 14.017,95% CI = 4.752～41.348,P<0.001)were significant factors affecting vaccination.Among the 13 prefectures and cities,Dehong(20),Zhaotong(21)and Lincang(14)had the largest number of unvaccinated people.Conclusion After the mass vaccination,the rate of adverse reaction in HIV/AIDS population is low,the symptoms are mild,the correct and scientific advice and guidance from doctors and the full understanding of the harmfulness of the disease,the safety,prevention and effectiveness of the vaccine are the key to complete vaccination and put an end to vaccine hesitancy.

Objective Pancreatic cancer(PC)is a malignant tumor of the digestive tract that is difficult to diagnose early,easily metastasizes and relapses,and resistant to conventional chemotherapy.PC is a very difficult disease to treat.The key regulatory factors of PC resistance,such as epithelial-mesenchymal transition phenotypic cells,tumor stem cells,and miRNAs,have been reviewed in the past few years,and some new regulatory factors have been discovered as supplements.This review mainly focuses on the characteristics and properties of the key regulatory factors of PC chemotherapy resistance including long noncoding RNAs,nuclear factor KB and exosomes,drug resistance mechanisms,and treatment related strategies,and future treatment directions were predicted.

Eighteen compounds were isolated from the methanol extract of the fruits of Litsea cubeba by silica gel, ODS, Sephadex LH-20 column chromatography, semi-preparative RP-HPLC, chiral HPLC and recrystallization. Their structures were elucidated by spectroscopic analyses and by comparison with reported spectroscopic data and physicochemical properties, and the absolute configurations of the enantiomers were established by experimental and calculated electronic circular dichroism spectra. These compounds were identified as (+)-(R)-4-hydroxypiperitenone (1a), (-)-(S)-4-hydroxypiperitenone (1b), (3S,4S,6R)-3,6-dihydroxy-1-menthene (2), (4S,5R)-4-hydroxy-5-isopropyl-2-methylcyclohex-2-en-1-one (3), (R)-6-hydroxy-3-(2-hydroxypropan-2-yl)-6-methylcyclohex-2-enone (4), (4S,6R)-4-hydroxy-6-isopropyl-3-methylcyclohex-2-enone (5), (1R,3S,4R)-3-hydroxy isopulegol (6), subamone (7), (6S)-3,7-dimethyl-7-hydroxy-2(Z)-octen-6-olide (8), (6S)-6,7-dihydroxy-3,7-dimethyloct-2(Z)-enoate (9), holostylactone (10), sesamin (11), dimethylmatairesinol (12), p-hydroxybenzoylcarbinol (13), syringaldehyde (14), p-hydroxybenzaldehyde (15), 4-hydroxy-3-methoxybenzaldehyde (16), 5,4ʹ-dihydroxy-7-methoxyflavone (17). Among them, compounds 1a and 1b were a pair of new monoterpenoid enantiomers, 8 and 9 were new natural products, 2-7, 10, 11 and 17 were isolated from Litsea genus for the first time. The in vitro anti-inflammatory effects of compounds 1-17 were evaluated using lipopolysaccharide-stimulated RAW264.7 cells, the results showed that compound 14 exhibited significant anti-inflammatory activity with NO inhibitory rate of 66.27% at a concentration of 40 μmol·L^-1.

Objective To explore the characteristics of speech prosody chunking,affect,focus and interaction function in patients with non-fluent aphasia after stroke. Methods From December,2023 to March,2024,patients with non-fluent aphasia after stroke(experimental group,n=25)and healthy subjects(control group,n=25)were recruited from Shanghai Fifth Rehabilitation Hospital,and the two groups were compared in terms of chunking,affect,focus and interaction performance using a self-ad-ministered speech prosody function assessment tool and acoustic analyzing instrument. Results In chunking prosody,there were differences in auditory discrimination(Z=-4.856,P<0.001),auditory recog-nition of"two chunks"(Z=-3.024,P=0.002),and subjective scores,total pause duration,average pause dura-tion,average syllabic duration and structural sonic rate(|Z|>2.911,P<0.001)of imitating"two chunks"and au-tonomously outputing"two chunks"and"three chunks"between two groups.In affect prosody,there were differ-ences in listening to distinguish different emotions(Z=-3.322,P=0.001),listening to identify"like emotion"(Z=-3.481,P=0.001),and the subjective score(Z=-6.214,P<0.001),average intensity(Z=-3.581,P<0.001)and standard deviation of intensity(Z=-3.181,P=0.001)of imitating"like emotion"between two groups;there were differences in the subjective score(Z=-5.510,P<0.001),average intensity(Z=-3.429,P=0.001),standard deviation of intensity(Z=-4.777,P<0.001)and fundamental frequency variation range(t=1.852,P=0.029)of autonomously outputing"like emotion"between two groups.In focus prosody,there were differences in listening to distinguish different focuses(Z=-2.658,P=0.008),listening to identify the"end of sentence"focus(Z=-2.023,P=0.011),and the peak stress intensity of imitating the"first sentence"focus(t=8.294,P<0.001);the subjective score(|Z|>5.102,P<0.001)and peak stress intensity(t>8.298,P<0.001)of imitating the"mid-sentence"and"end-sentence",and the subjective score(Z=-4.371,P<0.001)and peak stress intensity(t=8.842,P<0.001)of autonomously outputing the focus of the"first sentence"between two groups;there were differences in the subjective score(|Z|>4.970,P<0.001),peak stress intensity(t>9.373,P<0.001)and stress duration(|t|>2.912,P<0.01)of autonomously outputing the focus of the"mid-sentence"and"end-sentence".In the interaction prosody,there were no significant difference in auditory resolution and au-ditory recognition between two groups(P>0.05),however,there were significant differences in the subjective score(|Z|>4.938,P<0.001)and the fundamental frequency slope k(|t|>4.609,P<0.001)of the interrogative tone both in imitative output and autonomous output. Conclusion Patients with non-fluent aphasia showed significant abnormalities in the recognition and expression of"2 chunks""like emotion""sentence-final focus"and"questioning tone."

Objective:To explore whether the food additive sodium benzoate(NAB) induces pancreatic inflammation and β cell apoptosis through the benzoylation(Kbz) modification pathway.Methods:In vivo experiments: C57BL/6J male mice(8 weeks old, 18-20 g) were randomly divided into normal control group(double distilled water feeding) and NAB feeding group(1 g/kg NAB feeding). Blood glucose were measured. After 20 weeks, fasting serum insulin, interleukin(IL)-18, IL-1β, and benzoyl-CoA levels were detected by ELISA method. Bax, IL-18, Pan-Kbz and Pan-Kac were detected by immunohistochemistry staining. In vitro experiments: β-TC-6 cells were cultured with NAB(6 mmol/L) or benzoyl-CoA(100 μmol/L) as stimulator and acyltransferase P300 inhibitor A485(10 μmol/L) as intervention factor. 24 hours later, inflammation, apoptosis, insulin secretion and Pan-Kbz level were detected by qRT-PCR, ELISA and Western blotting.Results:In the in vivo experiments, compared to the NC group, mice in the NAB group exhibited impaired glucose tolerance, decreased fasting insulin levels, significantly increased serum benzoyl coenzyme A concentrations, relatively elevated pancreatic IL-1β, IL-18, and Bax protein expressions, increased levels of Pan-Kbz, while Pan-Kac levels were downregulated(all P<0.05); In vitro experiments, NAB dose-dependently inhibited insulin secretion, promoted the release of Pan-Kbz and inflammatory factors IL-18 and TNF- α, inhibited Bcl-2 expression and up-regulated Bax expression, A485 reversed NAB-induced Pan-Kbz modification, improved NAB-induced inflammation and apoptosis, and promoted insulin secretion(all P<0.05). Conclusion:NAB may induce pancreatic inflammation, β-cell apoptosis, and impair insulin secretion through Kbz modification pathway.

Objective:To investigate the toxic effect of chlorambucil combined with ibrutinib on mantle cell lymphoma(MCL)cell line Jeko-1 and its related mechanism.Methods:The MCL cell line Jeko-1 was incubated with different concentrations of chlorambucil or ibrutinib or the combination of the two drugs,respectively.CCK-8 assay was used to detect the proliferation of the cells,and Western blot was used to measure the protein expression levels of BCL-2,caspase-3,PI3K,AKT and P-AKT.Results:After Jeko-1 cells were treated with chlorambucil(3.125,6.25,12.5,25,50 μmol/L)and ibrutinib(3.125,6.25,12.5,25,50 μmol/L)alone for 24,48,72h respectively,the cell proliferation was inhibited in a time-and dose-dependent manner.Moreover,the two drugs were applied in combination at low doses(single drug inhibition rate＜50％),and the results showed that the combination of two drugs had a more significant inhibitory effect(all P＜0.05).Compared with the control group,the apoptosis rate of the single drug group of chlorambucil(3.125,6.25,12.5,25,50 μmol/L)and ibutinib(3.125,6.25,12.5,25,50 μmol/L)was increased in a dose-dependent manner.The combination of the two drugs at low concentrations(3.125,6.25,12.5 μmol/L)could significantly increase the apoptosis rate compared with the corresponding concentration of single drug groups(all P＜0.05).Compared with control group,the protein expression levels of caspase-3 in Jeko-l cells were upregulated,while the protein expression levels of BCL-2,PI3K,and p-AKT/AKT were downregulated after treatment with chlorambucil or ibrutinib alone.The combination of the two drugs could produce a synergistic effect on the expressions of the above-mentioned proteins,and the differences between the combination group and the single drug groups were statistically significant(all P＜0.05).Conclusion:Chlorambucil and ibrutinib can promote the apoptosis of MCL cell line Jeko-1,and combined application of the two drugs shows a synergistic effect,the mechanism may be associated with the AKT-related signaling pathways.

Objective To explore the correlation between speech fluency and diadochokinetic rate in children aged 7～11 years with cochlear implant.Methods Speech samples were collected from 62 children aged 7～11 years with cochlear implant using language retelling task and diadochokinetic rate test task.Their speech rate,articulation rate,syllable duration and pause duration were analyzed.The data were input into ICF converter to obtain the im-pairment limit of each parameter and analyze the speech fluency and diadochokinetic rate characteristics.Partial cor-relation analysis was performed for speech rate,articulation rate,syllable duration and pause duration by two tasks.Results ① For children with cochlear implant,the mean ICF impairment limit of diadochokinetic rate was 1.3± 0.1,the mean ICF impairment limit of fluency in retelling was 1.0±0.3,with various degree of impairment in both tasks.② There was a moderate or low correlation between speech rate,articulation rate,syllable duration in retell-ing task and those in diadochokinetic rate task(0.3＜|r |≤0.8).There was a low correlation between pause dura-tion in retelling task and speech rate and pause duration in diadochokinetic rate task(0.3＜|r |≤0.5).Conclusion The speech fluency and diadochokinetic rate of children aged 7～11 years with cochlear implant is underdeveloped,and the poor articulation movement ability limits their development of speech fluency.