OBJECTIVE To investigate the targeting effect of folic acid-modified crebanine nanoparticles （FA-Cre@PEG- PLGA NPs， hereinafter referred to as “NPs”） combined with ultrasound irradiation on M109 cells in vitro and in vivo after administration， and explore the anti-tumor mechanism. METHODS CCK-8 assay was used to detect the inhibitory effect of NPs combined with ultrasound irradiation on the proliferation of M109 cells， and the best ultrasound time was selected. Using human lung cancer A549 cells as a control， the targeting of NPs combined with ultrasound irradiation to M109 cells was evaluated by free folic acid blocking assay and cell uptake assay. The effects of NPs combined with ultrasound irradiation on the migration， invasion， apoptosis， cell cycle and reactive oxygen species （ROS） levels of M109 cells were detected by cell scratch test， Transwell chamber test and flow cytometry at 1 h after 958401536@qq.com administration； the changes of mitochondrial membrane potential （MMP） were observed by fluorescence inverted microscope. A mouse subcutaneous tumor model of M109 cells was constructed， and the in vivo tumor targeting of NPs combined with ultrasound irradiation was investigated by small animal in vivo imaging technology. RESULTS NPs combined with ultrasound irradiation could significantly inhibit the proliferation of M109 cells， and the optimal ultrasound time was 1 h after administration. The free folic acid could antagonize the inhibitory effect of NPs on the proliferation of M109 cells， and combined with ultrasound irradiation could partially reverse this antagonism. Compared with A549 cells， the uptake rate of NPs in M109 cells was significantly higher （P＜0.01）， and ultrasound irradiation could promote cellular uptake. NPs combined with ultrasound irradiation could inhibit the migration and invasion of M109 cells and block the cell cycle in the G0/G1 and G2/M phases. Compared with control group， the apoptosis rate of M109 cells and ROS level were increased significantly （P＜0.01）， while the MMP decreased significantly （P＜0.01） in the different concentration （100， 200， 300 μg/mL） groups of M109 cells. Compared with the mice in non-ultrasound group， the fluorescence intensity and tumor-targeting index of the tumor site in the 0 h ultrasound group were significantly enhanced （P＜0.05 or P＜0.01）. CONCLUSIONS NPs combined with ultrasound irradiation have a strong targeting effect on M109 cells in vitro and in vivo， the anti-tumor mechanism includes inhibiting cell migration and invasion， blocking cell cycle， and inducing apoptosis.

ObjectiveTo investigate the effect of folic acid-modified crebanine polyethylene glycol-polylactic acid hydroxyacetic acid copolymer（PEG-PLGA） nanoparticles（FA-Cre@PEG-PLGA NPs， hereinafter referred to as NPs） combined with ultrasonic irradiation on subcutaneous tumor of liver cancer in Kunming（KM） mice. MethodsEighty-four healthy male KM mice were utilized to establish a subcutaneous tumor model of mouse hepatocellular carcinoma with H22 cells， then mice were randomly divided into model group， placebo group， hydroxycamptothecin group（8 mg∙kg^-1）， low， medium and high dose crebanine raw material groups（2， 2.5， 3 mg∙kg^-1， hereinafter referred to as the low， medium and high dose crebanine groups， respectively）， low， medium and high dose NPs groups（2， 2.5， 3 mg∙kg^-1）， and low， medium and high dose NPs combined with ultrasonic irradiation groups（2， 2.5， 3 mg∙kg^-1， hereinafter referred to as the low， medium and high dose combination groups， respectively）. The corresponding doses of drugs were administered via tail vein injection， the model group received no treatment， while the placebo group was injected with an equivalent amount of normal saline. Dosing was conducted for a total of 10 times on alternate days. The body mass of the mice was monitored， and parameters such as body mass change rate， thymus index， spleen index， tumor volume， tumor weight， relative tumor growth rate（T/C）， and tumor inhibition rate（TGI） were calculated. Pathological changes in liver and kidney tissues as well as the tumor were observed by hematoxylin-eosin（HE） staining. Additionally， the levels of aspartate aminotransferase（AST）， alanine aminotransferase（ALT）， blood urea nitrogen（BUN） and creatinine（CREA） in serum of mice were detected by biochemical method. Furthermore， the effect of ultrasound on the distribution of NPs in subcutaneous tumors of mouse hepatocellular carcinoma was observed by in vivo imaging technique. ResultsAmong different treatment methods， the combination of NPs and ultrasound irradiation had the best therapeutic effect. Compared with the model group， the body mass growth rates of mice in the medium and high combination groups decreased， while the thymus index and spleen index increased， but there was no statistically significant difference in serum AST， ALT， BUN and CREA levels， indicating that NPs combined with ultrasound irradiation had little effect on the normal physiological state of the body， oth groups had TGI>40% and T/C<60%， indicating a clear anti-tumor effect. Pathological analysis showed that compared with the NPs groups， the combination groups exhibited varying degrees of necrosis in tumor cells， accompanied by less damage to the liver and kidneys. In vivo imaging of small animals showed that compared with the high dose NPs group， the high dose combination group had stronger tumor targeting ability（P<0.01）. ConclusionNPs combined with ultrasonic irradiation can not only effectively targeted the drug to the tumor site， inhibit the subcutaneous tumor growth of mouse liver cancer， but also decrease damage to liver and kidney tissues.

OBJECTIVE To provide references for further improving the management level of Chinese herbal pieces covered by the healthcare security drug catalog （hereinafter referred to as “healthcare security covered Chinese herbal pieces”）. METHODS Policy documents related to healthcare security covered Chinese herbal pieces were retrieved from official websites of National Healthcare Security Administration and medical insurance bureaus of various provinces （autonomous regions， municipalities directly under the central government）. Using text analysis， the current management status of healthcare security covered Chinese herbal pieces in various provinces was analyzed from two dimensions： management regulations and catalog formats. RESULTS In terms of the management regulations for healthcare security covered Chinese herbal pieces， some provinces implemented both national and provincial standards for Chinese herbal pieces， while a small number of provinces adopted national standards alongside their own provincial standards. Regarding the payment categories of healthcare security covered Chinese herbal pieces， most were classified as category A， though some provinces managed them as category B， and others included both categories A and B or category C. In terms of applicants， there were three kinds： only medical institutions， only herbal piece enterprises， or both medical institutions and herbal piece enterprises being allowed to apply. During the application process， some provinces required preliminary evaluations by local healthcare security departments with recommended lists submitted， while some provinces omitted preliminary evaluations and relied solely on unified evaluation by provincial healthcare security departments. Regarding the methods for catalog formulation and adjustment， there was little variation among the provinces. In terms of the catalog format for healthcare security covered Chinese herbal pieces， some provinces had supplemented the catalog fields based on the national medical insurance catalog. In contrast， some provinces had relatively simple catalogs. Regarding the sorting of the herbal pieces catalog， some catalogs were arranged by the number of Chinese character strokes in the names of the herbal pieces， but most catalogs lacked clear sorting rules. CONCLUSIONS Significant resultshave been achieved in formulating management measures and the catalog of healthcare security covered Chinese herbal pieces. However， there is still a great necessity to develop targeted and adaptable management clauses based on local conditions and the characteristics of Chinese herbal pieces. The content and format of healthcare security drug catalog of Chinese herbal pieces should be improved； in addition， continuous tracking of the latest management policies is also essential to improve the accuracy and operability of formulated catalog.

Objective To evaluate the efficacy and safety of budesonide combined with pulmonary surfactant(PS)in the treatment of meconium aspiration syndrome(MAS)in neonates.Methods PubMed,Cochrane Central Register of Controlled Trials(Central),Embase,Web of Science,SinoMed,VIP,WanFang Data and CNKI databases were electronically searched to collect randomized controlled trials(RCTs)of budesonide combined with PS in the treatment of neonatal MAS from inception to September 2,2023.Two researchers independently screened literature,extracted data and assessed the risk of bias of the included studies,meta-analyses were performed by using the RevMan 5.4 software.Results A total of 6 RCTs involving 544 patients were included.The results of meta-analysis showed that compared with PS group,budesonide combined with PS group had higher overall effective rate(RR=1.29,95％CI 1.17 to 1.41,P＜0.001),shorter hospital stay(MD=-6.35,95％CI-9.25 to-3.46,P＜0.001)and shorter time of oxygen inhalation(MD=-1.61,95％CI-2.23 to-0.98,P＜0.001),shorter the duration of ventilator use(MD=-26.46,95％CI-35.98 to-16.95,P＜0.001),improved the blood gas analysis indexes at each time after treatment(P＜0.05);In terms of safety,the incidence of total complications and adverse reactions in budesonide combined with PS group was significantly lower(RR=0.35,95％CI 0.25 to 0.47,P＜0.001).Subgroup analysis showed that the incidence of persistent pulmonary hypertension of the newborn(PPHN)in the budesonide combined with PS group was decreased(RR=0.38,95％CI 0.19 to 0.74,P=0.004),and the incidence of pneumorrhagia was decreased(RR=0.26,95％CI 0.10 to 0.69,P=0.007),and the difference was statistically significant;the incidence of heart failure and sepsis was not statistically significant compared with the PS group(P＞0.05).Conclusion Current evidence shows that budesonide combined with PS in the treatment of neonatal meconium aspiration syndrome can improve the symptoms and signs of MAS children,improve the blood gas analysis index,accelerate disease rehabilitation,shorten the course of the disease,can help reduce the risk of complications and PPHN,pneumorrhagia,and doesn't increase the incidence of heart failure,sepsis.Due to the limited quantity of the included studies,more high-quality and large-sample RCTs are needed to further validate the above conclusions.

Objective: To investigate the prevalence of hyperactivity behavior in children aged 3-6 in Yunnan Province, to explore its relationship with neuropsychological development, so as to provide clues for early prevention and intervention of attention deficit hyperactivity disorder (ADHD) in children. Methods: A total of 1 321 children aged 3 to 6 from 10 kindergartens in 5 prefectures (cities) of Yunnan Province were selected by stratified random sampling method from October 2022 to May 2023. Teacher Rating Scale (TRS) was used to investigate childrens hyperactive behavior and coexistent behavior. A qualified evaluator applied the Developmental Scale for Children Aged 0-6 Years to assess the development of 5 ability areas of gross motor movement，fine movement，adaptive ability，language and social behavior. Statistical analysis was performed using Wilcoxon rank sum test and χ2 test. Binary Logistic regression was applied to analyze the score of their hyperactivity behavior and its relationship with other behavior problems and neuropsychological development. Results: The detection rate of hyperactivity behavior was 8.6% in children aged 3 to 6 years, 12.8% in boys and 4.1% in girls (χ2=31.53, P<0.01). The detection rate of hyperactivity in 3yearold children was 13.9%, which was higher than that in 4yearold (9.2%) and 5yearold children (7.0%) (χ2=8.73, P<0.05). The detection rate of inattentionpassivity of rural children (14.6%) was higher than that of urban children (5.9%) (χ2=22.23, P<0.01). Binary Logistic regression analysis showed that the higher the level of adaptive development, the lower the risk of hyperactivity (OR=0.58, 95%CI=0.39-0.86), the higher the risk of hyperactivity (OR=0.57, 95%CI=0.35-0.91), the higher the risk of conduct problems (OR=0.57, 95%CI=0.37-0.87), inattentionpassivity (OR=0.49, 95%CI=0.33-0.74) were also at lower risk (P<0.05). Children with higher levels of fine motor development had a lower risk of inattentionpassivity (OR=0.59, 95%CI=0.37-0.93, P<0.05). Conclusions Hyperactivity in boys and inattentionpassivity in rural children requires more attention. It is necessary to strengthen childrens early adaptive ability and fine motor training to prevent hyperactive behavior and inattention.

OBJECTIVE To establish the project approval evaluation system for traditional Chinese medicine （TCM） preparations in medical institutions guided by new drug conversion， to improve the success rate of approval for TCM preparations in medical institutions and lay the foundation for the later drug conversion. METHODS Research and development team used the literature research method and brainstorming method to list and organize relevant elements of project evaluation and determine the initial indicator system. Experts were consulted using the Delphi method to confirm the evaluation index. The weights were calculated based on the proportion of importance scores for each indicator and assigned specific scores to each item. The indicator system was used to evaluate 31 TCM preparations applied for filing by various departments of our hospital from April to July 2023. RESULTS After two rounds of 17 experts’ consultation， the final TCM preparation system included five primary indicators， i.e. theoretical basis， clinical research foundation， pharmaceutical foundation， prescription， and clinical value， as well as 17 secondary indicators including prescription source， traditional Chinese medicine theory， clinical positioning and so on. Human experience was considered as the item which would be rejected as one vote. Based on the above indicator system， our hospital further improved the filing and project approval process for TCM preparations in medical institutions. Among the 31 TCM preparations applied for filing by various departments from April to July 2023， 8 TCM preparations with a score ≥65 were selected for development. CONCLUSIONS The evaluation system is objective， comprehensive， and highly operable. It is suitable for the selection of TCM preparations in medical institutions before research and development.

Objective:To analyze the effect of depressive state on Alzheimer's disease(AD)mice,3xTg-AD mice were stimulated with chronic social frustration stress(CSDS)and chronic mild unpredictable stress(CUMS),to estab-lish an early AD-induced depression mouse model,and to detect cognitive and behavioral changes,activation of micro-glia in the hippocampus and neuronal loss.Methods:Three-month-old mice were subjected to 8-day stress stimulation alternately,the depressive state of the mice was evaluated by behavior,the evaluation criteria were formulated,and the cognitive behavior was detected and analyzed,and the hippocampal brain tissue sections were stained with immunofluo-rescence to observe the deposition of β-amyloid(Aβ)and the aggregation of microtubule-associated protein(tau),mi-croglia activation and neuronal loss.Results:Depression-related behavioral results showed that the CSDS+CUMS group had depression-related phenotypes.Cognitive-behavioral testing showed that the new object recognition index of the mice in the CSDS+CUMS group was significantly reduced(P＜0.05),and the Morris water maze showed that the spatial memory ability of the CSDS+CUMS group was significantly reduced(P＜0.05),but there was no obvious fear memory loss in the CSDS+CUMS group in the conditioned fear experiment.The results of immunofluorescence staining showed that Aβ deposition appeared in the hippocampus at 4 months of age,the activated microglia increased(P＜0.001),and a certain degree of neuronal loss appeared in the CSDS+CUMS group(P＜0.001);At 8 months of age,the CSDS+CUMS group showed tau protein aggregation early.Conclusion:We established a model of AD-induced de-pression in AD mice,in which 3xTg-AD mice experienced early decline in learning memory and increased AD-related pathological deposition of neurons in the hippocampus,accompanied by microglial activation and neuronal loss.

Separation/conversion disorders in functional coma with pseudocataplexy are rare.On De-cember 9,2021,a young female patient with separation/conversion disorders was treated in the Department of Neurology in the First Affiliated Hospital of Shandong First Medical University.The main symptoms were episodic consciousness disorders,sudden fainting,and urinary incontinence.Complete laboratory tests and cranial mag-netic resonance imaging showed no obvious abnormalities.Standard multi-channel sleep monitoring and multiple sleep latency tests were performed.The patient was unable to wake up during nap and underwent stimulation tests.There was no response to orbital pressure,loud calls,or tapping,while the α rhythm in all electroenceph-alogram leads and the increased muscular tone in the mandibular electromyography indicated a period of wakeful-ness.The results of 24-hour sleep monitoring suggested that the patient had sufficient sleep at night and thus was easy to wake up in the morning.The results of daytime unrestricted sleep and wake-up test showed that the patient took one nap in the morning and one nap in the afternoon.When the lead indicated the transition from N3 to N2 sleep,a wake-up test was performed on the patient.At this time,the patient reacted to the surrounding environ-ment and answered questions correctly.Because the level of orexin in the cerebrospinal fluid was over 110 pg/mL,episodic sleep disorder was excluded and the case was diagnosed as functional coma accompanied by pseudocata-plexy.The patient did not present obvious symptom remission after taking oral medication,and thus medication withdrawl was recommended.Meanwhile,the patient was introduced to adjust the daily routine and mood.The follow-up was conducted six months later,and the patient reported that she did not experience similar symptoms after adjusting lifestyle.Up to now,no similar symptoms have appeared in multiple follow-up visits for three years.Functional coma with pseudocataplexy is prone to misdiagnosis and needs to be distinguished from true co-ma and episodic sleep disorders.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To explore the otherness of orthotopic injection of cell suspensions and transplantation of tumor tissue blocks to establish orthotopic implantation models of hepatocellular carcinoma in mice,and to provide a technical reference for the establishment of an orthotopic implantation model.Methods Healthy KM mice were divided into four groups:group A,direct injection of H22 cells;group B,direct injection of H22 ascitic cells;group C,transplantation of tissues;and group D,direct injection of saline.Activity and weight changes were observed regularly in each group and survival times were recorded.Liver tumor formation,tumor size,abdominal organ adhesion degree,and metastasis were observed in all groups.B-ultrasound imaging was performed,concentrations of alpha fetoprotein(AFP)and abnormal prothrombin(DCP)were detected,and liver histopathological changes were detected by hematoxylin and eosin staining.Results Mice molding operation time in groups A,B,and C were(3.36±0.44)min,(3.30±0.41)min,and(5.68±0.65)min,respectively.After modeling for 25 days,the rates of model formation in groups A,B,and C were all 100.0%.Severe abdominal adhesions occurred in 40.0%of mice in group A and 60.0%in group B,but in no mice in group C or D.Ascites occurred in 40.0%,100.0%,and 0.0%and abdominal wall tumors in 30.0%,60.0%,and 0.0%of mice in groups A,B,and C,respectively,while 40.0%of mice in group B also had liver metastasis.B-ultrasound imaging,detection of serum AFP and DCP levels,and histopathological result showed smooth liver margins,uneven echo and slightly lower echo mass,maintained high AFP and DCP secretion,and large numbers of inflammatory cells and tumor cells in mice in groups A,B,and C.Conclusions At day 25,all three methods can thus be used to establish orthotopic transplantation models of HCC.Among these,inj ection of cell suspensions demonstrated the advantage of simplicity in operation and the presence of multiple metastatic nodules within the liver,compared to transplantation of tumor tissue.Conversely,transplantation of tumor tissue showed the advantage of causing less impact on the abdomen and other organs when compared to inj ection of cell suspensions.