OBJECTIVE To review the current research progress on pharmacoeconomics evaluation related to spinal muscular atrophy （SMA）， in order to provide valuable insights for clinical treatment， screening and medical insurance payment decision- making. METHODS A computerized search was conducted across multiple databases including PubMed， Web of Science， Embase， Scopus， Cochrane Library， EBSCOhost， CNKI， VIP， CBM and Wanfang database as well as other important health technology assessment （HTA） websites， such as National Institute for Health and Care Research，International Society of Technology Assessment in Health Care， Agency for Healthcare Research and Quality， etc. The pharmacoeconomics evaluation studies related to SMA were collected from the inception to December 31st， 2023. The literature/reports were rigorously screened based on predefined inclusion and exclusion criteria by two researchers， and the essential information from the included literature/ reports was extracted using Excel 2019. The quality of the included literature/reports was evaluated by Consolidated Health Economic Evaluation Reporting Standards 2022. RESULTS Finally， 9 articles and 15 HTA reports were included， with overall good quality of literature， but poor quality of HTA reports. There were a total of 24 studies on the pharmacoeconomics evaluation of SMA， including treatment options such as nusinersen sodium， sovaprevir， risperidone， and best supportive therapy.The review results showed that nusinersen sodium was not cost-effective in the treatment of SMA； there was no consensus on the economic viability of treatment options such as risperidone and sovaprevir； newborn/prenatal screening combined withmedication therapy was cost-effective. CONCLUSIONS newborn/prenatal screening combined with SMA medication therapy demonstrates economic advantages. It is suggested to further investigate the cost-effectiveness of new SMA drugs and SMA screening in China， taking localization parameters and medical insurance prices into account， and gradually incorporate SMA screening into the scope of neonatal genetic disease detection， in order to alleviate the financial burden of patients’ families and healthcare systems.

Objective To observe the effect of a new cell delivery tool(MSC exo)on the proliferation of pancreatic cancer by transferring targeted genes.Methods Transmission Electron Microscope(TEM)and Nanoparticle Tracking Analysis(NTA)were used to identify human mesenchymal stem cell exosomes(MSC-exo)and transport miR-450a-5p into CFPAC-1,to explore the effect of miR-450a-5p targeting BZW2 on inhibiting the proliferation of pancreatic cancer cells.Results The expression of miR-450a-5p was low in pancreatic cancer tissue(P<0.05),and the expression of CD63 and TSG101 of MSC-exo-miR-450a-5p in CFPAC-1 cells was higher than that of MSC-exo by Western blot(P<0.05).CCK-8 and EdU results showed that MSC-exo-miR-450a-5p significantly inhibited the proliferation of CFPAC-1 cells(P<0.05).Cell scratch and Transwell experiments showed that MSC-exo-miR-450a-5p can inhibit the migration and invasion of CFPAC-1 cells(P<0.05).Through dual luciferase assay,it was confirmed that miR-450a-5p targets BZW2,and RT-qPCR and Western blotting showed a negative correlation(P<0.05)between miR-450a-5p and BZW2 expression.Overexpression of BZW2,CCK-8,EdU,cell scratch,and Transwell experiments confirmed that pc-BZW2 reversed the anti-cancer function of MSC-exo-miR-450a-5p on CFPAC-1.Western blot detected PCNA,Ki-67,MMP2,MMP9,and the results were consistent with the above experiments(P<0.05).Conclusion hMSC exo is a new delivery system,targeting BZW2 to transport miR-450a-5p to inhibit the biological malignancy of pancreatic cancer cells,which provides an important clue for the research of targeted treatment of pancreatic cancer.

ObjectiveTo characterize the chemical constituents of Dayuanyin based on ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry（UPLC-Q-Exactive Orbitrap MS）. MethodThe detection was performed on a Thermo Acclaim™ RSLC 120 C₁₈ column（2.1 mm×100 mm， 2.2 μm）， the mobile phase was acetonitrile（A）-0.1% formic acid aqueous solution（B） for gradient elution （0-7.5 min， 10%-19%A； 7.5-12 min， 19%-22.5%A； 12-23 min， 22.5%-27%A； 23-27 min， 27%-56%A； 27-35 min， 56%-84%A； 35-36 min， 84%-90%A）， the flow rate was 0.3 mL·min^-1， and the column temperature was 30 ℃. The data were collected in the positive and negative ion modes by heated electrospray ionization（HESI）， and the detection range was m/z 80-1 200. Combining the retention time of the reference substance， fragment ions， databases such as PubChem and related literature， Xcalibur 3.0 was used to identify the chemical constituents of Dayuanyin. ResultA total of 161 compounds were identified， including 14 alkaloids， 60 flavonoids， 16 terpenoids， 26 saponins， 18 phenylpropanoids， 16 organic acids and 11 others. ConclusionThe established method can effectively and quickly identify the chemical components in Dayuanyin， and clarify its chemical composition， which can provide a basis for the development of compound preparations of this famous classical formula.

Objective:To investigate the efficacy of neostigmine combined with raw rhubarb enema on severe acute pancreatitis (SAP) patients with intra-abdominal hypertension (IAH).Methods:The clinical data of 89 SAP patients, who were admitted and underwent continuous renal replacement treatment (CRRT) in intensive care unit (ICU) department of the First Affiliated Hospital of Hebei North University from January 2018 to June 2022, were retrospectively analyzed. Patients were divided into control group ( n=44) and experimental group ( n=45) according to the treatment mode. Raw rhubarb enema plus sodium sulfate topical application were administrated twice a day for 7 days in control group; besides the treatment above, intramuscular injection of neostigmine 0.5 mg twice a day for 7 days was given in experimental group. Intra-abdominal pressure was monitored, acute physiology and chronic health evaluation (APACHE)Ⅱ, kidney disease: improving global outcome stage (KDIGO), lung injury score (LIS) were recorded, and serum leukocyte, CRP, procalcitonin (PCT), IL-6, IL-8 and tumor necrosis factor (TNF)-ɑ level were examined before and after treatment in both groups. The primary endpoint was the amount change of intra-abdominal pressure within 24 hours, and secondary endpoints included increased fecal volume within 7 days after treatment, new abdominal compartment syndrome (ACS), new organ dysfunction, vascular complications, length of ICU stay, total length of stay, survival rate and treatment intervention and occurrence of complications within 6 months after the end of treatment. Results:Intra-abdominal pressure began to decrease at 9 hours after treatment both in control group and experimental group. Compared with that before treatment, the intra-abdominal pressure of the two groups decreased significantly after 7 days of treatment, and the decrease rate of the experimental group within 7 days was obviously higher than that of the control group, with statistical significance (all P values <0.05). Compared with those before treatment, APACHEⅡ, KDIGO and LIS in both groups were significantly decreased, but the decreases in experimental group were more remarkable than those in control group (all P values <0.05). After treatment, the serum WBC count and the levels of inflammatory factors CRP, PCT, IL-6, IL-8, TNF-ɑ in experimental group were obviously lower than those in control group with statistical significance (all P values <0.05). Compared with control group, the change of intra-abdominal pressure in experimental group was significantly increased after 24-hour treatment, and the fecal volume was also obviously increased on day 1, 2, 3, 5 and 7 after treatment (all P values <0.05). However, there were no significantly statistical differences on the severity of intra-abdominal pressure, new occurrence of ACS and organ failure, vascular complication, ICU hospitalization and total length of stay and survival rate between two groups. After 6-month follow-up, the recurrence of pancreatitis and its treatment intervention between two groups were not statistically significant. Conclusions:The adjuvant treatment of neostigmine could reduce intra-abdominal pressure, increase defecation volume in SAP patients and alleviate SAP condition, which might be related to reducing the release of inflammatory cytokines.

Objective:To summarize the electrophysiological characteristics of neuronal intranuclear inclusion disease (NIID) and explore the value of electrophysiological examination in NIID auxiliary diagnosis.Methods:Twenty NIID patients diagnosed by pathological biopsy and genetic confirmation (15 were symptomatic, 5 were asymptomatic), admitted to Department of Neurology, Affiliated Hospital of Xuzhou Medical University from February 2020 to June 2022 were chosen. Peripheral motor/sensory nerve conduction, needle electromyography, F wave, repetitive electrical stimulation, skin sympathetic reflex (SSR), and tremor were analyzed. Peripheral nerve conduction and SSR parameters were compared between 15 patients with symptomatic NIID (symptomatic NIID group) and 11 age- and gender-matched normal control subjects (control group).Results:(1) All 15 patients with symptomatic NIID were with abnormal electrophysiological findings: 14 patients had abnormal peripheral nerve conduction, including 14 with slowed motor nerve conduction velocity (MCV), 4 with reduced composite muscle action potential (cMAP) wave amplitude, 12 with slowed sensory nerve conduction velocity (SCV), and 3 with reduced sensory nerve action potential (sNAP) wave amplitude, and overall slowed nerve conduction velocity and relatively preserved wave amplitude were noted; 4 patients had neurogenic lesions by needle electromyography; 13 patients had prolonged F-wave latency at varied degrees; 12 showed abnormal SSR; 4 exhibited synchronous tremor from 4.0 to 7.5 Hz. (2) In 5 patients with asymptomatic NIID, 3 had abnormal peripheral nerve conduction, including 3 with slowed MCV, 2 with slowed SCV, and 1 with reduced sNAP wave amplitude; 3 showed abnormal SSR. (3) Significant differences in MCV and SCV, some cMAP and sNAP amplitudes, and SSR latency and amplitude were noted in nerves of the upper and lower extremities between the symptomatic NIID group and control group ( P<0.05). Conclusion:Peripheral nerve damages are common in patients with NIID, especially myelin damage and autonomic nerve injury, and some patients may have electrophysiological abnormalities before clinical symptoms; therefore, peripheral nerve conduction and SSR can be recommended as auxiliary screening tools for NIID.

OBJECTIVE To evaluate the cost -effectiveness of tislelizumab in the second -line treatment of advanced or metastatic esophageal squamous cell carcinoma （ESCC）in China .METHODS A three -state Markov model was constructed to assess the cost -effectiveness of tislelizumab versus chemotherapy in the second -line treatment of advanced or metastatic ESCC and programmed death receptor 1（PD-L1）positive patients . The cycle length of the model was 1 month，and the time horizon of the model was set as 10 years. The discount rate of cost and utility was 5%. One-way sensitivity analysis ，probability sensitivity analysis and scenario analysis were used to verify the robustness of the base -case analysis results . RESULTS The results of the base-case analysis showed that compared with chemotherapy ，the incremental cost -effectiveness ratio （ICER）of tislelizumab in the second-line treatment of advanced or metastatic ESCC and PD -L1-positive patients were 26 864.01 yuan/QALY and 37 510.07 yuan/QALY，respectively，which was much lower than 1 time per capita gross domestic product （GDP）in 2021（80 976 yuan）. Results of scenario analysis showed that the ICER was less than 1 times per capita GDP ，regardless of the chemotherapy regimens（paclitaxel，docetaxel or irinotecan ）used. With the extension of the simulation time limit ，the ICER of tirelizumab regimen gradually decreased ，and the reduction rate gradually E-mail：lishunping@sdu.edu.cn decreased，but they were all less than 1 time China ’s per capita GDP in 2021. The results of the one -way sensitivity analysis showed that the 3 parameters with the most significant impact on the ICER were progression -free survival of tislelizumab group ，price of tislelizumab ，and the proportion of patients receiving follow-up treatment in the tislelizumab group . The results of the probability sensitivity analysis showed that the probability of tislelizumab with cost -effectiveness in the treatment of advanced or metastatic ESCC patients and PD -L1-positive patients were 99.09% and 99.94%，respectively，when using 3 times per capita GDP as the willingness -to-pay threshold . CONCLUSIONS Tislelizumab has economic advantages over chemotherapy alone in the second -line treatment of advanced or metastatic ESCC patients.

Occupational therapy can not only promote the development of motor and cognitive functions in children with developmental or other disabilities, but also improve their self-care ability, learning ability, participation skills and other activities.In 2019, the Aust Occup Ther J published a systematic review on the effects of occupational therapy interventions on disabled children, aiming to summarize the best evidence of occupational therapy and help occupational therapists and families to choose the effective treatment regimens.In this article, the systematic review was interpreted in light of the current status of domestic child occupational therapy, so as to allow clinicians to compare the pros and cons of different treatment methods and improve the efficacy.

Objective: To explore the status of medication adherence among patients with depressive disorder and analyze its potential influencing factors. Methods: A total of 406 patients with depression who visited our hospital from January 2015 to December 2017 were selected as subjects of study. General data of patients were collected at the time of consultation, and drug adherence questionnaire was used to score the patients at 6 months of follow-up. According to the score, 406 patients were divided into high adherence group, middle adherence group and low adherence group, the correlation between medication adherence and humanistic factors, chronic diseases and course of disease was analyzed. Results: Compared with the low adherence group, the proportion of age (>60 years old), education (<6 years), no spouse, peasant, monthly income (<3 000 yuan), self-funded medical treatment, insomnia history, solitude and negative life events decreased significantly in the middle and high adherence groups. Cadre ratio and the proportion of workers in the middle adherence group increased significantly (P<0.05). Compared with the low adherence group, the course of disease in the middle and high adherence group was significantly shorter (P<0.01). Logistic regression analysis showed that education < 6 years, no spouse, farmers, low income, self-paid medical treatment, solitude, negative life events, course of disease were independently correlated with low adherence of depression patients (P<0.05 or P<0.01). Conclusions Depression patients have low adherence with medication, so targeted health education should be carried out. Especially for patients with a long course of illness, continuous nursing and long-term follow-up should be done well.Mobilizing family support system , caring for and respecting patients can effectively reduce the occurrence of negative life events. It can improve the medication adherence of depressive patients and promote their early recovery.

Objective:To investigate therapeutic efficacy and mechanisms of action of oncolytic agent derived from herpes simplex virus type 2 (oHSV2) in a xenograft mouse model bearing CT26 colorectal cancer. Methods:BALB/c mice were subcutaneously inoculated with CT26 cells to establish a xenograft mouse model of colorectal cancer. 1) After intratumoral administration of oHSV2, enzyme-linked im-munosorbent assay was used to determine granulocyte-macrophage colony-stimulating factor (GM-CSF) expression levels in the blood. 2) Model mice were divided into three groups:PBS group (negative control), oHSV2 group, and 5-fluorouracil (5-FU) group (positive control). After drug administration, drug effectiveness was evaluated on the basis of weight, tumor volume, general state, and survival time. 3) Cells from the draining lymph nodes (TDLN) and tumor were surgical y removed and used to quantify mature dendritic cel s (DCs) and T lym-phocytes by flow cytometry. Result:1) In the CT26 xenograft model, level of GM-CSF continuously elevated. At day 8, peak value was attained in the blood at concentration of 3150±327.1 pg/mL. Then, GM-CSF expression gradually reduced as time progressed. 2) In in vivo study, both oHSV2 and 5-FU exerted antitumor effects relative to PBS group (50 days vs. 36 days, P<0.01;51 days vs. 36 days, P<0.01), and oHSV2 proved to be less toxic and safer. At day 28, the 5-FU group presented highly significant difference in mouse body weight compared with that of PBS group (16.61 g vs. 22.07 g, P<0.01). However, oHSV2 group did not show statistical y significant change (al P>0.05). Skin of virus injection region did not present necrosis and ulceration. 3) In the TDLN, the frequency of DC was increased when treated with oHSV2 compared with the control group (6.49%vs. 3.73%, P<0.01). Similarly, the percentage of CD4+and CD8+T-cel s from the oHSV2-treated group was signifcantly higher than mock-treated tumors (15%vs. 8.57%, P<0.01;8.19%vs. 5.15%, P<0.01). However, number of cells in the 5-FU group were significantly reduced with respect to that of the negative group (al P<0.01). Conclusion:oHSV2 exerted potent antitumor effects in a murine colorectal cancer model. Compared with 5-FU, oHSV2 treatment caused fewer side effects. Such antitumor effect may be induced by stimulation of immune activity by GM-CSF production.

Purpose To explore the difference of expression and prognostic significance of SP1,KLF4 and p21 in low grade ovarian serous carcinoma (LGSC) and high grade ovarian serous carcinoma (HGSC).Methods The expression of SP1,KLF4 and p21 protein was examined with immunohistochemistry EliVision method in cases with LGSC and HGSC.Kaplan-Meier analysis and Cox multivariate survival analysis were used to assess the impact of SP1,KLF4 and p21 expression on prognosis of LGSC and HGSC.Results SP1,KLF4 and p21 expression were detected respectively in 74.5％,17.0％ and 11.7％ HG-SC cases,and in 65.2％,34.8％ and 26.1％ LGSC cases.Compared to control group,the expression level of SP1 was significantly higher (P ＜ 0.05),but the expression level of KLF4 and p21 were significantly lower (P ＜0.05).There was no significant difference of SP1,KLF4 and p21 expression between HGSC and LGSC (P ＞ 0.05).The expression of SP1,KLF4 and p21 were associated with FIGO stage,meanwhile SP1 associated with residual tumor size in HGSC (P ＜ 0.05).There was a significant negative correlation between SP1 and KLF4,p21 proteins in HGSC (P ＜ 0.05).Kaplan-Meier analysis revealed that there were significantly poor overall survival (OS) of 5 years for patients with HGSC displaying high expression of SP1,or low expression of KLF4 and p21 (P ＜0.05),but no significantly improved OS for patients with LGSC (P ＞ 0.05).Cox analysis showed that SP1 overexpression is an independent prognosis factor for HGSC.Conclusion Overexpression of SP1 and low expresion of KLF4 and p21 contribute to carcinogenesis of HGSC and LGSC.They are associated with a poor prognosis of HGSC,but not LGSC,meanwhile SP1 is an independant prognosis factor for HGSC.