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.

BACKGROUND: There is little published evidence about the role of non-alcoholic fatty liver disease (NAFLD) in the progression from prehypertension to hypertension. This study was conducted to investigate the association of NAFLD and its severity with the risk of hypertension developing from prehypertension. METHODS: The study cohort comprised 25,433 participants from the Kailuan study with prehypertension at baseline; those with excessive alcohol consumption and other liver diseases were excluded. NAFLD was diagnosed by ultrasonography and stratified as mild, moderate, or severe. Univariable and multivariable Cox proportional hazard regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident hypertension according to the presence and 3 categories of severity of NAFLD. RESULTS: During a median of 12.6 years of follow-up, 10,638 participants progressed to hypertension from prehypertension. After adjusting for multiple risk factors, patients with prehypertension and NAFLD had a 15% higher risk of incident hypertension than those without NAFLD (HR = 1.15, 95% CI 1.10-1.21). Moreover, the severity of NAFLD was associated with the incidence of hypertension, which was higher in patients with more severe NAFLD (HR = 1.15 [95% CI 1.10-1.21] in the mild NAFLD group; HR = 1.15 [95% CI 1.07-1.24] in the moderate NAFLD group; and HR = 1.20 [95% CI 1.03-1.41] in the severe NAFLD group). Subgroup analysis indicated that age and baseline systolic blood pressure may modify this association. CONCLUSIONS NAFLD is an independent risk factor for hypertension in patients with prehypertension. The risk of incident hypertension increases with the severity of NAFLD.
Humans ; Non-alcoholic Fatty Liver Disease/complications* ; Prehypertension/diagnosis* ; Risk Factors ; Hypertension ; Incidence

Objective:To investigate the application value of the anatomically oriented "six steps with six windows" approach in laparoscopic radical total gastrectomy.Methods:The retros-pective cohort study was conducted. The clinicopathological data of 121 patients who underwent laparoscopic radical total gastrectomy in Henan Provincial People′s Hospital from January 2019 to February 2022 were collected. There were 53 males and 68 females, aged (68±12)years. Of the 121 patients, 72 patients using the traditional approach in the surgery were divided into the control group, and 49 patients using the "six steps with six windows" approach in the surgery were divided into the experiment group. Observation indicators: (1) surgical situations; (2) postoperative situations. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Count data were described as absolute numbers or percen-tages, and comparison between groups was conducted using the chi-square test. Results:(1) Surgical situations. All 121 patients underwent laparoscopic radical total gastrectomy successfully, without laparotomy conversion. The operation time, volume of intraoperative blood loss, number of lymph nodes dissected were (250±50)minutes, (150±34)mL, 41±6 in the control group, versus (180±16)minutes, (55±13)mL, 51±5 in the experiment group, showing significant differences in the above indicators between the two groups ( t=11.04, 21.47, 9.42, P<0.05). (2) Postoperative situations. The times of postoperative analgesic injection, time to postoperative ?rst ?atus, duration of postoperative hospital stay, postoperative pathological staging (stage Ⅰ, stage Ⅱ, stage Ⅲ), incidence of postoperative complication were 3.4±1.6, (4.0±1.4)days, (13.1±2.0)days, 9, 32, 31, 15.3%(11/72) in the control group, versus 3.5±1.7, (4.1±1.5)days, (13.1±1.7)days, 6, 25, 18, 16.3%(8/49), showing no significant difference in the above indicators between the two groups ( t=0.35, 0.18, 0.03, Z=0.55, χ2=0.02, P>0.05). There was no perioperative death in both groups of patients. Conclusion:Appli-cation of the anatomically oriented "six steps with six windows" approach in laparoscopic radical total gastrectomy is safe and feasible.

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.

Objective:To analyze the incidence, biochemical and molecular characteristics, and gene mutation spectrum of neonatal methylmalonic acidemia (MMA) in Shaanxi province.Methods:This study involved 146 152 newborns undergoing neonatal screening for methylmalonic acidemia by tandem mass spectrometry in Northwest Women's and Children's Hospital from January 2014 and December 2019. Clinical manifestations and follow-up data of newborns diagnosed with MMA and their acylcarnitine profiles and gene mutations were analyzed. According to whether they had elevated homocysteine or not, these patients were divided into two groups, the complicated group and the isolated MMA group. The control neonates were those excluded from having methylmalonic acid by re-examination. Kruskal-Wallis and Mann-Whitney U test was conducted for statistical analysis. Results:(1) Twenty-one cases of MMA were confirmed with an incidence of 1/6 960, including 11 cases (52.4%) of isolated MMA (isolated MMA group) and 10 (47.6%) complicated by elevated homocysteine (complicated group). Eight patients in the isolated group had symptoms within one month after birth, mainly feeding difficulties, vomiting, drowsiness, poor response and infection, and five died. Patients in the complicated group were all diagnosed before developing typical clinical symptoms, and no developmental abnormalities were reported during follow-up. (2) Blood propionyl carnitine and its ratios to acetylcarnitine and free carnitine in the isolated MMA and complicated groups were higher than those in the control group [ M (min-max), 9.26 (3.70-37.78) μmol/L and 7.27 μmol/L (3.58-13.62 μmol/L) vs 4.51 μmol/L (1.48-8.69 μmol/L), H=23.239; 1.12 (0.32-2.43) and 0.74 (0.36-1.90) vs 0.25 (0.09-0.45), H=47.061; 0.94 (0.12-1.92) and 0.56 (0.18-1.03) vs 0.17 (0.06-0.38), H=36.868; all P<0.001]. The blood methionine level in the complicated group was significantly lower than that in the isolated MMA group [7.64 μmol/L (3.40-19.25 μmol/L) vs 24.22 μmol/L (10.73-56.55 μmol/L), U=3.000, P<0.001]. (3) All 21 patients carried complex heterozygous mutations or homozygous mutations in pathogenic genes, including 15 distinct MMUT mutations and 13 distinct MMACHC mutations. In the isolated MMA group, the most common mutation was c.323G>A (p.Arg108His) in the MMUT gene with a positive rate of 13.6%, and an unreported mutation, c.1676+11A>G, with unidentified clinical significance, was also found. The most common mutations in the complicated group were c.609G>A (p.Trp203Ter) and c.567dupT (p.Ile190fs) in the MMACHC gene, and the positive rates were both 20.0%. Moreover, two unreported variants, c.430-2A>C and c.648_650delAGA (p.216_217delSEinsS), were detected and suspected to be pathogenic. Conclusions:MMA is not uncommon in Shaanxi province. Children with isolated MMA tend to be more severe clinically. The identification of hotspot mutations, including c.609G>A (p.Trp203Ter) and c.567dupT (p.Ile190fs) in MMACHC gene and c.323G>A (p.Arg108His) in MMUT gene, provides a foundation for further genetic screening, counseling, and prenatal diagnosis, and is conducive to reduce the mortality and disability rate of neonatal MMA.

Objective To provide a scientific basis for the formulation of effective incentive measures for rural health workers,by analyzing the factors influencing their work enthusiasm and constructing an incentive mechanism framework.Methods A field questionnaire survey and personal in-depth interview were conducted on 803 health technicians from 45 township health centers in Shandong,Anhui and Shanxi provinces.The study covered economic,management,education and career supports aspects,and the data were analyzed in descriptive,multi-level model and correlation analyses.Results The work enthusiasm scoring of rural health workers was 89.83 + 9.54.Workload,doctor-patient relationship,work competence and income index were the four influencing factors,with the differences showing statistical significance(P ＜0.05).The income index (income expectancy/real income affects work) influences the enthusiasm negatively,while the rest of the factors were positive.Work enthusiasm was positively correlated with three dimensions of job performance.The satisfaction of interpersonal relationship,workload and competence were positively correlated with work enthusiasm.The correlation indexes are respectively 0.35,0.33 and 0.21 (P ＜ 0.01).Conclusions To motivate primary health institutions and their health workers,the authorities should focus on the economic factors,and take into account non-economic ones,while improving the performance-based wage system and creating a fair workplace culture.

Objective To explore the expressions and significance of brain natriuretic peptide (BNP),hypersensitive C-reactive protein (hs-CRP),human fibrinogen (Fib),D-Dimer and blood gas analysis in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and pulmonary hypertension (PH).Methods Totally 135 patients with AECOPD were divided into single AECOPD group (n =75) and AECOPD + PH group (n =60).The value of pulmonary systolic pressure (PASP) was measured by echocardiography.Serum BNP,hs-CRP,D-Dimer,Fib levels and arterial blood gas analysis indexes such as p(CO2) and p(O2) were compared between two groups.Results The levels of hs-CRP,BNP,D-Dimer and p(CO2) in AECOPD + PH group were significantly higher than those in AECOPD group (P ＜ 0.05),while p (O2) in AECOPD + PH group was significantly lower than that in AECOPD group.Multiple linear regression analysis showed that the levels of hs-CRP,Fib,BNP,D-Dimer and p (CO2) were positively correlated with pulmonary artery pressure (P ＜ O.05),and p (02) was negatively correlated with PASP (P ＜ 0.05).Conclusion The hs-CRP,Fib,BNP,and D-Dimer participate in the formation of AECOPD complicated with pulmonary hypertension,and systemic inflammation plays an important role in the pathogenesis of AECOPD complicated with pulmonary hypertension.

Objective To explore the expressions and significance of brain natriuretic peptide (BNP),hypersensitive C-reactive protein (hs-CRP),human fibrinogen (Fib),D-Dimer and blood gas analysis in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and pulmonary hypertension (PH).Methods Totally 135 patients with AECOPD were divided into single AECOPD group (n =75) and AECOPD + PH group (n =60).The value of pulmonary systolic pressure (PASP) was measured by echocardiography.Serum BNP,hs-CRP,D-Dimer,Fib levels and arterial blood gas analysis indexes such as p(CO2) and p(O2) were compared between two groups.Results The levels of hs-CRP,BNP,D-Dimer and p(CO2) in AECOPD + PH group were significantly higher than those in AECOPD group (P ＜ 0.05),while p (O2) in AECOPD + PH group was significantly lower than that in AECOPD group.Multiple linear regression analysis showed that the levels of hs-CRP,Fib,BNP,D-Dimer and p (CO2) were positively correlated with pulmonary artery pressure (P ＜ O.05),and p (02) was negatively correlated with PASP (P ＜ 0.05).Conclusion The hs-CRP,Fib,BNP,and D-Dimer participate in the formation of AECOPD complicated with pulmonary hypertension,and systemic inflammation plays an important role in the pathogenesis of AECOPD complicated with pulmonary hypertension.

AIM To establish the HPLC fingerprints of flavonoids in Ziziphi spinosae Semen and to determine the contents of two constituents.METHODS With spinosin as a reference peak,the HPLC fingerprints of ten batches of samples were established.The analysis of methanol extract of flavonoids in Ziziphi spinosae Semen was performed on a 30 ℃ thermostatic Agilent TC-C18column (4.6 mm × 250 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1％ acetic acid flowing at 1 mL/min in a gradient elution manner,and the detection wavelength was set at 280 nm.RESULTS There were ten common peaks in the HPLC fingerprints,eight of which (vicenin-Ⅱ,glucosylvitexin,isospinosin,spinosin,6'-pyridyloylspinosin,6'-p-hydroxybenzoylspinosin,6'-feruloylspinosin and 6'-p-coumaroylspinosin) were identified.Spinosin and 6'-feruloylspinosin showed good linear relationships within the ranges of 15.00-40.00 μg and 5.00-14.00 μg,whose average recoveries (RSDs)were 100.5％ (1.6％) and 100.4％ (1.6％),respectively.CONCLUSION This accurate,simple and reliable method can be used for the quality control of flavonoids in Ziziphi spinosae Semen.

Objective To evaluate ketamine-induced cerebral protection in mice with traumatic brain injury (TBI) by magnetic resonance imaging (MRI).Methods Thirty-two pathogen-free healthy male C57BL/6 mice,aged 8 weeks,weighing 26-30 g,were divided into 4 groups using a random number table:control group (group C,n=7),ketanine group (group K,n=7),TBI group (n=9) and TBI plus ketamine group (group TBI+K,n =9).TBI was produced with a pneumatically driven controlled cortical impact device.Ketamine 150 mg/kg was intraperitoneally injected at l h after operation in TBI+K and K groups,while the equal volume of normal saline was given instead in TBI and C groups.Open field test was conducted at 24 h,72 h and 7 days after operation.The animals in TBI and TBI+K groups were scanned by T1-weighted MRI at 6,24 and 72 h after operation,the animals in C and K groups were scanned by MRI at 24 h after operation,and the development of cerebral edema was observed.Results MRI scan showed no cerebral edema in C and K groups,and different degrees of cerebral edema were found in TBI and TBI+K groups.Compared with group C,the locomotor distance was significantly shortened at 24 and 72 h after operation in group TBI (P＜0.05).Compared with group TBI,the size of cerebral edema was significantly decreased,and the locomotor distance was prolonged at 24 and 72 h after operation in group TBI+K (P＜0.05 or 0.01).Conclusion MRI method further clarifies that ketamine can produce cerebral protection to some extent in mice with TBI.