OBJECTIVE To evaluate the cost-effectiveness of cefiderocol versus best available therapy （BAT） or standard-of- care （SOC） for the treatment of confirmed or suspected carbapenem-resistant Gram-negative bacterial （CRGNB） serious infections from the perspective of the Chinese healthcare system， and to explore its reasonable pricing. METHODS A decision tree model was constructed based on data from two phase Ⅲ clinical trials （CREDIBLE-CR and GAME CHANGER） to simulate the cost- effectiveness of cefiderocol in two scenarios： salvage therapy for confirmed CRGNB infection （scenario 1） and empirical therapy for suspected CRGNB infection （scenario 2）. The primary outcome measure was the incremental cost-effectiveness ratio （ICER）. The willingness-to-pay （WTP） was set at 1 to 3 times China’s per capita GDP in 2024. To verify the robustness of the results， one- way and probabilistic sensitivity analyses were conducted， and based on these， a reasonable price range for cefiderocol in the Chinese market was explored. RESULTS The results for scenario 1 showed that the clinical cure rate in the cefiderocol group was higher than that in the BAT group （47.50% vs. 34.21%）， but its ICER was 415 065.03 yuan per cured case， exceeding three times China’s GDP per capita. Scenario 2 revealed that the ICER for cefiderocol relative to SOC was as high as 1 362 446.16 yuan per cured case， far exceeding the WTP. Sensitivity analysis indicated that the treatment duration and price of cefiderocol were key factors affecting its cost-effectiveness. In the two scenarios described above， the unit price of cefiderocol must fall below 683.47 and 242.00 yuan/g， respectively， to be considered cost-effective. CONCLUSIONS Based on the current market price， cefiderocol lacks sufficient cost-effectiveness for treating confirmed or suspected CRGNB serious infections within China’s healthcare system. To improve its accessibility， price negotiations or a tiered medical insurance payment strategy are required.

BACKGROUND:Ankylosing spondylitis is a chronic inflammatory disease with chronic rheumatic immunity.Soft tissue ossification and fusion and spinal stiffness can cause biomechanical changes. OBJECTIVE:To reconstruct the lumbar-sacral intervertebral disc in ankylosing spondylitis patients with lumbar kyphosis by finite element analysis,and to study the range of motion of each segment of T11-S1 and the biomechanical characteristics of annulus fibrosus and nucleus pulposus. METHODS:The imaging data were obtained from an ankylosing spondylitis patient with lumbar kyphosis.The original CT image data of continuously scanned spine were imported into Mimics 21.0 in DICOM format,and T11-S1 was reconstructed respectively.The established model was imported into 3-Matic software in the format of"Stl"to reconstruct the intervertebral disc,and the fibrous intervertebral disc model was obtained.The improved model was further imported into Hypermesh software,and the vertebra,nucleus pulposus,annulus fibrosus and ligament were mesh-divided.After the material properties were given,the model was imported into ABAQUS software to observe the range of motion of each vertebral body in seven different working conditions of T11-S1,and analyze the biomechanical characteristics of each segment of annulus fibrosus and nucleus pulposus. RESULTS AND CONCLUSION:(1)The range of motion of L1 vertebrae was higher than that of other vertebrae under six different working conditions:extension,forward flexion,rotation(left and right),and lateral flexion(left and right).The maximum range of motion was 2.18° during L1 vertebral flexion,and the minimum range of motion was 0.12° during L5 vertebral extension.(2)The annular fiber flexion at L2-L3 segments was greater than the extension(P<0.05),and the annular fiber flexion at L3-L4 and L4-L5 segments was less than the extension(P<0.05).The left rotation of L1-L2 annular fibers was greater than the right rotation(P<0.05).The left flexion of the annulus was greater than the right flexion in L1-L2,L2-L3,L3-L4,L4-L5 and L5-S1 segments(P<0.05).(3)The nucleus pulposus stresses of T11-L12,L1-L2,L2-L3,L3-L4 and L4-L5 segments in forward flexion were greater than in extension(P<0.05).The left rotation of T12-L1 and L3-L4 segments was smaller than the right rotation(P<0.05),and that of T11-T12,L1-L2,and L2-L3 segments was larger than the right rotation(P<0.05).The left flexion was larger than the right flexion in the T11-S1 segment.(4)It is concluded that in ankylosing spondylitis patients with lumbar kyphosis,the minimum range of motion of the vertebral body is located at the L5 vertebral body in extension.To prevent fractures,it is recommended to avoid exercise in the extension position.During the onset of lumbar kyphosis in patients with ankylosing spondylitis,the maximum stress of the annulus fibrosus and nucleus pulposus is located in the L1-L2 segment,which is fixed and will not alter with the change of body position.The late surgical treatment and correction of deformity should focus on releasing the pressure of the annulus fibrosus and nucleus pulposus in this segment to avoid the rupture of the annulus fibrosus and the injury of the nucleus pulposus.

Objective : To investigate the epidemiological characteristics of severe fever with thrombocytopenia syndrome (SFTS) in Dongyang City, Zhejiang Province from 2017 to 2022, so as to provide insights into SFTS prevention and control. Methods: Data pertaining to patients with SFTS in Dongyang City from 2017 to 2022 were collected from Notifiable Infectious Disease Reporting System of Chinese Disease Prevention and Control Information System. The epidemiological and clinical characteristics of patients with SFTS were descriptively analyzed, and the trends in incidence of SFTS was evaluated using annual percent change (APC). Results: A total of 32 SFTS cases were reported in Dongyang City from 2017 to 2022, with mean annual incidence of 0.63/105, and 8 cases died, with a fatality rate of 25.00%. The incidence of SFTS appeared a tendency towards a rise from 2017 to 2022 (APC=40.697%, P<0.05). The male to female ratio of SFTS cases was 0.78∶1, and farmer was the predominant occupation (31 cases, 96.88%). SFTS predominantly occurred among individuals at ages of 51 to 69 years (20 cases, 62.50%), and the incidence peaked during the period between March and May and between July and August (28 cases, 87.50%). SFTS cases were reported in 11 out of the 18 townships (streets) in Dongyang City, with the highest number found in Zuocun Township (8 cases, 28.13%), and had the lowest platelet count of (41.46±5.19)×109 platelets/L, with the lowest count of (3.00 to 67.00) ×109 platelets/L. All the SFTS cases had a history of mountain forest and farmland activities 2 weeks prior to onset of the disease, and 5 cases (15.63%) had a history of tick bites. Conclusions The incidence of SFTS appeared a tendency towards a rise in Dongyang City from 2017 to 2022, and SFTS was highly prevalent in spring and summer, with high incidence among farmers. Intensified health education of SFTS is recommended among residents in high-incidence areas.

Objective To prepare quercetin nanocrystals,improve their dissolution rate,and investigate the effects of different stabilizer types and ratios on the stability of nanocrystals.Methods Quercetin nanocrystals were prepared by solvent ultrasonication,and three different stabilizers(polyvinylpyrrolidone-K30,poloxamer F188 and sodium dodecyl sulfate)were compared.The particle size was used as a screening index to investigate the stability of placement,the microscopic morphology of nanocrystals was characterized by scanning electron microscopy,infrared spectroscopy and X-ray diffraction,and the mechanism of action between stabilizers and nanocrystals was discussed.Results Through experimental screening,the results showed that povidone K30 had the best stable performance,the nanocrystals were also in the form of rod crystals,and the dissolution rate of nanocrystals was significantly higher than that of active pharmaceutical ingredients.Conclusion The type and amount of stabilizer will affect the stability of nanocrystals.

Background: Neurolytic celiac plexus block (NCPB) is a typical treatment for severe epigastric cancer pain, but the therapeutic effect is often affected by the variation of local anatomical structures induced by the tumor. Greater and lesser splanchnic nerve neurolysis (SNN) had similar effects to the NCPB, and was recently performed with a paravertebral approach under the image guidance, or with the transdiscal approach under the guidance of computed tomography. This study observed the feasibility and safety of SNN via a transdiscal approach under fluoroscopic guidance. Methods: The follow-up records of 34 patients with epigastric cancer pain who underwent the splanchnic nerve block via the T11-12 transdiscal approach under fluoroscopic guidance were investigated retrospectively. The numerical rating scale (NRS), the patient satisfaction scale (PSS) and quality of life (QOL) of the patient, the dose of morphine consumed, and the occurrence and severity of adverse events were recorded preoperatively and 1 day, 1 week, 1 month, and 2 months after surgery. Results: Compared with the preoperative scores, the NRS scores and daily morphine consumption decreased and the QOL and PSS scores increased at each postoperative time point (P < 0.001). No patients experienced serious complications. Conclusions SNN via the transdiscal approach under flouroscopic guidance was an effective, safe, and easy operation for epigastric cancer pain, with fewer complications.

Objective:To investigate the level of sleep quality among females treated firstly by IVF-ET and to find the moderate role of mindfulness in the relationship between stigma and sleep quality.Methods:From April 2018 to September 2018, we invited 380 IVF-ET females in the fertility hospital of Shandong Province to participate in the study and to finish a questionnaire survey including the Pittsburgh Sleep Quality Index(PSQI), the Mindful Attention Awareness Scale(MAAS), the simple measuring scale of stigma, and the general information questionnaire.Results:The average score of PSQI was (4.82±2.29), and the prevalence of sleep distress(PSQI>5) was 31.3%(118/380). Spearman correlation analysis showed that PSQI score was positively correlated with stigma( r=0.156, P=0.002), the infertility time( r=0.110, P=0.032), and the treatment time( r=0.142, P=0.005 ), was negatively correlated with mindfulness level( r=-0.325, P<0.001). The hierarchical regression showed that mindfulness level could moderate the correlation between stigma and sleep quality( P<0.001, Δ R2=2.8%). Furthermore, the Johnson-Neyman technique revealed that, within a specific region that was mindfulness above 72, the moderating role was significant. Conclusion:The sleep distress was common among females treated firstly by IVF-ET. Mindfulness level could moderate the correlation between stigma and sleep quality. It is suggested that the reproductive center should strengthen publicity and education to reduce the stigma level of patients, and carry out mindfulness related intervention to further improve their sleep quality.

Objective: To investigate the relationship between the expression of mucin 1 and collagen Ⅳ and the clinical characteristics in invasive breast cancer by using the quantum dots immunofluorescence imaging technique. Methods: The expressions of mucin 1 and collagen Ⅳ were detected simultaneously by quantum dots immunofluorescence imaging technique in 94 cases of breast cancer from July 2007 to July 2010 in Affiliated Hospital of Guilin Medical University. The correlation of mucin 1 and collagen Ⅳ quantitative parameters with clinicopathological features and the prognosis were also analyzed. Results: The positive rates of mucin 1 in human breast cancer tissues marked by quantum dots immunofluorescence imaging technique and immunohistochemistry were 73.4 % (69/94) and 69.1 % (65/94), the positive rates of collagen Ⅳ were 53.2 % (50/94) and 47.9 % (45/94), and the differences were not statistically significant (both P > 0.05) Quantum dots immunofluorescence imaging technique was consistent with conventional immunohistochemistry (IHC) in detecting the expressions of mucin 1 and collagen Ⅳ in human breast cancer tissues (κ = 0.763, P = 0.000; κ=0.759, P = 0.000). The expression of mucin 1 was negatively correlated with collagen Ⅳ (r = -0.883, P < 0.01). The expressions of mucin 1 and collagen Ⅳ were respectively associated with tumor size (F = 3.683, P = 0.029; F = 4.922, P = 0.009), histological grading (F = 3.529, P = 0.033; F = 3.912, P = 0.023), lymph node metastasis (t = -4.868, P = 0.000; t = 3.868, P = 0.000), pathological stage (t = -8.337, P = 0.000; t = 5.962, P = 0.000) and 5-year disease free survival rate (both P = 0.000), and the differences were statistically significant (all P < 0.05). Conclusion The co-detection of mucin 1 and collagen Ⅳ by using quantum dots immunofluorescence imaging technique provides direct evidence determining the biologic behaviors of breast cancer and evaluating the prognosis.

OBJECTIVE:To establish a method for the detection of volatile constituents from the leaves and fruits of Piper ni-grum. METHODS:HS-SPME-GC-MS was used. The chromatographic conditions:column was HP-5 MS quartz elastic capillaries, carrier gas was high purity helium(99.999%),flow rate was 1.0 mL/min,the inlet temperature was 250 ℃,initial temperature of column was 50 ℃(temperature programmed),split injection with split ratio of 10:1. MS conditions:ionization mode was electron impact ion source,ionization energy was 80 eV,ion source temperature was 230 ℃,quadrupole temperature was 150 ℃,trans-mission line temperature was 280 ℃,electron multiplier voltage was 1588 V,mass scanning range was m/z 30-400. The spectra were retrieved using RTLPEST3. L and NIST08. L,and the relative contents of the volatile constituents were determined by area normalization method. RESULTS:There were 28 volatile constituents in the leaves and 15 in the fruits,respectively accounting for 67.13% and 36.85%. The major volatile constituents of leaves were β-caryophyllene (15.72%),limonene (9.39%),3-carene (9.32%),β-pinene(6.80%),α-terpine(4.98%),etc.,the main volatile constituents of fruits were 1,7,7-trimethyl-2-vinylbicyclo [2.2.1]hept-2-ene(10.45%),espatulenol(8.28%),caryophyllene oxide(4.81%),etc. 5 constituents were owned in both. CON-CLUSIONS:The study basically clears the main volatile constituents from the leaves and fruits of P. nigrum,and verifies existing obvious differences.

Objective To investigate the effect of ursolic acid (UA) on the colorectal tumor and microenvironment in mice,and to provide a theoretical basis for the clinical application of UA.Methods The models of subcutaneous transplanted tumor of mouse CT26 cells was established.The models were divided into four groups:control group,tumor bearing group,tumor beating dimethyl sulfoxide (DMSO) group and tumor beating UA group.Tbe serum levels of interleukin-6 (IL-6) were detected by enzyme linked immunosorbent assay (ELISA).The number and percentage of myeloid-derived suppressor cell (MDSC) in the spleen of mice were analyzed by flow cytometry.The mRNA levels of IL-6 and signal transducer and activator of transcription 3 (STAT3) in tumor were examined by real-time quantitative polymerase chain reaction (RT-PCR).The protein levels of STAT3 and p-STAT3 in tumor were detected by Western blotting.Results The results showed that UA could significantly decrease the number of spleen MDSC.The accounts of spleen MDSC of tumor bearing UA group (249.60 ± 17.12) was lower than that of tumor beating DMSO group (366.40 ± 34.08),and the difference was statistically significant (P =0.021).The serum level of IL-6 in tumor bearing UA group [(46.40 ± 17.05) pg/ml] was decreased than that in tumor bearing DMSO group [(94.27 ±21.51) pg/ml],and the difference was statistically significant (P =0.012).The expression levels of IL-6 and STAT3 mRNA in tumor tissues of tumor bearing UA group (0.12 ±0.01,0.21 ±0.08) were lower than those of tumor bearing DMSO group (0.69 ± 0.14,0.79 ± 0.06),and the differences were statistically significant (P =0.008;P =0.003).The protein expression levels of STAT3 and p-STAT3 in tumor tissues of tumor bearing UA group (0.81 ±0.02,0.28 ±0.04) were lower than those of tumor bearing DMS0 group (0.98 ±0.02,0.91 ±0.22),and the differences were statistically significant (P =0.027;P =0.029).Conclusion UA may inhibit the activation of STAT3 signaling pathway and the amplification of MDSC in microenvironment by reducing IL-6,thus to enhance the function of immune-killing tumor cells to regulate tumor immune microenvironment and inhibit the immune escape of mouse colorectal cancer cells.

Objective To prepare a peptide monoclonal antibody (McAb)against human papillomavirus 18E6 separately,and identify its specificity and pathogenicity.Metheds The advantage epitope peptide was designed and synthesized by ABCpred and Bcepred,and then used to immunize BALB/c mice after coupling with bovine serum albumin (BSA).And the McAb was prepared by hybridoma technique.HPV18E6 gene was amplified from cervical swab specimen containing HPV18 and insert-ed into expression vector pET-28a.The constructed recombinant plasmid was transformed to E.coli BL21(DE3)for expres-sion under induction of isopropyl thio-β-D-galactoside.The expressed protein was used to identified the McAb had been pre-pared.Results The hybridoma cell lines could constantly produce MAbs against HPV18E6 peptides.Sequencing proved that recombinant plasmid pET-28a-HPV18E6 was constructed correctly.Western blotting showed that the anti-HPV18E6 pep-tides antibody could specifically recognize HPV18E6.Conclusion A monoclonal antibody against the advantage epitope pep-tide of human papillomavirus 18E6 prepared could specifically recognize HPV18E6 specifically.