Objective To explore the safety of Yttrium-90 resin microsphere selective internal radiation therapy (⁹⁰Y-SIRT) on malignant liver tumors. Methods A retrospective analysis was conducted on 64 patients with malignant liver tumors who underwent ⁹⁰Y-SIRT from February 2023 to November 2024 at Weifang People’s Hospital. The clinical characteristics of the patients and the occurrence of adverse reactions after treatment were analyzed to assess the safety of ⁹⁰Y-SIRT. Results Among the 64 patients, there were 52 males (81.25%) and 12 females (18.75%); the average age was (56.29±11.08) years. Seven patients (10.94%) had tumors with maximum diameter of less than 5 cm, 38 patients (59.38%) had tumors with maximum diameter of 5-10 cm, and 19 patients (29.68%) had tumors with maximum diameter of greater than 10 cm. There were 47 cases (73.44%) of solitary lesions and 17 cases (26.56%) of multiple lesions; 53 cases (82.81%) were primary liver cancers and 11 cases (17.19%) were metastatic liver cancers. Of the 64 patients, 63 successfully completed the Technetium-99m macroaggregated albumin (^99mTc-MAA) perfusion test and received the ⁹⁰Y-SIRT; one patient received ⁹⁰Y-SIRT after the second ^99mTc-MAA perfusion test due to a work error. The most common adverse reactions included grade 1 alanine aminotransferase (ALT) elevation in 26 cases (40.62%) and grade 2 in 2 cases (9.37%), grade 1 aspartate aminotransferase (AST) elevation in 27 cases (42.18%) and grade 2 in 7 cases (10.93%); grade 1 nausea in 17 cases (26.56%) and grade 2 in 6 cases (9.37%); grade 1 abdominal pain in 12 cases (18.75%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%); grade 1 vomiting in 11 cases (17.18%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%). Conclusion The adverse reactions of ⁹⁰Y-SIRT for treating malignant liver tumors are mild, indicating good safety.

BACKGROUND: To evaluate the efficacy and safety of the first cohort of people in China treated with a responsive neurostimulation system (Epilcure TM , GenLight MedTech, Hangzhou, China) for focal drug-resistant epilepsy in this study. METHODS: This multicenter, before-and-after self-controlled study was conducted across 8 centers from March 2022 to June 2023, involving patients with drug-resistant epilepsy who were undergoing responsive neurostimulation (RNS). The study was based on an ongoing multi-center, single-blind, randomized controlled study. Efficacy was assessed through metrics including median seizure count, seizure frequency reduction (SFR), and response rate. Multivariable linear regression analysis was conducted to explore the relationships of basic clinical factors and intracranial electrophysiological characteristics with SFR. The postoperative quality of life, cognitive function, depression, and anxiety were evaluated as well. RESULTS: The follow-up period for the 19 participants was 10.7 ± 3.4 months. Seizure counts decreased significantly 6 months after device activation, with median SFR of 48% at the 6th month (M6) and 58% at M12 ( P  <0.05). The average response rate after 13 months of treatment was 42%, with 21% ( n  = 4) of the participants achieving seizure freedom. Patients who have previously undergone resective surgery appear to achieve better therapeutic outcomes at M11, M12 and M13 ( β  <0, P  <0.05). No statistically significant differences were observed in patients' scores of quality of life, cognition, depression and anxiety following stimulation when compared to baseline measurements. No serious adverse events related to the devices were observed. CONCLUSIONS: The preliminary findings suggest that Epilcure TM exhibits promising therapeutic potential in reducing the frequency of epileptic seizures. However, to further validate its efficacy, larger-scale randomized controlled trials are required. REGISTRATION Chinese Clinical Trial Registry (No. ChiCTR2200055247).
Humans ; Female ; Male ; Drug Resistant Epilepsy/therapy* ; Adult ; Young Adult ; Middle Aged ; China ; Adolescent ; Treatment Outcome ; Quality of Life ; Single-Blind Method ; Seizures ; Electric Stimulation Therapy/methods*

OBJECTIVE To compare the hepatotoxicity of raw Polygonum cuspidatum and its vinegar-processed， ginger- processed， and wine-processed products in mice. METHODS Acute toxicity was assessed using the maximum tolerated dose approach. Male Kunming mice were randomly assigned to blank group， raw drug group， vinegar-processed group， ginger-processed group and wine-processed group， with 16 mice in each group. Mice in the treatment groups received oral gavage of the corresponding preparation at a total dose of 192 g/kg （single gavage volume of 40 mL/kg， administered three times at 5-hour interval）. During the experiment， the mortality and general condition of mice in each group were observed. Eight mice from each group were sacrificed at 48 hours， and the remaining eight at 14 days after the last administration. Organ coefficients， serum biochemical indices and liver histopathology were compared among the groups. RESULTS No mortality was observed in any group throughout the study. At 4 hours after the last administration， mice in all treatment groups exhibited transient alterations in urine and feces， which resolved at 14 days after the last administration. No significant differences in body weight or average food intake were observed among groups at any time point （P＞0.05）. At 48 hours after the last administration， all treatment groups showed varying degrees of liver injury， most severe in the wine-processed group， followed by the raw drug group， and mildest in the vinegar- processed group. Compared with the blank group， liver coefficients were significantly elevated in the wine-processed group， while serum levels of alanine transaminase， aspartate transaminase， total bilirubin （TBil） and alkaline phosphatase （ALP） were significantly increased in the raw drug and wine-processed groups. Additionally， the serum levels of TBil and ALP were significantly elevated in the ginger-processed group （P＜0.05）. At 14 days after the last administration， liver histopathology and all quantitative indicators showed partial recovery. Serum levels of liver function parameters were markedly reduced compared with 48 hours after the last administration （P＜0.05）. CONCLUSIONS Both raw and processed P. cuspidatum exhibit hepatotoxicity， which is closely associated with the processing method， and the severity of hepatotoxicity follows the order： wine-processed product＞raw product＞ginger-processed product＞vinegar- processed product.

OBJECTIVE To investigate the correlation between the expression levels of tissue inhibitor of metalloproteinases 1(TIMP-1)and drosophila mothers against DDP homolog 4(Smad4)in vocal cord precancerous lesions and postoperative recurrence and malignant transformation.METHODS The clinical and pathological data of 162 patients with vocal cord precancerous lesions admitted to the First Affiliated Hospital of Zhengzhou University from August 2018 to August 2021 were retrospectively analyzed.The expression of TIMP-1 and Smad4 in the surgically removed precancerous tissues(precancerous lesion group)and adjacent normal mucosal tissues(control group)were detected by immunohistochemical method.The relationship between the positive rate of TIMP-1 and Smad4 and clinicopathological features was analyzed.Kaplan-Meier method and Cox regression analysis were used to analyze the effect on postoperative recurrence and malignant transformation.RESULTS Compared with the normal mucosa of the control group,the positive rate of TIMP-1 was higher and the positive rate of Smad4 was lower in the precancerous lesion group(P<0.05).The positive rates of TIMP-1 and Smad4 in patients with different lesion ranges,anterior commissure involvement and different degree of epithelial dysplasia were different(P<0.05).Postoperative follow-up lasted from 24 to 60 months,with a median follow-up time of 36 months.During the follow-up,6 patients were lost to follow-up,with a follow-up rate of 96.30%(156/162).During the follow-up,35 patients had postoperative recurrence(21.60%)and 16 patients had postoperative malignant transformation(9.88%).Kaplan-Meier survival analysis showed that the postoperative recurrence rate and malignant change rate of TIMP-1 positive patients were higher than those of TIMP-1 negative patients(P<0.05),amd the recurrence rate and malignant change rate of Smad4-negative patients were higher than those of Smad4-positive patients(P<0.05).Multivariate Cox regression analysis showed that laryngeal reflux,lesion scope>1/2,moderate/severe dysplasia,TIMP-1 positive and Smad4 negative were independent risk factors for recurrence(P<0.05),and age>60 years old,anterior union involved,TIMP-1 positive and Smad4 negative were independent risk factors for malignant transformation(P<0.05).CONCLUSION The patients with high expression of TIMP-1 and low expression of Smad4,positive expression of TIMP-1 and negative expression of Smad4 have higher risk of postoperative recurrence and malignant transformation.

Objective:To explore the correlation between time in range (TIR) after short-term treatment and glycated hemoglobin after 3 months (HbA lc-3m) in patients with newly-diagnosed type 2 diabetes mellitus (T2DM). Methods:In this cross-sectional study, a total of 94 patients with newly-diagnosed T2DM who received treatment in the Department of Endocrinology of Inner Mongolia Autonomous Region People′s Hospital were enrolled from January 2018 to September 2022. The patients were followed-up for 3 months and had complete medical record. TIR was divided into three groups according to different target ranges of blood glucose (TIR1: TIR with blood glucose between 3.9 and 10.0 mmol/L, TIR2: TIR with blood glucose between 3.9 and 7.8 mmol/L, TIR3: TIR with fasting, premeal or bedtime blood glucose <6.1 mmol/L and 2 h postprandial blood glucose <8.0 mmol/L). The patients were divided into two groups based on whether their HbA 1c-3m level was less than 6.5%, and the baseline data and variations in TIR for distinct target glucose levels were compared between the two groups. Spearman′s correlation analysis and binary logistic regression analysis were used to analyze the relationship between baseline indicators, TIR after short-term treatment and HbA 1c-3m. Receiver operating characteristic curve (ROC) was drawn to evaluate the predictive ability of different TIR after short-term therapy for HbA 1c-3m. Results:There were statistically significant differences in TIR1 [81.0 (67.5, 94.6)% vs 71.4 (51.7, 85.7)%], TIR2 [57.7 (29.7, 70.8)% vs 40.9 (22.4, 52.3)%] and TIR3 [23.8 (10.2, 39.5)% vs 13.0 (4.8, 25.0)%] between patients with a HbA 1c-3m<6.5% and patients with a HbA 1c-3m≥6.5% (all P<0.05). Spearman correlation analysis showed that among all the patients with newly-diagnosed T2DM, TIR1, TIR2 and TIR3 were all negatively correlated with HbA 1c-3m [6.4 (6.1, 6.9)%] ( r=-0.322, -0.348, -0.303, respectively, all P<0.01). Logistic regression analysis showed that after adjusting for the confounding factors, TIR1 ( OR=1.021, 95% CI: 1.002-1.041; P=0.034), TIR2 ( OR=1.024, 95% CI: 1.006-1.043; P=0.011), TIR3 ( OR=1.037, 95% CI: 1.010-1.065; P=0.008) were all independently related to HbA 1c-3m. When HbA lc-3m<6.5% was taken as the target value, the area under the ROC curve: TIR1 was 0.639 (95% CI: 0.528-0.751), TIR2 was 0.671 (95% CI: 0.560-0.782), TIR3 was 0.659 (95% CI: 0.549-0.770), respectively. When HbA lc-3m<7.0% was taken as the target value, the area under the ROC curve: TIR1 was 0. 730 (95% CI: 0.619-0.841), TIR2 was 0.744 (95% CI: 0.642-0.846), TIR3 was 0.701 (95% CI: 0.588-0.814). There was no significant difference in the area among the three statistics ( P>0.05). Conclusions:For newly-diagnosed T2DM patients, TIR after short-term treatment is negatively correlated with HbA 1c after 3 months and has good predictive value for it.

Objective:To investigate the levels of osteoporosis-related biomarkers in individuals with subclinical hypothyroidism complicated by type 2 diabetes mellitus.Methods:A cross-sectional study. From January 2021 to June 2022, 40 patients with subclinical hypothyroidism, 40 patients with type 2 diabetes, 40 patients with type 2 diabetes complicated with subclinical hypothyroidism, and 40 individuals receiving physical examination in Shanxi Bethune Hospital were selected as subjects in this study. The glucose and lipid metabolism indexes and bone metabolism indexes of the subjects were detected, and the differences and correlations of the metabolic indexes among the groups were analyzed by t-tests, nonparametric tests or correlation analysis. Results:Compared with healthy group, beta C-terminal cross-linked telopeptides of type Ⅰ collagen (β-CTX) level in type 2 diabetes group was higher [(344.60±125.61) vs (227.56±68.33) pg/ml] ( t=-5.176, P<0.001), osteocalcin (OC) and total procollagen type 1 aminoterminal peptide (t-PINP) were both lower [(15.76±4.70) vs (28.02±5.83)ng/ml, (43.49±13.63) vs (59.58±15.80) ng/ml] ( t=10.352, t=4.874, P<0.001). The β-CTX level in type 2 diabetes patients complicated with hypothyroidism was higher than that in patients with simple subclinical hypothyroidism [(380.51±122.22) vs (212.41±44.17) pg/ml] ( t=-8.180 ,P<0.001), but the levels of OC and t-PINP were both lower [(13.67±4.06) vs (26.12±4.55) ng/ml, (38.76±9.53) vs (61.50±12.31) ng/ml] ( t=12.897, P<0.001); but there was no significant difference in the three biomarkers between patients with type 2 diabetes mellitus complicated by subclinical hypothyroidism and those with type 2 diabetes mellitus alone. [β-CTX: (380.51±122.22) vs (344.60±125.61) pg/ml, OC: (13.67±4.06) vs (15.76±4.70) ng/ml, t-PINP: (38.76±9.53) vs (43.49±13.63) ng/ml] ( t=1.296,1.890,-1.799 ,all P>0.05). In the patients with type 2 diabetes mellitus complicated by subclinical hypothyroidism, the β-CTX was positively correlated with fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c)( r=0.293,0.487,all P<0.05), while OC and t-PINP were negatively correlated with FBG and HbA1c ( r=-0.560,-0.502,-0.289,-0.326, P<0.05). Conclusion:Changes of serum osteoporosis-related biomarkers in subclinical hypothyroidism patients with type 2 diabetes indicate the increased risk of osteoporosis in those patients.

Background Per- and polyfluoroalkyl substances (PFAS) are a class of persistent organic pollu-tants. Industrial production and consumer use of PFAS are the primary sources of exposure in urban areas. E-waste recycling activities are also a significant source of environmental PFAS exposure. Objective To compare exposure profiles between traditional and emerging PFAS in neonatal cord blood collected from an e-waste recycling area and a general exposure area characterized by modern economic development (hereafter referred to as general exposure area). Methods Based on a birth cohort study conducted in 2018, 85 pregnant women were recruited (36 participants from an e-waste recycling area and 49 participants from a general exposure area). Neonatal cord blood was collected at delivery. Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to detect 28 common PFAS in the blood. A structured questionnaire was used to gather sociodemographic characteristics of the pregnant women. Mann-Whitney U tests were used to compare PFAS exposure levels in neonatal cord blood between the e-waste recycling area and the general exposure area. Multiple linear regression models were used to explore the influence of residing in the e-waste recycling area on neonatal PFAS exposure, with area as the independent variable and the natural logarithm of PFAS exposure levels as the dependent variable. Results A total of 22 PFAS were positive in neonatal cord blood, of which 13 congeners were 100% detectable in the samples from both areas. The median ∑PFAS exposure levels in neonatal cord blood were 14.19 ng·mL⁻¹ and 14.02 ng·mL⁻¹ for the e-waste recycling area and the general exposure area, respectively, with linear perfluorooctanoic acid (L-PFOA) showing the highest median concentration (5.49 ng·mL⁻¹ and 6.39 ng·mL⁻¹, respectively). The results of Mann-Whitney U tests showed that the median exposure levels of long-chain perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoDA), and perfluorotridecanoic acid (PFTrDA), as well as emerging alternatives 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) and 8:2 chlorinated polyfluorinated ether sulfonate (8:2 Cl-PFESA), were higher in the e-waste recycling area than in the general exposure area. In contrast, the median exposure levels of short-chain perfluoropentanoic acid (PFPeA) and perfluorohexanoic acid (PFHxA), as well as perfluorooctanoic acid (PFOA) branched isomers, including perfluoro-6-methylheptanoic acid (iso-PFOA), perfluoro-5-methylheptanoic acid (5m-PFOA), and perfluoro-4-methylheptanoic acid (4m-PFOA), were lower in the e-waste recycling area than in the general exposure area (P<0.05). The multiple linear regression models showed that, compared to the general exposure area, neonatal cord blood in the e-waste recycling area had significantly higher exposure levels of long-chain PFDA, PFUnDA, PFDoDA, PFTrDA, and emerging alternatives 6:2 Cl-PFESA and 8:2 Cl-PFESA, with odds ratios of 1.95 (95%CI: 1.39-2.75), 2.10 (95%CI: 1.58-2.75), 2.12 (95%CI: 1.39-3.25), 2.64 (95%CI: 1.63-4.22), 3.46 (95%CI: 2.34-5.10), and 3.25 (95%CI: 2.01-5.26), respectively. Conversely, the exposure levels of short-chain PFPeA, PFHxA, and branched PFOA (br-PFOA) were significantly lower, with odds ratios of 0.44 (95%CI: 0.38-0.52), 0.30 (95%CI: 0.16-0.57), and 0.50 (95%CI: 0.38-0.67), respectively. Conclusion PFAS are widely present in neonatal cord blood in both the e-waste recycling area and the general exposure area. Compared to the general exposure area, the neonatal cord blood samples in the e-waste recycling area show higher exposure levels of certain long-chain perfluoroalkyl carboxylic acids (PFCA) and emerging PFAS alternatives, while the neonatal cord blood samples in the general exposure area show higher exposure levels of some short-chain PFCA and PFOA branched isomers.

Objective:To investigate and compare the clinical outcomes of the arterial pre-occlusion technique(APOT) and the traditional technique in the surgery of locally advanced pancreatic cancer with arterial involvement after conversion therapy.Methods:This is a retrospective cohort study. The clinical data of 145 patients with locally advanced pancreatic cancer with arterial involvement admitted to the Department of Hepato-Biliary-Pancreatic Surgery of the First Hospital Affiliated to Naval Medical University,from January 2020 to December 2022 were retrospectively analyzed. All patients completed neoadjuvant therapy for tumors, and the feasibility of radical surgical treatment was determined by a multidisciplinary collaborative team evaluation before surgery. According to whether the intraoperative artery was pre-occluded, 145 patients were divided into two groups, including 28 cases in the APOT group(16 males, 12 females, aged (59.0±9.4) years), and 117 cases in the routine surgery group(76 males, 41 females, aged (55.1±8.2) years). To ensure comparability of baseline data between the APOT group and the routine surgery group, a 1∶2 match was performed using the propensity score matching method, and the caliper value was 0.006 45. The t-test,the Mann-Whitney U test, χ2 test or Fisher′s exact test were used to compare the data between the two groups,respectively. Results:After matching the propensity score,there were 28 cases in the APOT group and 56 cases in the routine surgery group. There were no significant differences in gender,age,preoperative comorbidities,preoperative body mass index,surgical approaches,chemotherapy regimen,stereotactic body radiation therapy ratio,tumor markers,and type of invaded artery between the two groups (all P>0.05).The arterial occlusion time M(IQR) in the APOT group was 7.0(3.8)minutes(range:3 to 15 minutes),and no ischemic manifestations were observed in the distal target organs that blocked blood vessels after surgery. The operation time was (170.3±57.7)minutes in the APOT group and (235.0±80.2)minutes in the routine surgery group,and the difference was statistically significant ( t=-3.800, P<0.01). The APOT group also experienced less intraoperative blood loss(650(588)ml vs. 800(600)ml; U=1 026.500, P=0.021). No significant differences were found between the groups in combined vein resection and reconstruction,celiac trunk resection,early postoperative complications, readmission rates at 30 days,and postoperative length of stay(all P>0.05). Extra-arterial dissection was performed in all patients,with arterial resection and reconstruction in 3 cases: 2 cases in the APOT group(1 case involving the superior mesenteric artery and 1 case involving the common hepatic artery) and 1 case in the routine group(involving the common hepatic artery). Postoperative abdominal bleeding occurred in 4 cases,with 3 cases in the routine group,1 case in the routine group. The R0 resection rate was 85.7%(24/28) in the APOT group and 80.4%(45/56) in the routine group,without significant differences between the groups( P=0.763). The median overall survival time was 27.6 months for the APOT group and 22.5 months for the routine group,while the median disease-free survival was 11.7 months and 16.8 months,respectively,with no significant differences between the two groups( P=0.532, P=0.927). Conclusion:The arterial pre-occlusion technique can be used for extra-arterial dissection in patients with locally advanced pancreatic cancer involving the arteries,reducing surgery time and intraoperative blood loss.

Objective To express recombinant Burkholderia pseudomallei(B.pseudomallei)type Ⅲ secretion system BipD protein,prepare its polyclonal antibodies and verify their immunological traits.Methods The recombinant pET-28a-BipD plasmid was generated,and the pET-28a-BipD-carried E.coli BL21(DE3)bacteria were induced with isopropyl-β-d-thiogalactoside(IPTG)to express recombinant BipD(rBipD)protein.The rBipD was obtained by affinity chromatography using His Trap column,then mixed with Fredrick's adjuvant to immunize BALB/c mice by intraperitoneal injection in order to obtain anti-rBipD polyclonal antibodies.The immunoreactivity of rBipD was detected by Western blot assay using rabbit anti-melioidosis serum and the serum from melioidosis patients.The immunogenicity of rBipD was evaluated using Western blotting and immunofluorescence staining.Finally,rBipD was used to establish an indirect ELISA to detect serum antibodies of clinical melioidosis patients.Results The recombinant plasmid pET-28a-BipD was successfully constructed and transformed into E.coli BL21(DE3)to induce rBipD expression with IPTG treatment.The obtained rBipD had a relative molecular weight of 36×103 and a purity of 95.4％,and had good immunogenicity and immunoreactivity.It could induce the production of specific antibodies after immunizing mice,and mouse polyclonal antibodies against rBipD were prepared with the titer of 1∶512 000.rBipD of 5.0 μg/mL produced specific immune response with the serum of melioidosis patients,but had no specific reaction with the serum of tuberculosis patients,with statistical difference(P＜0.01).Conclusion rBipD with immunological activity is successfully prepared and purified,and its polyclonal antibodies are also developed,which provide a good tool for clinical immunological diagnosis and study of immune mechanism of B.pseudomallei infection.