OBJECTIVE To explore the independent risk factors of voriconazole （VCZ）-related liver injury in elderly patients with hypoproteinemia. METHODS Elderly patients with invasive fungal infection and hypoproteinemia who were hospitalized in the respiratory intensive care unit of our hospital and treated with VCZ from August 2020 to July 2023 were selected. They were divided into group A （liver injury group） and group B （non-liver injury group） based on whether the liver injury occurred after using VCZ. Pearson correlation analysis was used to analyze the correlation between minimum concentration （cmin） of VCZ and inflammatory factor[C-reactive protein （CRP）， procalcitonin （PCT）， interleukin-6 （IL-6）]， as well as liver function [alanine transaminase （ALT）， aspartate transaminase （AST）， alkaline phosphatase （ALP）， gamma-glutamyl transpeptidase （GGT）， total bilirubin （TBIL）]； univariate analysis was performed by using χ 2 test； Logistic regression analysis was used to analyze the independent risk factors affecting the occurrence of liver injury. RESULTS A total of 320 patients were included in the study， of whom 56 developed liver injury， with an incidence of 17.50%. The VCZ cmin in group A was significantly higher than group B （P＝ 0.021）. CRP， PCT， IL-6， and TBIL were correlated with VCZ cmin （P＜0.05）. CRP， PCT， IL-6， and TBIL had a significant impact on VCZ cmin （P＜0.05）. VCZ cmin， PCT， and TBIL were independent risk factors for liver injury （P＜0.05）. The patients with VCZ cmin≥3.76 mg/L had a significantly increased risk of liver injury. CONCLUSIONS VCZ cmin， PCT， and TBIL are independent risk factors for the occurrence of liver injury in elderly patients with hypoproteinemia. For patients with high PCT and TBIL， VCZ cmin and liver function should be closely monitored during VCZ treatment to reduce the risk of liver injury.

Objective To analyze the factors associated with pain after arthroscopic rotator cuff bridge suture.Methods According to the inclusion and exclusion criteria,the data of 112 patients with unilateral rotator cuff injury who received arthroscopic bridge suture in our department were collected and were investigated in the form of telephone follow-up.In this study,SPSS 23.0 was used to input data and conduct statistical analysis.Logistic regression analysis was used to analyze the correlation between the above influencing factors and postoperative pain.Results A total of 112 patients were included for statistical analysis,single factor analysis revealed,including course of disease,smoking history,preoperative University of California,Los Angeles(UCLA)score,Constant score,numeric rating scale(NRS),size of rotator cuff tear,whether it was full-thickness tear and degree of tendon retraction might be related to postoperative pain(P<0.05).The age,gender,body mass index(BMI),drinking history,diabetes and hypertension were not related to postoperative pain(P>0.05).Multiple linear regression analysis concluded that there were four factors related to postoperative pain,and the correlation degree was preoperative NRS,preoperative UCLA score,tear size and smoking history.Conclusion The causes of postoperative pain after arthroscopic rotator cauff repair are complex and diverse.Analyzing the cause of postoperative pain can effectively reduce the pain of patients and promote the recovery of shoulder joint function.

Background The senescence of alveolar type II epithelial cells is an important driving factor for the progression of silicotic fibrosis, and the regulatory effects of oxamate on the senescence of alveolar type II epithelial cells is still unclear. Objective To explore whether lactate dehydrogenase inhibitor oxamate can alleviate silicotic fibrosis in mice by inhibiting senescence of alveolar type II epithelial cellsMethods This study was divided into two parts: in vivo experiments and in vitro experiments. In the first part, forty SPF C57BL/6J male mice were randomly divided into four groups with 10 in each group: control group, silicosis model group, low-dose oxamate treatment group, and high-dose oxamate treatment group. The silicotic mouse model was established by intratracheal instillation of 50 μL SiO₂ suspension (100 mg·mL⁻¹). The treatment models were prepared by intraperitoneal injection of 100 μL oxamate (225 mmol·L⁻¹ and 1125 mmol·L⁻¹). In the second part, induction of MLE-12 mouse alveolar type II epithelial cells was conducted with SiO₂. The in vitro experimental groups were ① SiO₂ induction groups: control group, 50 μg·mL⁻¹ SiO₂ group, 100 μg·mL⁻¹ SiO₂ group, and 200 μg·mL⁻¹ SiO₂ group, and ② oxamate treatment groups: control group, SiO₂ group (100 μg·mL⁻¹), low-dose oxamate (25 mmol·L⁻¹) treatment group, and high-dose oxamate (50 mmol·L⁻¹) treatment group. Pathological morphology of lung tissues was evaluated after hematoxylin-eosin (HE) staining; deposition of collagen in lung tissues was evaluated after sirius red staining; positive co-expression of prosurfactant protein C (Pro-SPC) and β-galactosidase was detected by immunofluorescence staining; positive expression of β-galactosidase in MLE-12 cells was detected by immunofluorescence staining. The protein expression levels of collagen type I (CoL I), fibronectin1 (FN1), hexokinase 2 (HK2), pyruvate kinase isozyme type M2 (PKM2), lactate dehydrogenase A (LDHA), p-ataxia telangiectasia and Rad3-related kinase (ATR), and cyclin-dependent kinase inhibitors p21, and p16 were detected by Western blotting. Results Compared with the control group, the protein expression levels of HK2, PKM2, LDHA, p-ATR, p21, and p16 were significantly upregulated in the silicosis model group and the SiO₂-induced MLE-12 cells (P＜0.05). The in vivo studies showed that, compared with the control group, the silicon nodule area, the collagen deposition area, the proportion of β-galactosidase positive cells, and the protein expression levels of CoL I, FN1, LDHA, p-ATR, p21, and p16 were significantly upregulated in the silicosis model group (P＜0.05). Compared with the silicosis model group, the oxamate treatment groups showed significant downregulation of the silicon nodule area, the collagen deposition area, the proportion of β-galactosidase positive cells, and the the CoL I, FN1, LDHA, p-ATR, p21, and p16 protein expression levels, and the high-dose oxamate treatment group showed a higher efficacy on these indicators than the low-dose oxamate treatment group (P＜0.05). The in vitro studies showed that, compared with the control group, the proportion of β-galactosidase positive cells and the protein expression levels of p-ATR, p21, and p16 were significantly upregulated in the SiO₂-induced group (P＜0.05). Compared with the SiO₂ group, the proportion of β-galactosidase positive cells and the LDHA, p-ATR, p21 and p16 protein expression levels were significantly downregulated in the oxamate treatment groups, and the high-dose oxamate treatment group showed a higher efficacy on these indicators than the low-dose oxamate treatment group (P＜0.05). Conclusion Lactate dehydrogenase inhibitor oxamate can alleviate silicotic fibrosis in mice by inhibiting the senescence of alveolar type II epithelial cells.

Objective To compare the blood glucose control effect and safety between insulin degludec and insulin aspart and insulin aspart 30 in non-obese patients with type 2 diabetes mellitus(T2DM).Methods Non-obese patients with T2DM were divided into treatment group and control group according to different treatment methods.The control group was treated with insulin aspart 30,and the treatment group was treated with insulin degludec and insulin aspart.Pancreatic islet related indicators[fasting C-peptide(FCP)and 2-hour postprandial C-peptide(2 h CP)],blood glucose control effect[fasting blood glucose(FBG),2-hour postprandial blood glucose(2 h PG)and glycated hemoglobin(HbA1c)],serum 25-hydroxyvitamin D[25(OH)D]and the risk of hypoglycemia were compared between the two groups.Results There were 41 cases in treatment group and 39 cases in control group.After treatment,FCP levels in treatment group and control group were(0.84±0.09)and(1.07±0.14)nmol·L-1;2 h CP levels were(1.03±0.15)and(1.69±0.17)nmol·L-1;FBG levels were(5.46±0.57)and(6.18±0.67)mmol·L-1;2 h PG levels were(8.17±0.85)and(9.03±0.94)mmol·L-1;HbA1 c were(5.35±0.57)％and(6.47±0.68)％;25(OH)D levels were(26.33±2.75)and(20.54±2.17)nmol·L-1,all with significant difference(all P＜0.05).The incidence rates of non-severe hypoglycemia in treatment group and control group were 14.63％and 35.90％,with statistically significant difference(P＜0.05).The incidence rates of severe hypoglycemia in treatment group and control group were 9.76％and 12.82％;the incidence rates of nocturnal hypoglycemia were 19.51％and 17.95％,without statistically significant difference(all P＞0.05).Conclusion The overall therapeutic effect of insulin degludec and insulin aspart on non-obese patients with T2DM is better than that of insulin aspart 30.The former can effectively regulate blood glucose and pancreatic islet cell function,lower the risk of non-severe hypoglycemia.

Objective Recombinase-aided polymerase chain reaction(RAP)is a sensitive,single-tube,two-stage nucleic acid amplification method.This study aimed to develop an assay that can be used for the early diagnosis of three types of bacteremia caused by Staphylococcus aureus(SA),Pseudomonas aeruginosa(PA),and Acinetobacter baumannii(AB)in the bloodstream based on recombinant human mannan-binding lectin protein(M1 protein)-conjugated magnetic bead(M1 bead)enrichment of pathogens combined with RAP. Methods Recombinant plasmids were used to evaluate the assay sensitivity.Common blood influenza bacteria were used for the specific detection.Simulated and clinical plasma samples were enriched with M1 beads and then subjected to multiple recombinase-aided PCR(M-RAP)and quantitative PCR(qPCR)assays.Kappa analysis was used to evaluate the consistency between the two assays. Results The M-RAP method had sensitivity rates of 1,10,and 1 copies/μL for the detection of SA,PA,and AB plasmids,respectively,without cross-reaction to other bacterial species.The M-RAP assay obtained results for<10 CFU/mL pathogens in the blood within 4 h,with higher sensitivity than qPCR.M-RAP and qPCR for SA,PA,and AB yielded Kappa values of 0.839,0.815,and 0.856,respectively(P<0.05). Conclusion An M-RAP assay for SA,PA,and AB in blood samples utilizing M1 bead enrichment has been developed and can be potentially used for the early detection of bacteremia.

Objective Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in vivo.Methods Fluorescent microspheres (100 nm, 3 μm, and 10 μm) were given once at a dose of 200 mg/(kg·body weight). The fluorescence intensity (FI) in observed organs was measured using the IVIS Spectrum at 0.5, 1, 2, and 4 h after administration. Histopathology was performed to corroborate these findings.Results In the 100 nm group, the FI of the stomach and small intestine were highest at 0.5 h, and the FI of the large intestine, excrement, lung, kidney, liver, and skeletal muscles were highest at 4 h compared with the control group (P < 0.05). In the 3 μm group, the FI only increased in the lung at 2 h (P < 0.05). In the 10 μm group, the FI increased in the large intestine and excrement at 2 h, and in the kidney at 4 h (P < 0.05). The presence of nano-/microplastics in tissues was further verified by histopathology. The peak time of nanoplastic absorption in blood was confirmed.Conclusion Nanoplastics translocated rapidly to observed organs/tissues through blood circulation;however, only small amounts of MPs could penetrate the organs.

Objective To investigate the clinical effect of apical microsurgery combined with guided bone regeneration(GBR)on refractory apical periodontitis and masticatory function.Methods A total of 82 patients with refractory apical periodontitis admitted to our hospital from June 2019 to September 2021 were selected as the study subjects,and they were divided into the control group and the com-bined group according to the random number table,with 41 cases in each group.The control group was treated with apical microsurgery,and the combined group was treated with apical microsurgery combined with GBR.The clinical efficacy,masticatory function and the levels of bone absorption markers[Wnt3a,osteoprotegerin(OPG),receptor activator of nuclear factor-κB ligand(RANKL)]of patients in the two groups were compared.Results The total effective rate of the combined group(100%)was higher than that of the control group(85.37%),the difference was statistically significant(P<0.05).The masticatory efficiency and bite force of patients in both groups increased gradually 3,6 and 12 months after operation(P<0.05),which were higher in the combined group compared with the control group(P<0.05).The tooth mobility of patients in both groups decreased gradually 3,6 and 12 months after operation,and the tooth mobility of patients 3 and 6 months after operation in the combined group were lower than those in the control group(P<0.05).The levels of Wnt3a and OPG of patients 1 week after operation in both groups increased,which were higher in the combined group compared with the control group(P<0.05).The RANKL level of gingival crevicular fluid of patients 1 week after operation in both groups decreased,and which was lower in the combined group compared with the control group(P<0.05).Conclusion The microapical surgery combined with GBR is effective for refractory apical periodontitis,which can effectively inhibit bone resorption,and improve masticatory function.

Objective To investigate the effects and mechanisms of icariin on changes in fear memory in post-traumatic stress disorder(PTSD)rats.Methods Thirty male SD rats were used to construct a rat model of single prolonged stress(SPS).The model rats were randomly divided into the SPS,icariin,and icariin + K252a(tyrosine kinase receptor B inhibitor)groups(n= 10 each;another 10 normal rats were used as the control group).The icariin and icariin + K252a groups were administered 20 mg/kg icariin by gavage once per day after SPS,while the control and SPS groups were administered the same dose of normal saline.K252a cells were injected into the lateral ventricles.After 2 weeks,anxiety,depression,and fear memory disorder in rats in each group were detected by the mine experiment,ele-vated cross maze experiment,and conditional fear test.The binding activity of icariin to brain-derived neurotrophic factor(BDNF)and the BDNF and TrkB expressions in the rat amygdala were detected by immunohistochemistry.The relative expressions of BDNF and TrkB pro-teins were detected by Western blotting.The expressions of postsynaptic density protein 95(PSD95)and synaptophysin(SYN)in the rat amygdala were detected using immunofluorescence.Results Icariin showed strong binding to BDNF.Compared with the control group,the times of entering the central area and the percentage of movement distance in the central area in the SPS group and the icariin+K252a group were significantly reduced.The open arm entry(OE)and arm opening time(OT)were significantly reduced,the freezing time and defecation times were significantly increased,and the expressions of the BDNF,TrkB,PSD95,and SYN proteins were significantly reduced(P<0.05).Compared with the SPS group,the icariin group rats had significantly increased times of entering the central area and percentages of movement distance in the central area,significantly increased OE and OT,significantly reduced the time of immobilization and defecation,and significantly increased the expressions of BDNF,TrkB,PSD95,and SYN proteins(P<0.05).Conclusion Icariin effectively alleviated the fear memory impairment induced by SPS in rats.This protective effect is related to BDNF/TrkB signaling pathway activation and upregulated PSD95 and SYN expression.

Objective:To investigate the clinical characteristics, diagnosis, treatment, and prognosis of primary thyroid lymphoma (PTL) .Methods:A retrospective analysis was conducted on the clinical and pathological data of 34 newly diagnosed PTL patients admitted to Beijing Tongren Hospital from September 2010 to February 2023. The Kaplan-Meier survival curve and Log-rank test were used for survival analysis, and the Cox regression model was applied for univariate analysis of prognostic factors.Results:All 34 PTL patients presented with cervical mass as the initial clinical manifestation. There were 9 males and 25 females. The pathological diagnosis was diffuse large B-cell lymphoma (DLBCL) in 29 patients and mucosa-associated lymphoid tissue (MALT) lymphoma in 5 patients. Among the DLBCL patients, 6 had B symptoms, 17 had an Eastern Cooperative Oncology Group (ECOG) score of ≥2, the Ann Arbor staging was stage Ⅰ-Ⅱ in 21 cases and stage Ⅲ-Ⅳ in 8 cases, the tumor diameter was ≥10 cm in 4 cases, and 14 had concurrent Hashimoto thyroiditis; 27 cases received chemotherapy, with 21 cases achieving complete remission (CR), 2 cases partial remission (PR), and 6 cases of disease progression; the 5-year progression-free survival and overall survival rates were 78.9% and 77.4%, respectively; univariate survival analysis showed that B symptoms, tumor diameter ≥10 cm, and Ann Arbor stage Ⅲ-Ⅳ were significant factors affecting patient prognosis ( P<0.05). MALT lymphoma patients were all in stages Ⅰ-Ⅱ, had an ECOG score of 0-1, and were without B symptoms. All patients underwent surgical resection, with 4 cases achieving CR and 1 case PR. Conclusion:PTL is more common in females with concurrent Hashimoto thyroiditis, with the majority of pathological types being B-cell lymphoma. The main treatment is chemotherapy, supplemented by radiotherapy and surgery, and the prognosis is relatively favorable.

Objective:To observe the changes in the nutritional status of pediatric patients after allogeneic hematopoietic stem cell transplantation(allo-HSCT)for one year,and to analyze the risk factors.Methods:We collected data from 88 pediatric patients who underwent allo-HSCT at the Department of Hematology and Oncology in Children's Hospital of Nanjing Medical University between May 2018 and November 2022.All pediatric patients underwent nutritional status analysis before transplantation,at enrollment,3 months,6 months and 1 year after allo-HSCT.Linear regression model was used to analyze the risk factors for growth rate.Results:The body mass index Z score(BMI-Z)before allo-HSCT was(0.096±1.349),and decreased to(-0.258±1.438)、(-0.715±1.432)、(-0.584±1.444)at enrollment,3 months,6 months after allo-HSCT,and(-0.130±1.317)at 1 year after allo-HSCT(P<0.001).There was no significant change in BMI-Z between pre-transplantation and 1 year after transplantation(P=1.000).Height for age Z score(HAZ)before transplantation was(0.137±1.305)and decreased to(-0.083±1.267)、(-0.221±1.299)、(-0.269±1.282)in 3 months,6 months and 1 year after allo-HSCT(P<0.001).Multivariate linear regression showed that age≥10 years old(P=0.015)and chronic graft-versus-host disease(cGVHD)(P=0.005)were independent risk factors for change in HAZ.Conclusion:The BMI-Z of pediatric patients treated with allo-HSCT returned to the pre-transplantation level after one year,while HAZ continued to decrease.Allo-HSCT may cause impaired growth rate in pediatric patients.Attention should be paid to HAZ changes in pediatric patients before and after allo-HSCT,especially in pediatric patients≥10 years old of age and those with cGVHD.Effective nutritional intervention should be provided in time.