Objective:To analyze the sensitivity of cytoplasmic light-chain immunofluorescence with fluorescence in situ hybridization in bone marrow smears (new FISH) for detecting cytogenetic abnormalities in multiple myeloma (MM) .Methods:42 MM patients admitted to the First Affiliated Hospital of Nanjing Medical University from April 2022 to October 2023 were enrolled. The patients with MM were detected by new FISH and CD138 immunomagnetic bead sorting technology combined with FISH (MACS-FISH) or cytoplasmic immunoglobulin FISH (cIg-FISH) to analyze cytogenetic detection results using combination probes which included 1q21/1p32, p53, IgH, IgH/FGFR3 [t (4;14) ], and IgH/MAF [t (14;16) ].Results:In 23 patients with MM, the abnormality detection rates of cIg-FISH and new FISH were 95.7% and 100.0%, respectively ( P>0.05). The detection rates of 1q21+, 1p32-, p53 deletion, and IgH abnormalities by cIg-FISH and new FISH were consistent, which were 52.2%, 8.7%, 17.4%, and 65.2%, respectively. The results of the two methods further performed with t (4;14) and t (14;16) in patients with IgH abnormalities were identical. The positive rate of t (4;14) was 26.7%, whereas t (14;16) was not detected. In 19 patients with MM, the abnormality detection rates of MACS-FISH and new FISH were 73.7% and 63.2%, respectively ( P>0.05). The positivity rate of 1q21+, 1p32- and IgH abnormalities detected by MACS-FISH were slightly higher than those detected by new FISH; however, the differences were not statistically significant (all P values >0.05) . Conclusion:The new FISH method has a higher detection rate of cytogenetic abnormalities in patients with MM and has good consistency with MACS-FISH and cIg-FISH.

Aim To investigate the relationship between triglyceride-glucose(TyG)index and the risk of hy-pertension in middle-aged and older adults in China,and to provide scientific basis for the prevention and treatment of hypertension.Methods Data were obtained from the China health and retirement longitudinal study(CHARLS)in 2011.A multi-stage stratified sampling method was used to select participants.Restricted cubic spline regression model was used to analyze the dose-response relationship between TyG index and the risk of hypertension.Multivariate unconditional Logistic regression model was used to evaluate the association between TyG index and the risk of hyperten-sion.Results A total of 9 987 subjects were included in the analysis,with an average age of(59.16±9.43)years,including 4 707 males(47.13％).The restricted cubic spline regression model showed that the risk of hypertension in-creased with the elevation of TyG index,and there was a linear association(overall association test P＜0.000 1,non-linear association test P=0.201 9).The results of multivariate Logistic regression model showed that compared with Q1(TyG index＜8.23),the OR(95％CI)of hypertension with Q2(8.23≤ TyG index＜8.59),Q3(8.59 ≤ TyG index＜9.04)and Q4(TyG index≥9.04),were 1.09(0.95～1.26),1.53(1.33～1.76)and 1.77(1.52～2.06),respectively.Conclusions With the increase of TyG index,the risk of hypertension gradually increased.TyG index may be an inde-pendent risk factor of hypertension.

The effect of aspirin eugenol ester(AEE)on the metabolism of rats was investigated to provide theoretical references for the clinical rational use of the drug.Firstly,the appropriate con-centration of AEE suspension was prepared.Wistar rats were randomly divided into three groups:the normal group,the AEE low-dose group(18 mg/kg),and the AEE high-dose group(72 mg/kg).The rats in the dosing group were dosed once daily,and the Wistar rats in the normal group were dosed once daily with an equal volume of 0.5％sodium carboxymethylcellulose solution.The feces and urine were collected after 7 days of continuous gavage,and the feces and urine were ana-lyzed by ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spec-trometry(UPLC-QTOF-MS/MS)for non-targeted metabolomics and Metabo Analyst 5.0 was used for metabolic pathway enrichment.The results showed that the dose of AEE selected in this experiment was not toxic to the growth of rats.The results of the metabolomics study found that 10 and 8 differential metabolites were identified in rat feces and urine,respectively,involving meta-bolic pathways such as phenylalanine,tyrosine and tryptophan biosynthesis,phenylalanine metabo-lism,steroid hormone biosynthesis,biosynthesis of unsaturated fatty acids,aminosugar and nucleo-tide sugar metabolism,fatty acid biosynthesis,and β-alanine metabolism.AEE had no significant effect on the body weight of rats(P＞0.05),but AEE could affect the metabolism of rat organ-ism.Fecal metabolites were mainly involved in metabolic pathways including unsaturated fatty acid biosynthesis,tyrosine metabolism,fatty acid biosynthesis,and steroid hormone biosynthesis;urina-ry metabolites were mainly involved in metabolic pathways including purine metabolism,fatty acid biosynthesis,arginine,and proline metabolism.Therefore,the metabolic effects of AEE on rats are mainly closely related to the regulation of lipid metabolism,amino acid metabolism,and energy metabolism.The results of this experiment can provide some references for the efficacy and clinical application of AEE in animals.

Despite exciting achievements with some malignancies, immunotherapy for hypoimmunogenic cancers, especially glioblastoma (GBM), remains a formidable clinical challenge. Poor immunogenicity and deficient immune infiltrates are two major limitations to an effective cancer-specific immune response. Herein, we propose that an injectable signal-amplifying nanocomposite/hydrogel system consisting of granulocyte-macrophage colony-stimulating factor and imiquimod-loaded antigen-capturing nanoparticles can simultaneously amplify the chemotactic signal of antigen-presenting cells and the "danger" signal of GBM. We demonstrated the feasibility of this strategy in two scenarios of GBM. In the first scenario, we showed that this simultaneous amplification system, in conjunction with local chemotherapy, enhanced both the immunogenicity and immune infiltrates in a recurrent GBM model; thus, ultimately making a cold GBM hot and suppressing postoperative relapse. Encouraged by excellent efficacy, we further exploited this signal-amplifying system to improve the efficiency of vaccine lysate in the treatment of refractory multiple GBM, a disease with limited clinical treatment options. In general, this biomaterial-based immune signal amplification system represents a unique approach to restore GBM-specific immunity and may provide a beneficial preliminary treatment for other clinically refractory malignancies.

Enterotoxigenic Escherichia coli（ETEC）infection can induce watery diarrhea，leading to dehydration，electrolyte disturbance，and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera（rBS/WC）vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC，as well as the effectiveness，safety，and health economics of rBS/WC vaccine，National Clinical Research Center for Child Health（The Children’s Hospital，Zhejiang University School of Medicine）and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.

Skin ulcers are the most prevalent consequence of diabetes mellitus, and people with diabetic ulcers have a substantially greater death risk than those who do not have ulcers. Herbal medications have gained wide concern in recent years due to their multi-component, multi-target, and multi-pathway synergistic therapeutic effects. Clinical trials have demonstrated the safety and efficacy of herbal treatments in diabetic refractory ulcers. To systematically evaluate the healing effect of herbs on diabetic wounds, a literature search was conducted, the mechanism of action of 15 herbal extracts in promoting diabetic wound healing were reviewed, and the classification based on traditional Chinese medicine theory was discussed, which could provide a reference for the precise treatment and exploitation of herbal medicines for diabetic ulcers.

Objective:To investigate the effect of different spray-coagulation time of argon plasma coagulation (APC) injury on the Glisson system primary branche(G1) in the hepatic portal of pigs.Methods:Fifty clean healthy domestic pigs (27 females and 23 males, aged 7 to 14 months) were selected, with the body weighted (100.0±9.5) kg. They were randomly divided into five groups (A, B, C, D, and E), with 10 pigs in each group. G1 models were made and sprayed by APC for 1, 2, 3, 4, and 5 seconds. The damage, maximum damage area, maximum damage depth, and damage of the three branches of the Glisson system (the first branches of the portal vein, intrahepatic bile duct, and hepatic artery) were compared among the groups. The pigs were divided into two groups based on whether the three branches were damaged or not: the three-branch damage group ( n=23) and the control group ( n=27). The maximum damage area and maximum damage depth were compared between the two groups. Results:After the APC spraying, circular or elliptical damage appeared on the surface of the G1, with changes such as yellow-brown color, brown color, charred appearance, and defects. Under the microscope, G1 capsule was found to be deficient, the fibrous tissue beneath the capsule was ruptured, and the structures of small blood vessels and small bile ducts were incomplete. " Burn marks" and damage to the three branches of the Glisson system in G1 were also observed, and the damage was more severe at the center of the spray-coagulation. As the spray-coagulation time increased, the maximum damage area of the G1 model also increased, and the two were positively correlated ( r=0.90, P<0.001). The maximum damage depth was also positively correlated with spray-coagulation time ( r=0.97, P<0.001). The numbers of pigs with damage to the three branches of the Glisson system in Groups A-E were 0, 2, 5, 6, and 10, respectively, and the number of pigs with damage increased with the spray-coagulation time. In the three-branch damage group, the spray-coagulation time, maximum damage area, and maximum damage depth were all higher than those in the control group (without three-branch damage), and the differences were statistically significant (all P<0.05). Conclusion:The degree of damage to G1 caused by APC is positively correlated with the spray-coagulation time, and damage to the three branches of the Glisson system in G1 is related to the maximum damage area, maximum damage depth, and APC spray-coagulation time.

There is currently a huge worldwide demand for donor kidneys for organ transplantation. Consequently, numerous marginal donor kidneys, such as kidneys with microthrombi, are used to save patients' lives. While some studies have shown an association between the presence of microthrombi in donor kidneys and an increased risk for delayed graft function (DGF) (McCall et al., 2003; Gao et al., 2019), other studies have demonstrated that microthrombi negatively impact the rate of DGF (Batra et al., 2016; Hansen et al., 2018), but not graft survival rate (McCall et al., 2003; Batra et al., 2016; Gao et al., 2019). In contrast, Hansen et al. (2018) concluded that fibrin thrombi were not only associated with reduced graft function six months post-transplantation but also with increased graft loss within the first year of transplantation. On the other hand, Batra et al. (2016) found no significant differences in the DGF rate or one-year graft function between recipients in diffuse and focal microthrombi groups. To date, however, the overall influence of donor kidney microthrombi and the degree of influence on prognosis remain controversial, necessitating further research.
Humans ; Thrombotic Microangiopathies ; Transplantation, Homologous ; Tissue Donors ; Kidney ; Allografts

Objective:To explore the clinical efficacy of liver transplantation for Wilson's disease(WD).Methods:From January 1999 to November 2021, clinical data were retrospectively reviewed for 16 recipients with WD undergoing liver transplantation.There were 9 males and 7 females with an age range of 29.5(14~54)years.They were followed up by telephone, outpatient services and hospitalization.The starting point of follow-up was operation date.And recipient death was an endpoint.Postoperative survival, improvement of neuropsychiatric symptom, changes of corneal K-F ring, altered levels of liver function and serum copper-protein at Month 1 post-operation were observed.The follow-up deadline was November 24, 2021.Results:15 recipients underwent classical orthotopic liver transplantation and the other one recipient underwent living-related liver transplantation.No perioperative deaths occurred.All 16 recipients were followed up for 122(6~260)months.The 1-, 5-, and 10-year survival rates were 93.8%、85.2%and 75.8%, respectively.Among 10 recipients with corneal K-F ring positive with varying degrees after operation and was disappeared in 2 recipients at 7 and 11 months.Among 5 recipients with neuropsychiatric manifestation, 4 recipients showed ameliorative neuropsychic symptoms with varying degrees after operation and 1 recipient died.All the levels of liver function and serum copper-protien of all recipients recovered obviously in 1 month and the 1-, 5-, and 10-year post-operation.Conclusions:Classical orthotopic liver transplantation and living-related liver transplantation not only effectively improves copper metabolism of patient with WD and relieves their severe neurological manifestation, but also improves their life and prolongs survival, which is worthy of clinical promotion.

Objective:To investigate the clinical significance of cc-chemokine receptor 7 (CCR7) as a potential diagnostic or differential marker for chronic lymphocytic leukemia (CLL).Methods:A total number of 643 patients with B-cell chronic lymphoproliferative diseases (B-CLPD) admitted to the First Affiliated Hospital of Nanjing Medical University from January 2015 to December 2018 were enrolled. The patients included 327 cases of CLL, 58 cases of mantle cell lymphoma (MCL), 34 cases of follicular lymphoma (FL), 36 cases of marginal zone lymphoma (MZL), 10 cases of hair-cell leukemia or its variants (HCL/HCLV-v), 40 cases of Waldorf′s macroglobulinemia (WM), 48 cases of CD5 +B-cell chronic lymphoproliferative disease unclassified (B-CLPD-U) and 90 cases of CD5 -B-CLPD-U. At the same time, 20 samples from healthy people from the medical examination center of our hospital were used as normal controls. Flow cytometry was used to detect the immune-phenotype and CCR7 expression level in B-CLPD patients, and Fluorescence in situ hybridization (FISH) was used to analyze the genomic alterations: the ataxia telangiectasia mutant gene (ATM) deletion, the 13q14 deletion, the P53 deletion and trisomy 12. Sanger sequencing was used to analyze gene mutations of splicing factor 3B subunit 1 (SF3B1), NOTCH1, tumor protein 53 (TP53) and immunoglobulin heavy chain variable region (IGHV). Measurement data were compared by Mann-Whitney test, and the positive rates were compared by chi-square test. The diagnostic value and optimal positive cutoff value of CCR7 were calculated using receiver operating characteristic (ROC) curve. Results:The positive rates of CCR7 expression in typical CLL and atypical CLL were 90.8% (257/283) and 84.1% (37/44), respectively, and there was no significant difference of the positive rates (χ 2=1.228, P=0.268) between groups. The positive expression rates of CCR7 in CLL, MCL, CD5 +B-CLPD-U, CD5 -B-CLPD-U, FL, WM, HCL/HCL-v and MZL were 89.9% (294/327), 10.3% (6/58), 6.3% (3/48), 8.9% (8/90), 0, 0, 0 and 13.9% (5/36) respectively, and the median mean fluorescence intensity (MFI) was 278 (246, 307), 114 (106, 128), 112 (106, 117), 110 (104, 121), 108 (105, 119), 111 (105, 124), 112 (108, 115) and 109 (105, 120) respectively. Compared with CLL, the positive expression rates of CCR7 in other types of B-CLPDs were lower significantly (χ 2=181.3, 177.8, 232, 164.7, 180.8, 62.6, 129, P<0.01). In addition, the sensitivity, specificity and accuracy of CCR7 for distinguishing CLL from other types of B-CLPD were 89.9%, 93.0% and 92.3%, respectively. The positive expression rate of CD49d in CCR7 +CLL patients was 13.9%, which was significantly lower than that in CCR7 -CLL patients (42.1%) (χ 2=7.6, P=0.01). The coincidence rate of 13q14 deletion was 50.3% in CCR7 +CLL patients, which was significantly higher than that in CCR7 -CLL patients (20%) (χ 2=6.56, P=0.01). Conclusions:The CC-chemokine receptor 7 (CCR7) antigen is an effective marker for the diagnosis and identification of chronic lymphocytic leukemia (CLL). The expression level of CCR7 in clinical specimens can distinguish CLL from other pathological subtypes of B-CLPDs.