Aim To investigate the role of tryptophan 2,3-dioxygenase(TDO2)in cisplatin-acute kidney in-jury(Cis-AKI)and to explore the mechanism of TDO2 in relation to apoptosis in tubular epithelial cells(TECs)to investigate the mechanism of TDO2 associ-ated with apoptosis.Methods An AKI model was es-tablished by intraperitoneal injection of cisplatin(Cis).Colorimetric assay was used to detect CRE and BUN levels,and PAS staining was employed to observe renal injury in mice.Immunohistochemistry was used to detect TDO2 protein expression and distribution and macrophage(F4/80+)infiltration;immunofluores-cence was used to detect the co-localization of TDO2 with the tubular marker LTL;TUNEL staining was used to detect apoptosis in mouse kidney;flow cytome-try was used to detect overexpression of human renal cortical proximal tubular epithelial cells(HK2)and apoptosis after administration of the TDO2 inhibitor 680C91;Western blot was used to detect TDO2 and NF-κB pathway protein levels in HK2 cells after over-expression and inhibition of TDO2.Results In the o-verall animal experiments,Cis-AKI mice showed signif-icantly higher levels of CRE and BUN and obvious tu-bular damage compared with the control group;at the same time,the renal tissues of Cis-AKI mice showed increased expression of F4/80,and the proportion of apoptotic cells in kidney cells was increased.Immuno-histochemistry and immunofluorescence showed that the expression of TDO2 increased,mainly localized in TECs.In cellular experiments,HK2 cells overexpress-ing TDO2 increased the proportion of apoptosis,and the expression of TDO2,p-IKBα,and p-p65 proteins was elevated,and p-IKBα/IκBα and p-p65/p65 were ele-vated;furthermore,the proportion of apoptosis was re-duced by the administration of 680C91,and the expres-sion of p-IκBα,and p-p65 proteins decreased,and the expression of p-IKBα/IKBα,and p-p65/p65 de-creased.Conclusions Elevated TDO2 in TECs is in-volved in the pathological mechanism of Cis-AKI,which may be related to its induction of apoptosis in TECs and activation of the NF-κB signaling pathway and consequently renal injury.

A subset of patients with multiple myeloma(MM)present with reduced serum vitamin B12 levels at initial diagnosis;however,its clinical significance and underlying mechanisms remain unclear.Vitamin B12 plays a crucial role in hematopoiesis and immune regulation.This study aims to elucidate its association with extramedullary diseases,immune function,and prognosis in MM patients.A retrospec-tive analysis was conducted of 92 newly diagnosed MM patients,who received treatment at the Second Af-filiated Hospital of Soochow University between January 2020 and December 2023.Patients were classi-fied into a low vitamin B12 group(n=37)and a normal vitamin B12 group(n=55)based on their ser-um vitamin B12 levels.The findings revealed that the incidence of extramedullary infiltration was signifi-cantly higher in the low vitamin B12 group than in the normal group(26.5％vs.17.0％,P=0.031).Survival analysis demonstrated that patients with low vitamin B12 levels had significantly shorter overall survival(OS)and progression-free survival(PFS)(OS:P=0.0123;PFS:P=0.0136).Additionally,these patients showed a decreasing trend in peripheral blood total T cell,CD4+T cell,and CD8+T cell counts,with serum vitamin B12 levels showing a significant positive correlation with the total T cell count(R=0.2717,P=0.0135)and CD4+T cell count(R=0.2175,P=0.0497).In conclusion,reduced serum vitamin B12 levels at initial diagnosis are significantly associated with poor prognosis in MM pa-tients and may serve as a potential prognostic biomarker.Furthermore,vitamin B12 deficiency may con-tribute to immune dysfunction,particularly impaired T cell immunity,and a higher incidence of extr-amedullary diseases.

Objective To investigate the status of population dynamics and distribution changes of Aedes aegypti in Guangdong Province.Methods Continuous monitoring was conducted from May 2018 to July 2024 in Wushi Town and Qishui Town,Leizhou City,Zhanjiang City,Guangdong Province.Additionally,a survey of the distribution of Ae.aegypti along the Leizhou Peninsula coast was carried out.Results The density of Ae.aegypti in Zhanjiang showed a gradual decline from 2018 to 2024.The last detection of adult Ae.aegypti in Wushi Town was in September 2021,and the last larva was found in October 2023.No Ae.aegypti was detected in Qishui Town during surveys from 2021 to 2024.A survey of 18 coastal villages in the Leizhou Peninsula revealed no detections of Ae.aegypti.Conclusions This study provides a basis for understanding the distribution and population density fluctuations of Ae.aegypti,assessing its invasion risk,and scientifically conducting relevant prevention and control efforts.

ObjectiveBased on functional near-infrared spectroscopy (fNIRS), we investigated the brain activity characteristics of gross motor tasks in children with autism spectrum disorder (ASD) and motor dysfunctions (MDs) to provide a theoretical basis for further understanding the mechanism of MDs in children with ASD and designing targeted intervention programs from a central perspective. MethodsAccording to the inclusion and exclusion criteria, 48 children with ASD accompanied by MDs were recruited into the ASD group and 40 children with typically developing (TD) into the TD group. The fNIRS device was used to collect the information of blood oxygen changes in the cortical motor-related brain regions during single-handed bag throwing and tiptoe walking, and the differences in brain activation and functional connectivity between the two groups of children were analyzed from the perspective of brain activation and functional connectivity. ResultsCompared to the TD group, in the object manipulative motor task (one-handed bag throwing), the ASD group showed significantly reduced activation in both left sensorimotor cortex (SMC) and right secondary visual cortex (V2) (P<0.05), whereas the right pre-motor and supplementary motor cortex (PMC&SMA) had significantly higher activation (P<0.01) and showed bilateral brain region activity; in terms of brain functional integration, there was a significant decrease in the strength of brain functional connectivity (P<0.05) and was mainly associated with dorsolateral prefrontal cortex (DLPFC) and V2. In the body stability motor task (tiptoe walking), the ASD group had significantly higher activation in motor-related brain regions such as the DLPFC, SMC, and PMC&SMA (P<0.05) and showed bilateral brain region activity; in terms of brain functional integration, the ASD group had lower strength of brain functional connectivity (P<0.05) and was mainly associated with PMC&SMA and V2. ConclusionChildren with ASD exhibit abnormal brain functional activity characteristics specific to different gross motor tasks in object manipulative and body stability, reflecting insufficient or excessive compensatory activation of local brain regions and impaired cross-regions integration, which may be a potential reason for the poorer gross motor performance of children with ASD, and meanwhile provides data support for further unraveling the mechanisms underlying the occurrence of MDs in the context of ASD and designing targeted intervention programs from a central perspective.

A subset of patients with multiple myeloma(MM)present with reduced serum vitamin B12 levels at initial diagnosis;however,its clinical significance and underlying mechanisms remain unclear.Vitamin B12 plays a crucial role in hematopoiesis and immune regulation.This study aims to elucidate its association with extramedullary diseases,immune function,and prognosis in MM patients.A retrospec-tive analysis was conducted of 92 newly diagnosed MM patients,who received treatment at the Second Af-filiated Hospital of Soochow University between January 2020 and December 2023.Patients were classi-fied into a low vitamin B12 group(n=37)and a normal vitamin B12 group(n=55)based on their ser-um vitamin B12 levels.The findings revealed that the incidence of extramedullary infiltration was signifi-cantly higher in the low vitamin B12 group than in the normal group(26.5％vs.17.0％,P=0.031).Survival analysis demonstrated that patients with low vitamin B12 levels had significantly shorter overall survival(OS)and progression-free survival(PFS)(OS:P=0.0123;PFS:P=0.0136).Additionally,these patients showed a decreasing trend in peripheral blood total T cell,CD4+T cell,and CD8+T cell counts,with serum vitamin B12 levels showing a significant positive correlation with the total T cell count(R=0.2717,P=0.0135)and CD4+T cell count(R=0.2175,P=0.0497).In conclusion,reduced serum vitamin B12 levels at initial diagnosis are significantly associated with poor prognosis in MM pa-tients and may serve as a potential prognostic biomarker.Furthermore,vitamin B12 deficiency may con-tribute to immune dysfunction,particularly impaired T cell immunity,and a higher incidence of extr-amedullary diseases.

Aim To investigate the role of tryptophan 2,3-dioxygenase(TDO2)in cisplatin-acute kidney in-jury(Cis-AKI)and to explore the mechanism of TDO2 in relation to apoptosis in tubular epithelial cells(TECs)to investigate the mechanism of TDO2 associ-ated with apoptosis.Methods An AKI model was es-tablished by intraperitoneal injection of cisplatin(Cis).Colorimetric assay was used to detect CRE and BUN levels,and PAS staining was employed to observe renal injury in mice.Immunohistochemistry was used to detect TDO2 protein expression and distribution and macrophage(F4/80+)infiltration;immunofluores-cence was used to detect the co-localization of TDO2 with the tubular marker LTL;TUNEL staining was used to detect apoptosis in mouse kidney;flow cytome-try was used to detect overexpression of human renal cortical proximal tubular epithelial cells(HK2)and apoptosis after administration of the TDO2 inhibitor 680C91;Western blot was used to detect TDO2 and NF-κB pathway protein levels in HK2 cells after over-expression and inhibition of TDO2.Results In the o-verall animal experiments,Cis-AKI mice showed signif-icantly higher levels of CRE and BUN and obvious tu-bular damage compared with the control group;at the same time,the renal tissues of Cis-AKI mice showed increased expression of F4/80,and the proportion of apoptotic cells in kidney cells was increased.Immuno-histochemistry and immunofluorescence showed that the expression of TDO2 increased,mainly localized in TECs.In cellular experiments,HK2 cells overexpress-ing TDO2 increased the proportion of apoptosis,and the expression of TDO2,p-IKBα,and p-p65 proteins was elevated,and p-IKBα/IκBα and p-p65/p65 were ele-vated;furthermore,the proportion of apoptosis was re-duced by the administration of 680C91,and the expres-sion of p-IκBα,and p-p65 proteins decreased,and the expression of p-IKBα/IKBα,and p-p65/p65 de-creased.Conclusions Elevated TDO2 in TECs is in-volved in the pathological mechanism of Cis-AKI,which may be related to its induction of apoptosis in TECs and activation of the NF-κB signaling pathway and consequently renal injury.

Objective:To investigate the effect of different isoforms of RBBP6 on the proliferation of multiple myeloma (MM) cells after alternative splicing mediated by splicing factor SRSF1. Methods:RT-PCR was used to detect the expression levels of RBBP6 mRNA splicing isoforms regulated by SRSF1. The GEO database was used to analyze the changes of RBBP6 isoform 1 in the progression of plasma cell disease,and survival analysis was used to evaluate the value of this gene in the prognosis of MM patients. In vitro loss-of-function and gain-of-function experiments were conducted by transfecting control siRNA,RBBP6 isoform 1 siRNA,empty vector (EV),OE-RBBP6 isoform 3 into MM.1S cells,then the expression levels of RBBP6 isoform 1 and RBBP6 isoform 3 were detected by real-time PCR and Western blot. CCK-8 assay was performed to detect the cell proliferation ability. Results:Knockdown of SRSF1 increased the expression of RBBP6 isoform 3 and decreased the expression of RBBP6 isoform 1. RBBP6 isoform 1 was closely related to the progression of plasma cell disease,and the high expression of RBBP6 isoform 1 was associated with poor prognosis in patients with MM. Downregulation of RBBP6 isoform 1 expression and overexpression of RBBP6 isoform 3 both reduced the proliferation ability of MM cells. And after downregulating the expression of RBBP6 isoform 1,the level of p53 protein in MM cells was significantly increased (P<0.05). Conclusion:In MM,splicing factor SRSF1 can cause alternative splicing abnormalities in RBBP6. The RBBP6 isoform 1 promotes MM cell proliferation,while the RBBP6 isoform 3 inhibits MM cell proliferation,and the mechanism may be related to regulating the p53 pathway.

Aim To investigate the mechanism of treatment of hepatolenticular degeneration with Garde-nia and Rhubarb decoction based on network pharma-cology and animal experiments.Methods The chemi-cal components and target sites of Gardenia and Rhu-barb decoction were retrieved using the Traditional Chi-nese Medicine System Pharmacology Analysis Platform(TCMSP).The disease targets were obtained by searching the databases of DisGeNET,GeneCards.The PPI network of active compound target sites was constructed using the STRING database.GO function and KEGG pathway enrichment analysis were per-formed using the DAVID database to predict the action pathway.A copper-loaded WD rat model was estab-lished by intragastric administration of copper sulfate pentahydrate.A total of 36 rats were randomly divided into the normal group,model group,penicillamine group and the low,medium and high dose groups of gardenia rhubarb.The relevant indicators and patho-logical changes of liver tissue were detected in WD rats.Results Network pharmacology screening identi-fied 68 potential active components of Gardenia and Rhubarb Decoction,30 intersection targets of diseases and drugs,involving key targets such as TNF,IL10,IGF1,IL1B,TP53,CASP3,PPARG,IL6,CXCL8,IL1A,TGFB1,mainly related to signal pathways such as MAPK,AGE-RAGE signaling pathway in diabetic complications.In the animal experiments,compared with the normal group,the urine copper,liver copper,blood copper,liver coefficient,serum and liver ALT,AST,TNF-α,CASP3,P53 levels in the model group rats significantly increased(P＜0.05);hepatocyte swelling,cytoplasm loose reticular appearance,feath-er-like degeneration and reticular necrosis were ob-served in liver tissue pathology;compared with the model group,the urine copper,liver copper,blood copper,liver coefficient,serum and liver ALT,AST,TNF-α,CASP3,P53 levels in the penicillamine group and Gardenia and Rhubarb decoction groups were sig-nificantly reduced(P＜0.05),and the degree of re-ticular necrosis in the rat liver cells in the penicilla-mine group and the Gardenia and Rhubarb decoction group was significantly reduced.Conclusions Garde-nia and Rhubarb decoction has the effect of regulating copper metabolism and reducing liver injury.The mechanism of action may be related to reversing apop-tosis and downregulating protein expression of TNF-α,CASP3,P53 in MAPK signaling pathway.

Objective To explore medium and long term efficacy of oblique lateral interbody fusion(OLIF)in treating lumbar specific infection.Methods From October 2017 to January 2021,24 patients with lumbar specific infection were treated by OLIF combined with vertebral screw internal fixation,including 15 males and 9 females,aged from 27 to 61 years old with an average of(43.0±15.0)years old;the courses of disease ranged from 6 to 24 months with an average of(14.0±7.0)months;7 patients with L2-L3,12 patients with L3-L4 and 5 patients with L4-L5;19 patients with tuberculosis infection and 5 patients with brucella infection.The amount of intraoperative blood loss,operative time and complications were recorded,and erythro-cyte sedimentation rate(ESR),C-reactive protein(CRP),visual analogue scale(VAS),Japanese Orthopaedic Association(JOA)score and American Spinal Injury Association(ASIA)rating were compared before and one month after opertaion.Re-sults All patients were followed up from 9 to 24 months with an average of(13.0±6.0)months.Operative time was(132.5±21.4)min,and intraoperative blood loss was(227.3±43.1)ml.ESR and CRP were decreased from(82.34±18.62)mmol·h-1 and(53.08±21.84)mg·L-1 before operation to(33.52±17.31)mmol·h-1 and(15.48±8.36)mg·L-1 at one month after opera-tion,respectively(P＜0.05).VAS was decreased from(7.52±1.36)before opertaion to(1.74±0.87)at one month after opera-tion(P＜0.05).JOA was increased from(17.86±3.95)before operation to(24.72±3.19)at one month after operation(P＜0.05).Four patients had neurological symptoms before operation,and were classified to grade D according to ASIA classifica-tion,who were recovered to grade E at 1 month after operation.One patient was suffered from psoas major muscle injury after operation,and returned to normal at 3 weeks.One patient was suffered from abdominal distension and difficulty in defecation,and relieved after gastrointestinal decompression and enema.No complications such as abdominal organ injury and poor wound healing occurred in all patients.Conclusion OLIF combined with vertebral screw internal fixation is a new minimally invasive surgical method for the treatment of lumbar specific infection,especially the lesion located on the middle lumbar vertebra.It has advantages of less trauma,short operation time,less blood loss,convenient operation,complete removal of the lesion,safety and effectiveness,and has good medium-and long-term efficacy for lumbar specific infection.

Objective To explore the difference in efficacy of metoprolol versus ivabradine in the treatment of postural orthostatic tachycardia syndrome(POTS)in the elderly after COVID-19 infection.Methods A total of 110 patients diagnosed with POTS at our department from Decem-ber 1,2022 to January 31,2023 were included.According to their drug regimen,they were divided into metoprolol group(62 patients)and ivabradine group(48 patients).On the 28th day of out-patient follow-up,the resting heart rate,heart rate of 10 min of standing,symptom disappearance rate,hospitalization rate,and mortality rate were compared between the two groups.Results On the 28th day of treatment,the resting heart rate and postural heart rate for 10 min were decreased in both groups when compared with the levels at initial diagnosis(P＜0.01).And there were no significant differences in the two types of heart rate between the two groups on the 28th day(71.0±7.0 vs 72.1±7.0,P=0.401;76.5±7.2 vs 77.4±7.6,P=0.573).No obvious differences were observed between the two groups in symptom disappearance rate,hospitalization rate,or mortality rate(88.7％vs 89.6％,3.2％vs2.1％,0％vs 0％,P＞0.05).Conclusion Metoprolol and ivabradine can effectively treat POTS in the elderly patients after COVID-19 infection.