Identifying the genetic association between systemic lupus erythematosus and the risk of autoimmune liver diseases.

BACKGROUND: Previous studies on the relationship between systemic lupus erythematosus (SLE) and autoimmune liver diseases (AILDs) are inconclusive. Therefore, we employed Mendelian randomization (MR) to explore the causal associations between SLE and AILDs. METHODS: A two-sample MR analysis was performed using summary-level statistics sourced from genome-wide association study (GWAS) datasets. Inverse-variance weighting (IVW), MR‒Egger, and weighted median (WM) were further supported by several sensitivity analyses. RESULTS: We detected causal genetic associations between SLE and primary biliary cholangitis (PBC) (odds ratio (OR) = 1.31, 95% CI = 1.15-1.51, P < 0.01; adjusted OR = 1.63, 95% CI = 1.39-1.90, P < 0.01) and between SLE and primary sclerosing cholangitis (PSC) (OR = 1.09, 95% CI = 1.01-1.08, P = 0.03; adjusted OR = 1.10, 95% CI = 1.00-1.21, P = 0.04). No causal association was found between SLE and autoimmune hepatitis. CONCLUSIONS: We are the first to use MR analysis to explore the causal relationships between SLE and various AILDs, revealing an increased risk of PBC and PSC in individuals with SLE.

Risk factors for significant histological changes in both HBeAg positive and negative treatment-naive chronic hepatitis B with persistently normal alanine aminotransferase level.

BACKGROUND: Chronic hepatitis B virus (HBV) infection remains a serious health issue, and determining the optimal time for antiviral therapy is challenging. We aimed to assess liver histological changes in patients with HBeAg-positive chronic hepatitis B (CHB) and those with HBeAg-negative CHB who had persistently normal alanine aminotransferase and to determine the association between significant liver injury and various clinical parameters. METHODS: We retrospectively included, in this study, 339 treatment-naïve patients with chronic HBV infections who had persistently normal alanine aminotransferase and underwent liver biopsy from 2013 to 2023. Histologic assessment was based on the Metavir scoring system to evaluate the association between clinical characteristics and the severity of liver inflammation and fibrosis. RESULTS: Among the included participants, 138 were HBeAg-positive and 201 were HBeAg-negative. Lower hepatitis B surface antigen (HBsAg) (P = 0.003) and higher aspartate aminotransferase (AST) (P = 0.002) levels were associated with significant necroinflammation, whereas increasing age (P = 0.004) and lower HBV DNA (P < 0.001) levels were associated with significant fibrosis in HBeAg-positive patients with normal ALT levels. Higher HBV-DNA (P = 0.001) and AST levels(P < 0.001) were associated with significant necroinflammation, and higher AST(P < 0.001) levels were associated with significant fibrosis in HBeAg-negative patients. CONCLUSIONS: A substantial proportion of patients with HBV infection who had normal ALT presented significant liver injury. HBsAg and AST were independent predictive factors for evaluating inflammation, while HBV DNA load and age were independent predictive factors for evaluating fibrosis in the HBeAg-positive group. HBV DNA load and AST were independent predictive factors for evaluating inflammation, while AST were independent predictive factors for evaluating fibrosis in the HBeAg-negative group.

Development and validation of a noninvasive prediction model for significant hepatic liver fibrosis in Chinese patients with autoimmune hepatitis.

INTRODUCTION AND OBJECTIVES: Autoimmune hepatitis (AIH) is a prevalent noninfectious liver disease. However, there is currently a lack of noninvasive tests appropriate for evaluating liver fibrosis in AIH patients. The objective of this study was to develop and validate a predictive model for noninvasive assessment of significant liver fibrosis (S ≥ 2) in patients to provide a reliable method for evaluating liver fibrosis in individuals with AIH. MATERIALS AND METHODS: The clinical data of 374 AIH patients were analyzed. A prediction model was established through logistic regression in the training set, and bootstrap method was used to validate the models internally. In addition, the clinical data of 109 AIH patients were collected for external verification of the model.The model was expressed as a nomogram, and area under the curve (AUC) of the receiver operating characteristic (ROC), calibration curve, and decision curve analysis were used to evaluate the accuracy of the prediction model. RESULTS: Logistic regression analysis revealed that age, platelet count (PLT), and the A/G ratio were identified as independent risk factors for liver fibrosis in AIH patients (P < 0.05). The diagnostic model that was composed of age, PLT and A/G was superior to APRI and FIB-4 in both the internal validation (0.872, 95%CI: 0.819-0.924) and external validation (0.829, 95%CI: 0.753-0.904). CONCLUSIONS: Our predictive model can predict significant liver fibrosis in AIH patients more accurately, simply, and noninvasively.

Psoas abscess: an uncommon disorder.

BACKGROUND: Psoas abscess (PA) is an uncommon disease that has been increasingly reported in the recent years. We reviewed patients with PA and analyzed their clinical characteristics to improve our understanding of this rare disorder. METHODS: We retrospectively reviewed the clinical presentations, microbiology, and outcomes of patients with PA between 2011 and 2022 at the Zhejiang Provincial People's Hospital in China. RESULTS: There were 40 adult patients identified with the discharge diagnosis of PA. The mean age was 60 years, and 67.5% of the patients were male. Primary symptoms were typically nonspecific. In all, 20 abscesses were considered secondary, and the most common was infective spondylitis. The most common causative organism for primary PA was Staphylococcus aureus, followed by Escherichia coli, whereas multiple bacterial species were found in secondary abscesses. The overall in-hospital mortality rate was 5%. Patients with secondary PA had a longer hospital stay. CONCLUSION: PA, as a serious infectious condition, usually presents with nonspecific symptoms and laboratory test results, making early diagnosis difficult. These profiles differed from those reported in the present study. The initial clinical status and subsequent imaging studies can lead to favorable outcomes.

Establishment and evaluation of an early prediction model of hepatorenal syndrome in patients with decompensated hepatitis B cirrhosis.

BACKGROUND AND AIM: In China, hepatorenal syndrome is a serious complication in the decompensated stage of hepatitis B cirrhosis, which requires early clinical intervention, so the early diagnosis of hepatorenal syndrome is crucial. This study establishes a new predictive model based on serum biomarkers for the early diagnosis of hepatorenal syndrome. METHODS: Patients with decompensated hepatitis B cirrhosis who met the inclusion and exclusion criteria were retrospectively enrolled. Patients were randomly assigned to the training dataset and validation dataset at a 7:3 ratio. Univariate and multivariate logistic regression analyses were used to screen the risk factors for hepatorenal syndrome. The identified risk factors were used to establish and verify a model. RESULTS: This study included 255 patients with decompensated hepatitis B cirrhosis, including 184 in the training group and 71 in the validation group. The multivariate logistic regression model was established in the training group and verified in the validation group. Logistic regression showed that hemoglobin (OR 0.938, 95% CI 0.908-0.969), total bilirubin (OR 1.014, 95% CI 1.008-1.021) and creatinine (OR 1.079, 95% CI 1.043-1.117) were independent risk factors for hepatorenal syndrome (P < 0.05). These were used to establish the model. In the training group and the validation group, the area under the ROC curve of the nomogram for the diagnosis of hepatorenal syndrome was 0.968 and 0.980, respectively. CONCLUSION: The three serum biomarkers, including hemoglobin, total bilirubin and creatinine, can be used as independent early predictors of hepatorenal syndrome in patients with decompensated hepatitis B cirrhosis.

Syntheses of heterometallic organic frameworks catalysts via multicomponent postmodification: For improving CO2 photoreduction efficiency.

To enhance the economic viability of photocatalytic materials for carbon capture and conversion, the challenge of employing expensive photosensitizer must be overcome. This study aims to improve the visible light utilization with zirconium-based metal-organic frameworks (Zr-MOFs) by employing a multi-component post-synthetic modification (PSM) strategy. An economical photosensitiser and copper ions are introduced into MOF 808 to enhance its photoreduction properties. Notably, the PSM of MOF 808 shows the highest CO yield up to 236.5 µmol g-1 h-1 with aHCOOH production of 993.6 µmol g-1 h-1 under non-noble metal, and its mechanistic insight for CO2 reaction is discussed in detail. The research results have important reference value for the potential application of photocatalytic metal-organic frameworks.

Successful treatment of cutaneous protothecosis with fluconazole: A case report and epidemiology study of Prototheca infection in China.

BACKGROUND: Protothecosis is an infection of humans and animals caused by a rare conditionally pathogenic fungus (prototheca). It can occur in immunocompromised or normal patients. AIMS: To describe the epidemiology of prototheca infection in China. METHODS: We report a case of successful treatment of cutaneous protothecosis with fluconazole and analyzed the epidemiological characteristics, risk factors, clinical manifestations, diagnosis, treatment and prognosis of prototheca infections in China. RESULTS: We describe this case and 29 cases of prototheca infections in China. At present, Prototheca wickerhamii (Pw) infection is the most common infection in China, and single or combined itraconazole is the preferred treatment. CONCLUSIONS: These results provide detailed information and relevant clinical treatment strategies for the diagnosis and treatment of protothecosis in China.

CuZn dendritic alloys: their template-free electrochemical preparation and morphology-dependent wettability.

In this paper, we report a preparation of CuZn dendritic microstructures through a tunable template-free electrochemical approach. By simply tunning the applied depositing current, the morphology of the product can be well controlled. The growth mechanism of CuZn dendritic alloys was also verified. The experimental results suggest that the growth of the grass-like structures obtained at 5 mA is driven by diffusion limited aggregation, while the driving force of the formation of CuZn dendrites obtained at 10 mA and 15 mA is gas bubbling worked as the dynamic template. The contact angle test shows the modified CuZn dendritic products possess superhydrophobic property. Additionally, through annealing of CuZn alloys in argon as the protective gas, derivative Cu/ZnO composite materials can be produced.

Three-years misdiagnosis of Niemann Pick disease type B with novel mutations in SMPD1 gene as Budd-Chiari syndrome.

BACKGROUND: The chronic visceral subtype of acid sphingomyelinase deficiency, commonly known as Niemann Pick disease type B (NPDB), is a relatively rare autosomal recessive genetic disorder that is caused by mutations in the SMPD1 gene. NPDB with sea-blue histiocytes (SBH) clinically mimics Budd-Chiari syndrome (BCS), as it lacks specific clinical characteristics. This makes its diagnosis difficult. CASE PRESENTATION: Here, we report a case of NPDB with SBH that was misdiagnosed as BCS for three years. A 20-year-old female with abdominal distension, hepatosplenomegaly, and haematological anomalies was initially diagnosed with BCS based on her imaging finding of a thin hepatic vein and rapid blood flow at the confluence of the hepatic vein and inferior vena cava. Her bone marrow cytology found sea-blue histiocytes. Liver biopsy showed foamy cytoplasm in hepatocytes surrounded by numerous Kupffer cells. Sequencing analysis of the SMPD1 gene led to the finding of two missense mutations in the heterozygous state: C.829 T > C (p.Trp277Arg) in exon 2 (novel) and c.1805G > A (p.Arg602His) in exon 6 (already described). These findings established the diagnosis of NPDB. CONCLUSION: The patient presented with hepatosplenomegaly, haematological anomalies, and dyslipidaemia. Thus, NPDB should be considered following the exclusion of related diseases. The diagnosis of NPDB was suspected by clinical symptoms and routine laboratory tests and was confirmed by liver biopsy and gene sequencing. The novel mutation c.829 T > C in exon 2 of the SMPD1 gene has never been reported and needs to be further investigated.

Coagulation Mechanism and Compressive Strength Characteristics Analysis of High-Strength Alkali-Activated Slag Grouting Material.

In deep coal mining, grouting reinforcement and water blockage are the most effective means for reinforcing the rock mass of extremely broken coal. However, traditional cement grouting materials are not suitable for use in complex strata because of their insufficient early mechanical strength and slow setting time. This study innovatively proposes using alkali-activated grouting material to compensate for the shortcomings of traditional grouting materials and strengthen the reinforcement of extremely unstable broken coal and rock mass. The alkali-activated grouting material was prepared using slag as raw material combined with sodium hydroxide and liquid sodium silicate activation. The compressive strength of specimens cured for 1 d, 3 d, and 28 d was regularly measured and the condensation behavior was analyzed. Using X-ray diffraction and scanning electron microscopy, formation behavior of mineral crystals and microstructure characteristics were further analyzed. The results showed that alkali-activated slag grouting material features prompt and high strength and offers the advantages of rapid setting and adjustable setting time. With an increase in sodium hydroxide content, the compressive strength first increased (maximum increase was 21.1%) and then decreased, while the setting time continued to shorten. With an increase in liquid sodium silicate level, the compressive strength increased significantly (and remained unchanged, maximum increase was 35.9%), while the setting time decreased significantly (and remained unchanged). X-ray diffraction analysis identified the formation of aluminosilicate minerals as the main reason for the excellent mechanical properties and accelerated coagulation rate.

Mechanical Properties and Coagulation Characteristics of Flue Gas Desulfurization Gypsum-Based Polymer Materials.

To resolve problems caused by the accumulation of flue gas desulfurization gypsum (FGDG) in the environment, a polymer material was prepared using FGDG, granulated blast furnace slag (GBFS), fly ash (FA), and solid sodium silicate (SSS). The compressive strength of these polymer specimens cured for 3, 28, and 60 d was regularly measured, and their condensation behavior was analyzed. Both the formation behavior of mineral crystals and microstructure characteristics were analyzed further using X-ray diffraction and scanning electron microscopy. The compressive strength of pure FGDG polymer specimen (whose strength is generated by particle condensation crystallization) is insufficient and the condensation is slow. The addition of appropriate amounts of GBFS, FA, and SSS can continuously and considerably improve the compressive strength and shorten the setting time. The optimal proportions of FGDG, GBFS, and FA are 50%, 20%, and 30%, respectively, with the SSS addition amount of 20 g. The incorporation of GBFS, FA, and SSS can promote the polymerization of calcium, silicon, and aluminum in FGDG to form silicate and aluminosilicate minerals. Their formation is the main reason for the increased compressive strength and accelerated coagulation.

Lnc524369 promotes hepatocellular carcinoma progression and predicts poor survival by activating YWHAZ-RAF1 signaling.

BACKGROUND: Liver cancer is one of the most highly malignant cancers, characterized by easy metastasis and chemoradiotherapy resistance. Emerging evidence indicates that long noncoding RNAs (LncRNAs), including Lnc524369, are highly involved in the initiation, progression, radioresistance, and chemoresistance of hepatocellular carcinoma (HCC). However, the function of Lnc524369 remains unclear. AIM: To explore the function of Lnc524369 in HCC. METHODS: To investigate the effect of Lnc524369, tissue from 41 HCC patients were analyzed using CCK8, migration, and invasion assays. Lnc524369 and YWHAZ (also named 14-3-3ζ) mRNA were detected by qPCR, and YWHAZ and RAF1 proteins were detected by western blot in liver cancer cell lines and human HCC tissues. The Cancer Cell Line Encyclopedia (CCLE) databases, STRING database, Human Protein Atlas database, and the TCGA database were used for bioinformatic analysis. RESULTS: Lnc524369 was significantly upregulated in the nucleus of liver cancer cells and human HCC tissues. Overexpression of Lnc524369 was associated with the proliferation, migration, and invasion of liver cancer cells. YWHAZ and RAF1 proteins and YWHAZ mRNA were overexpressed in liver cancer, which could be attenuated by overexpression of Lnc524369. Lnc524369 and its downstream target YWHAZ and RAF1 proteins were negatively associated with overall survival time. CONCLUSION: Lnc524369 might be a promising target of HCC as it can enhance liver cancer progression and decrease the overall survival time of HCC by activating the YWHAZ/RAF1 pathway.

Atypical pneumonia caused by Chlamydia psittaci during the COVID-19 pandemic.

OBJECTIVES: Here, we retrospectively described the diagnosis and treatment of 32 cases diagnosed with Chlamydia psittaci pneumonia during the COVID-19 pandemic. METHODS: Clinical information was collected from all the patients. Reverse transcription-PCR and ELISAs were conducted for the detection of COVID-19 using nasal swabs and bronchoalveolar lavage fluid (BALF) samples. Metagenomic next-generation sequencing (mNGS) was performed for the identification of causative pathogens using BALF, peripheral blood and sputum samples. End-point PCR was performed to confirm the mNGS results. RESULTS: All 32 patients showed atypical pneumonia and had infection-like symptoms that were similar to COVID-19. Results of reverse transcription-PCR and ELISAs ruled out COVID-19 infection. mNGS identified C. psittaci as the suspected pathogen in these patients within 48 hours, which was validated by PCR, except for three blood samples. The sequence reads that covered fragments of C. psittaci genome were detected more often in BALF than in sputum or blood samples. All patients received doxycycline-based treatment regimens and showed favorable outcomes. CONCLUSION: This retrospective study, with the highest number of C. psittaci pneumonia enrolled cases in China so far, suggests that human psittacosis may be underdiagnosed and misdiagnosed clinically, especially in the midst of the COVID-19 pandemic.

Primary bone anaplastic lymphoma kinase positive anaplastic large-cell lymphoma: A case report and review of the literature.

BACKGROUND: Primary bone lymphoma (PBL) is an uncommon extranodal disease that represents approximately 1%-3% of lymphomas. Anaplastic lymphoma kinase (ALK) positive anaplastic large-cell lymphoma (ALCL) is an extremely rare type of PBL. The aim of this report is describe the symptoms, diagnosis, and treatment of primary bone ALK-positive ALCL. CASE SUMMARY: A 66-year-old man presented to our hospital with neck and shoulder pain and intermittent fever that lasted for 1 mo. After extensive evaluation, positron emission tomography-computed tomography (CT) examination showed multiple osteolytic bone lesions without other sites lesions. CT-guided biopsy of the T10 vertebral body was performed, and the pathology results showed that neoplastic cells were positive for ALK-1, CD30, and CD3. A diagnosis of primary bone ALK positive ALCL was ultimately made. The patient was in partial response after four cycle soft cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy, and we planned to repeat the biopsy and radiological examination after completion of the fifth cycle of therapy. CONCLUSION: Primary bone ALK positive ALCL is a rare disease and physicians should keep in mind that ALCL can present with isolated osseous involvement without nodal involvement, and lymphoma should be considered in the differential diagnosis of primary bone lesions.

Diagnosis and treatment of an inborn error of bile acid synthesis type 4: A case report.

BACKGROUND: Inborn error of bile acid synthesis type 4 is a peroxisomal disease with impaired bile acid synthesis caused by a-methylacyl-CoA racemase (AMACR) gene mutation. The disease is usually found in children with mild to severe liver disease, cholestasis and poor fat-soluble vitamin absorption. At present, there is no report of inborn errors of bile acid synthesis type 4 in adults with liver disease and poor fat-soluble vitamin absorption. CASE SUMMARY: A 71-year-old man was hospitalized in our department for recurrent liver dysfunction. The clinical manifestations were chronic liver disease and yellow skin and sclera. Serum transaminase, bilirubin and bile acid were abnormally increased; and fat-soluble vitamins decreased. Liver cirrhosis and ascites were diagnosed by computed tomography. The patient had poor coagulation function and ascites and did not undergo liver puncture. Genetic testing showed AMACR gene missense mutation. The patient was diagnosed with inborn error of bile acid synthesis type 4. He was treated with ursodeoxycholic acid, liver protection and vitamin supplementation, and jaundice of the skin and sclera was reduced. The indicators of liver function and the quality of life were significantly improved. CONCLUSION: When adults have recurrent liver function abnormalities, physicians should be alert to genetic diseases and provide timely treatment.

Pneumocystis jirovecii and Legionella pneumophila coinfection in a patient with diffuse large B-cell lymphoma: A case report.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a common non-Hodgkin's lymphoma. R-CHOP is a protocol for long-term chemotherapy for DLBCL patients. Long-term chemotherapy can lead to low immunity and increase the risk of opportunistic pathogen infections in immunocompromised patients. CASE SUMMARY: We report a case of coinfection with Pneumocystis jirovecii (P. jirovecii) and Legionella pneumophila (L. pneumophila) in a patient with DLBCL. The patient was a 40-year-old female who was diagnosed with DLBCL and was admitted due to pulmonary infection. P. jirovecii and L. pneumophila were detected in her bronchoalveolar lavage fluid by hexamine silver staining, isothermal amplification and metagenomic sequencing. CONCLUSION: To the best of our knowledge, this is the first case of P. jirovecii and L. pneumophila coinfection found in a DLBCL patient. Clinicians should be aware of the risk of complicated infection in patients undergoing long-term chemotherapy.

Multicenter analysis and a rapid screening model to predict early novel coronavirus pneumonia using a random forest algorithm.

ABSTRACT: Early determination of coronavirus disease 2019 (COVID-19) pneumonia from numerous suspected cases is critical for the early isolation and treatment of patients.The purpose of the study was to develop and validate a rapid screening model to predict early COVID-19 pneumonia from suspected cases using a random forest algorithm in China.A total of 914 initially suspected COVID-19 pneumonia in multiple centers were prospectively included. The computer-assisted embedding method was used to screen the variables. The random forest algorithm was adopted to build a rapid screening model based on the training set. The screening model was evaluated by the confusion matrix and receiver operating characteristic (ROC) analysis in the validation.The rapid screening model was set up based on 4 epidemiological features, 3 clinical manifestations, decreased white blood cell count and lymphocytes, and imaging changes on chest X-ray or computed tomography. The area under the ROC curve was 0.956, and the model had a sensitivity of 83.82% and a specificity of 89.57%. The confusion matrix revealed that the prospective screening model had an accuracy of 87.0% for predicting early COVID-19 pneumonia.Here, we developed and validated a rapid screening model that could predict early COVID-19 pneumonia with high sensitivity and specificity. The use of this model to screen for COVID-19 pneumonia have epidemiological and clinical significance.

A rapid screening model for early predicting novel coronavirus pneumonia in Zhejiang Province of China: a multicenter study.

Novel coronavirus pneumonia (NCP) has been widely spread in China and several other countries. Early finding of this pneumonia from huge numbers of suspects gives clinicians a big challenge. The aim of the study was to develop a rapid screening model for early predicting NCP in a Zhejiang population, as well as its utility in other areas. A total of 880 participants who were initially suspected of NCP from January 17 to February 19 were included. Potential predictors were selected via stepwise logistic regression analysis. The model was established based on epidemiological features, clinical manifestations, white blood cell count, and pulmonary imaging changes, with the area under receiver operating characteristic (AUROC) curve of 0.920. At a cut-off value of 1.0, the model could determine NCP with a sensitivity of 85% and a specificity of 82.3%. We further developed a simplified model by combining the geographical regions and rounding the coefficients, with the AUROC of 0.909, as well as a model without epidemiological factors with the AUROC of 0.859. The study demonstrated that the screening model was a helpful and cost-effective tool for early predicting NCP and had great clinical significance given the high activity of NCP.

Analysis of the clinical characteristics of thirteen patients with Weber-Christian panniculitis.

BACKGROUND: Weber-Christian disease (WCD) is an uncommon, idiopathic disease that is challenging to diagnose and has an unclear treatment protocol. We reviewed thirteen patients with WCD and analyzed their clinical characteristics. The purpose of this article was to improve the understanding of this rare disorder. METHODS: Thirteen cases of WCD were analyzed retrospectively regarding their clinical manifestation, laboratory results, misdiagnoses, therapy, and outcome. RESULTS: Of the thirteen patients diagnosed with WCD, the majority were female (male to female ratio, 2:11), with a mean patient age of 50.1 years. Subcutaneous nodules were the most commonly reported symptom, followed by fever, arthralgias/arthritis, and myalgia. The laboratory results were typically nonspecific. In total, 61.5% patients were misdiagnosed before pathology confirmed the diagnosis of WCD. Most patients were treated with corticosteroids and/or immunosuppressants. Two patients were treated surgically. While long-term remission was successfully achieved in some patients, others had recurrent symptoms. CONCLUSION: WCD was predominantly observed in female patients in our cohort. Subcutaneous nodules and fever were the most common clinical characteristics. In addition, the patients' laboratory test results were nonspecific, which led to a high misdiagnosis rate. In this study population, corticosteroid and/or immunosuppressant treatments were efficacious therapeutic interventions for WCD.Key Points•Subcutaneous nodules and fever were the most common clinical characteristics in Weber-Christian panniculitis.•Misdiagnosis rate was higher in Weber-Christian panniculitis patient; tumors, bacterial infections and rheumatic diseases were the most common misdiagnoses.•Corticosteroid and/or immunosuppressant therapy was effective in most Weber-Christian panniculitis patients.

Restraint stress induces lymphocyte reduction through p53 and PI3K/NF-kappaB pathways.

Restraint stress, either physical or psychological, can modulate immune function. However, the mechanisms associated with stress-induced lymphocyte reduction remains to be elucidated. We have previously shown that chronic stress induces Fas-mediated lymphocyte reduction. Here, we investigated the mechanisms by which restraint stress modulates lymphocyte reduction. Our data have shown that inhibition of p53 by the p53 inhibitor PFT-alpha attenuates stress-induced reduction in lymphocyte numbers. These results were verified using p53 knockout mice, suggesting a pivotal role of p53 in this process. In addition our data have indicated that PI3K/nuclear factor kappa B (NF-kappaB) signaling pathway plays an important role in the stress-induced lymphocyte reduction. Our study thus demonstrates that restraint stress promotes lymphocyte reduction through p53 and PI3K/NF-kappaB pathways.