OBJECTIVE: To summarize the clinical features and management of two brothers affected with X-linked inhibitor of apoptosis protein (XIAP) deficiency. METHODS: This study retrospectively analyzed the clinical presentations, treatment, and follow-up of two brothers with XIAP deficiency diagnosed at Shanghai Children's Hospital in 2020, and summarized similar cases recorded in databases such as PubMed, Wanfang, Chinese Medical Association Journals, and WIP from January 2006 to November 2024. This study was approved by the Medical Ethics Committee of our hospital (Ethics No.: 2025R128-E01). RESULTS: Patient 1 was the younger brother, who presented at 8 years of age with growth retardation, folliculitis, erythema nodosum, and perineal abscess. Sequencing revealed that he has carried a hemizygous c.566T>C (p.Leu189Pro) variant of the XIAP gene, which was inherited from his mother. He was allergic to infliximab treatment and underwent allogeneic stem cell transplantation (HSCT) in January 2021. During a follow-up of 3 years and 10 months post-transplantation, he showed no gastrointestinal symptoms and had a good outcome. Patient 2 was the elder brother, who presented at 10 years and 6 months of age with growth retardation, rash, and anal fistula. Genetic testing revealed the same variant. He was treated with oral azathioprine but did not have regular follow-ups. At 14-years-and-6-months of age, he had developed severe gastrointestinal infection and hemophagocytic lymphohistiocytosis, which was alleviated after treatment with antibiotics, glucocorticoids, immunoglobulin, and rituximab. He is currently being prepared for HSCT. A total of 13 publications were retrieved, which involved 64 patients from 23 families, with 23 different variants identified. The main clinical manifestations included splenomegaly (34 cases, 53.1%), hemophagocytic lymphohistiocytosis (27 cases, 42.2%), and inflammatory bowel disease or colitis (20 cases, 31.8%). There were significant phenotypic differences among patients from the same family. Thirteen patients (20.3%) underwent HSCT, with a survival rate of 61.5%. CONCLUSION For male children with early onset, poor treatment response, especially those with unexplained splenomegaly and IBD-like symptoms, early genetic testing is recommended. HSCT is a safe and effective treatment for XIAP deficiency. For patients with developmental delay, early onset, and severe IBD phenotype, early transplantation is recommended.
Humans ; Male ; X-Linked Inhibitor of Apoptosis Protein/deficiency* ; Child ; Genetic Diseases, X-Linked/therapy* ; Phenotype ; Siblings ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation

Objective:To assess the relationship between basophil levels and mortality in patients with intra-abdominal infection.Methods:Information on patients with intraperitoneal infection admitted to the intensive care unit were extracted from the MIMIC database.A time-dependent Cox regression model was used to adjust for confounders associated with 28-day mortality.Propensity score matching(PSM)was used to balance the baseline differences be-tween groups with different basophil levels,and a restricted cube chart(RCS)was used to show the relationship between basophil count and 28-day mortality in patients with intra-abdominal infection.Results:A total of 4403 patients with intra-abdominal infection were enrolled in the MIMIC database.Patients with high basophil levels have lower mortality than those with low basophil levels.There was an L-shaped curve between basophil level and 28-day mortality,with a cut-off value of 0.47×109/L.Cox regression analysis showed that basophil levels were an independent protective factor for mortal-ity in patients with intra-abdominal infection after adjusting for potential confounders(HR=0.586,95%CI:0.443-0.769).Protective factors for death at basophil levels remained after PSM adjusted for potential confounders(HR=0.628,95%CI:0.470-0.832).Conclusion:Basophil level is an independent protective factor for mortality in patients with intra-abdominal infection,and basophil levels should be dynamically monitored to better evaluate the prognosis of patients.

Objective:To assess the relationship between basophil levels and mortality in patients with intra-abdominal infection.Methods:Information on patients with intraperitoneal infection admitted to the intensive care unit were extracted from the MIMIC database.A time-dependent Cox regression model was used to adjust for confounders associated with 28-day mortality.Propensity score matching(PSM)was used to balance the baseline differences be-tween groups with different basophil levels,and a restricted cube chart(RCS)was used to show the relationship between basophil count and 28-day mortality in patients with intra-abdominal infection.Results:A total of 4403 patients with intra-abdominal infection were enrolled in the MIMIC database.Patients with high basophil levels have lower mortality than those with low basophil levels.There was an L-shaped curve between basophil level and 28-day mortality,with a cut-off value of 0.47×109/L.Cox regression analysis showed that basophil levels were an independent protective factor for mortal-ity in patients with intra-abdominal infection after adjusting for potential confounders(HR=0.586,95%CI:0.443-0.769).Protective factors for death at basophil levels remained after PSM adjusted for potential confounders(HR=0.628,95%CI:0.470-0.832).Conclusion:Basophil level is an independent protective factor for mortality in patients with intra-abdominal infection,and basophil levels should be dynamically monitored to better evaluate the prognosis of patients.

Objective:To explore the effect of Wuqinxi combined with resistance training on cardiac function and self-care ability in patients with chronic heart failure(CHF).Methods:This randomized controlled study enrolled 152 CHF patients admitted to Nanjing Hospital of Chinese Medicine between September 2018 and December 2022.Pa-tients were divided into control group(n=76)and intervention group(n=76).Patients in control group received routine intervention measure combined resistance training,while those in the intervention group received additional Wuqinxi.Both groups were intervened for 6 months.The clinical total effective rate,cardiac function,self-care ability and quality of life were compared between two groups.We also compared the incidence of adverse events and readmission rate during 6-month follow-up.Results:The total effective rate of the intervention group was sig-nificantly higher than that of the control group(93.2％vs.81.1％,P=0.003).Compared with patients in the control group,those in the intervention group had significant higher left ventricular ejection fraction(LVEF)[(50.08±8.37)％vs.(43.47±8.02)％]and 6min walking distance(6MWD)[(496.76±40.54)m vs.(406.76±28.65)m](P＜0.001 both);and significant lower left ventricular end-diastolic volume(LVEDV)[(109.82±9.90)ml vs.(165.29±12.26)ml],left ventricular end-systolic volume(LVESV)[(59.09±2.69)ml vs.(72.61±3.54)ml],score of the European Heart Failure Self-care Behaviour Scale(EHFScBS)[(26.49±3.24)points vs.(35.80±4.33)points],and Minnesota Living with Heart Failure Questionnaire(MLHFQ)total score[(43.78±4.50)points vs.(56.55±4.92)points](P＜0.001 all).The total incidence of adverse events(2.8％vs.12.3％)and readmission rate(1.4％vs.11.0％)in the intervention group were significantly lower than those of the control group(P＜0.05 both).Conclusion:Wuqinxi combined with resistance training may improve clinical efficacy,cardiac function,self-care ability,reduce incidence of adverse events and readmission,then improve quality of life in CHF patients.

Objective:To explore the effect of Wuqinxi combined with resistance training on cardiac function and self-care ability in patients with chronic heart failure(CHF).Methods:This randomized controlled study enrolled 152 CHF patients admitted to Nanjing Hospital of Chinese Medicine between September 2018 and December 2022.Pa-tients were divided into control group(n=76)and intervention group(n=76).Patients in control group received routine intervention measure combined resistance training,while those in the intervention group received additional Wuqinxi.Both groups were intervened for 6 months.The clinical total effective rate,cardiac function,self-care ability and quality of life were compared between two groups.We also compared the incidence of adverse events and readmission rate during 6-month follow-up.Results:The total effective rate of the intervention group was sig-nificantly higher than that of the control group(93.2％vs.81.1％,P=0.003).Compared with patients in the control group,those in the intervention group had significant higher left ventricular ejection fraction(LVEF)[(50.08±8.37)％vs.(43.47±8.02)％]and 6min walking distance(6MWD)[(496.76±40.54)m vs.(406.76±28.65)m](P＜0.001 both);and significant lower left ventricular end-diastolic volume(LVEDV)[(109.82±9.90)ml vs.(165.29±12.26)ml],left ventricular end-systolic volume(LVESV)[(59.09±2.69)ml vs.(72.61±3.54)ml],score of the European Heart Failure Self-care Behaviour Scale(EHFScBS)[(26.49±3.24)points vs.(35.80±4.33)points],and Minnesota Living with Heart Failure Questionnaire(MLHFQ)total score[(43.78±4.50)points vs.(56.55±4.92)points](P＜0.001 all).The total incidence of adverse events(2.8％vs.12.3％)and readmission rate(1.4％vs.11.0％)in the intervention group were significantly lower than those of the control group(P＜0.05 both).Conclusion:Wuqinxi combined with resistance training may improve clinical efficacy,cardiac function,self-care ability,reduce incidence of adverse events and readmission,then improve quality of life in CHF patients.

OBJECTIVES: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.
Animals ; Hesperidin/therapeutic use* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Male ; Stress, Psychological/drug therapy* ; Brain/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Serotonin/metabolism* ; Gastrointestinal Microbiome/drug effects* ; Behavior, Animal/drug effects* ; Rats ; Brain-Gut Axis/drug effects* ; Chronic Disease ; Colon/drug effects*

Objective:Toexplore the influencing factors of postoperative recurrence of com-plex anal fistula surgery and construct a column chart model.Methods:A total of 421 patients undergoing complex anal fistula surgery admitted to our hospital from March 2018 to October 2023 were selected as the study objects,and were divided into the modeling group(n=295)and the verification group(n=126)according to a ratio of about 7∶3.In addition,the patients in the modeling group were divided into the non-recurrence group(n=252)and the recurrence group(n=43).The influencing factors of postoperative recurrence of complex anal fistula in the modeling group were analyzed by multi-factor Logistic regression RMS package in R software was applied to construct a column chart prediction model for the risk of postoperative recurrence of complex anal fistula.The predictive performance of the model was evaluated using ROC curves,H-L fit tests,and calibration curves.Results:There was no significant difference between the modeling group and the validation group in terms of comorbidities,anal fistula location,surgical method,and whether to regularly change dressing at the hospital after surgery(P＞0.05).There were obvious differences between the recurrence group and the non recurrence group in terms of the location of anal fistula(x2=6.259),history of anal fistula surgery(x2=6.310),presence of perianal abscess(x2=5.287),and regularly visit the hospital for dressing changes after surgery(x2=3.974)(P＜0.05).Multi-variate logistic regression showed that high anal fistula(OR=8.232),history of anal fistula surgery(OR=11.658),concurrent perianal abscess(OR=11.245),and failure to regularly visit the hospital for dressing changes after surgery(OR=5.997)were independent risk factors for postoperative recur-rence of complex anal fistula(P＜0.05).The area under ROC curve of the modeling group was 0.840(95％CI:0.793～0.880),and the sensitivity and specificity were 81.40％and 86.51％,respectively.In the verification group,the area under ROC curve was 0.858(95％CI:0.785～0.914),and the sen-sitivity and specificity were 87.50％and 81.82％,respectively The two calibration curves showed minor difference between the predicted and actual values,and the H-L fit test showed well con-sistency in the model predictions.Conclusion:Complex anal fistula patients who have a high-position anal fistula,history of anal fistula surgery,concurrent perianal abscess,and failure to regu-larly visit the hospital for dressing changes after surgery have a higher risk of postoperative recur-rence.A risk model constructed based on these factors is helpful for clinical prediction and inter-vention,reducing the risk of postoperative recurrence.

Objective:To investigate the clinical features of nontuberculous mycobacteria (NTM) disease patients with positive anti-interferon γ (IFN-γ) autoantibody.Methods:Forty-three adult human immunodeficiency virus-uninfected patients with NTM disease hospitalized in Huashan Hospital, Fudan University and Jing′an Branch, Huashan Hospital, Fudan University from July 2021 to August 2023 were included. Clinical data and NTM strain information of the patients were collected. The plasma levels of anti-IFN-γ autoantibodies were detected by enzyme-linked immunosorbent assay, and the patients were divided into antibody positive group and antibody negative group. The clinical characteristics and laboratory examination results between the two groups were compared. The independent sample t test, Mann-Whitney U test and chi-square test were used for statistical analysis. Multivariate logistic regression analysis was used to determine the correlation factors of positive anti-IFN-γ autoantibodies. Results:Among the 43 patients, 13 cases (30.2%) were positive for anti-IFN-γ autoantibodies and 30 cases (69.8%) were negative. The proportions of patients with NTM disseminated infection (9/13 vs 30.0%(9/30))and combined bacterial infection (5/13 vs 6.7%(2/30)) in antibody positive group were both higher than those in antibody negative group, and the differences were both statistically significant ( χ2=5.74 and 6.73, respectively, both P<0.05). The white blood cell count, platelet count, the proportion of platelet count >350×10 9/L of antibody positive patients were all higher than those of antibody negative group, while the white sphere ratio was lower than that of antibody negative group, with statistical significance ( t=2.42, 3.02, χ2=9.77 and t=3.66, respectively, all P<0.05). Erythrocyte sedimentation rate, C-reactive protein, procalcitonin, globulin, immunoglobulin G, immunoglobulin A and immunoglobulin M in antibody positive patients were all higher than those in antibody negative group, and the differences were all statistically significant ( U=99.50, 112.00, 115.50, 61.50, 76.50, 99.00 and 83.00, respectively, all P<0.05). Mycobacterium abscessus complex (seven cases and 11 cases, respectively) and Mycobacterium avium complex (five cases and 13 cases, respectively) were the main isolated strains in antibody positive and antibody negative patients. Multivariate logistic regression analysis showed that combined with bacterial infection (odds ratio ( OR)=21.83, 95% confidence interval ( CI) 1.94 to 245.71), NTM disseminated infection ( OR=7.64, 95% CI 1.10 to 53.26), platelet count>350×10 9/L ( OR=14.31, 95% CI 1.91 to 107.04) were risk factors for anti-IFN-γ autoantibodies positive (all P<0.05). Conclusions:Patients with positive anti-IFN-γ autoantibodies have higher probability of having elevated levels of systemic inflammation. Anti-IFN-γ autoantibody test is recommended for patients with NTM disease who present with co-bacterial infection, NTM disseminated infection, or elevated platelet count (>350×10 9/L).

Objective To evaluate the bioequivalence of test product and reference product in a single dose of amoxicillin clavulanate potassium tablet under fasting and fed conditions in healthy volunteers.Methods An open label,randomized,single dose,four-period,crossover bioequivalence study was designed.Fasting and postprandial tests were randomly divided into 2 administration sequence groups according to 1:1 ratio,amoxicillin clavulanate potassium tablet test product or reference product 375 mg,oral administration separately,liquid chromatography tanden mass spectrometry was applied to determine the concentration of amoxicillin and clavulanate potassium in plasma of healthy subjects after fasting or fed administration,while Phoenix WinNonlin 8.2 software were used for pharmacokinetics(PK)parameters calculation and bioequivalence analysis.Results Healthy subjects took the test product and the reference product under fasting condition,the main PK parameters of amoxicillin are as follows:Cmax were(5 075.57±1 483.37)and(5 119.86±1 466.73)ng·mL-1,AUC0_twere(1.32 × 104±2 163.76)and(1.30 × 104±1 925.11)ng·mL-1,AUC0-∞were(1.32 × 104±2 175.40)and(1.31 ×104±1 935.86)ng·mL-1;the main PK parameters of clavulanic acid are as follows:Cmax were(3 298.27±1 315.23)and(3 264.06±1 492.82)ng·mL-1,AUC0-twere(7 690.06±3 053.40)and(7 538.39±3 155.89)ng·mL-1,AUC0-∞were(7 834.81±3 082.61)and(7 671.67±3 189.31)ng·mL-1;the 90％confidence intervals of Cmax,AUC0-tand AUC0-∞ after logarithmic conversion of amoxicillin and clavulanate potassium of the two products were all within 80.00％-125.00％.Healthy subjects took the test and reference product under fed condition,the main PK parameters of amoxicillin are as follows:Cmax were(4 514.08±1 324.18)and(4 602.82±1 366.48)ng·mL-1,AUC0-twere(1.15 × 104±1 637.95)and(1.15 × 104±1 665.69)ng·mL-1,AUC0-∞ were(1.16 × 104±1 646.26)and(1.15 × 104±1 607.20)ng·mL-1;the main PK parameters of clavulanic acid are as follows:Cmax were(2 654.75±1 358.29)and(2 850.51±1 526.31)ng·mL-1,AUC0-twere(5 882.82±2 930.06)and(6 161.28±3 263.20)ng·mL-1,AUC0-∞ were(6 022.70±2 965.05)and(6 298.31±3 287.63)ng·mL-1;the 90％confidence intervals of Cmax,AUC0-t and AUC0-∞ after logarithmic conversion of amoxicillin and clavulanate potassium of the two products were all within 80.00％-125.00％.Conclusion The two formulations were bioequivalent to healthy adult volunteers under fasting and fed conditions.