OBJECTIVE To provide a reference for clinical pharmacists to participate in the treatment of rare and complex cases of CTLA-4 haploid deficiency combined with severe malnutrition. METHODS The clinical pharmacist participated in the diagnosis and treatment of a complex case of CTLA-4 haploid deficiency with severe malnutrition， type 1 diabetes， blood coagulation abnormalities with gastrointestinal bleeding and virus infection， assisted the doctor to develop an individualized parenteral nutrition program， and dynamically adjusted the ratio of glucose and insulin （from 3.9∶1 to 15.6∶1）. When patient had severe coagulation abnormalities and gastrointestinal bleeding， the clinical pharmacist recommended discontinuing fat emulsion and switching to glucose amino acid dual energy supply； when the patient had a high fever accompanied by a sudden drop in platelets， the clinical pharmacist recommended to improve the second-generation sequencing of plasma metagenomics. Based on positive results for both EB virus and cytomegalovirus， the clinical pharmacist recommended to discontinue meropenem and switch to ganciclovir for antiviral treatment； when the patient experienced systemic itching and mental excitement， the clinical pharmacist quickly diagnosed as an adverse reaction of ganciclovir and recommended to switch to acyclovir for antiviral treatment. The clinical pharmacist simultaneously carried out parenteral nutrition medication education， and standardized infusion speed， and continuously monitored bleeding-related indicators. RESULTS The physician adopted the advice of the clinical pharmacist. After comprehensive intervention， the patient’s body temperature returned to normal， gastrointestinal bleeding stopped， coagulation indicators significantly improved， blood sugar control reached the standard， and the condition improved and the patient was discharged. CONCLUSIONS Clinical pharmacists rely on comprehensive pharmaceutical services to balance the benefits and risks of treatment for rare and complex cases. They play a key role in individualized nutrition planning， refined blood glucose control， infection identification and anti-infection optimization， and identification and treatment of adverse drug reactions to ensure patient medication safety and efficacy.

Objective:To explore the occurrence and clinical characteristics of nephrogenic systemic fibrosis (NSF) induced by gadolinium-based contrast agents (GBCA).Methods:CNKI, Wanfang, VIP and PubMed databases were searched (as of October 28, 2024) and case reports on GBCA-related NSF were collected; the following information was extracted, including the publication year of the literature, country, patient gender, age, basic kidney diseases and renal replacement therapy, variety of GBCA used, exposure frequency, time of occurrence or diagnosis of NSF, clinical manifestations, pathological examination, main intervention measures and outcomes. The data were analyzed by descriptive statistics.Results:A total of 45 case reports were collected, involving 97 patients. The literature were reported mainly from the United States and published mainly in 2006 and 2007. Number of the relevant literature decreased significantly after 2008, but there were still new cases reports in China in the following years (for example, in 2023). Among the 97 patients, 53 (54.6%) were male and 44 (45.4%) were female; the age ranged from 9 to 83 years with a median age of 53 years. One patient was with severe malnutrition, while the other 96 had severe basic kidney diseases, including chronic kidney disease in 85 (88.5%) patients and acute kidney injury in 11 (11.5%) patients. Variety of GBCA exposed was described in 76 patients, including gadodiamide in 67 (88.2%) patients. Exposure frequency of GBCA before NSF occurrence was described in 88 patients, 48 (54.5%) of which were exposed only once and 23 (26.1%) were exposed twice. Time from the first GBCA exposure to the occurrence of NSF was described in 92 patients, with the shortest time of 2 days and the longest time of more than 10 years; 70.7% (65/92) occurred within 3 months after GBCA exposure. All patients had typical skin symptoms of NSF, which were confirmed by pathological examination. Among them, 43 (44.3%) had joint disorders, 9 patients had eye involvement, a few patients had cardiac fibrosis, respiratory failure, metabolic acidosis, rhabdomyolysis, muscle necrosis, etc. Follow-up information was described in 82 patients with a range of 4 months to 11 years. Among them, 21 patients (25.6%) died, mainly due to the basic kidney diseases and complications; 11 (13.4%) were severely disabled; 7 (8.5%) were mildly disabled or slowly deteriorated; 43 (52.4%) had stable disease or slightly improved condition.Conclusion:NSF caused by GBCA mainly occurs in patients with severe basic renal diseases, mostly caused by gadodiamide. Severe skin damage is often accompanied by joint involvement or even disability, and the overall prognosis is poor.

Numerous studies have shown that depression is main-ly associated with the abnormal expression of connexin 43(Cx43)in astrocytes(Astro)and its mediated dysfunction of gap junction(GJ).However,the molecular mechanism of post-translational modifications targeting Cx43 to regulate neuroin-flammation-associated depression is still unclear.Post-transla-tional modifications of Cx43 mainly include phosphorylation of specific amino acid sites by PKC,PKA,PKG,MAPK and PTK,and protein degradation of Cx43 through the K48/K63 polyubiq-uitylation and deubiquitination pathways,which ultimately lead to protein degradation through K48/K63 polyubiquitination and deubiquitination.These modifications are ultimately involved in the regulation of neuroinflammatory responses through the associ-ation of GJ function.In this paper,we systematically review the role of Cx43 post-translational modifications in neuroinflamma-tion,with the aim of further exploring the potential application of targeting these modifications to modulate the inflammatory re-sponse mechanism in improving depressive symptoms.

Objective To investigate the dosimetric effects of tumor treating fields(TTFields)patches on different radiotherapy modes for glioblastoma(GBM)patients who wear TTFields patches during radiotherapy,thereby providing dosimetric guidance for determining the appropriate radiotherapy mode.Methods With the TTFields data from GBM patients,artifact-free radiotherapy CT images were obtained utilizing 3D-printed TPU TTFields patches(3D-Print-TTFields)and anthropomorphic phantoms,and then a TTFields-synchronized radiotherapy image model was constructed.Furthermore,the treatment planning system was used to construct a dosimetric calculation model for TTFields-synchronized radiotherapy by simulating and fitting the ray attenuation rate of TTFields patches measured by accelerators.Using these models,3 kinds of radiotherapy plans were simulated and developed.Specifically,P1 simulated the conventional radiotherapy mode;P2 simulated the TTFields-combined radiotherapy mode(TTF-Com-RT),in which patients underwent radiotherapy using the P1 plan while wearing TTFields patches;and P3 simulated the TTFields-synchronized radiotherapy(TTF-Syn-RT)mode where the TTFields patches were worn throughout the entire radiotherapy process.The paired t-test was used to analyze dosimetric parameters such as target dose(D95),average scalp dose(D-skin),conformity index(CI)and homogeneity index(HI)in 3 plans(P1,P2,and P3),as well as the D95 and D-skin parameters for intensity-modulated radiotherapy(IMRT)and volumetric modulated arc therapy(VMAT)techniques in the P3 plan.Results The D95 simulated by P2 decreased by 1.35%as compared with P1(P<0.05),and the D95 simulated by P3 was 1.31%higher than that in P2(P<0.05).Compared with P1,P2 and P3 increased the D-skin by 12.56%and 14.30%,respectively(P<0.05),and the D-skin simulated by P3 increased by 1.55%as compared with P2(P<0.05).However,there were trivial differences in D95 between P3 and P1,CI and HI among all plans,D95 and D-skin between IMRT and VMAT techniques in P3 plan(P>0.05).Conclusion Based on GBM patient data,CT simulation images obtained from 3D-Print-TTFields combined with anthropomorphic phantom are artifact-free and meet radiotherapy requirements.The target and scalp dose differences between TTF-Com-RT and TTF-Syn-RT are less than 2%,and the dosimetric difference of TTF-Syn-RT using IMRT/VMAT techniques is insignificant.Therefore,clinicians can choose radiotherapy modes and techniques according to actual needs.

Objective To retrospectively analyze the clinical risk factors and prognosis of perioperative myocardial injury(MINS)in non-cardiac surgery patients admitted to the intensive care unit(ICU).Methods A total of 478 postoperative patients admitted to the Department of Intensive Medicine,Minhang Hospital,Fudan University from Jan 2020 to Dec 2023 were selected.They were divided into MINS group(n=302)and normal group(n=176)based on whether myocardial injury occurred within 7 days after surgery.The differences in clinical characteristics between the two groups were compared,and risk factors for perioperative myocardial injury were identified.Risk factors for mortality in the MINS group were analyzed with 30-day mortality as the clinical endpoint.Results The prevalence of acute physiology and chronic health evaluation Ⅱ(Apache Ⅱ)score,coronary artery disease,and chronic kidney disease were all higher in the MINS group than those in the normal group,with statistically significant differences(P<0.05).The proportion of emergency surgeries,co-infection,and perioperative hypotension were significantly different between the MINS group and the normal group(P<0.05).Multivariate logistic regression analysis revealed that chronic kidney disease,emergency surgery,co-infection,and intraoperative and postoperative hypotension were risk factors for MINS occurrence.Prognostic analysis indicated that perioperative hypotension was a risk factor for 30-day mortality in MINS patients.Conclusion MINS is closely associated with patients'underlying conditions,timing of surgery,and perioperative hypotension status,and especially perioperative hypotension affects the final outcomes.

Central nervous system(CNS)degenerative disorders refer to a spectrum of pathological alterations triggered by struc-tural damage to cerebral neural tissues,clinically manifested as diverse neurological dysfunction syndromes,including multiple sclerosis(MS),neurodegenerative diseases(NDs),and ische-mic stroke.The hallmark pathological features of these disorders involve irreversible neuronal damage and decompensation of functional neural networks,ultimately leading to progressive neurological deficits.Notably,with the accelerating global popu-lation aging,the incidence of these diseases has surged signifi-cantly.According to WHO statistics,they now rank among the top three global causes of disability and mortality.Current re-search has confirmed that the pathogenesis of CNS degenerative disorders exhibits high heterogeneity,encompassing multifaceted pathophysiological processes such as genetic predisposition,oxi-dative stress,protein misfolding,and metabolic dysregulation.This intricate pathogenic network not only complicates clinical differential diagnosis but also poses substantial challenges to the development of precision therapeutic strategies.Importantly,re-cent studies have revealed that mitochondrial homeostasis disrup-tion-induced inflammatory cascades(termed mitochondrial in-flammation)play a pivotal regulatory role in neurodegenerative progression.Key molecular mechanisms include impaired mito-phagy,aberrant mitochondrial DNA(mtDNA)release and NL-RP3 inflammasome activation.This review systematically deci-phers the molecular regulatory network of mitochondrial inflam-mation,with a focus on its biological effects in critical pathologi-cal events such as blood-brain barrier disruption,microglial hy-peractivation and neuronal apoptosis.The overarching aim is to provide a theoretical foundation for developing innovative thera-peutic strategies targeting mitochondrial homeostasis restoration.

Objective To investigate the possible association between cross-domain associative memory(AM)impairment and hippocampal subfield volumes in patients with schizophrenia(SCZ).Methods We enrolled 28 SCZ patients from Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,and 28 healthy controls(HCs)between 2019 and 2021.Based on an innovative AM paradigm and automated segmentation,3D-T1 weighted data of the objects were processed with PhiPipe and FreeSurfer.Differences in subfield volums between the two groups were analyzed using ANCOVA,while their relationship with AM scores was assessed using Pearson correlation.Results SCZ patients exhibited significantly poorer AM performance across three conditions compared with HCs.Marginally significant reductions were observed in the total volume of bilateral hippocampus,encompassing both the hippocampal head and body.Significant volume reductions were identified in the bilateral presubiculum and parasubiculum.The volumes of bilateral presubiculum head(r=0.273,P=0.042),parasubiculum(r=0.397,P=0.002),and CA1 head(r=0.382,P=0.004)exhibited positive correlations with cross-domain AM performance.Conclusion The bilateral presubiculum and parasubiculum,as hippocampal subregions significantly associated with cross-modal AM deficits in SCZ,may play a crucial role in the pathology of AM.

Objective To investigate the dosimetric effects of tumor treating fields(TTFields)patches on different radiotherapy modes for glioblastoma(GBM)patients who wear TTFields patches during radiotherapy,thereby providing dosimetric guidance for determining the appropriate radiotherapy mode.Methods With the TTFields data from GBM patients,artifact-free radiotherapy CT images were obtained utilizing 3D-printed TPU TTFields patches(3D-Print-TTFields)and anthropomorphic phantoms,and then a TTFields-synchronized radiotherapy image model was constructed.Furthermore,the treatment planning system was used to construct a dosimetric calculation model for TTFields-synchronized radiotherapy by simulating and fitting the ray attenuation rate of TTFields patches measured by accelerators.Using these models,3 kinds of radiotherapy plans were simulated and developed.Specifically,P1 simulated the conventional radiotherapy mode;P2 simulated the TTFields-combined radiotherapy mode(TTF-Com-RT),in which patients underwent radiotherapy using the P1 plan while wearing TTFields patches;and P3 simulated the TTFields-synchronized radiotherapy(TTF-Syn-RT)mode where the TTFields patches were worn throughout the entire radiotherapy process.The paired t-test was used to analyze dosimetric parameters such as target dose(D95),average scalp dose(D-skin),conformity index(CI)and homogeneity index(HI)in 3 plans(P1,P2,and P3),as well as the D95 and D-skin parameters for intensity-modulated radiotherapy(IMRT)and volumetric modulated arc therapy(VMAT)techniques in the P3 plan.Results The D95 simulated by P2 decreased by 1.35%as compared with P1(P<0.05),and the D95 simulated by P3 was 1.31%higher than that in P2(P<0.05).Compared with P1,P2 and P3 increased the D-skin by 12.56%and 14.30%,respectively(P<0.05),and the D-skin simulated by P3 increased by 1.55%as compared with P2(P<0.05).However,there were trivial differences in D95 between P3 and P1,CI and HI among all plans,D95 and D-skin between IMRT and VMAT techniques in P3 plan(P>0.05).Conclusion Based on GBM patient data,CT simulation images obtained from 3D-Print-TTFields combined with anthropomorphic phantom are artifact-free and meet radiotherapy requirements.The target and scalp dose differences between TTF-Com-RT and TTF-Syn-RT are less than 2%,and the dosimetric difference of TTF-Syn-RT using IMRT/VMAT techniques is insignificant.Therefore,clinicians can choose radiotherapy modes and techniques according to actual needs.

Objective To investigate the possible association between cross-domain associative memory(AM)impairment and hippocampal subfield volumes in patients with schizophrenia(SCZ).Methods We enrolled 28 SCZ patients from Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,and 28 healthy controls(HCs)between 2019 and 2021.Based on an innovative AM paradigm and automated segmentation,3D-T1 weighted data of the objects were processed with PhiPipe and FreeSurfer.Differences in subfield volums between the two groups were analyzed using ANCOVA,while their relationship with AM scores was assessed using Pearson correlation.Results SCZ patients exhibited significantly poorer AM performance across three conditions compared with HCs.Marginally significant reductions were observed in the total volume of bilateral hippocampus,encompassing both the hippocampal head and body.Significant volume reductions were identified in the bilateral presubiculum and parasubiculum.The volumes of bilateral presubiculum head(r=0.273,P=0.042),parasubiculum(r=0.397,P=0.002),and CA1 head(r=0.382,P=0.004)exhibited positive correlations with cross-domain AM performance.Conclusion The bilateral presubiculum and parasubiculum,as hippocampal subregions significantly associated with cross-modal AM deficits in SCZ,may play a crucial role in the pathology of AM.

Objective To retrospectively analyze the clinical risk factors and prognosis of perioperative myocardial injury(MINS)in non-cardiac surgery patients admitted to the intensive care unit(ICU).Methods A total of 478 postoperative patients admitted to the Department of Intensive Medicine,Minhang Hospital,Fudan University from Jan 2020 to Dec 2023 were selected.They were divided into MINS group(n=302)and normal group(n=176)based on whether myocardial injury occurred within 7 days after surgery.The differences in clinical characteristics between the two groups were compared,and risk factors for perioperative myocardial injury were identified.Risk factors for mortality in the MINS group were analyzed with 30-day mortality as the clinical endpoint.Results The prevalence of acute physiology and chronic health evaluation Ⅱ(Apache Ⅱ)score,coronary artery disease,and chronic kidney disease were all higher in the MINS group than those in the normal group,with statistically significant differences(P<0.05).The proportion of emergency surgeries,co-infection,and perioperative hypotension were significantly different between the MINS group and the normal group(P<0.05).Multivariate logistic regression analysis revealed that chronic kidney disease,emergency surgery,co-infection,and intraoperative and postoperative hypotension were risk factors for MINS occurrence.Prognostic analysis indicated that perioperative hypotension was a risk factor for 30-day mortality in MINS patients.Conclusion MINS is closely associated with patients'underlying conditions,timing of surgery,and perioperative hypotension status,and especially perioperative hypotension affects the final outcomes.