OBJECTIVE To provide valuable insights for the adjustment of anti-infectious regimens， identification of adverse reactions， and individualized pharmaceutical care in patients with critically severe scrub typhus. METHODS Clinical pharmacists actively participated in the pharmaceutical care process for a patient with severe scrub typhus leading to mixed shock undergoing continuous renal replacement therapy and extracorporeal membrane oxygenation. Initially， the patient received meropenem （1 g， q12 h， ivdrip）， in combination with doxycycline （0.1 g， q12 h， po）， which was later switched to meropenem （1 g， q8 h， ivdrip） along with omacycline （100 mg， qd， ivdrip） due to impaired gastrointestinal function. However， as the patient’s condition progressively deteriorated and the infection became uncontrolled， the clinical pharmacists recommended that the clinicians adjust the anti-infective regimen to meropenem （2 g， q8 h， ivdrip） combined with tigecycline （100 mg for first dose； 50 mg， q12 h for maintenance； ivdrip）. The clinicians followed the advice of the clinical pharmacists. After treatment， the patient’s symptoms exhibited significant improvement， accompanied by a notable decrease in inflammatory markers， indicating that the infection had been successfully controlled. However， due to continuously increasing bilirubin levels， in order to reduce the risk of drug-induced liver injury， the clinicians changed tigecycline to azithromycin （0.5 g， qd， ivdrip） following the recommendation of the clinical pharmacists. RESULTS Ultimately， metagenomic next-generation sequencing of the bronchoalveolar lavage fluid and blood specimens indicated that Orientia tsutsugamushi had been completely eradicated in the patient. CONCLUSIONS Tigecycline may be a viable therapeutic choice for patients with severe scrub typhus. In the context of critically ill patients with scrub typhus， combining tigecycline with azithromycin might potentially enhance the efficacy in eliminating Orientia tsutsugamushi.

Objective To evaluate the efficacy and safety of Qingre Jiedu recipe in the treatment of bipolar depression.Methods A randomized,double-blind,Chinese medicine and western medicine placebo control design was used in this study.Totally 80 subjects with bipolar depression and fiery internal depression that met the enrollment criteria,were divided into the experimental group(EG,40 cases of western medicine simulation tablets+Chinese medicine formula granules)and the control group(CG,40 cases of western medicine+Chinese medicine placebo)according to a 1∶1 ratio at last,7 cases dropped out after enrollment,EG 36 cases,CG 37 cases.TCM Heat Internal Depression Syndrome(TCMHIDS),Hamilton Depression Scale-24 Item(HAMD-24),Hamilton Anxiety Scale(HAMA),Hypomania Checklist-33(HCL-33),Young Manic Rating Scale(YMRS)and Treatment Emergent Symptom Scale(TESS)scores were assessed at baseline and at the 2nd,4th and 8th week after treatment.Important signs and adverse events were recorded.Blood routine,hepatic and renal function,urine routine and electrocardiogram were performed during the screening period and the 8th week after treatment.For the patients who dropped out of the examination program,the examination item are identical to those at week 8.The primary outcome measure was the change in HAMD score from baseline to 8th week.Secondary outcome evaluation indicators included the changes of TCMHIDS,HAMA,HCL-33 and YMRS scores from baseline to 8th week.Results The scores of the HAMD-24 between EG and CG decreased significantly compared with the baseline at different time-point,and the difference was statistically significant(P＜0.01).However,the scores of the EG on the HAMD-24 decreased more significantly compared with the CG at the 4th and 8th week,and this difference was statistically significant(P＜0.01).The TCMHIDS and HAMD scores between two groups decreased compared with the baseline at different time-point,and this difference was statistically significant(P＜0.01).However,the TCMHIDS and HAMD scores of the EG decreased more significantly ot the 4th and 8th week,compared with the CG,and this difference was statistically significant(P＜0.01).Both YMRS and HCL-33 scores decreased more significantly between two groups at different time-point,compared with the baseline,and this differences was statistically significant,but there was no difference between two groups.Conclusion TCM Qingre Jiedu recipe could effectively relieve depression and anxiety mood of bipolar depression,with more advantages than western medicine.In addition,it showed a certain effect on hypomania or manic-related symptoms of bipolar disorder,No risk of turning to hypomania or manic,better safety and less adverse reactions were observed.

Objective To explore the association between phase angle(PhA)and sarcopenia in middle-aged and elderly patients with type 2 diabetes mellitus(T2DM),and to evaluate its predictive value for the risk of sarcopenia in these patients.Methods We collected data from 356 middle-aged and elderly T2DM patients hospitalized in the Department of Endocrinology,Nanjing Drum Tower Hospital Group Suqian Hospital from March 2022 to June 2024,including 274 patients with diabetes only and 82 patients with T2DM combined with sarcopenia.A Logistic regression analysis was conducted to assess the relationship between phase angle and sarcopenia.The predictive value of PhA for sarcopenia in T2DM patients was analyzed using the receiver operating characteristic(ROC)curve,and the trend of PhA with the severity of sarcopenia in T2DM patients was tested by the Jonckheere-Terpstra method.Results Univariate analysis showed that the PhA value in the T2DM with sarcopenia group was significantly lower than that in the diabetes alone group,with a statistically significant difference(P<0.05).Additionally,height,body mass,body mass index(BMI),waist circumference,arm circumference,calf circumference,fasting insulin,postprandial 2 h insulin,fasting C-peptide,postprandial 2 h C-peptide,triglycerides,albumin,blood urea nitrogen,body composition indicators,6 m walking speed,muscle mass,and muscle strength-related indicators were significantly lower in the T2DM with sarcopenia group compared to the diabetes alone group.Age,duration of diabetes,glycated hemoglobin,25-hydroxyvitamin D[25-(OH)D]were significantly higher in the T2DM with sarcopenia group,with statistically significant differences(P<0.05).Multivariate Logistic regression analysis indicated that,after adjusting for other factors,PhA remained associated with sarcopenia in T2DM patients(P<0.05),with a decreased PhA increasing the risk of sarcopenia.ROC curve analysis showed that the area under the curve(AUC)for PhA predicting sarcopenia in T2DM patients was 0.769(95% CI:0.710-0.829),indicating the predictive efficacy of PhA.Trend analysis demonstrated a significant negative correlation between PhA and the severity of sarcopenia in T2DM patients(P<0.05).Conclusion The PhA is significantly associated with sarcopenia in patients with T2DM.It can serve as an early predictive and diagnostic tool for sarcopenia in individuals with T2DM.

Objective To investigate the pharmacokinetic(PK)profile of ripretinib in patients with advanced gastrointestinal stromal tumors(GISTs)in real-world settings.Methods The PK data of eight advanced GIST patients treated with ripretinib and the steady-state trough concentration(Cmin)blood samples of 54 advanced GIST patients treated with ripretinib were collected from November 2023 to March 2025 at the First Affiliated Hospital of Sun Yat-sen University.A validated liquid chromatography-tandem mass spectrometry method was used to quantify ripretinib and DP-5439 concentrations.The PK profiles of ripretinib were characterized.Cmin was compared across various dosages.The correlations among PK parameters of ripretinib and DP-5439,and clinical features impacting PK were explored.Results All patients reached Cmin approximately 24 hours post-dose for ripretinib and DP-5439.The median time to maximum con-centration(Tmax)for both ripretinib and DP-5439 was 3.16 hours.The steady-state Cmin,maximum plasma concentration(Cmax),and area under the plasma concentration-time curve from 0 to 24 hours(AUC0-24 h)of ripretinib,DP-5439,and their combined total were found to be highly correlated(all r>0.85,all P<0.05).In patients receiving 150 mg once-daily(n=44),the median Cmin(range)was 381.66(40.90-1 045.48)ng/mL for ripretinib,589.08(25.28-1 168.11)ng/mL for DP-5439,and 998.00(66.18～2 381.48)ng/mL for total,with coeffi-cients of variation(CVs)of 59.4%,57.2%,and 53.6%.In the 300 mg group(n=11),the median Cmin(range)was 1 024.51(251.36-2 030.51)ng/mL for ripretinib,1 122.34(111.54-2 682.57)ng/mL for DP-5439,and 1 924.58(404.37-4 766.08)ng/mL for total,with CVs of 59.5%,57.3%,and 54.8%.Univariate analysis showed that no significant correlation was found between age or BMI and the dose-corrected Cmin of ripretinib and DP-5439(all P>0.05),and the median dose-corrected Cmin of ripretinib and DP-5439 was slightly lower in male patients than in female patients(P<0.05).In the multiple linear regression analysis,male patients were observed to have a lower median dose-cor-rected Cmin of DP-5439 than female patients(P=0.024),but no statistical difference was found in that of ripretinib(P>0.05).Conclusions In advanced GIST patients receiving ripretinib,ripretinib and DP-5439 reached Cmin 24 hours post-dose,just before the next administra-tion.The ripretinib,DP-5439,and total Cmin showed significant correlations with their AUC0-24 h,which indicated that Cmin could serve as an indicator of ripretinib exposure.The PK features of ripretinib in advanced GIST patients exhibit significant inter-individual variability.

Inflammatory bowel disease (IBD) is an intestinal disease with uncertain etiology and complex mechanism. The interaction between environment and gene is a risk factor of IBD, which includes abnormal DNA methylation. In this review, we discuss the abnormal DNA methylation in IBD patients, and illustrate the interaction between gut microbiota and host through DNA methylation and its mechanism. Finally, we look forward to the prospect of regulating the interaction between gut microbiota and host through DNA methylation in the treatment of IBD.

Objective To explore the pharmaceutical care clinical pharmacists provide for anti-infective therapy in patients undergoing continuous renal replacement therapy(CRRT)after lung transplantation.Methods The clinical pharmacist utilized a limited sampling strategy and participated in the entire anti-infective treatment process for an adult lung transplant recipient based on pharmacokinetic monitoring results.The CRRT duration was flexibly adjusted,the dosing regimen was optimized,and adverse drug reactions were monitored.Result The clinical pharmacist assisted the physician in optimizing the polymyxin B anti-infective therapy post-transplantation,leading to successful infection control and patient discharge.Conclusion Clinical pharmacists can conduct real-time drug concentration monitoring in lung transplant patients based on pharmacokinetic characteristics,develop individualized dosing regimens,and improve medication safety and efficacy during anti-infective therapy.

Objective To investigate their potential differences in brain functional characteristics from a neuroimaging perspective,functional magnetic resonance imaging(fMRI)was employed.Methods Twenty chronic fatigue syndrome(CFS)patients were recruited and underwent assessments of traditional Chinese medicine(TCM)syndrome patterns,fatigue severity scores,and resting-state fMRI scans.First,correlation analysis was performed between fatigue scores and TCM symptom scores.Symptom clusters significantly associated with fatigue were categorized into spleen deficiency and liver stagnation groups.Principal component analysis(PCA)was then applied to identify the dominant symptom components for each group.These components were subsequently mapped onto whole-brain functional activity to compare the neural signatures between the two syndromes.Finally,the brain functional profiles of spleen deficiency and liver stagnation were compared with publicly available neurotransmitter receptor maps to explore their distinct neurochemical substrates.Results Symptoms correlated with fatigue severity included exhaustion,dizziness,chest tightness,bitter taste in the mouth,epigastric fullness,poor appetite,irritability,lumbar soreness,sallow complexion,dry eyes,and five-center-heat.The brain mapping results revealed that spleen deficiency-related symptoms(poor appetite,sallow complexion,reduced food intake,dizziness)were primarily associated with the left thalamus and left parahippocampal gyrus.Liver stagnation-related symptoms(dry eyes,chest tightness,irritability,bitter taste)were linked to the left parahippocampal gyrus and right middle occipital gyrus(lingual region).The functional brain spectrum of the two syndromes showed significant negative correlations.Moreover,the spleen deficiency spectrum was closely associated with vesicular acetylcholine transporter(VAChT)receptor density.The liver stagnation spectrum correlated with D2 dopamine receptor density.Both spectrums were significantly related to glucose metabolic density but exhibited opposing directional trends.Conclusion CFS patients with spleen deficiency and liver stagnation demonstrate distinct central functional activities and neurochemical substrates,along with opposing brain activity patterns.Clinically,differentiating between these two syndrome patterns is critical for applying targeted TCM interventions.

Objective:To investigate the clinical characteristics, postoperative complications, and risk factors for pouchitis in surgical patients with ulcerative colitis (UC).Methods:This was a retrospective observational study. The clinical data of 336 UC patients who had undergone surgical treatment at the Inflammatory Bowel Disease Center of the Department of General Surgery, Jinling Hospital Affiliated to Nanjing University Medical School from February 2014 to February 2024 were enrolled. The study patients were stratified into 2014-2019 ( n = 158) and 2020–2024 groups ( n = 178), these being the periods before and after biologics were covered for treatment of UC by national insurance in China in 2020. Clinical characteristics and surgical complications were analyzed and compared between the 2014-2019 and 2020-2024 groups. Multivariable logistic regression was performed to identify the risk factors associated with pouchitis in UC patients undergoing total proctocolectomy with ileal pouch-anal anastomosis (TPC-IPAA). Results:The study cohort comprised 336 UC patients, 193 (57.4%) of whom were men. The median preoperative disease course was 48.0 months and the mean age at colectomy was 46.4±15.4 years. TPC-IPAA had been performed on 275 patients (81.8%), 129 in the 2014-2019 group and 146 in the 2020-2024 group. Sixty-one patients had undergone total or subtotal colectomy, 29 in the 2014-2019 group and 32 in the 2020-2024 group. 262 (78.0%) UC patients underwent surgery due to medical refractory. Ninety-nine (29.5%) had used biopharmaceuticals within 2 months prior to surgery, 63 (18.8%) of them having received infliximab. A smaller proportion of patients had undergone surgery for UC that was refractory to medications in the 2020–2024 group than in the 2014–2019 group (73.0% [130/178] vs. 83.5% [132/158], χ 2=5.384, P=0.020), the patients were older at colectomy (48.0±15.4 years vs. 44.6±15.2 years, t=-2.008, P=0.045), the body mass index was higher (20.2±3.1 kg/m 2 vs. 19.4±3.2 kg/m 2, t=-2.201, P=0.028), the Mayo score prior to surgery was lower ( M[ Q1, Q3]: 11.0 [9.2, 12.0 points] vs. 12.0 [11.0, 12.0) points, Z=-4.242, P=0.001), the rate of Charlson Comorbidity Index ≥ 3 scores was higher (27.0% [48/178] vs. 17.1% [27/158], χ 2=5.384, P=0.020), a greater percentage of patients had received biologics prior to surgery (41.0% [73/178) vs. 16.5% [26/158], χ 2=24.285, P<0.001), and intraoperative blood loss was greater ( M[ Q1, Q3]: 100.0 [100.0, 150.0] ml vs. 50.0 [30.0, 100.0] ml, Z=-7.054, P<0.001) despite the operation time being shorter (253.8±74.6 minutes vs. 315.2±96.8 minutes, t=6.265, P<0.001). Among the 275 patients undergoing TPC-IPAA, 95 (34.6%) had early complications (within 30 days after surgery), 20 (7.3%) of which were Clavien-Dindo Grade III–IV complications. Among these patients, 50 (18.2%) had ileus or small bowel obstruction, 11 in the 2014-2019 group and 39 in the 2020-2024 group; this difference is statistically significant (χ 2=15.225, P<0.001). Ninety-one patients (33.1%) had late complications (more than 30 days after surgery), 75 (27.3%) being pouchitis (36 in the 2014-2019 group and 39 in the 2020-2024 group); this difference is not statistically significant (χ 2=0.049, P=0.824). Five patients (1.8%) had undergone pouch excision with permanent ileostomy. Among the 61 patients who had undergone total or subtotal colectomy, 26 (42.6%) developed early postoperative complications, including 10 (16.4%) Clavien-Dindo Grade III-IV complications and one death (1.6%), the last being attributable to multiorgan dysfunction. Three patients (4.9%) had late complications; the difference in incidence of postoperative complications between the 2014-2019 and 2020-2024 groups is not statistically significant (both P>0.05). Multivariable analysis identified intraoperative blood transfusion (OR: 2.12, 95% CI: 1.19–3.75, P=0.010) and interval to stoma closure > 120 days (OR: 2.05, 95%CI: 1.16-3.62, P = 0.013) as independent risk factors for development of pouchitis in UC patients undergoing TPC-IPAA. Conclusion:Surgical treatment of UC remains safe in the biologics era. Proactive strategies to reduce intraoperative blood transfusion and achieve timely stoma closure may reduce the risk of pouchitis in UC patients undergoing TPC-IPAA.

Objective To explore the association between phase angle(PhA)and sarcopenia in middle-aged and elderly patients with type 2 diabetes mellitus(T2DM),and to evaluate its predictive value for the risk of sarcopenia in these patients.Methods We collected data from 356 middle-aged and elderly T2DM patients hospitalized in the Department of Endocrinology,Nanjing Drum Tower Hospital Group Suqian Hospital from March 2022 to June 2024,including 274 patients with diabetes only and 82 patients with T2DM combined with sarcopenia.A Logistic regression analysis was conducted to assess the relationship between phase angle and sarcopenia.The predictive value of PhA for sarcopenia in T2DM patients was analyzed using the receiver operating characteristic(ROC)curve,and the trend of PhA with the severity of sarcopenia in T2DM patients was tested by the Jonckheere-Terpstra method.Results Univariate analysis showed that the PhA value in the T2DM with sarcopenia group was significantly lower than that in the diabetes alone group,with a statistically significant difference(P<0.05).Additionally,height,body mass,body mass index(BMI),waist circumference,arm circumference,calf circumference,fasting insulin,postprandial 2 h insulin,fasting C-peptide,postprandial 2 h C-peptide,triglycerides,albumin,blood urea nitrogen,body composition indicators,6 m walking speed,muscle mass,and muscle strength-related indicators were significantly lower in the T2DM with sarcopenia group compared to the diabetes alone group.Age,duration of diabetes,glycated hemoglobin,25-hydroxyvitamin D[25-(OH)D]were significantly higher in the T2DM with sarcopenia group,with statistically significant differences(P<0.05).Multivariate Logistic regression analysis indicated that,after adjusting for other factors,PhA remained associated with sarcopenia in T2DM patients(P<0.05),with a decreased PhA increasing the risk of sarcopenia.ROC curve analysis showed that the area under the curve(AUC)for PhA predicting sarcopenia in T2DM patients was 0.769(95% CI:0.710-0.829),indicating the predictive efficacy of PhA.Trend analysis demonstrated a significant negative correlation between PhA and the severity of sarcopenia in T2DM patients(P<0.05).Conclusion The PhA is significantly associated with sarcopenia in patients with T2DM.It can serve as an early predictive and diagnostic tool for sarcopenia in individuals with T2DM.

Objective To explore the association between mid-upper arm circumference(MUAC)and sarcopenia in middle-aged and elderly patients with type 2 diabetes mellitus(T2DM).Methods A total of 402 middle-aged and elderly patients with T2DM admitted to Nanjing Drum Tower Hospital Group Suqian Hospital from March 2022 to October 2024 were selected.Among them,308 patients with simple diabetes mellitus were included in non-sarcopenia group,and 94 patients with combined sarcopenia were included in sarcopenia group.Multivariate Logistic regression analysis was used to determine the association between MU AC and sarcopenia in middle-aged and elderly patients with T2DM.The predictive ability of MUAC for sarcopenia in middle-aged and elderly patients with T2DM was evaluated by using the receiver operating characteristic curve.Results There were statistically significant differences in age,body mass index,MUAC,triglycerides,direct bilirubin,alanine aminotransferase,aspartate aminotransferase,appendicular skeletal muscle mass,appendicular skeletal muscle mass index,grip strength and 6-meter walking speed between two groups of patients(P＜0.05).The results of multivariate Logistic regression showed that a smaller MUAC and increased age were both risk factors for sarcopenia in middle-aged and elderly patients with T2DM(P＜0.05).The optimal cutoff value of MUAC for diagnosing sarcopenia in middle-aged and elderly patients with T2DM:27.90cm for males and 26.95cm for females.Conclusion MUAC is associated with sarcopenia in middle-aged and elderly patients with T2DM and can be used for the early identification and diagnosis of middle-aged and elderly T2DM patients with sarcopenia.