Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

OBJECTIVE: To investigate the feasibility and prognostic implications of assessing volume status during early fluid resuscitation in septic patients based on estimated plasma volume status (ePVS). METHODS: A prospective study was conducted. Patients with sepsis admitted to intensive care unit (ICU) of the First Affiliated Hospital of Kunming Medical University from March to December in 2023 were enrolled. The general information and laboratory indicators at ICU admission were recorded, and ePVS, sequential organ failure assessment (SOFA) score, acute physiology and chronic health status evaluation II (APACHE II) score were calculated. The vital signs, arterial blood gas analysis and volume status related indicators before liquid resuscitation (T0h) and 3 hours (T3h) and 6 hours (T6h) of fluid resuscitation were recorded. The diameter and variability of the inferior vena cava (IVC) were measured by ultrasound, and ePVS, percentage change value of estimated plasma volume status (ΔePVS%), difference in central venous-to-arterial partial pressure of carbon dioxide (Pcv-aCO₂), and lactate clearance rate (LCR) were calculated. Patients were divided into sepsis group and septic shock group based on the diagnosis at ICU admission, and septic patients were subdivided into survival group and death group based on their 28-day survival status. The differences in clinical data between the groups were compared. The correlation between ePVS or ΔePVS% and volume status related indicators during early liquid resuscitation was analyzed by Spearman rank sum correlation test. The predictive value of each variable for 28-day survival in patients with sepsis was analyzed by receiver operator characteristic curve (ROC curve), and 28-day death risk factors were analyzed by Logistic regression method. RESULTS: Fifty-four septic patients were enrolled in the final analysis, including 17 with sepsis and 37 with septic shock; 34 survived at 28 days and 20 died, with a 28-day survival rate of 63.0%. Compared with the sepsis group, the septic shock group had a lower venous ePVS at ICU admission [dL/g: 4.96 (3.67, 7.15) vs. 7.55 (4.36, 10.07), P < 0.05]. Compared with the death group, the survival group had higher T6h arterial and venous ΔePVS%, and albumin [Alb; T6h arterial ΔePVS% (%): 11.57% (-1.82%, 31.35%) vs. 0.48% (-5.67%, 6.02%), T6h venous ΔePVS%: 9.62% (3.59%, 25.75%) vs. 1.52% (-9.65%, 7.72%), Alb (g/L): 27.57±4.15 vs. 23.77±6.97, all P < 0.05], lower SOFA score, APACHE II score, AST, T0h Lac, and T3h and T6h norepinephrine dosage [SOFA score: 9.00 (8.00, 10.00) vs. 11.50 (9.25, 14.50), APACHE II score: 18.00 (14.75, 21.25) vs. 25.50 (21.00, 30.00), AST (U/L): 34.09 (23.20, 56.64) vs. 79.24 (25.34, 196.59), T0h Lac (mmol/L): 1.75 (1.40, 2.93) vs. 3.25 (2.33, 5.30), norepinephrine dosage (mg): 0.98 (< 0.01, 3.10) vs. 4.60 (1.05, 8.55) at T3h, 1.82 (0.38, 5.30) vs. 8.20 (2.80, 17.73) at T6h, all P < 0.05]. While there were no significantly differences in other basic data and ePVS at all of the time points before and after resuscitation between the two groups. Correlation analysis showed that T6h venous ePVS was significantly positively correlated with T6h IVC variability in septic patients (r = 0.360, P < 0.05), T0h arterial ePVS was significantly negatively correlated with T3h and T6h liquid intake volume (r₁ = -0.367, r₂ = -0.280, both P < 0.05), and venous ePVS at ICU admission was significantly positively correlated with NT-proBNP at ICU admission (r = 0.409, P < 0.05). T6h venous ΔePVS% was significantly positively correlated with T3h liquid intake volume and T6h LCR (r₁ = 0.286, r₂ = 0.286, both P < 0.05), and significantly negatively correlated with T6h urine volume and T6h change value of Pcv-aCO₂ (ΔPcv-aCO₂; r₁ = -0.321, r₂ = -0.371, both P < 0.05). ROC curve analysis showed that the area under the ROC curve (AUC) of T6h venous ΔePVS% for predicting 28-day survival in septic patients was 0.726 [95% confidence interval (95%CI) was 0.578-0.875, P = 0.006], with a sensitivity of 82.4%, a specificity of 60.0%, and an optimal cut-off value of 3.09%. Binary multifactorial Logistic regression analysis showed that an increase in T6h venous ΔePVS% was a protective factor for 28-day death in patients with sepsis on early fluid resuscitation [odds ratio (OR) = 0.900, 95%CI was 0.834-0.972, P = 0.007]. CONCLUSIONS ePVS may have potential for assessing the volume status of septic patients during early fluid resuscitation. The ΔePVS% during early fluid resuscitation may help to identify septic patients with a poor prognosis.
Humans ; Prognosis ; Fluid Therapy ; Sepsis/physiopathology* ; Prospective Studies ; Plasma Volume ; Intensive Care Units ; Resuscitation ; Male ; Female ; Middle Aged ; Shock, Septic/therapy*

Objective To evaluate and compare the maturity of autografts and allografts as well as the postoperative clinical outcomes 10 years after anterior cruciate ligament reconstruction(ACLR).Methods A retrospective analysis was conducted on 64 patients who underwent anterior cruciate liga-ment reconstruction,with an average follow-up period of about 10 years.Autografts were used in 36 cases(56.2%),and allografts in 28 cases(43.8%).Both groups were recorded the knee Lysholm scores,IKDC subjective scores,and stability tests results(KT-1000 side-to-side difference and Lach-man test).Moreover,graft maturity was assessed using the knee magnetic resonance imaging(MRI),and the Signal-to-Noise Quotient(SNQ)for both types of grafts was measured.Results No significant differences were observed between the autograft and allograft groups in the average follow-up time(10.1±2.1 and 10.5±1.8 years)(P=0.376),the SNQ value(24.1±8.8 and 23.2±8.7)(P= 0.652),the Lysholm score(90±10.3 and 89.4±8.9)(P=0.805)and the anterior joint stability dur-ing follow-up(P=0.923).Moreover,the average IKDC score and incidence of abnormal tension of the ligament measured by KT1000 of the autograft group were higher than the allograft group[(84.5±8.3)vs.(80.4±7.8),P=0.075;14.3%vs.8.3%,P=0.724].Meanwhile,ACL re-tear occurred to two cas-es in the autograft group(5.6%)and the allograft group(7.1%),respectively,showing no significant dif-ference(P=0.795).Conclusion Ten years after ACLR,no significant differences are found in graft ma-turity,clinical outcomes,or joint stability between patients using autografts and allografts.Moreover,the rate of graft re-tear is comparable between the two groups.

Objective To investigate the clinical efficacy of drug eluting stents vs metal bare stents for femoral popliteal arteriosclerosis obliterans.Methods The clinical data of 47 patients with femoral popliteal arte-riosclerosis obliterans receiving endovascular therapy from October 2020 to June 2021 were retrospectively ana-lyzed.A total of 24 cases received drug-eluting stents(DES group)and 23 cases underwent metal bare stents(BMS group).Results All patients successfully completed the operation without any adverse events.There was no statistical difference in ABI between the DES group and the BMS group at 7 days and 3 months after surgery,and ABI growth value of the DES group was higher than that of the BMS group at 6,12 and 24 months after surgery(P<0.05).There was no significant difference in the primary patency rate at 6 months after surgery,However,the primary patency rate in DES group was higher than that in BMS group at 12 and 24 months after surgery(91.7%vs.65.2%,83.3%vs.56.5%,P<0.05).For the target lesion revascularization rate of the two groups,DES group had a significant advantage over BMS group(4.0%vs.26.1%,P<0.05).Conclusion DES had better clinical efficacy and advantage over bare metal stent for the treatment of femoral popliteal arteriosclerosis obliterans.

Since the first case of corona virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the end of 2019, the virus has spread rapidly around the world and has become a global public health problem. In the process of this virus epidemic, compared with the general population, cancer patients are considered to be highly susceptible people, especially the lung cancer patients. Some studies have shown that angiotensin converting enzyme 2 (ACE2) may be the pathway for SARS-CoV-2 to infect the host. At the same time, ACE2 is often abnormally expressed in non-small cell lung cancer. Therefore, understanding the respective mechanisms of ACE2 in COVID-19 and non-small cell lung cancer has extremely important reference value for the study of vaccines and therapeutic drugs, and also provides meaningful guidance for the protection of patients with lung cancer during the epidemic. This article reviews the possible invasive mechanism of ACE2 in SARS-CoV-2 and its abnormal expression in non-small cell lung cancer.

Objective    To systematically evaluate the efficacy and safety of jejunostomy tube versus nasojejunal tube for enteral nutrition after radical resection of esophageal cancer. Methods    PubMed, EMbase, Web of Science, The Cochrane Library, CNKI, Wanfang, VIP and CBM databases were searched to collect the clinical effects of jejunostomy tube versus nasojejunal nutrition tube after radical resection of esophageal cancer from inception to October 2021. Meta-analysis was performed using RevMan 5.4 software. Results    Twenty-six articles were included, including 17 randomized controlled studies and 9 cohort studies, with a total of 35 808 patients. Meta-analysis results showed that: in the jejunostomy tube group, the postoperative exhaust time (MD=–4.27, 95%CI –5.87 to –2.66, P=0.001), the incidence of pulmonary infection (OR=1.39, 95%CI 1.06 to 1.82, P=0.02), incidence of tube removal (OR=0.11, 95%CI 0.04 to 0.30, P=0.001), incidence of tube blockage (OR=0.47, 95%CI 0.23 to 0.97, P=0.04), incidence of nasopharyngeal discomfort (OR=0.04, 95%CI 0.01 to 0.13, P=0.001), the incidence of nasopharyngeal mucosal damage (OR=0.13, 95%CI 0.04 to 0.42, P=0.008), the incidence of nausea and vomiting (OR=0.20, 95%CI 0.08 to 0.47, P=0.003) were significantly shorter or lower than those of the nasojejunal tube group. The postoperative serum albumin level (MD=5.75, 95%CI 5.34 to 6.16, P=0.001) was significantly better than that of the nasojejunal tube group. However, the intraoperative operation time of the jejunostomy tube group (MD=13.65, 95%CI 2.32 to 24.98, P=0.02) and the indent time of the postoperative nutrition tube (MD=17.81, 95%CI 12.71 to 22.91, P=0.001) were longer than those of the nasojejunal nutrition tube. At the same time, the incidence of postoperative intestinal obstruction (OR=6.08, 95%CI 2.55 to 14.50, P=0.001) was significantly higher than that of the nasojejunal tube group. There were no statistical differences in the length of postoperative hospital stay or the occurrence of anastomotic fistula between the two groups (P>0.05). Conclusion    In the process of enteral nutrition after radical resection of esophageal cancer, jejunostomy tube has better clinical treatment effect and is more comfortable during catheterization, but the incidence of intestinal obstruction is higher than that of traditional nasojejunal tube.

Objective To systematically evaluate the effect of sequence of pulmonary artery and vein transection in thoracoscopic lobectomy on the efficacy and safety of patients with non-small cell lung cancer. Methods PubMed, EMbase, Web of Science, The Cochrane Library, CNKI, Wanfang, VIP and CBM databases were searched for the researches on The post-operative efficacy of pulmonary arteriovenous and pulmonary vein resection sequence in thoracoscopic lobectomy for non-small cell lung cancer. The retrieval time is from the database construction to May 2022. Meta-analysis was performed using RevMan 5.4 software. Results Eight articles were included, including 3 randomized controlled studies and 5 cohort studies, with a total of 1810 patients. Meta-analysis results showed that: The operative time (MD=13.34, 95%CI(7.36, 19.32), P < 0.0001) and intraoperative blood loss (MD=45.29, 95%CI(40.24, 50.35), P < 0.0001) in the group with priority pulmonary vein resection were significantly higher than those in the group with priority pulmonary vein resection. The difference was statistically significant. However, the benefits of OS (HR=1.34, 95%CI (1.12, 1.60), P=0.001) and DFS (HR=1.44, 95%CI(1.18, 1.76), P=0.0003) in the group of priority pulmonary vein transection were significantly better than those in the group of priority pulmonary artery transection, with statistically significant differences. Conclusion Priority pulmonary vein transection during thoracoscopic lobectomy effectively improved patients' OS and DFS, resulting in higher survival benefit for patients with non-small cell lung cancer, but intraoperative bleeding and operation time are more than those with priority pulmonary artery transection.

Objective    To explore the application of Toumai® minimally invasive endoscopic robot in thoracic surgery, and to observe its safety and short-term surgical efficacy. Methods    Three patients were enrolled from October to December 2021, including 1 male (69 years) and 2 females (47 years and 22 years). All 3 patients received surgery with Toumai® endoscopic surgical robot, including radical lung cancer surgery in 2 patients and mediastinal tumor resection in 1 patient. Results    All 3 patients were successfully operated without conversion to thoracotomy, complication or death. For the male lobectomy patient, the total operation time was 120 min, the intraoperative blood loss was 100 mL, the catheter drainage time was 4 days and the hospital stay time was 5 days. For the female lobectomy patient, the total operation time was 103 min, the intraoperative blood loss was 100 mL, the catheter drainage time was 4 days and the hospital stay time was 5 days. For the female mediastinal tumor patient, the total operation time was 81 min, the intraoperative blood loss was 50 mL, the catheter drainage time was 3 days and the hospital stay time was 3 days. Conclusion    The Toumai® minimally invasive endoscopic surgical robot is safe and effective in thoracic surgery. Compared with Da Vinci surgical robot, Toumai® has the same 3D visual field experience and smooth operation.

Objective:To study the treatment outcomes of transjugular intrahepatic portal shunt (TIPS) on refractory hepatic sinus obstruction syndrome (HSOS) caused by Gynura segetum.Methods:The clinical data of 15 patients with refractory HSOS caused by Gynura segetum treated at the Department of Vascular Surgery, Henan Provincial People's Hospital from January 2017 to April 2021 were retrospectively analyzed. There were 7 males and 8 females, with ages ranging from 30 to 85 years, mean ± s. d. (61.2±14.1) years. Albumin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, glutamyl transferase, and portal vein pressure were compared before and after TIPS. The liver function and renal function of these patients were followed up.Results:When compared with pre-operation, the albumin, alanine aminotransferase, aspartate aminotransferase and other indexes were significantly improved after TIPS (all P<0.05). The portal vein pressure of 15 patients significantly decreased from the preoperative volume of (41.7±3.5) cmH 2O (1 cmH 2O=0.098 kPa) to (28.3±4.4) cmH 2O ( t=10.41, P<0.001). The preoperative liver function was Child-Pugh grade A in 1 patient, grade B in 8 patients, grade C in 6 patients. The postoperative Child-Pugh grading was grade A in 14 patients and grade B in 1 patient. Ascites, gastrointestinal bleeding, abdominal pain, abdominal distention and spontaneous peritonitis all disappeared in these 15 patients. Postoperative hepatic encephalopathy developed in 2 patients and hepatic myelopathy in 1 patient. Conclusion:TIPS for treatment of HSOS caused by Gynura segetum resulted in a rapid recovery of liver function, rapid symptomatic relief, with a low incidence of hepatic encephalopathy/hepatic myelopathy.

Objective:To evaluate the relationship between heme oxygenase-1 (HO-1) and peroxisome proliferator-activated receptor γ (PPARγ) during alveolar macrophage polarization in a mouse model of endotoxin-induced acute lung injury (ALI).Methods:Thirty clean-grade male C57BL/6 mice (24 wide-type mice and 6 HO-1 knockout mice), aged 6-8 weeks, weighing 18-22 g, were studied.Wide-type mice were divided into 4 groups ( n=6 each) using a random number table method: control group (C group), ALI group, ALI+ HO-1 agonist hemin group (ALI+ H group), and ALI+ hemin+ PPARγ antagonist T0070907 group (ALI+ H+ T group).HO-1 knockout mice in which the ALI model was developed served as ALI+ HO-1 -/- group.ALI model was developed by injecting lipopolysaccharide (LPS) 15 mg/kg via the tail vein in anesthetized animals.T0070907 1.5 mg/kg was intraperitoneally injected at 1 h before LPS administration in ALI+ H+ T group, and hemin 50 mg/kg was intraperitoneally injected at 30 min before LPS administration in ALI+ H group and ALI+ H+ T group.Mice were sacrificed at 12 h after LPS administration, and lung tissues were obtained to measure the wet to dry weight ratio (W/D ratio), to observe pathological changes which were scored, and to determine the F4/80+ /CD86+ labeled M1 alveolar macrophages and the F4/80+ /CD206+ labeled M2 alveolar macrophages (by flow cytometry), contents of M1 macrophage-related genes inducible nitric oxide synthase (iNOS) and M2 macrophage-related genes Arginase-1 (Arg-1) (by enzyme-linked immunosorbent assay), and the expression of HO-1 and PPARγ (by Western blot). Results:Compared with C group, the lung injury score, W/D ratio, levels of CD86 and CD206, and contents of iNOS and Arg-1 were significantly increased, and PPARγ expression was up-regulated in the other four groups ( P<0.05), and HO-1 protein expression was up-regulated in ALI, ALI+ H and ALI+ H+ T groups ( P<0.05).Compared with ALI group, the lung injury score, W/D ratio, and levels of CD86 and iNOS were significantly increased, the levels of CD206 and Arg-1 were decreased, and the expression of HO-1 and PPARγ was down-regulated in ALI+ HO-1 -/- group, the lung injury score, W/D ratio and levels of CD86 and iNOS were significantly decreased, the levels of CD206 and Arg-1 were increased, and the expression of HO-1 and PPARγ was up-regulated in ALI+ H group ( P<0.05), and no significant change was found in the parameters mentioned above in ALI+ H+ T group ( P>0.05).Compared with ALI+ H group, the lung injury score, W/D ratio and levels of CD86 and iNOS were significantly increased, the levels of CD206 and Arg-1 were decreased, the expression of PPARγ was down-regulated ( P<0.05), and no significant change was found in the expression of HO-1 in ALI+ H+ T group ( P>0.05). Conclusions:HO-1 can up-regulate the expression of PPARγ, inhibit the polarization of alveolar macrophages toward M1 phenotype and promote the polarization toward M2 phenotype, thus playing an endogenous protective role in endotoxin-induced ALI in mice.