Natural Products Treat Atopic Dermatitis via NF-κB Signaling Pathway： A Review / 中国实验方剂学杂志

Atopic dermatitis （AD） is a chronic， recurrent， inflammatory， and pruritus skin disease caused by multiple internal and external factors， ranking first in the global burden of skin diseases. Due to the adverse reactions and high costs of conventional treatments and biologics， the development of natural products has attracted much attention. The nuclear factor-κB （NF-κB） signaling pathway is a key pathway for inhibiting inflammation and modulating immunity. This paper summarizes the pharmacological effects and molecular mechanisms of natural products such as flavonoids， alkaloids， phenols， terpenoids， coumarins， glycosides， and anthraquinones via NF-κB signaling pathway， aiming to provide guidance for the development of natural products. Basic studies have shown that natural products have high safety and efficacy. Oral or topical administration of natural products can regulate the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）， mitogen-activated protein kinase （MAPK）， nuclear factor erythroid 2-related factor 2 （Nrf2）， high mobility group box 1 protein （HMGB1）/receptor for advanced glycation endproducts （RAGE）， and nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3） signaling pathways to exert anti-inflammatory， anti-allergy， antioxidant activities， thus reversing the pathological changes of AD. However， it is worth noting that the clinical application of natural products is still insufficient， and more rigorous clinical trials are still needed to verify their effects. The basic experiments and clinical evidence prove that natural products may play a role in alleviating AD， which provide a basis for evaluating the functioning mechanism of natural active substances and enrich the candidates for the development of potential drugs.

Wilson's Disease in Traditional Chinese and Western Medicine： A Review / 中国实验方剂学杂志

Wilson's disease （WD） is a copper metabolism disorder caused by mutations in the ATP7B gene， with diverse phenotypes and complex pathogenesis. It is one of the few rare diseases that can achieve good clinical efficacy through standardized treatment. Since there are few systematic reviews of this disease， we summarize the pathogenesis and treatment methods of WD from traditional Chinese and western medicine by reviewing the literature related to WD. In western medicine， ATP7B gene mutation is considered as the root cause of WD， which affects copper transport and causes copper metabolism disorders. The excessive copper deposited in the body will result in oxidative stress， defects in mitochondrial function， and cell death. Western medicine treatment of WD relies mainly on drugs， and copper antagonists are the first choice in clinical practice， which are often combined with hepatoprotective and antioxidant therapy. Surgery is a common therapy for the patients with end-stage WD， and gene therapy provides an option for WD patients. According to the traditional Chinese medicine （TCM） theory， WD is rooted in constitutional deficiency and copper accumulation and triggered by dampness-heat accumulation or phlegm combined with stasis. The patient syndrome varies in different stages of the disease， and thus the treatment should be based on syndrome differentiation. The TCM treatment method of nourishing the liver and kidneys and warming the spleen and kidneys can address the root cause. The methods of clearing heat and drying dampness， resolving phlegm and dispelling stasis， and soothing liver and regulating qi movement can be adopted to treat symptoms. On the basis of syndrome differentiation， special prescriptions for the treatment of WD have been formulated， such as Gandou decoction， Gandouling， and Gandou Fumu decoction， which have been widely used in clinical practice. TCM and western medicine have their own advantages and shortcomings. The integrated Chinese and western medicine complementing with each other demonstrates great therapeutic potential. This paper summarizes the pathogenesis and treatment of WD with integrated Chinese and western medicine， aiming to provide a reference for the clinical diagnosis and treatment of this disease.

Validation of a fast and reliable liquid chromatography tandem mass spectrometry for simultaneous quantitation of Voriconazole, Posaconazole and Linezolid in human serum / 中华检验医学杂志

Objective:To establish a high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of voliconazole (VRC), posaconazole (PCZ), and linazolam (LNZ) in human serum.Methods:This study is a methodological validation by LC-MS/MS. The blood concentration results of VRC, PCZ, and LNZ in our hospital′s anti-infection patients were collected. Voriconazole, Posaconazole, and Linezolid were accurately weighed and prepared. Linezolid-[2H3] was used as the internal standard. After gradient elution on the ACE PFP column, the residuals were analyzed by LC-MS/MS in the positive electrospray ionization mode and multiple reaction monitor (MRM) mode. The method′s linearity, precision, lower limit of detection, and recovery rate were validated according to standard guidelines.Results:The linear correlation coefficient ( r) of the standard curve was above 0.99 ( r>0.99). The linear range of VRC and PCZ were 0.10 mg/L~10.00 mg/L, and the lower limit of detection were 0.01 mg/L. The linear range of LNZ was 0.50 mg/L~50.00 mg/L, and the lower limit of detection was 0.05 mg/L. The recoveries of VRC, PCZ and LNZ were 90.96%-103.18%, 91.84%-99.17%, and 97.04%-100.41%, respectively. Intra-and inter-batch precision (% CV) for VRC were less than 8.30%. Intra-and inter-batch precision (% CV) for PCZ was less than 9.78%. Intra-and inter-batch precision (% CV) for LNZ was less than 7.14%. Drug concentrations in 155 cases of VRC, 44 cases of PCZ, and 59 cases of LNZ were detected. Conclusion:We have established an LC-MS/MS method for the rapid, accurate, highly specific determination of VRC, PCZ, and LNZ concentrations in human serum. This method is suitable for analyzing large clinical sample sets.

The risk factors of postoperative continuous renal replacement therapy application in Stanford type A acute aortic dissection / 中华胸心血管外科杂志

Objective:To investigate the risk factors of postoperative continuous renal replacement therapy application in Stanford type A acute aortic dissection.Methods:This retrospective study included 527 patients with Stanford type A acute aortic dissection from November 2015 to February 2018 in Beijing Anzhen Hospital. They were divided into 2 groups according to whether or not needed postoperative continuous renal replacement therapy, group CRRT(78 cases) and group None CRRT(449 cases). Binary logistic regression analysis was used to analyze the risk factors of continuous renal replacement therapy. Results:Of all the patients, the percentage of using continuous renal replacement therapy was 14.8%(78/527), and the mortality of 30 days after surgery was 8.5%(45/527). The independent risk factors associated with CRRT were preoperative serum creatinine(sCr)( OR=1.012, 95% CI: 1.005-1.019, P<0.001), transfusion of red blood cell in surgery( OR=1.141, 95% CI: 1.071-1.216, P<0.001), transfusion of platelet in surgery( OR=1.307, 95% CI: 1.084-1.576, P=0.005), the total amount of drainage( OR=1.000, 95% CI: 1.000-1.000, P=0.036), and the time of extubation after surgery( OR=1.004, 95% CI: 1.001-1.008, P=0.013). Conclusion:The risk factors of CRRT after emergency surgery of Stanford type A acute aortic dissection are preoperative serum creatinine, transfusion of red blood cell in surgery, transfusion of platelet in surgery, the total amount of drainage and the time of tracheal extubation after surgery. We need to focus on those risk factors in our daily job and manage them timely and properly, in order to improve patients’ prognosis.

An enriched environment can promote nerve regeneration in a mouse model of sciatic nerve compression / 中华物理医学与康复杂志

Objective:To document any effect of environmental enrichment on nerve regeneration in a mouse model of sciatic nerve compression and explore its mechanism.Methods:A crushed sciatic nerve model was successfully established in 22 C57BL/6 mice, and they were then randomly divided into an intervention group and a control group. The mice of the intervention group were raised in a cage with an enriched environment, while those of the control group were kept in a standard cage. Two weeks later, both groups′ gait was analyzed and the compound muscle action potential (CMAP) of the sciatic nerve was measured. The proportion of myelinated sciatic nerve fibers was examined using toluidine blue staining, and the expression of myelin basic protein (MBP), growth associated protein-43 (GAP43) and p75 neurotrophin receptor (p75 NTR) was measured using immunofluorescence intensity. Results:①The latency of the CMAP [(1.05±0.04)ms] was significantly shortened in the intervention group compared with the control group and the amplitude was significantly higher. ②Gait analysis showed a significant increase in the average contact intensity, stride length and stride rate of the intervention group compared with the control group. However, the step axis angle of the intervention group was significantly smaller than in the control group on average. ③The stained nerve fibers in the intervention group were orderly and dense, and the average number of myelinated fibers was significantly greater than in the control group. ④Quantitative analysis of the immunofluorescence showed that the levels of MBP, GAP43 and p75 NTR in the sciatic nerves of the intervention group were, on average, significantly higher than in the control group. Conclusion:An enriched environmental can promote the regeneration and functional recovery of crushed sciatic nerves by promoting the proliferation and myelination of Schwann cells.

Uptake characteristics of 68Ga-FAPI-04 and 18F-FDG in surgical wounds after radical surgery for gastrointestinal adenocarcinoma / 中华核医学与分子影像杂志

Objective:To explore the uptake characteristics and temporal changes of 68Ga-fibroblast activation protein inhibitors (FAPIs) and 18F-FDG in the anastomotic site of reconstructed digestive tracts after radical surgery for gastrointestinal adenocarcinoma. Methods:A cohort of 43 patients (28 males, 15 females; age range 28-79 years) who underwent radical surgery for gastrointestinal adenocarcinoma and underwent 18F-FDG PET/CT follow-up between November 2020 and June 2022 in the First Affiliated Hospital of the Air Force Medical University was prospectively included. One week after the 18F-FDG PET/CT examination, 68Ga-FAPI-04 PET/CT imaging was performed. ROIs were drawn on the PET images at the highest uptake level of anastomotic sites of reconstructed digestive tract and abdominal wall incisions, and SUV max and target-to-background ratio (TBR) were determined. χ2 test, one-way analysis of variance, Kruskal-Wallis rank sum test (Bonferroni correction) and Wilcoxon signed-rank test were supplied. Results:There were 86 surgical wounds (13 gastric-intestinal anastomotic sites, 14 esophagus-intestinal anastomotic sites, 16 intestinal-intestinal anastomotic sites, and 43 abdominal wall incisions) included. In 68Ga-FAPI-04 PET imaging, SUV max of gastric-intestinal anastomotic sites was higher than that of abdominal wall incisions, with a statistically significant difference (adjusted P=0.014). The TBR did not show statistically significant differences among different types of surgical wounds ( H=3.88, P=0.275). In 18F-FDG PET imaging, SUV max of gastric-intestinal, esophagus-intestinal, and intestinal-intestinal anastomotic sites were all higher than that of abdominal wall incisions, with statistically significant differences (adjusted all P<0.001). There were no statistically significant differences in TBR among different types of surgical wounds ( H=3.02, P=0.388). In 68Ga-FAPI-04 PET imaging, the TBR of all types of anastomotic sites exhibited a decreasing trend with increasing postoperative time. Except for intestinal-intestinal anastomotic sites, the differences in TBR between < 0.5-year and ≥ 1.5-year groups were statistically significant for other types of surgical wounds (adjusted P<0.05). In 18F-FDG PET imaging, the TBR of abdominal wall incisions showed a decreasing trend with increasing postoperative time. However, the TBR of other types of surgical wounds did not show a decreasing trend, and the differences in TBR among different time groups were not statistically significant ( H values: 0.53-2.75, P values: 0.252-0.768). In comparing the two PET imaging agents, for all surgical wounds within the <0.5-year and 0.5-1.5-year groups, the 68Ga-FAPI-04 TBR was consistently higher than the 18F-FDG TBR ( z values: -3.17 and -2.55, P values: 0.002 and 0.011). However, in the ≥1.5-year group, the TBR values tended to be consistent, and the differences were not statistically significant ( z=-0.70, P=0.485). Conclusions:The 18F-FDG uptake in the anastomotic sites of reconstructed digestive tracts reaches a low level under half a year after surgery and does not significantly change over time, while the 68Ga-FAPIs uptake remains relatively high within the first 1.5 years after surgery but decreases over time. These patterns suggest that clinical attention should be paid to the differential diagnosis of anastomotic inflammation or fibrosis, which resulting in agent uptake and local tumor recurrence.

Comparison of therapeutic effects between anatomical reconstruction of the coracoclavicular ligament at the original insertion point and clavicular hook plate fixation in the treatment of acromioclavicular joint dislocation / 中华骨科杂志

Objective:To compare the clinical efficacy of anatomical reconstruction of coracoclavicular ligament at the original insertion point and clavicular hook plate fixation in the treatment of acromioclavicular joint dislocation.Methods:Retrospective analysis was made on the data of 67 patients with acromioclavicular joint dislocation who received surgical treatment in the Department of Orthopaedics of the First Affiliated Hospital of Nanjing Medical University from June 2015 to January 2021. According to the surgical method, they were divided into reconstruction group (using the technique of anatomical reconstruction of coracoclavicular ligament at the original insertion point) and hook plate group (using the clavicular hook plate). There were 37 cases in the reconstruction group, including 26 males and 11 females, aged 47.2±9.6 years (range, 18-65 years), 13 cases on the left and 24 cases on the right. Among the 37 patients, 8 were sports injuries, 14 were falls, 11 were traffic accidents, and 4 were external force injuries. The average time from injury to surgery was 8.3±2.3 days. There were 30 cases in the hook plate group, including 24 males and 6 females, aged 47.4±9.7 years (range, 18-67 years), 12 cases on the left and 18 cases on the right. Among the 30 patients, 7 were sports injuries, 11 were falls, 9 were traffic accidents, and 3 were external force injuries. The average time from injury to surgery was 7.9±2.6 days. The surgical time, incision length, intraoperative bleeding, hospital stay, postoperative coracoclavicular separation ratio, and postoperative complications were compared between the two groups. Constant-Murley score and visual analog scale (VAS) were used to assess the shoulder joint function and pain degree of patients.Results:Both groups of patients were followed up, with a follow-up time of 12.3±0.4 months for the reconstruction group and 12.2±0.5 months for the hook plate group. The operation time (105.8±10.0 min), incision length [12.0 (11.0, 13.0) cm] and hospitalization time (6.8±2.1 d) in the reconstruction group were longer than those in the hook plate group [48.3±4.9 min, 10.0 (10.0, 11.0) cm, and 5.5±2.7 d], while the intraoperative blood loss (75.1±3.9 ml) was less than that in the hook plate group (90.3±6.3 ml), the differences were statistically significant ( P<0.05). The VAS [4.0 (3.0, 5.0), 3.0 (3.0, 3.0), 2.0 (1.0, 2.0) points] and Constant-Murley score (65.4±4.5, 84.9±2.5, 90.1±2.5 points) of the reconstruction group at 3 days, 3 months, and 12 months after surgery were better than those of the hook plate group [5.0 (4.0, 5.0), 4.0 (4.0, 4.0), 3.0 (3.0, 4.0) and 56.9±3.5, 79.6±4.0, 86.8±2.4 points], the difference was statistically significant ( P<0.05). At the last follow-up, there was a statistically significant difference in the separation ratio of coracoclavicular distance between the reconstruction group (0.12±0.08) and the hook plate group 0.22±0.15 ( t=3.25, P=0.002). There was no significant difference ( Z=-0.52, P=0.605) in the separation ratio of acromioclavicular distance [0.16 (0.05, 0.25) and 0.16 (0.04, 0.40)]. In the hook plate group, 6 cases had shoulder joint foreign body sensation and 2 cases had acromioclavicular joint redislocation (both Rockwood type III). Because the shoulder joint function did not affect their daily life, neither patient underwent secondary surgery. And no case of acromioclavicular joint redislocation occurred in the reconstruction group. Conclusion:Compared with the clavicular hook plate fixation, anatomic reconstruction of coracoclavicular ligament at the original insertion point in the treatment of acromioclavicular joint dislocation can reduce the pain of the shoulder joint earlier, which has the characteristics of small trauma, good effect, and reduces the steps of internal fixation removal, and has good clinical curative effect.

Effect of modified blood management strategies on blood loss and transfusion rate during outpatient total hip arthroplasty / 中华骨科杂志

Objective:To explore the impact of a modified blood management strategy on blood loss and transfusion rates during outpatient total hip arthroplasty(THA).Methods:The retrospective research was performed in a total of 125 patients (125 hips) who underwent outpatient primary THA from January 2019 to December 2021 at a medical center. According to whether a modified blood management protocol was used or not, all patients were divided into two groups. Group A was used the original perioperative blood management strategies (1 g tranexamic acid, intravenously, 10 minutes before skin incision), and group B was used the modified perioperative blood management strategy (on the basis of the original protocol, 2 g tranexamic acid was sprayed locally in the joint cavity before the incision was closed, 1 g tranexamic acid was injected intravenously 3 hours after surgery, and 1 g tranexamic acid was injected intravenously again on the first day after surgery). There were 52 cases in group A, including 32 males and 20 females, aged 58.5±9.8 years (range, 39-69 years), 13 cases were developmental hip dysplasia (Crowe I°-II°), 24 cases were avascular necrosis of the femoral head, 10 cases were hip osteoarthritis, 3 cases were ankylosing spondylitis involving hip joint, and 2 cases were femoral neck fracture. Among the 73 patients in group B, there were 43 males and 30 females, aged 55.8±10.4 years (range, 42-67 years), including 17 cases of developmental hip dysplasia (Crowe I°-II°), 32 cases of avascular necrosis of the femoral head, 16 cases of hip osteoarthritis, 7 cases of ankylosing spondylitis involving hip joint, and 1 case of femoral neck fracture. Intraoperative blood loss, transfusion, deep vein thrombosis (DVT) events (vascular ultrasound, 2w Postop.), the hemoglobin (Hb) drop, the hematocrit (Hct) drop and other complications were recorded.Results:After using the modified strategy, the intraoperative blood loss was significantly reduced (305.6±38.6 ml vs. 416.2±88.3 ml, t=9.51, P<0.001), and the drop of hemoglobin was significantly decreased (18.1±4.0 g/L vs. 22.3±5.8 g/L, t=4.97, P<0.001). The drop of Hct also decreased significantly (7.3%±0.7% vs. 9.6%±1.3%, t=10.21, P<0.001), and total blood loss decreased significantly (720.6±57.4 ml vs. 919.6±86.3 ml, t=15.49, P<0.001). The hidden blood loss was also significantly lower than that in group A (414.9±71.1 ml vs. 503.5±96.4 ml, t=5.91, P<0.001). One patient (in group A) developed intra-articular hemorrhage 2 h after surgery and was transferred back to the inpatient ward for treatment after transfusion. Three patients (2.4%, 1 in group A and 2 in group B) developed symptomatic anemia and were discharged successfully after conservative treatment. Calf muscular venous thrombosis occurred in 3 patients (2.4%), but no symptomatic deep vein thrombosis occurred in all patients. Conclusion:According to this retrospective research, the use of modified blood management strategy during outpatient THA can further reduce intraoperative blood loss, hidden blood loss and postoperative hematocrit drop, and does not increase the occurrence of perioperative thrombosis-related complications.

A retrospective research of combined anterior and posterior approach in total hip arthroplasty for fused/ankylosed hips / 中华骨科杂志

Objective:To investigate the safety and efficacy of a combined anterior and posterior approach in total hip arthroplasty (THA) for fused/ankylosed hip.Methods:37 patients who underwent THA for fused/ankylosed hip from January 2015 to December 2020 were retrospectively analyzed, including 28 males and 9 females, with an average age of 47.9±12.0 years (range, 26-72 years). Etiologies included 23 cases of ankylosing spondylitis, 9 cases of infectious arthritis of the hip in youth, and 5 cases of traumatic arthritis after acetabulum or femoral neck fracture. All patients underwent THA with combined anterior and posterior approach. These factors include operation time, blood loss, amount of transfused blood, blood transfusion rate, preoperative and postoperative Harris score, postoperative range of motion of the hip, and perioperative complications, etc. were evaluated. Postoperative radiography of the hip was performed to evaluate acetabular abduction angle, anterior inclination angle, the prosthesis fixation, osteolysis and heterotopic ossification around the hip.Results:A total of 37 patients were enrolled. The mean operative time was 147.6±16.8 min (range, 129-190 min); the mean estimated blood loss (EBL) was 850.0±10.8 ml (range, 600-1,200 ml); the blood transfusion rate was 59% (22/37), and the mean blood transfusion was 420±45.0 ml (range, 0-800 ml). All patients were followed up for 4.2±0.9 years (range, 1.2-7.2 years). The average abductor angle of the acetabular was 43.7°±5.4° (range, 31°-55°), and the average inclination angle was 20.9°±6.7° (range, 10°-35°); the preoperative Harris score was 47.1±9.9 (range, 40-55) and the mean Harris score at the last follow-up was 83.4±12.4 (range, 75-90). The preoperative range of motion of the hip in all directions was 0°. Postoperative hip range of motion was good, with a mean hip flexion of 95.5°±12.2° (range, 80°-110°), mean extension of 10.5°±3.4° (range, -10°-25°), and mean abduction of 38.0°±8.2° (range, 10°-50°). Postoperative complications were minor, including 2 case with poor wound healing, 2 cases with paresthesia or tingling sensation in the anterior or anterolateral thigh, which returned to normal within 3 months after surgery, and no deep infection or dislocation occurred. The acetabular cup was in poor position in 2 cases and the femoral stem was varus in 1 case, but the prosthesis was stable and no treatment was needed. All the acetabular cups and femur stems were confirmed with bone ingrowth on the last follow-up radiographs, and one patient had heterotopic ossification (Brooker grade 1). No osteolysis or wear of the acetabular liner was observed.Conclusion:Combined anterior and posterior approach (Gibson posterolateral approach + modified Hardinge approach) in THA for fusion/ankylosed hip can fully expose the operative field and sufficiently release the soft tissue, and the function of hip recovered well postopratively.

The learning curve of MAKO-assisted total knee arthroplasty / 中华骨科杂志

Objective:To explore the learning curve of MAKO-assisted total knee arthroplasty.Methods:From May 2021 to September 2022, 136 patients were conducted MAKO-assisted total knee arthroplasty in the PLA General Hospital, including 37 males and 99 females, 65.53±7.01 years old (range 54-80 years). All cases were patients with unilateral knee osteoarthritis. The operations were performed by three surgeons, respectively. Sixty-one cases were performed by surgeon 1, 47 cases were performed by surgeon 2, and 28 cases were performed by surgeon 3. Record the time of each step during the operation, and measure the limb alignment in X-ray. The statistical difference between the two groups was compared by t test by SPSS. The cumulative sum control chart (CUSUM) learning curve was modeled by curve fitting and R2 was used to testify the goodness. Results:The total operation time of the three surgeons was 114.3±25.1 min, 109.8±10.9 min, and 118.6±15.1 min, respectively. The time of each step in the first 10 cases and the last 10 cases of operator 1-3 was counted. The osteotomy time of surgeons 1, 2 and 3 in the final 10 cases was less than that in the initial 10 cases (surgeon 1: 13.5 ± 3.41 min vs. 8.0±1.58 min, t=4.30, P=0.001; surgeon 2: 13.7±3.02 min vs. 8.0± 2.58 min, t=4.77, P=0.001; surgeon 3: 15.3±3.97 min vs. 11.0±2.38 min, t=2.87, P=0.010), and the difference was statistically significant. The CUSUM of osteotomy was calculated and the curve was fitted. The highest point of the curve of the three surgeons was in the 16th, 18th and 12th patients, respectively, and the time of osteotomy continued to decline after passing the peak. No statistical differences were found in surgery time for the remaining steps. Comparing the lower alignment angles of intraoperative planning and postoperative X-ray films, the overall difference was greater than 1 degree. The difference was 1.41°±1.32° for operator 1, 1.34°±1.22° for operator 2, and 1.04°±0.88° for operator 3. The percentages of fully accurate implant size planning were 85.2%(52/61), 76.7%(36/47), and 85.7%(24/28), respectively. Conclusion:For MAKO-assisted total knee arthroplasty, the operator can decrease the operation time by practice, which is mainly reflected in the shortening of the osteotomy time. The learning curve threshold is around in the 15th case. The increase in the number of surgeries did not bring about changes in the accuracy of lower extremity alignment.

Clinicopathologic features and imaging manifestations of focal nodular hyperplasia-like nodules in cirrhosis liver / 中华肝胆外科杂志

A kind of focal lesions called focal nodular hyperplasia-like nodules (FNH-LNs) was found in liver cirrhosis, especially in alcoholic cirrhosis, which is similar to focal nodular hyperplasia in histology. The imaging features of FNH-LNs show hyperenhancement in arterial phase, hypoenhancement in portal venous phase or delayed phase. FNH-LNs are easily misdiagnosed as hepatocellular carcinoma (HCC). With reviewing the relating articles in China and abroad, this article summarizes the etiology, clinicopathological features and imaging manifestations of FNH-LNs, so as to distinguish FNH-LNs and HCC in cirrhosis and guide selection of treatment.

Research progress on continuous blood purification in the treatment of severe acute pancreatitis / 中国医师杂志

Severe acute pancreatitis (SAP) is a common gastrointestinal disease, often accompanied by systemic inflammatory reactions and organ dysfunction. SAP has an acute onset, severe condition, rapid progression, and poor prognosis. The development of SAP is closely related to the excessive release of inflammatory factors. In the comprehensive treatment of SAP, continuous blood purification (CBP) can clear inflammatory mediators, improve the stability of Internal environment, improve organ function, reduce blood lipids, regulate immunity, and significantly improve the condition of SAP patients. It is an important means of treating SAP. This article reviews the research progress of CBP in the treatment of SAP.

Research progress on the role of pyroptosis in the occurrence and development of peritoneal fibrosis / 中国医师杂志

Peritoneal dialysis is a recognized renal replacement therapy. Long term peritoneal dialysis will lead to changes in the morphology and function of the peritoneum, that is, peritoneal fibrosis, which is a known cause of the loss of peritoneal ultrafiltration capacity. Pyroptosis is a special type of soluble programmed cell death, characterized by cell swelling, rupture, secretion of cell contents and significant proinflammatory effect. The pyroptosis can be divided into typical and atypical pathways, and the inflammatory body of NOD like receptor heat protein domain related protein 3 (NLRP3) is the most important initiator. Current evidence shows that high glucose peritoneal dialysis fluid can induce peritoneal Mesothelium to scorch, and the inflammation and cell damage caused by it can aggravate the progress of peritoneal fibrosis. Different signal pathways have been proved to regulate the occurrence of pyroptosis. The latest research has proved that some potential targeted methods to inhibit pyroptosis can effectively inhibit the inflammation of peritoneal mesothelium and alleviate peritoneal fibrosis. This article mainly discusses the molecular mechanism of pyroptosis and the relationship between pyroptosis and peritoneal fibrosis.

Sivelestat protects acute kidney injury by inhibiting the PI3K/AKT pathway in septic rats / 中华危重病急救医学

Objective:To explore the protective effect of sivelestat (SV) against sepsis-induced acute kidney injury (AKI) and its molecular mechanism.Methods:According to the random number table method, 64 male Wistar rats were divided into sham operation group (Sham group), sepsis due to cecal ligation and puncture group (CLP group), low dose of SV treatment group (SL group, 50 mg/kg SV was injected into the tail vein at 12 hours and 24 hours after CLP), and high dose of SV treatment group (SH group, 100 mg/kg SV was injected into the tail vein at 12 hours and 24 hours after CLP), with 16 rats in each group. 48 hours after CLP, the 48-hour survival of rats were recorded, all rats were sacrificed and samples were harvested. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of kidney injury molecule-1 (KIM-1), interleukins (IL-1β, IL-6), tumor necrosis factor-α (TNF-α) and neutrophil elastase (NE). Hematoxylin-eosin (HE) staining was used to observe histopathological changes and assess renal tubule injury score. Masson staining was used to detect the collagen volume fraction (CVF) of kidney tissue. Western blotting was used to detect the protein expressions of phosphatidylinositol 3-kinase (PI3K), phosphorylation PI3K (p-PI3K), protein kinase B (AKT), phosphorylation AKT (p-AKT), nuclear factor-κB p65 (NF-κB p65) and NE. The protein expressions of p-PI3K, p-AKT, NF-κB p65 were detected by immunohistochemistry.Results:Compared with Sham group, the 48-hour survival rate of CLP group was significantly reduced. Histopathological results showed that large tubular epithelial cells and brush margins were shed, tubular casts were formed, some tubular atrophy, glomerular hyperemia, renal interstitial inflammatory cell infiltration and increased renal tubular injury score. Renal interstitial fibrosis was obvious and CVF increased. The levels of KIM-1, IL-1β, IL-6, TNF-α and NE in serum were significantly elevated in the CLP group. The proteins expression of inflammatory pathway-related p-PI3K/PI3K, p-AKT/AKT, NF-κB p65 and NE were significantly increased in kidney tissue. It suggested that septic rats had renal injury and the PI3K/AKT inflammatory pathway was activated. Compared with CLP group, there was no significant difference in 48-hour survival in SL group and SH group (68.75%, 75.00% vs. 56.25%, both P > 0.05), but kidney injury was significantly relieved. Specifically: renal tubular injury score and CVF significantly decreased [tubular injury score: 2 (1, 2), 1 (1, 1) vs. 2 (2, 3); CVF: (22.36±0.86)%, (18.74±1.05)% vs. (58.38±0.79)%, all P < 0.05]; the serum levels of KIM-1, IL-1β, IL-6, TNF-α and NE also decreased significantly [KIM-1 (ng/L): 145.03±8.88, 117.58±7.02 vs. 158.22±12.00; IL-1β (ng/L): 108.32±9.00, 92.98±8.06 vs. 133.78±8.48; IL-6 (ng/L): 124.33±10.11, 115.42±8.17 vs. 165.19±5.70; TNF-α (ng/L): 321.56±19.29, 289.68±21.57 vs. 424.88±22.76, NE (mol/L): 93.84±9.14, 75.01±10.56 vs. 113.45±6.39, all P < 0.05]; the proteins expression of inflammatory pathway-related p-PI3K/PI3K, p-AKT/AKT, NF-κB p65 and NE were significantly decreased (p-PI3K/PI3K: 0.93±0.06, 0.67±0.04 vs. 1.27±0.08; p-AKT/AKT: 0.78±0.09, 0.47±0.05 vs. 0.96±0.12; NF-κB p65/GAPDH: 1.43±0.13, 0.85±0.08 vs. 1.88±0.17; NE/GAPDH: 1.45±0.06, 0.91±0.04 vs. 1.71±0.08, all P < 0.05), the positive expressions of p-PI3K, p-AKT and NF-κB p65 in kidney tissue were decreased [p-PI3K positive expression area: (13.36±1.84)%, (8.03±1.12)% vs. (21.56±1.20)%; p-AKT positive expression area: (21.57±0.91)%, (15.21±2.76)% vs. (30.81±2.12)%; NF-κB p65 positive expression area: (25.17±1.38)%, (17.07±2.11)% vs. (37.85±2.50)%, all P < 0.05]. Serum inflammatory factor level, and PI3K/AKT pathway related protein, NF-κB p65, NE protein expression level and p-PI3K, p-AKT, NF-κB p65 positive area and other indicators in renal tissue in SH group were further lower than those in SL group (all P < 0.05). Conclusions:SV can ameliorate sepsis-induced AKI. The mechanism may be related to the inhibition of PI3K/AKT pathway, and high dose of SV has better efficacy.

Effect of SIRT1 regulating Nrf2/HO-1 signaling pathway on sepsis-induced acute lung injury / 中华危重病急救医学

Objective:To investigate whether silence information regulator 1 (SIRT1) could regulate nuclear factor E2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) signaling pathway and its role in acute lung injury (ALI) in sepsis rats.Methods:Twenty-four male Sprague-Dawley (SD) rats were randomly divided into sham operation group (Sham group), cecal ligation and puncture (CLP) induced sepsis group (CLP group), sepsis+SIRT1 specific agonist group (CLP+SRT1720 group,10 mg/kg SRT1720 was intraperitoneally injected 2 hours before CLP), sepsis+SIRT1 specific inhibitor group (CLP+EX527 group, 10 mg/kg EX527 was intraperitoneally injected 2 hours before CLP), with 6 rats in each group. The rats were killed 24 hours after modeling and their lung tissues were taken for pathological score (Smith score), superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), tumor necrosis factor-α (TNF-α), interleukins (IL-6, IL-1β), and SIRT1, Nrf2 and HO-1 mRNA and protein expression were detected.Results:The lung tissue of the CLP group mice was severely damaged, the alveolar interval was widened and a large number of inflammatory cells infiltrated, and there was visible pulmonary capillary hyperemia. The Smith score, the levels of TNF-α, IL-6, IL-1β, MDA and 8-OHdG were significantly increased, the levels of SOD, GSH, SIRT1, Nrf2 and HO-1 were significantly decreased in CLP group. After using SIRT1 specific agonist, the lung injury in CLP+SRT1720 group was significantly alleviated compared with that in CLP group, Smith score and lung tissue TNF-α, IL-6, and IL-1β levels were significantly decreased [Smith score: 2.83±0.75 vs. 5.67±0.52, TNF-α (ng/L): 36.78±5.36 vs. 66.99±5.44, IL-6 (ng/L): 23.97±3.76 vs. 45.70±4.16, IL-1β (ng/L): 16.76±1.39 vs. 39.64±2.59, all P < 0.05], SOD activity and GSH content increased [SOD (kU/g): 115.88±3.31 vs. 101.65±1.09, GSH (μmol/g): 8.42±0.81 vs. 5.74±0.46, both P < 0.05], MDA and 8-OHdG contents decreased [MDA (μmol/g): 5.24±0.33 vs. 9.86±0.66, 8-OHdG (ng/L): 405.76±8.54 vs. 647.12±10.64, both P < 0.05], the mRNA and protein expressions of SIRT1, Nrf2 and HO-1 were increased [SIRT1 mRNA (2 -ΔΔCT): 1.49±0.15 vs. 0.64±0.03, Nrf2 mRNA (2 -ΔΔCT): 1.19±0.08 vs. 0.84±0.02, HO-1 mRNA (2 -ΔΔCT): 1.80±0.41 vs. 0.64±0.11, SIRT1 protein (SIRT1/β-actin): 1.03±0.06 vs. 0.52±0.05, Nrf2 protein (Nrf2/β-actin): 1.14±0.10 vs. 0.63±0.05, HO-1 protein (HO-1/β-actin): 1.01±0.11 vs. 0.73±0.03, all P < 0.05]. The lung injury in CLP+EX527 group was more severe than that in CLP group, Smith score and lung tissue TNF-α, IL-6, IL-1β levels were significantly increased [Smith score: 8.00±0.89 vs. 5.67±0.52, TNF-α (ng/L): 87.15±4.23 vs. 66.99±5.44, IL-6 (ng/L): 66.79±2.93 vs. 45.70±4.16, IL-1β (ng/L): 58.99±2.12 vs. 39.64±2.59, all P < 0.05], SOD activity and GSH content decreased [SOD (kU/g): 72.84±3.85 vs. 101.65±1.09, GSH (μmol/g): 3.30±0.67 vs. 5.74±0.46, both P < 0.05], the contents of MDA and 8-OHdG were increased [MDA (μmol/g): 14.14±0.70 vs. 9.86±0.66, 8-OHdG (ng/L): 927.66±11.47 vs. 647.12±10.64, both P < 0.05], the mRNA and protein expressions of SIRT1, Nrf2 and HO-1 were decreased [SIRT1 mRNA (2 -ΔΔCT): 0.40±0.07 vs. 0.64±0.03, Nrf2 mRNA (2 -ΔΔCT): 0.48±0.07 vs. 0.84±0.02, HO-1 mRNA (2 -ΔΔCT): 0.27±0.14 vs. 0.64±0.11, SIRT1 protein (SIRT1/β-actin): 0.20±0.05 vs. 0.52±0.05, Nrf2 protein (Nrf2/β-actin): 0.45±0.01 vs. 0.63±0.05, HO-1 protein (HO-1/β-actin): 0.36±0.08 vs. 0.73±0.03, all P < 0.05]. Conclusions:In the rat model of ALI induced by sepsis, SIRT1 can regulate the activation of Nrf2/HO-1 signaling pathway, upregulate the expression of downstream antioxidant enzymes, reduce oxidative stress injury, and then alleviate the ALI induced by sepsis in rats.

The expression of miR-122 in the liver of rats infected with Clonorchis sinensis and its correlation with inflammatory cytokines / 中华地方病学杂志

Objective:To observe the expression changes of microRNA(miR)-122 in liver tissue of rats infected with Clonorchis sinensis and its correlation with expression level of inflammatory cytokines. Methods:Totally 24 SPF grade Wistar male rats were selected and randomly divided into a control group (100 μl physiological saline gavage), a 4-week infection group (100 Clonorchis sinensis metacercariae gavage), and an 8-week infection group (100 Clonorchis sinensis metacercariae gavage) based on body weight (100-120 g) using a random number table method, with 8 rats in each group. Starting from the third week of infection, rat feces were collected and directly smeared with physiological saline for identification of Wistar rat animal models infected with Clonorchis sinensis. After 4 and 8 weeks of infection, the rats in the 4- and 8-week infection groups were euthanized, while 4 rats in the control group were euthanized, respectively. The heart blood and left lobe liver tissue and serum samples were collected from each group of rats. Using hematoxylin-eosin (HE) staining to observe liver pathological damage under the light microscope, real-time fluorescence quantitative PCR to detect the expression level of miR-122 in liver tissue, and Luminex 200 liquid suspension chip to detect the expression levels of serum inflammatory cytokines [tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6 (IL-6)]. The correlation between miR-122 and inflammatory cytokines was analyzed using Pearson correlation. Results:Under the light microscope, the morphology of hepatocytes in control group was normal, and no inflammatory cell infiltration was observed. There was inflammatory cells such as lymphocyte, eosinophil and other inflammatory cell infiltration around the portal area in the 4-week infection group. The hepatocytes of the 8-week infected rats were arranged in a disordered manner, with varying degrees of swelling, loose and lightly stained cytoplasm, and some hepatocytes showed watery degeneration; additionally, bile duct dilation and thickening of the bile duct wall were observed in the liver tissue. There were statistically significant differences of liver miR-122 (1.00 ± 0.32, 2.57 ± 0.60, 3.63 ± 1.63), serum TNF-α [(0.14 ± 0.06), (0.43 ± 0.09), (0.61 ± 0.10) ng/ml], and IL-6 expression levels [(0.03 ± 0.01), (1.06 ± 0.24), (1.48 ± 0.33) ng/ml] in control group, 4- and 8-week infection groups ( F = 13.36, 69.99, 82.23, P < 0.001). There was no statistically significant difference in expression level of IL-1β between different groups ( F = 2.15, P = 0.141). The Pearson correlation analysis showed that the expression level of miR-122 was positively correlated with the expression levels of inflammatory cytokines TNF-α and IL-6 ( r = 0.67, 0.80, P < 0.001). Conclusion:Clonorchis sinensis infection can increase the expression of miR-122 in the host liver tissue, and the miR-122 is closely related to the expression levels of inflammatory cytokines TNF-α and IL-6.

Rapid authentication of different herbal medicines by heating online extraction electrospray ionization mass spectrometry / 药物分析学报

The rapid and accurate authentication of traditional Chinese medicines(TCMs)has always been a key scientific and technical problem in the field of pharmaceutical analysis.Herein,a novel heating online extraction electrospray ionization mass spectrometry(H-oEESI-MS)was developed for the rapid and direct analysis of extremely complex substances without the requirement for any sample pretreatment or pre-separation steps.The overall molecular profile and fragment structure features of various herbal medicines could be completely captured within 10-15 s,with minimal sample(＜0.5 mg)and solvent consumption(＜20 μL for one sample).Furthermore,a rapid differentiation and authentication strategy for TCMs based on H-oEESI-MS was proposed,including metabolic profile characterization,characteristic marker screening and identification,and multivariate statistical analysis model validation.In an analysis of 52 batches of seven types of Aconitum medicinal materials,20 and 21 key compounds were screened out as the characteristic markers of raw and processed Aconitum herbal medicines,respectively,and the possible structures of all the characteristic markers were comprehensively identified based on Com-pound Discoverer databases.Finally,multivariate statistical analysis showed that all the different types of herbal medicines were well differentiated and identified(R2X＞0.87,R2Y＞0.91,and Q2＞0.72),which further verified the feasibility and reliability of this comprehensive strategy for the rapid authentication of different TCMs based on H-oEESI-MS.In summary,this rapid authentication strategy realized the ultra-high-throughput,low-cost,and standardized detection of various complex TCMs for the first time,thereby demonstrating wide applicability and value for the development of quality standards for TCMs.

Comparison of early clinical outcomes between SuperCap and direct anterior approaches for total hip arthroplasty / 中国骨伤

OBJECTIVE@#To compare the short-term clinical efficacy of SuperCap approach and direct anterior approach in total hip arthroplasty.@*METHODS@#Clinical data of 70 patients who underwent minimally invasive SuperCap approach and DAA THA in January 2016 to June 2017 were retrospective analyzed. These patients were divided into two groups:SuperCap approach group(SuperCap group) and direct anterior approach group(DAA group). There were 15 males and 15 females in SuperCap group, aged from 45 to 71 years old, and the follow-up time ranged from 24 to 30 months. There were 24 males and 16 females in Group B, aged from 51 to 76 years and the follow-up time ranged from 24 to 36 months. Hemoglobin level of the 3rd day after operation, transfusion rate, acetabular abduction angle, anteversion angle and creatine kinase level of the 3rd day after operation, Harris score of 3 months and the last time, VAS score of 1 week and the last time were recorded and compared. Complications were recorded at the final follow-up.@*RESULTS@#All patients were followed up, the follow-up time of SuperCap group ranged from 24 to 30 months, that of DAA group ranged from 24 to 36 months. No significant differences were found in hemoglobin level on the 3rd day after operation, transfusion rate, Harris score or VAS score between two group (P>0.05). There was no significant difference in Harris score between 3 months after operation and the final follow-up in both groups (P>0.05). There were no significant difference in VAS scores of 6 weeks after operation and on the final follow-up neither(P>0.05). The level of creatine kinase in SuperCap group was significant lower than that in DAA group(P<0.05). Until the final follow-up, there was no significant difference in the incidence of complications between the two groups(P>0.05).@*CONCLUSION@#The clinical effect of minimally invasive SuperCap approach after total hip arthroplasty is comparable to that of DAA approach with less soft tissue injury. Patients can recover rapidly after operation and it is a safe and effective surgical approach for surgeons with short learning curve.

Intervention Effect of Gandou Fumu Decoction on Renal Fibrosis in TX Mice Through JAK/STAT Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the protective effect and underlying mechanism of Gandou Fumu decoction （GDFMT） on renal fibrosis in a mouse model of Wilson's disease. MethodSixty adult male toxic milk （TX） mice were randomly divided into a model group， high-， medium-， and low-dose GDFMT groups， and a positive control （penicillamine） group， and another 12 wild-type mice were assigned to the normal group. The high-， medium-， and low-dose GDFMT groups were administered GDFMT at 13.92， 6.96， 3.48 g·kg-1， respectively， and the positive control group received penicillamine at 0.1 g·kg-1， while the model and normal groups were given an equal volume of 0.9% saline solution by gavage once a day for 4 consecutive weeks. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of blood urea nitrogen （BUN）， creatinine （CRE）， type Ⅲ procollagen （PC-Ⅲ）， and type Ⅳ collagen （C-Ⅳ） in the serum. Histological changes in the mouse kidneys were examined by hematoxylin-eosin （HE） and Masson's trichrome staining. Immunofluorescence was used to assess the protein expression of leptin， Janus kinase 2 （JAK2）， and signal transducer and activator of transcription （STAT） in renal cells. Real-time polymerase chain reaction （Real-time PCR） was performed to analyze the mRNA expression levels of leptin， leptin receptor（OB-R）， JAK2， and STAT. Western blot was used to detect the expression of transforming growth factor-β1 （TGF-β1） and monocyte chemoattractant protein-1 （MCP-1）. ResultCompared with the normal group， the model mice exhibited a significant increase in BUN， CRE， PC-Ⅲ， and C-Ⅳ levels （P<0.01）. Compared with the model group， the high- and medium-dose GDFMT groups and the penicillamine groups showed significant decreases in these parameters （P<0.05， P<0.01）， with the high-dose GDFMT group demonstrating the most significant reduction （P<0.01）. The histological examination of renal tissue revealed fibrosis in the model group， while the fibrotic damage was mitigated to varying degrees after drug intervention， with improvement in fibrosis. Immunofluorescence results showed that leptin， JAK2， and STAT3 protein expression levels were significantly upregulated in the renal fibrosis of the model group. After GDFMT intervention， the fluorescence intensity decreased， with the high-dose GDFMT group showing the lowest intensity. Real-time PCR results demonstrated that leptin， OB-R， JAK2， and STAT3 mRNA expression levels were significantly elevated in the model group compared with those in the normal group， while the high- and medium-dose GDFMT groups and the penicillamine group showed significant reductions in their expression levels （P<0.05， P<0.01）. Western blot analysis revealed that TGF-β1 and MCP-1 expression levels were significantly increased in the model group （P<0.01）， and the high- and medium-dose GDFMT groups exhibited significant reductions in their expression levels （P<0.01）. ConclusionGDFMT can alleviate renal fibrosis damage in TX mice， and its mechanism of action may be related to the regulation of leptin and the JAK/STAT signaling pathway.

Da Chengqitang in Treatment of Sepsis： A Review / 中国实验方剂学杂志

Sepsis is a systemic inflammatory syndrome induced by infection and other factors， with the number of patients worldwide exceeding 10 million each year. The pathophysiological mechanism is of this disease complex. Sepsis is often accompanied by endotoxin translocation， gastrointestinal dysfunction， inflammatory cytokine activation， immune dysregulation， coagulation disorder， multiple organ function impairment and many other body imbalances， as well as systemic inflammation， apoptosis， oxidative stress injury and other cell damage mechanisms. This disease causes a heavy medical burden due to the difficult diagnosis and treatment and the poor prognosis. Great progress has been achieved in the diagnosis and treatment of sepsis with traditional Chinese medicine （TCM） and western medicine. The value of western medicine in the diagnosis and treatment of sepsis is limited due to antibiotic resistance， hormone abuse， and high medical costs. Sepsis is classified as a warm disease or typhoid fever in TCM. Da Chengqitang is a classical formula in the Treatise on Typhoid Fever to deal with the excess syndrome of Yang brightness Fu-organ. Modern medicine has proved that Da Chengqitang has the effect of inhibiting oxidative stress， reducing inflammation， and delaying apoptosis by improving gastrointestinal dynamics and regulating intestinal microecology. On the basis of the previous theoretical basis and the rich experience in the medication， medical practitioners have proposed a new therapeutic concept of using Da Chengqitang in combination with western drugs from a holistic view involving both bacteria and toxicity for treating both the symptoms and the root cause， which has a wide range of application. The article reviews the classical research and latest findings of Da Chengqitang in the treatment of sepsis， with a view to clarifying the mechanism and advantages of this formula in the adjuvant treatment of sepsis， exploring its potential efficacy， and providing timely， adequate， and scientific theoretical support for the promotion of this formula in the clinical practice.