Two novel diketopiperazines (1 and 5), along with ten known compounds (2-4, 6-12) demonstrating significant skin inflammation inhibition, were isolated from a marine-derived fungus identified as Aspergillus sp. FAZW0001. The structural elucidation and configurational reassessments of compounds 1-5 were established through comprehensive spectral analyses, with their absolute configurations determined via single crystal X-ray diffraction using Cu Kα radiation, Marfey's method, and comparison between experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1, 2, and 8 exhibited significant anti-inflammatory activities in Propionibacterium acnes (P. acnes)-induced human monocyte cell lines. Compound 8 demonstrated the ability to down-regulate interleukin-1β (IL-1β) expression by inhibiting Toll-like receptor 2 (TLR2) expression and modulating the activation of myeloid differentiation factor 88 (MyD88), mitogen-activated protein kinase (MAPK), and nuclear factor κB (NF-κB) signaling pathways, thus reducing the cellular inflammatory response induced by P. acnes. Additionally, compound 8 showed the capacity to suppress mitochondrial reactive oxygen species (ROS) production and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation, thereby reducing IL-1β maturation and secretion. A three-dimensional quantitative structure-activity relationships (3D-QSAR) model was applied to compounds 5-12 to analyze their anti-inflammatory structure-activity relationships.
Humans ; Aspergillus/chemistry* ; Diketopiperazines/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Interleukin-1beta/genetics* ; Toll-Like Receptor 2/immunology* ; Propionibacterium acnes/drug effects* ; NF-kappa B/genetics* ; Molecular Structure ; Myeloid Differentiation Factor 88/immunology* ; Monocytes/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Cell Line

Objective:To investigate clinical curative effect of multiple composite tissues replantation with microsurgical technique in single hand.Methods:From May 2008 to December 2021, the clinical data of patients who underwent multiple composite tissue replantation in single hand in Chongming Hospital Affiliated to Shanghai University of Medicine & Health Sciences and Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, were retrospectively analyzed. According to the severed site, anatomical level, the injury cause, the severity of injury, the size of severed tissue, and replantation conditions (such as blood vessels for anastomosis), the severed tissue was evaluated and carried out modified classification (type Ⅰ-Ⅳ) before the operation, and the surgical plan was designed. The severed composite tissue was debrided in emergency, the severed bone and muscle tissue were fixed, and the arteries, veins and nerves were anastomosed by microsurgical technique under a high-power microscope. The ratio of arteries to veins was 1∶1-1∶2. If enough arteries and veins could not be found, arteriovenous shunt could be used to form arterial venous flap or venous arterialized flap, or form artery flap by just artery anastomosis, or form venous flap by just vein anastomosis. Then skin tissue was sutured after recanalization. After the operation, the patients received specialized treatment and guided rehabilitation exercise. The wound healing of hand, skin color, skin quality, swelling degree, sensation, pain degree of joint, and activity function were followed up after the operation. At the last follow-up, the patient’s self-evaluation of the treatment effect was divided into three levels: satisfactory, average, and unsatisfactory. One chief physician and one doctor-in-charge were responsible for the comprehensive evaluation of curative effect, according to the assessment standard for upper limb function issued by Chinese Medical Association of Hand Surgery. 80-100 points were excellent, 60-79 points were good, 40-59 points were fair, and <40 points were poor.Results:A total of 94 severed composite tissues in 35 patients, including of 20 male patients and 15 female patients were enrolled. The average age was 36.4 years (range, 16-65 years). Fifty severed tissues in 18 cases were classified into type Ⅰ, 40 severed tissues in 15 cases type Ⅱ, 4 severed tissues in 2 cases type Ⅲ. Among the 35 cases, 1 case of thumb pulp severed tissue was necrotic at the edge (0.3 cm×0.5 cm) due to local contusion, 1 case of index finger lateral severed tissue was necrotic at the edge (0.3 cm×0.8 cm) due to local avulsion injury, and healed after dressing change, and the other replanted composite tissue survived. The patients were followed up for 3 to 65 months (average, 18.5 months). The wounds were completely healed, and the color, elasticity, and quality of the replanted tissue was close to the surrounding normal skin. There was no obvious swelling or atrophy deformity of the hands. According to the patients’ self-assessment, 31 cases were satisfied and 4 cases were average. Comprehensive evaluation of hand function and appearance: excellent in 23 cases, good in 9 cases, fair in 3 cases, excellent and good rate was about 91.4% (32/35).Conclusion:Though multiple composite tissues replantation with microsurgical technique in single hand is difficult, and vascular anastomosis technical requirement is high, once surgery succeeds, the function and appearance can get good recovery, and patient satisfaction is also relatively high.

Objective:To investigate clinical curative effect of multiple composite tissues replantation with microsurgical technique in single hand.Methods:From May 2008 to December 2021, the clinical data of patients who underwent multiple composite tissue replantation in single hand in Chongming Hospital Affiliated to Shanghai University of Medicine & Health Sciences and Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, were retrospectively analyzed. According to the severed site, anatomical level, the injury cause, the severity of injury, the size of severed tissue, and replantation conditions (such as blood vessels for anastomosis), the severed tissue was evaluated and carried out modified classification (type Ⅰ-Ⅳ) before the operation, and the surgical plan was designed. The severed composite tissue was debrided in emergency, the severed bone and muscle tissue were fixed, and the arteries, veins and nerves were anastomosed by microsurgical technique under a high-power microscope. The ratio of arteries to veins was 1∶1-1∶2. If enough arteries and veins could not be found, arteriovenous shunt could be used to form arterial venous flap or venous arterialized flap, or form artery flap by just artery anastomosis, or form venous flap by just vein anastomosis. Then skin tissue was sutured after recanalization. After the operation, the patients received specialized treatment and guided rehabilitation exercise. The wound healing of hand, skin color, skin quality, swelling degree, sensation, pain degree of joint, and activity function were followed up after the operation. At the last follow-up, the patient’s self-evaluation of the treatment effect was divided into three levels: satisfactory, average, and unsatisfactory. One chief physician and one doctor-in-charge were responsible for the comprehensive evaluation of curative effect, according to the assessment standard for upper limb function issued by Chinese Medical Association of Hand Surgery. 80-100 points were excellent, 60-79 points were good, 40-59 points were fair, and <40 points were poor.Results:A total of 94 severed composite tissues in 35 patients, including of 20 male patients and 15 female patients were enrolled. The average age was 36.4 years (range, 16-65 years). Fifty severed tissues in 18 cases were classified into type Ⅰ, 40 severed tissues in 15 cases type Ⅱ, 4 severed tissues in 2 cases type Ⅲ. Among the 35 cases, 1 case of thumb pulp severed tissue was necrotic at the edge (0.3 cm×0.5 cm) due to local contusion, 1 case of index finger lateral severed tissue was necrotic at the edge (0.3 cm×0.8 cm) due to local avulsion injury, and healed after dressing change, and the other replanted composite tissue survived. The patients were followed up for 3 to 65 months (average, 18.5 months). The wounds were completely healed, and the color, elasticity, and quality of the replanted tissue was close to the surrounding normal skin. There was no obvious swelling or atrophy deformity of the hands. According to the patients’ self-assessment, 31 cases were satisfied and 4 cases were average. Comprehensive evaluation of hand function and appearance: excellent in 23 cases, good in 9 cases, fair in 3 cases, excellent and good rate was about 91.4% (32/35).Conclusion:Though multiple composite tissues replantation with microsurgical technique in single hand is difficult, and vascular anastomosis technical requirement is high, once surgery succeeds, the function and appearance can get good recovery, and patient satisfaction is also relatively high.

Objective To construct a prediction model for post-neoadjuvant therapy recurrent laryngeal nerve lymph node(RLN LN)status via clinical and CT image data in esophageal cancer patients pre-neoadjuvant therapy.Methods A retrospective analysis was conducted on 403 patients with locally advanced esophageal cancer who received neoadjuvant therapy and radical resection for esophageal cancer.All patients were divided into a training cohort(n=270)and a validation cohort(n=133)randomly according to a 2:1 ratio.Clinical and imaging features associated with positive RLN LN pathology were selected by univariate analysis.Multivariate logistic stepwise regression model was used to construct the prediction model.The prediction ability of the model was evaluated by receiver operating characteristic(ROC)curve.Results The basic model included neoadjuvant therapy and RLN LN short diameter,with an area under the curve(AUC)of 0.7(training cohort)and 0.65(validation cohort).The final prediction model included neoadjuvant therapy,human albumin,platelet count,largest lymph node enhancement characteristics,whether the largest lymph node was in the recurrent laryngeal region,and RLN LN short diameter,with AUC of 0.83[95％confidence interval(CI)0.768-0.899]and 0.76(95％CI 0.645-0.887)for the training and validation cohorts,respectively.Conclusion The model based on clinical data and imaging features pre-neoadjuvant therapy for esophageal cancer can assist in clinically predicting the post-neoadjuvant therapy RLN LN status.

Objective:To investigate the predictive value of preoperative γ-glutamyl transferase/lymphocyte count ratio (GLR) levels for postoperative tumor recurrence in liver transplant recipients with liver cancer.Methods:The clinical data of 158 recipients who were diagnosed with hepatocellular carcinoma (hereinafter referred to as liver cancer) and received liver transplantation at the No. 900 Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army from January 2008 to October 2022 were retrospectively analyzed. X-tile software, the Kaplan-Meier method, univariate and multivariate Cox regression, and other statistical methods were performed. The predictive value of preoperative GLR levels for postoperative tumor recurrence in liver transplant recipients with liver cancer and the risk factors for tumor recurrence in liver cancer patients post-liver transplantation were analyzed.Results:The X-tile software analysis confirmed that 96.8 was the optimal cutoff value for the preoperative GLR level to predict recurrence. The grouping threshold for survival analysis using the GLR cutoff value was 96.8. The tumor recurrence rates at 1, 3, and 5 years after surgery in the low-level GLR group (90 cases) and the high-level GLR group were 19.3% vs. 44.2%, 31.8% vs. 60.0%, and 34.1% vs. 62.9% (68 cases), respectively, and the differences were statistically significant between the two groups ( P<0.05). The Kaplan-Meier survival curve analysis results showed that the overall postoperative survival rate and recurrence-free survival rate were significantly lower in the high-level GLR group than the low-level GLR group ( P<0.05). The univariate Cox analysis result showed that there were statistically significant differences in preoperative aspartate aminotransferase, alpha fetoprotein, surgery time, maximum diameter of a solitary tumor, presence or absence of microvascular invasion, presence or absence of portal vein tumor thrombus, and preoperative GLR levels between the two groups ( P<0.05). Multivariate Cox analysis results showed that preoperative alpha-fetoprotein ≥400 ng/ml, GLR≥96.8, and the maximum diameter of a solitary tumor ≥5.0 cm were independent risk factors for postoperative tumor recurrence in liver transplant recipients with liver cancer ( P<0.05). Conclusion:GLR levels have a certain predictive value for postoperative tumor recurrence in liver transplant recipients with liver cancer. Furthermore, the postoperative tumor recurrence rate is relatively high when the preoperative GLR level in liver transplant recipients with liver cancer is ≥96.8.

Objectives:To investigate the association between normal-weight central obesity with new-onset cardiovascular disease and all-cause mortality risk. Methods:A prospective cohort study was conducted,selecting a total of 93885 participants from the Kailuan Study who had their first physical examination in 2006-2007.According to waist circumference (central obesity:male waist circumference ≥90 cm,female waist circumference ≥85 cm;no central obesity:male waist circumference<90 cm,female waist circumference<85 cm) and body mass index (BMI,normal weight:18.5 kg/m2≤BMI<24.0 kg/m2;overweight/obesity:BMI ≥24.0 kg/m2),the participants were divided into 4 groups:normal weight no central obesity group (G1 group),normal weight central obesity group (G2 group),overweight/obesity no central obesity group (G3 group) and overweight/central obesity group (G4 group);Using the Kaplan-Meier method,the cumulative incidence of new-onset cardiovascular diseases (including hemorrhagic stroke,ischemic stroke and myocardial infarction) and all-cause mortality in different groups was calculated,and the Log-rank test was used for intergroup comparisons.Furthermore,the associations between the different groups and the risk of new-onset cardiovascular diseases and all-cause mortality were analyzed using the multivariate Cox proportional hazard regression model. Results:After a median follow-up of 14.97 (14.55,15.17) years,the cumulative incidence of new-onset cardiovascular diseases in G1 group,G2 group,G3 group and G4 group was 7.62％,10.84％,8.67％,12.91％ respectively (log-rank P<0.05) and the cumulative incidence of all-cause mortality was 12.83％,19.72％,10.65％,16.33％ respectively (log-rank P<0.01).After adjusting for confounding factors,Cox regression analysis showed that the HR (95％CI) of new-onset cardiovascular diseases in G2 group,G3 group and G4 group were 1.14 (1.04-1.25),1.07 (1.01-1.14),1.27 (1.21-1.34),respectively compared with G1 group (all P<0.05).The HR (95％CI) of all-cause mortality were 1.06 (1.00-1.14),0.90 (0.85-0.95),0.97 (0.93-1.01) compared with G1 group,and P values were 0.07,<0.01,0.15,respectively.The results of sensitivity analysis were consistent with the above major studies after excluding overweight/obesity and cancer participants during follow-up. Conclusions:Normal-weight central obesity increases the risk of new-onset cardiovascular diseases and all-cause mortality.

Objective:To investigate the clinical effect and indications of the three kinds of pedicled perforator flaps in repairing soft tissue defects around the elbow joint.Methods:The clinical data of patients with soft tissue defects around the elbow joint, admitted to the Department of Center for Orthopaedic Repair and Reconstruction of Chongming Hospital Affiliated to Shanghai University of Medicine & Health Sciences (Xinhua Hospital Chongming Branch) from December 2013 to November 2022 were retrospectively analyzed. The distal based medial antebrachial neurocutaneous flap in the middle and distal part of the upper arm, the perforator pedicled propeller flap of inferior cubital artery or the V-Y advancement flap based on the perforator of proximal forearm posterior interosseous artery in the proximal forearm were respectively designed according to the location, appearance, size of the recipient site and the perforating point of the perforating vessel in the donor site to repair soft tissue defects around the elbow joint. The donor site was directly closed or covered by free skin grafting cut from the hidden area of the affected limb. The donor and recipient sites were followed up and observed to evaluate the curative effect from the following three aspects. (1) The self-evaluation of the curative effect was divided into three grades: satisfactory, general and unsatisfactory. (2) Elbow joint function evaluation: according to Mayo’s elbow joint function scoring standard which was divided into four grades: excellent, good, general and poor. (3) Comprehensive evaluation: the evaluation criteria for wound repair around the ankle joint of the lower extremity were used for scoring: 16 to 21 points as excellent, 11 to 15 points as good, 6 to 10 points as general, 0 to 5 points as poor, and the excellent and good ratio was calculated at the same time, that is, the sum of the number of excellent and good cases/the total number of cases×100%.Results:A total of 51 patients were enrolled, including 31 males and 20 females. The age ranged from 16 to 87 years old, with a mean of 56.1 years old. About the defect location, there were 20 cases in the anterior side of the elbow joint, 18 cases in the posterior side of the elbow joint, 8 cases in the medial side of the elbow joint, and 5 cases in the lateral side of the elbow joint. The defect sizes after debridement were from 3.5 cm×2.5 cm to 16.0 cm× 6.0 cm. Among the 51 patients, 21 cases were repaired by the distal based medial antebrachial neurocutaneous flap, 19 cases were repaired by the perforator pedicled propeller flap of inferior cubital artery, and the other 11 cases were repaired by the V-Y advancement flap based on the perforator of proximal forearm posterior interosseous artery. The sizes of the flaps were from 4.5 cm × 3.5 cm to 18.0 cm × 8.0 cm. Forty-six of the 51 patients got primary healing, and the other five had necrosis of different degrees at the distal edge of the flap (≤1.5 cm×1.0 cm), including 2 cases of the distal based medial antebrachial neurocutaneous flap, 2 cases of the perforator pedicled propeller flap of inferior cubital artery and 1 case of the V-Y advancement flap based on the perforator of proximal forearm posterior interosseous artery who were healed after dressing change. The patients were followed up for 3 to 60 months after the operation, with a mean of 12 months, the flaps in the recipient sites survived well, at the same time, the color and elasticity of the flaps were close to normal, and the two-point discrimination was 4-9 mm without bloated appearance. The elbow joint of the affected limb was stable and with good movement. No obvious deformity was observed, and the functional recovery was excellent. The incision of the donor site healed well and the scar was easily accepted. Self-evaluation: 39 patients were satisfied and 12 were general. Elbow joint function evaluation: excellent in 15 cases and good in 36 cases. Comprehensive evaluation: excellent in 17 cases, good in 30 cases, general in 4 cases, that meant the excellent and good ratio reached to 92%(47/51).Conclusion:The three kinds of pedicled perforator flaps have constant perforating vessels, abundant blood supply and simple operation. They can be used to repair soft tissue defects around the elbow joint while good clinical result can be obtained. The distal based medial antebrachial neurocutaneous flap is focused on the anterior and ulnar sides of the elbow joint, the perforator pedicled propeller flap of inferior cubital artery is focused on the elbow fossa, and the V-Y advancement flap based on the perforator of proximal forearm posterior interosseous artery is focused on the posterior and radial sides of the elbow joint.

Objective:To investigate the clinical effect and indications of the three kinds of pedicled perforator flaps in repairing soft tissue defects around the elbow joint.Methods:The clinical data of patients with soft tissue defects around the elbow joint, admitted to the Department of Center for Orthopaedic Repair and Reconstruction of Chongming Hospital Affiliated to Shanghai University of Medicine & Health Sciences (Xinhua Hospital Chongming Branch) from December 2013 to November 2022 were retrospectively analyzed. The distal based medial antebrachial neurocutaneous flap in the middle and distal part of the upper arm, the perforator pedicled propeller flap of inferior cubital artery or the V-Y advancement flap based on the perforator of proximal forearm posterior interosseous artery in the proximal forearm were respectively designed according to the location, appearance, size of the recipient site and the perforating point of the perforating vessel in the donor site to repair soft tissue defects around the elbow joint. The donor site was directly closed or covered by free skin grafting cut from the hidden area of the affected limb. The donor and recipient sites were followed up and observed to evaluate the curative effect from the following three aspects. (1) The self-evaluation of the curative effect was divided into three grades: satisfactory, general and unsatisfactory. (2) Elbow joint function evaluation: according to Mayo’s elbow joint function scoring standard which was divided into four grades: excellent, good, general and poor. (3) Comprehensive evaluation: the evaluation criteria for wound repair around the ankle joint of the lower extremity were used for scoring: 16 to 21 points as excellent, 11 to 15 points as good, 6 to 10 points as general, 0 to 5 points as poor, and the excellent and good ratio was calculated at the same time, that is, the sum of the number of excellent and good cases/the total number of cases×100%.Results:A total of 51 patients were enrolled, including 31 males and 20 females. The age ranged from 16 to 87 years old, with a mean of 56.1 years old. About the defect location, there were 20 cases in the anterior side of the elbow joint, 18 cases in the posterior side of the elbow joint, 8 cases in the medial side of the elbow joint, and 5 cases in the lateral side of the elbow joint. The defect sizes after debridement were from 3.5 cm×2.5 cm to 16.0 cm× 6.0 cm. Among the 51 patients, 21 cases were repaired by the distal based medial antebrachial neurocutaneous flap, 19 cases were repaired by the perforator pedicled propeller flap of inferior cubital artery, and the other 11 cases were repaired by the V-Y advancement flap based on the perforator of proximal forearm posterior interosseous artery. The sizes of the flaps were from 4.5 cm × 3.5 cm to 18.0 cm × 8.0 cm. Forty-six of the 51 patients got primary healing, and the other five had necrosis of different degrees at the distal edge of the flap (≤1.5 cm×1.0 cm), including 2 cases of the distal based medial antebrachial neurocutaneous flap, 2 cases of the perforator pedicled propeller flap of inferior cubital artery and 1 case of the V-Y advancement flap based on the perforator of proximal forearm posterior interosseous artery who were healed after dressing change. The patients were followed up for 3 to 60 months after the operation, with a mean of 12 months, the flaps in the recipient sites survived well, at the same time, the color and elasticity of the flaps were close to normal, and the two-point discrimination was 4-9 mm without bloated appearance. The elbow joint of the affected limb was stable and with good movement. No obvious deformity was observed, and the functional recovery was excellent. The incision of the donor site healed well and the scar was easily accepted. Self-evaluation: 39 patients were satisfied and 12 were general. Elbow joint function evaluation: excellent in 15 cases and good in 36 cases. Comprehensive evaluation: excellent in 17 cases, good in 30 cases, general in 4 cases, that meant the excellent and good ratio reached to 92%(47/51).Conclusion:The three kinds of pedicled perforator flaps have constant perforating vessels, abundant blood supply and simple operation. They can be used to repair soft tissue defects around the elbow joint while good clinical result can be obtained. The distal based medial antebrachial neurocutaneous flap is focused on the anterior and ulnar sides of the elbow joint, the perforator pedicled propeller flap of inferior cubital artery is focused on the elbow fossa, and the V-Y advancement flap based on the perforator of proximal forearm posterior interosseous artery is focused on the posterior and radial sides of the elbow joint.

Objective:To investigate the clinical experience of different types of femoral perforator flaps in the reconstruction of oral and maxillofacial head and neck defects.Methods:From January 2018 to January 2021, 573 patients with oral and maxillofacial head and neck defects reconstructed by femoral perforator flap were collected in the Department of Maxillofacial Oncology, the Third Affiliated Hospital of Air Force Military Medical University (age range of 21-76 years, with a male to female ratio of 1.23∶1). According to the type of perforator flap, the patients were divided into ALT group, AMT group, TFL flap group and free muscle flap group. The incidence of postoperative complications, wound healing time and drainage volume in femoral area were compared among the 4 groups.Results:The ALT flap was used in 527 cases: 22 flaps had vascular crisis, 14 flaps had infection, 8 flaps had necrosis, 519 flaps survived; the mean healing time of the wound was (14.50±3.19) days, and the mean drainage volume was (49.9±21.3) ml. 28 cases were repaired with AMT flap: 2 flaps had vascular crisis and 1 had infection. All the flaps survived; the mean healing time of the wound was (14.18±2.75) days, and the mean drainage volume was (50.3±23.0) ml. 11 cases were repaired by TFL flap: 1 flap had vascular crisis and 1 had infection. All the flaps survived. The mean healing time of the wound was (14.09±2.66) days, and the mean drainage volume was (54.1±25.0) ml. 7 cases were repaired by free muscle flap survived without vascular crisis, infection and other postoperative complications; the mean healing time of the wound was 14.14±1.86, and the mean postoperative drainage volume was (49.9±21.1) ml. There was no significant difference in complication rate (flap necrosis, vascular crisis, infection, etc.) and repair effect among 573 patients with different flap types. The postoperative follow-up was conducted for 6-24 months, and the donor area was smooth and good in appearance, without obvious scar or functional influence. The repair effect of the affected area was satisfactory.Conclusions:Although there is a certain proportion of perforator vessel variation in the femoral perforator flap, the flap can be designed freely according to different types of variation. The thigh perforator flap has an essential application value in the repair of oral and maxillofacial head and neck defects.

High-quality development is the primary task of building a socialist modern country in an all-round way. Organ donation and transplantation in China are evolving from high-speed growth to high-quality development, which put forward new requirements for the safe, stable and healthy operation of Organ Procurement Organization (OPO). Safety is the foundation and prerequisite for achieving the goal of high-quality development. As an independent and comprehensive department, internal audit should create new achievements in the new era. The department should include OPO and organ donation into the scope of internal audit, shift the emphasis upon the overall development of organ donation. Besides, it should fully consider the actual situation in different places, conduct all-round, objective and fair evaluation, provide evaluation and consulting services for OPO to properly implement organ donation, and give full play to the supervision and prevention role of internal audit.