Objective: To establish a method for determining the molecular weight and molecular weight distribution of Poly(Lactide-co-Glycolide Acid) (PLGA) using Size Exclusion Chromatography-Refractive Index-Multiangle Laser Light Scattering (SEC-RI-MALLS) and Size Exclusion Chromatography-Refractive Index (SEC-RID), and to compare the results obtained from these two methods.
Methods: For SEC-RI-MALLS, tetrahydrofuran was used as the mobile phase, Shodex GPC KF-803L was employed as the chromatographic column with a flow rate of 1 mL·min^-1, column temperature at 30 ℃, and an injection volume of 100 μL. For SEC-RID, tetrahydrofuran was also used as the mobile phase, Agilent PLgel 5 μm MIXD-D was used as the chromatographic column with a flow rate of 1 mL·min^-1, column temperature at 30 ℃, differential detector temperature at 35 ℃, and an injection volume of 20 μL. The molecular weight and molecular weight distribution were calculated using Agilent’s GPC software. The newly established methods were validated methodologically, and the molecular weight and molecular weight distribution of 13 batches of samples were determined.
Results: The precision, accuracy, stability, and repeatability tests for SEC-RI-MALLS showed RSD values of 1.35%, 1.58%, 1.53%, and 1.26%, respectively. The SEC-RID method exhibited good linearity (r=0.999 9), with RSD values for precision, accuracy, stability, and repeatability tests (n=6) of 2.05%, 1.62%, 1.30%, and 2.97%, respectively. The results obtained from SEC-RI-MALLS were lower than those from SEC-RID, and the molecular weight distribution coefficient was smaller, but the results from the paired T-test performed with the value measured by SEC-RID method and the value measured by SEC-RI-MALLS method multiplied a conversion coefficient of 1.5 showed no significant difference between the two methods.
Conclusion: Both methods are stable and reliable, and can be used for the determination of PLGA molecular weight and molecular weight distribution based on the specific situations.

BACKGROUND:Exosomes play a role in all stages of wound repair,and there is currently a large body of research on exosomes in skin wound repair,which has been shown to have great potential for clinical applications. OBJECTIVE:To summarize and discuss the main mechanisms and clinical applications of exosomes in the treatment of skin wounds,in order to promote the clinical translation of exosomes. METHODS:PubMed,clinicaltrials.gov,China National Knowledge Infrastructure,Food and Drug Administration database,and Chinese Clinical Trial Register were searched from inception to March 2023.The English search terms were"exosomes,wound healing,stem cells,chronic wound,immunoregulation,inflammation,skin,therapeutic use,isolation,characterization,infections".The Chinese search terms were"exosomes,wound healing,stem cells,immunomodulation,clinical applications".A total of 79 articles were included for the summary. RESULTS AND CONCLUSION:(1)Exosomes can improve and accelerate wound healing through inflammation regulation,immune protection,angiogenesis,cell proliferation and migration,and collagen remodeling.(2)Exosomes derived from stem cells have mature preparation techniques and related mechanism research,which is currently the mainstream research direction.Non-stem cell-derived exosomes have the advantages of convenience,economy,and easy production,and can be used as a supplement for clinical applications.(3)The clinical application of exosomes is still in its infancy,but has great potential for application.Various exosome modification techniques have laid the foundation for the future development of clinically personalized services and require further research.(4)The clinical translation of exosomes faces many challenges,such as low yield,high heterogeneity,lack of unified standards for isolation,purification,and quality control,and difficulties in storage.

Objectives:To compare the efficacy of the combination of excimer laser coronary angioplasty(ELCA)and drug-coated balloon(DCB)for in-stent restenosis(ISR)and to evaluate the impact of neointimal tissue characteristics on treatment outcomes. Methods:A total of 96 ISR lesions from 86 patients who underwent optical coherence tomography(OCT)evaluation and DCB with or without ELCA treatment at The First Medical Center of Chinese PLA General Hospital from January 2019 to May 2023 were retrospectively analyzed.ISR lesions were divided into ELCA+DCB group(n=30)and DCB group(n=66).Additionally,ISR lesions were classified as homogeneous and non-heterogeneous patterns based on the OCT characteristics of the neointimal tissue,and the impact on acute lumen gains was compared between different ISR patterns.Acute lumen gain(ΔMLA)was defined as the changes in minimum lumen area before and after the intervention. Results:The ELCA+DCB group had a significantly greater ΔMLA than the DCB group([3.2±0.8]mm2 vs.[2.6±1.4]mm2,P=0.015).Among the ISR with a homogeneous pattern,the ΔMLA of the ELCA+DCB group was significantly greater than that of the DCB group([3.0±0.9]mm2 vs.[2.2±1.1]mm2,P=0.030).There was no significant difference in ΔMLA between the two ISR groups with the non-homogeneous pattern([3.4±0.7]mm2 vs.[3.2±1.5]mm2,P=0.533).There was no death,the rate of target lesion revascularization was similar between the patients with lesions receiving DCB treatment and patients receiving ELCA +DCB treatment(7.4%vs.4.2%,P＞0.05). Conclusions:The combination of ELCA and DCB is an effective strategy for treating ISR,which can achieve greater acute lumen gain compared to DCB treatment alone,especially for the treatment of homogenous ISR pattern characterized by OCT.

OBJECTIVE To establish HPLC methods with different separation principles to analyze the relevant impurities in the APIs of bivalirudin from seven enterprises, to provide a basis for the comprehensive control of related substances of bivalirudin. METHODS Reversed-phase high performance liquid chromatography(RP-HPLC) was used to separate and analyze 11 kinds of impurities. Hydrophilic chromatography(HILIC)-HPLC was used to control four process impurities. Polymers were determined by size exclusion chromatography(SEC)-HPLC. RESULTS The established RP-HPLC could effectively separate the principal component and 11 impurities, the correction factors of 11 impurities were between 0.8−1.2, the detection concentration of bivalirudin was 0.1 μg·mL−1, and the detection limit was 0.004%. The established HILIC-HPLC could effectively separate the principal components and four process impurities, and the detection concentration of bivalirudin was 0.3 μg·mL−1, and the detection limit was 0.01%. Under SEC-HPLC conditions, the polymer and bivalirudin peaked sequentially, the resolution of the two was 2.9, the detection concentration of bivalirudin was 6 ng·mL−1, and the detection limit was 0.000 6%. Fifteen kinds of known impurities and polymers in 15 batches of samples from 7 enterprises were calculated by the self-control method of principal components, and the impurity contents from different enterprises had a certain correlation with their production processes. CONCLUSION The three different principles of the method have good specificity, high sensitivity, good durability, and reliable results, and can be used for quality control of substances related to bivalirudin.

Objective:To explore the clinical and genetic characteristics of a fetus diagnosed with Congenital myasthenic syndrome type 16 (CMS16).Methods:A couple who had visited Tianjin Medical University General Hospital in February 2018 due to "adverse outcome of two pregnancies" was selected as the study subject. Clinical data was gathered. Peripheral blood and amniotic fluid samples were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. Low-depth whole-genome sequencing was carried out to detect copy number variation (CNV) in the fetus.Results:The couple′s first pregnancy had resulted in a miscarriage at 27 + 5 weeks, when ultrasound had revealed pleural effusion and polyhydramnios in the fetus. Their second pregnancy was terminated at 30 + 5 weeks due to fetal hand malformations, polyhydramnios and pleural fluid. Both couple had denied family history of genetic conditions. For their third pregnancy, no CNV abnormality was detected, whilst a compound heterozygous variants, including a maternally derived c. 3172C>T (p.R1058W) and paternal c. 1431delG (p.K477fs*89) in the SCN4A gene were detected. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 3172C>T (p.R1058W) was predicted as a likely pathogenic variant (PM1+ PM2_supporting+ PP3+ PP4), whilst the c. 1431delG (p.K477fs*89) was predicted as a pathogenic variant (PVS1+ PM2_supporting+ PP4). Conclusion:The c. 3172C>T (p.R1058W) and c. 1431delG (p.K477fs*89) compound heterozygous variants of the SCN4A gene probably underlay the CMS16 in the third fetus.

Objectives:To identify the risk factors associated with delirium in intensive care unit (ICU) hospitalization of sepsis patients and construct a clinical prediction model to to provide a reference for the prevention and control of delirium in sepsis patients.Methods:Data were collected of sepsis patients admitted in the Intensive Care Unit in the Second Affiliated Hospital of Soochow University from September 2020 to August 2022.The patients were divided into delirium group and non-delirium group according to whether delirium occurred or not. Comparing of the differences in general and clinical data between the two groups, the independent risk factors for delirium were screened by backward stepwise regression method, and the delirium risk prediction model was constructed and evaluated. An independent risk factor analysis for delirium was conducted using a backward stepwise regression approach to identify significant predictors. A delirium risk prediction model was constructed based on the identified risk factors, followed by a comprehensive evaluation of the model's performance.Results:A total of 381 sepsis patients were included in the study, 114 patients (29.9%) developed delirium during the ICU hospitalization. Univariate analysis revealed statistically significant differences ( P< 0.05) between the delirium and non-delirium groups for several factors including age ≥ 65 years, blood transfusion, use of midazolam, use of adrenaline, APACHEⅡ score>15, SOFA score>4, metabolic acidosis, urea>7.1 mmol/L, coagulation disorders, lactate levels, and platelet count. Multivariate analysis identified age ≥ 65 years, use of midazolam, APACHEⅡ score>15, metabolic acidosis, urea>7.1 mmol/L, and coagulation disorders as independent risk factors for delirium in sepsis patients during ICU hospitalization.The predictive model was evaluated with an area under the ROC curve of 0.813, a non-significant Hosmer-Lemeshow goodness-of-fit test ( P=0.957>0.05), and a Brier score of 0.149 (<0.25), indicating good predictive performance and calibration. Clinical decision and impact curves demonstrated the model's favorable clinical applicability. Conclusions:The occurrence of delirium in ICU sepsis patients closely associate with six factors: age ≥ 65 years, use of midazolam, APACHEⅡ score>15, metabolic acidosis, urea>7.1 mmol/L, and coagulation disorders. This sepsis delirium prediction model has good clinical predictive ability and clinical applicability.

Objective:To investigate the effectiveness, safety, and advantages of modified radical neck dissection by gasless unilateral axillary approach (GUA-MRND) in the surgical management of selected patients with papillary thyroid cancer.Methods:We retrospectively analyzed patients with papillary thyroid cancer who underwent GUA-MRND (endoscopic group, n=16) versus unilateral open modified radical neck dissection (MRND) (open group, n=32) during the period from Jan. 2019 to Jun. 2021, including the differences in surgical efficiency, complication rate, and incisional satisfaction.Results:Compared MRND with GUA-MRND, the patients were younger ( P<0.05) , operative time and postoperative drainage anterior ( P<0.01) were slightly inferior in the latter, but it had obvious advantages in cervical swallowing discomfort and incision satisfaction evaluation ( P<0.05) . There was no significant difference in the incidence of temporary recurrent laryngeal nerve injury, intraoperative and postoperative bleeding, hematoma, infection, lymphatic or chylous leakage and supraclavicular numbness after surgery ( P>0.05) . The number of dissected lymph nodes in area II in the GUA-MRND was lower ( P<0.05) , but it was significantly higher ( P<0.01) in area III. And the average regional cleaning efficiency in the GUA-MRND was level Ⅲ (35.5%) , level Ⅵ (28.59%) , level Ⅳ (23.21%) , level Ⅱ (7.18%) and level Ⅴ (7.12%) , suggested that GUA-MRND had higher efficacy for level III, level Ⅵ and Level IV. Conclusion:GUA-MRND is safe, effective, and has high cosmetic satisfaction in the treatment of selected patients with lateral cervical lymph node metastases from papillary thyroid cancer.

Objective:To explore the application value of graded surgical strategy and balanced load concept for thoracolumbar osteoporotic compression fractures (OVCFs) with kyphosis.Methods:All of 56 patients of thoracolumbar OVCFs with kyphosis were studied, including 11 males and 45 females, with an average of 75.6±9.3 years old. All patients had back pain, and 32 patients had nerve compression, including 5 patients with aggravation of vertebral collapse after conservative treatment, and 1 patient with cement loosening after percutaneous kyphoplasty (PKP) in another hospital. A graded surgical strategy was developed according to the concept of balanced load, including whether there existed nerve compression, kyphosis, sagittal index (SI), vertebral collapse, load capacity of anterior and middle columns, and fracture reducibility. All patients were treated with anti osteoporosis therapy. 24 patients without nerve compression underwent posture reduction and PKP; 32 patients with nerve compression underwent open surgery: 5 patients with arcuate ky-phosis and SI≤15° underwent Ponte osteotomy; 15 patients with angular kyphosis or SI>15° underwent posterior pedicle subtraction osteotomy (PSO) or/and modified PSO including intervertebral space; 11 patients with SI>15° and severe vertebral collapse (the height of anterior and middle vertebral bodies <1/3 of the average height of adjacent vertebral bodies) or cement loosen after PKP underwent vertebrectomy and reconstruction, of which 4 patients underwent posterior vertebral column resection (PVCR), and 8 patients underwent combined surgery including anterior subtotal vertebrectomy with support and posterior pedicle fixation. The clinical efficacy was evaluated by pain visual analog score (VAS) and Oswestry dysfunction index (ODI).Results:All patients were followed up for 12-60 months, with an average of 24.2 months. For the 24 patients with PKP, the symptoms improved significantly, and 1 case had adjacent vertebral fracture that was improved after PKP again. For the 32 patients with open surgery, the intraoperative blood loss was 400-1 800 ml, with an average of 960 ml (PVCR > PSO and combined surgery > Ponte); the operation time was 2-7 h, with an average of 4.3±1.9 h. The neurological symptoms improved after the operation. During follow-up, the artificial vertebral body and titanium mesh collapsed in 3 cases, but did not continue to deteriorate, no vertebral fracture, internal fixation displacement or loosening failure occurred on X-ray films. At the last follow-up, the VAS score and ODI score of 56 patients decreased from 7.0±2.6 and 60.4±16.2 pre-operation to 1.4±1.1 and 9.5+5.8 respectively, and local kyphosis angle improved from 18.1±4.3 pre-operation to 5.6±4.3. According to the overall satisfaction of patients, the effect was fair in 12 cases, good in 30 cases, excellent in 14 cases, and the excellent and good rate was 78.6%.Conclusion:The graded surgical strategy for thoracolumbar OVCFs with kyphosis based on the concept of balanced load can restore the balanced load of the anterior and middle columns of the spine, reduce the fixation and fusion segments, and reduce the risk of internal fixation displacement and loosening failure.

Objective:To summarize the clinical experience of using V-shaped incision to excise scalp subcutaneous tumors.Methods:A retrospective analysis of the clinical data of patients with subcutaneous benign tumors admitted to the Department of Burns and Plastic Surgery of the Northern Theater General Hospital from August 2020 to December 2021 was conducted. The tumors were all above 3 cm in diameter and closely adhered to surrounding tissues, and all were removed using a V-shaped incision. During the operation, the scalp was incised along the design line, the V-shaped skin flap was lifted to affiliate the tumor removed. The incision was closed directly from the tip of "V" until the moderate tension attained. The scalp flap was spread smoothly on the wound surface, and the excess scalp tissue was removed to form a Y-shaped suture. The flap survival, complications, incision scar, hair growth around the incision and tumor recurrence were observed and followed up after operation.Results:A total of 20 cases were included, including 12 males and 8 females, with an average medical history of (3.6±1.9) years and a tumor diameter of (4.1±1.1) cm. There were 8 sebaceous cysts, 5 lipomas, and 7 epidermoid cysts. After operation, 18 flaps survived well, and 2 cases had epidermal necrosis at the tip of the flap, which healed after dressing change. During the follow-up period of 6-12 months, 3 patients experienced local scalp numbness, which improved within 3-6 months. In 20 cases, the scalp was flat, the incision scar was not hyperplastic, the scar was short visually, the surrounding hair grew normally, and no tumor recurrence happened.Conclusion:V-shaped incision is relatively easy to expose the tumor and can accurately remove excess skin. After operation, the scalp has a good flat appearance, so it is an ideal choice for large scalp subcutaneous tumors with close adhesion to the surrounding tissue.

Objective:To summarize the clinical experience of using V-shaped incision to excise scalp subcutaneous tumors.Methods:A retrospective analysis of the clinical data of patients with subcutaneous benign tumors admitted to the Department of Burns and Plastic Surgery of the Northern Theater General Hospital from August 2020 to December 2021 was conducted. The tumors were all above 3 cm in diameter and closely adhered to surrounding tissues, and all were removed using a V-shaped incision. During the operation, the scalp was incised along the design line, the V-shaped skin flap was lifted to affiliate the tumor removed. The incision was closed directly from the tip of "V" until the moderate tension attained. The scalp flap was spread smoothly on the wound surface, and the excess scalp tissue was removed to form a Y-shaped suture. The flap survival, complications, incision scar, hair growth around the incision and tumor recurrence were observed and followed up after operation.Results:A total of 20 cases were included, including 12 males and 8 females, with an average medical history of (3.6±1.9) years and a tumor diameter of (4.1±1.1) cm. There were 8 sebaceous cysts, 5 lipomas, and 7 epidermoid cysts. After operation, 18 flaps survived well, and 2 cases had epidermal necrosis at the tip of the flap, which healed after dressing change. During the follow-up period of 6-12 months, 3 patients experienced local scalp numbness, which improved within 3-6 months. In 20 cases, the scalp was flat, the incision scar was not hyperplastic, the scar was short visually, the surrounding hair grew normally, and no tumor recurrence happened.Conclusion:V-shaped incision is relatively easy to expose the tumor and can accurately remove excess skin. After operation, the scalp has a good flat appearance, so it is an ideal choice for large scalp subcutaneous tumors with close adhesion to the surrounding tissue.