Objective: To analyze the immunological characteristics and antibody changes of patients infected with the Omicron BA.1 and evaluate the possibility of secondary infection. Methods: A total of 104 patients infected with Omicron BA.1 in the Jinnan District of Tianjin from January 8 to February 2, 2022, were included in the study. The control group and case group were matched 1∶1 based on age, sex and vaccination status. Serum was collected from the case group and control group at 3, 6 and 9 months after infection. The serum levels of interleukin4 (IL-4), IL-5 and interferon-gamma (IFN-γ), as well as the positive rates of IgG, IgG1 and IgG2, were detected by ELISA. Results: The highest concentration of IFN-γ in the case group at 6 months after infection was 145.4 pg/ml, followed by a decrease in concentration. The concentrations of IL-4 and IL-5 began to decrease at 6 months after infection (all P<0.001). There was no significant difference in the IgG2 positive rate between the case group and the control group at 6 months after BA.1 infection. However, at 9 months, there was a significant decrease compared to the control group (P=0.003). The ratio of IFN-γ/IL4 at 3 months after infection in the case group was lower than that in the control group (P<0.001). There was no significant difference in the ratio between the case group and the control group at 9 months after infection. Conclusion: The cellular immune function has been impaired at 3 months after infection with BA.1, and the specific cellular immune and humoral immune functions decrease significantly after 6 months, and the risk of secondary infection increases.
Adult ; Humans ; Immunity, Humoral ; Coinfection ; Interleukin-4 ; Interleukin-5 ; Immunoglobulin G ; Interferon-gamma

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective: To analyze the immunological characteristics and antibody changes of patients infected with the Omicron BA.1 and evaluate the possibility of secondary infection. Methods: A total of 104 patients infected with Omicron BA.1 in the Jinnan District of Tianjin from January 8 to February 2, 2022, were included in the study. The control group and case group were matched 1∶1 based on age, sex and vaccination status. Serum was collected from the case group and control group at 3, 6 and 9 months after infection. The serum levels of interleukin4 (IL-4), IL-5 and interferon-gamma (IFN-γ), as well as the positive rates of IgG, IgG1 and IgG2, were detected by ELISA. Results: The highest concentration of IFN-γ in the case group at 6 months after infection was 145.4 pg/ml, followed by a decrease in concentration. The concentrations of IL-4 and IL-5 began to decrease at 6 months after infection (all P<0.001). There was no significant difference in the IgG2 positive rate between the case group and the control group at 6 months after BA.1 infection. However, at 9 months, there was a significant decrease compared to the control group (P=0.003). The ratio of IFN-γ/IL4 at 3 months after infection in the case group was lower than that in the control group (P<0.001). There was no significant difference in the ratio between the case group and the control group at 9 months after infection. Conclusion: The cellular immune function has been impaired at 3 months after infection with BA.1, and the specific cellular immune and humoral immune functions decrease significantly after 6 months, and the risk of secondary infection increases.
Adult ; Humans ; Immunity, Humoral ; Coinfection ; Interleukin-4 ; Interleukin-5 ; Immunoglobulin G ; Interferon-gamma

Erythromycin is a macrolide antibiotic produced by Saccharopolyspora erythraea. Its yield is greatly affected by the fermentation conditions and the bioreactor configurations. In this study, a novel scale-up method for erythromycin fermentation was developed based on computational fluid dynamics (CFD) and time constant analysis. Firstly, the dissolved oxygen (DO) was determined as a key parameter according to the physiological properties of S. erythraea cultivated in a 50 L bioreactor. It was found that the time constant of oxygen supply (t_mt) in a 500 m³ bioreactor should be less than 6.25 s in order to satisfy the organism's oxygen uptake rate (OUR). Subsequently, a 500 m³ bioreactor was designed using the time constant method combined with empirical correlations. The impeller combination with one BDT8 impeller at bottom and two MSX4 impellers at upper part was determined, and then validated by numerical simulation. The results indicated that the t_mt of the bioreactor (< 6.25 s) and the fluid properties, including gas hold-up, shear stress and fluid vector, met the requirements of erythromycin fermentation. Finally, the industrial production of erythromycin in the 500 m³ showed the design method was applicable in large scale fermentation.
Erythromycin ; Saccharopolyspora/genetics* ; Bioreactors ; Fermentation ; Anti-Bacterial Agents

Objective:To investigate the efficacy of continuous intravenous injection of hyaluronidase (HAase) combined with urokinase (UK) in the treatment of ischemia of hyaluronic acid (HA) arterial embolized skin flap.Methods:(1)Establish an animal model of superficial abdominal artery embolization with HA: 24 SD rats were used to make a square island flap (2 cm×2 cm, the width of the pedicle is 2 mm) on the left and right sides of the abdominal white line with superficial epigastric artery as feeding artery. The left and right flaps of rats were used as experimental group and control group. After the preparation of the experimental skin flap, HA 10 μl was injected into the superficial abdominal artery, while the self-control flap was only made and the vessels were peeled off without embolization.(2)The rats were randomly divided into A, B, C and D groups by drawing lots with 6 rats in each group, After the successful establishment of embolic animal model of 45 min, HAase(2 000 IU/kg)+ UK(50 000 IU/kg), HAase(2 000 IU/kg), UK(50 000 IU/kg) and normal saline were continuously infused through caudal vein with microinjection pump. The volume of solution in each group was 6 ml in 12 minutes. The general condition of rats and the skin color, edema, congestion and skin necrosis in the operation area of rats were observed, which were photographed and compared immediately, and at 3 days, 5 days and 7 days after embolization. The images were analyzed by Photoshop software, and the percentage of survival area of the flap after operation 7 days, was measured by pixel method. The percentage of survival area was compared by single factor analysis of variance (ANOVA) and head-to-head comparison by LSD- t test. Results:Immediately after operation, all the flaps in the four groups were pale and there was no obvious swelling. All the flaps showed different degrees of swelling within 3 days after operation, and the swelling basically disappeared within 3-5 days after operation, and gradually changed from dark red ecchymosis to dark purple or black. Seven days after operation, the necrotic area flap gradually hardened and its boundary was obvious. The skin flaps of the 4 groups showed different degrees of necrosis. The postoperative reaction of the flap was the slightest in group A, the performance of group B and C was similar, which were both between group A and group D, and there was the heaviest postoperative reaction in group D. At 7 days after operation, the percentage of survival area of flaps in groups A, B, C and D was 90.30%±5.95%, 52.63%±6.90%, 51.14%±5.95% and 7.70%±2.18%, respectively. The percentage of survival area of skin flap in group A was significantly higher than that in groups B, C and D (analysis of ANOVA: P<0.01; LSD- t test: P<0.01). Conclusions:Continuous intravenous infusion of HAase combined with UK can effectively alleviate the flap ischemia caused by HA artery embolism, increase tissue perfusion and increase the survival area of the flap.

Objective:To investigate the efficacy of continuous intravenous injection of hyaluronidase (HAase) combined with urokinase (UK) in the treatment of ischemia of hyaluronic acid (HA) arterial embolized skin flap.Methods:(1)Establish an animal model of superficial abdominal artery embolization with HA: 24 SD rats were used to make a square island flap (2 cm×2 cm, the width of the pedicle is 2 mm) on the left and right sides of the abdominal white line with superficial epigastric artery as feeding artery. The left and right flaps of rats were used as experimental group and control group. After the preparation of the experimental skin flap, HA 10 μl was injected into the superficial abdominal artery, while the self-control flap was only made and the vessels were peeled off without embolization.(2)The rats were randomly divided into A, B, C and D groups by drawing lots with 6 rats in each group, After the successful establishment of embolic animal model of 45 min, HAase(2 000 IU/kg)+ UK(50 000 IU/kg), HAase(2 000 IU/kg), UK(50 000 IU/kg) and normal saline were continuously infused through caudal vein with microinjection pump. The volume of solution in each group was 6 ml in 12 minutes. The general condition of rats and the skin color, edema, congestion and skin necrosis in the operation area of rats were observed, which were photographed and compared immediately, and at 3 days, 5 days and 7 days after embolization. The images were analyzed by Photoshop software, and the percentage of survival area of the flap after operation 7 days, was measured by pixel method. The percentage of survival area was compared by single factor analysis of variance (ANOVA) and head-to-head comparison by LSD- t test. Results:Immediately after operation, all the flaps in the four groups were pale and there was no obvious swelling. All the flaps showed different degrees of swelling within 3 days after operation, and the swelling basically disappeared within 3-5 days after operation, and gradually changed from dark red ecchymosis to dark purple or black. Seven days after operation, the necrotic area flap gradually hardened and its boundary was obvious. The skin flaps of the 4 groups showed different degrees of necrosis. The postoperative reaction of the flap was the slightest in group A, the performance of group B and C was similar, which were both between group A and group D, and there was the heaviest postoperative reaction in group D. At 7 days after operation, the percentage of survival area of flaps in groups A, B, C and D was 90.30%±5.95%, 52.63%±6.90%, 51.14%±5.95% and 7.70%±2.18%, respectively. The percentage of survival area of skin flap in group A was significantly higher than that in groups B, C and D (analysis of ANOVA: P<0.01; LSD- t test: P<0.01). Conclusions:Continuous intravenous infusion of HAase combined with UK can effectively alleviate the flap ischemia caused by HA artery embolism, increase tissue perfusion and increase the survival area of the flap.

Objective:To study the feasibility, safety and technique for laparoscopic anatomical liver resection of segment 8.Methods:The clinical data of 9 patients who underwent laparoscopic anatomical liver resection of segment 8 from January 2015 to December 2019 at Hunan Provincial People's Hospital were retrospectively analyzed. There were 6 males and 3 females, with age ranging from 29 to 67 years (average 53.6 years). The operation time, intraoperative blood loss , postoperative hospital stay, postoperative complications, and long-term survival and recurrence rates on follow-up were analysed.Results:Laparoscopic anatomical liver resection of segment 8 was successfully carried out in these patients. The mean operative time was 188.9 min(range 140-240 min). The mean estimated intraoperative blood loss was 117.8 ml (range 20-300 ml). The postoperative hospital stay was 6.9 days (range 3-12 days). One patient developed pleural effusion after operation and responded to conservative treatment. Another patients developed ascites with delayed extubation. The patient was successfully treated with conservative treatment. No patients developed complications above Clavien Dindo Ⅲa. There were no perioperative deaths. The postoperative pathological results showed hepatocellular adenoma ( n=2), hepatocellular carcinoma ( n=4), cholangiocarcinoma ( n=1), and metastatic liver cancer ( n=2). On follow-up for 12-58 months (median 22 months) one patient with hepatocellular carcinoma developed recurrence at 18 months after operation and was treated with microwave ablation. The other patients were well on follow-up. Conclusions:With adequate preoperative evaluation, reasonable case selection, rigorous surgical planning, and skilled laparoscopic techniques, laparoscopic anatomical liver resection of segment 8 was safe and feasible, and the short-term efficacy was good in this study.

OBJECTIVE: To the clinical characteristics and prognostic value of the patients with complete deletion of TET_JBP domain (ΔJBP) in TET2 acute myeloid leukemia (AML). METHODS: Next Generation Sequencing technology was used to determine the mutations of 34 AML-related genes (including TET2 gene). The I-TASSER tool was used to predict the tertiary structure of the full-length TET2 protein and TET_JBP structure deletion. RESULTS: Among 38 AML patients with TET2 mutations, 22(57.9%) showed truncation mutations, of which 16 (72.7%) produced TET2ΔJBP truncation mutants. Protein structure prediction showed that the deletion of TET_JBP domain lead to the significant changes of tertiary structure in TET2 protein. Compared with the patients in non-ΔJBP group, the age of patients in ΔJBP group were older (63 vs 54 years old, P=0.047), and the occurrence rate of CEBPA double mutation (CEBPA CONCLUSION AML patients with TET2ΔJBP truncation mutant shows lower CR rate, shorter EFS and OS after induction chemotherapy, which may be related to the poor prognosis, and co-mutation with CEBPA
DNA-Binding Proteins/genetics* ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Mutation ; Prognosis ; Proto-Oncogene Proteins/genetics* ; Remission Induction

BACKGROUND: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE). METHODS: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE. RESULTS: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively. CONCLUSIONS Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.

Objective: To explore the clinical application of supraclavicular fasciocutaneous island flap (SIF) in the repair of tracheal defect. Methods: From May 2016 to March 2021, the clinical data of 10 patients (8 males,2 females,aged 27-73 years old) were retrospectively analyzed who underwent repair surgery with SIF for trachea defects after resection of cervical or thoracic tumors, including 2 cases of laryngotracheal adenoid cystic carcinoma, 2 cases of laryngeal carcinoma, 3 cases of esophageal carcinoma, 2 cases of thyroid carcinoma and one case of parathyroid carcinoma. All of the primary tumors were at T4. The outcomes of 10 cases with tracheal defect repaired by SIF were evaluated. Results: The areas of the SIF were (3-7) cm × (6-10) cm, the thicknesses of the flaps were 8-11 mm, and the lengths of the pedicles were 10-15 cm. The blood supply of the SIF came from the transverse carotid artery. The skin defects of the donor areas of the shoulders were directly closed. After 1-60 months of follow-up, all the flaps survived. The flaps, tracheas as well as shoulder wounds healed well. Conclusion: The SIF is suitable for the repair of tracheal defects. It has perfect thickness compatible with the trachea. The technique is simple and microsurgical technique is not needed, with a good application prospect.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Reconstructive Surgical Procedures ; Retrospective Studies ; Skin Transplantation ; Surgical Flaps ; Trachea ; Treatment Outcome