Preimplantation polygenic testing， as a frontier technology in assisted reproduction， provides a new way to prevent genetic diseases and reduce birth defects. However， it may also trigger a series of ethical issues. Combined with the research progress of preimplantation polygenic testing， this paper explored the ethical issues that may be caused by this technology， including the risks and uncertain benefits for future offspring and the challenges of informed consent， the dilemmas of autonomous decision-making and genetic responsibility of prospective parents， as well as social risks such as the distortion of the view of life and health inequities. Given the technical safety issues and ethical challenges posed by preimplantation polygenic testing， it was proposed to revise the regulations related to preimplantation genetic testing， as well as improve the ethical review of preimplantation polygenic testing， genetic counseling services， and public education on genetic science and genetic ethics. These ethical countermeasures aim to prevent and mitigate risks and ensure that technology truly benefits human society.

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.

BACKGROUND:Current studies have confirmed that Ganoderma lucidum polysaccharides can promote nerve regeneration in neurodegeneration-related diseases.The occurrence of neurodegenerative diseases is closely related to mitochondrial dysfunction,but the role of Ganoderma lucidum polysaccharides on the regulation of apoptosis and mitochondrial function in neurodegenerative diseases is not yet clarified. OBJECTIVE:To explore the regulatory effects and mechanisms of Ganoderma lucidum polysaccharides on apoptosis and mitochondrial dysfunction in H2O2-induced SH-SY5Y cells. METHODS:SH-SY5Y cells were divided into three groups:control group,H2O2 group,and Ganoderma lucidum polysaccharides group.Cells in the control group were normally cultured.Cells in the H2O2 group were treated with 300 μmol/L H2O2 for 24 hours.In the Ganoderma lucidum polysaccharides group,the intervention with 300 μg/L Ganoderma lucidum polysaccharides was conducted first for 1-2 hours,followed by the addition of 300 μmol/L H2O2 for 24 hours.The mitochondrial membrane potential was detected by JC-1 kit.Apoptosis was detected by TUNEL staining kit.The activities of malondialdehyde and superoxide dismutase were detected by malondialdehyde test kit and superoxide dismutase test kit,respectively.The apoptosis and expression of mitochondrial dynamics-related proteins were detected by immunofluorescence staining and western blot assay. RESULTS AND CONCLUSION:(1)Compared with the control group,the mitochondrial membrane potential and superoxide dismutase activity were significantly reduced,as well as apoptotic rate and malondialdehyde levels were significantly increased in the H2O2 group(P<0.05).After treatment with Ganoderma lucidum polysaccharides,the membrane potential and superoxide dismutase activities were significantly increased,and apoptotic rate and malondialdehyde levels were significantly reduced compared with the H2O2 group(P<0.05).(2)The expression levels of pro-apoptotic proteins Bax and Caspase-3 were significantly increased,but the expression of anti-apoptotic protein Bcl-2 was significantly decreased in the H2O2 group compared with the control group(P<0.05).Compared with the H2O2 group,the levels of Bax and Caspase-3 were significantly decreased,but the expression of anti-apoptotic protein Bcl-2 was significantly increased in the Ganoderma lucidum polysaccharides group(P<0.05).(3)Compared with the control group,the expression of mitochondrial splitting proteins Fis1 and p-Drp1 was significantly increased,but the expression of mitochondrial fusion proteins OPA1,Mfn1,and Mfn2 was decreased in the H2O2 group(P<0.05).Compared with the H2O2 group,Fis1 and p-Drp1 expression was significantly reduced,but the expression levels of OPA1,Mfn1,and Mfn2 were significantly increased in the Ganoderma lucidum polysaccharides group(P<0.05).(4)The above results confirm that Ganoderma lucidum polysaccharides can attenuate H2O2-induced oxidative stress damage and apoptosis in SH-SY5Y cells by ameliorating mitochondrial dysfunction.

By targeting the key gene csgD involved in the biofilm formation of Escherichia coli, we employed molecular docking and molecular dynamics simulation to screen the active components of Chinese medicine with inhibitory effects on the biofilm formation from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). After the anti-biofilm properties of the active components were validated in vitro, data-independent acquisition (DIA) proteomics was employed to further identify the differential proteins involved in interfering with the biofilm formation of Escherichia coli. The mechanisms of inhibition were explored with consideration to the phenotype. Through virtual screening, we identified four candidate active components, including tannic acid, narirutin, salvianolic acid B, and rosmarinic acid. Among them, tannic acid demonstrated significant inhibitory effect on the biofilm formation of E. coli. The analysis of differential proteins, combined with relevant phenotype validation, suggested that tannic acid primarily affected E. coli by intervening in pilus assembly, succinic acid metabolism, and the quorum sensing system. This study provided a lead compound for the development of new drugs against biofilm-associated infections in the future.
Biofilms/drug effects* ; Escherichia coli/metabolism* ; Molecular Docking Simulation ; Drugs, Chinese Herbal/chemistry* ; Tannins/chemistry* ; Cinnamates/metabolism* ; Benzofurans/chemistry* ; Depsides/metabolism* ; Rosmarinic Acid ; Anti-Bacterial Agents/chemistry* ; Escherichia coli Proteins/genetics* ; Medicine, Chinese Traditional

Objective:To study the clinical, endoscopic and histological characteristics of heterotopic gastric mucosa in upper esophagus (HGMUE).Methods:A Total of 177 patients who underwent gastroscopy and were diagnosed as having HGMUE at the Endoscopy Center of Wuhan Union Hospital from January 2017 to December 2017 were included in the study. According to the gastroesophageal reflux disease symptom questionnaire (GERD-Q) scores, patients were divided into the HGMUE group (GERD-Q<8, n=101) and GERD+HGMUE group (GERD-Q≥8, n=76). The data of clinical, endoscopic and histological characteristics were analyzed. Results:Among the 177 HGMUE cases, there were 111 males (62.71%) and 66 females (37.29%), 76 (42.94%) with GERD, and 101 (57.06%) without GERD. The most common symptom was continuous clearing throat [54.24% (96/177)], followed by foreign body sensations of throat [48.59% (86/177)], and gastroesophageal reflux symptoms such as heartburn, chest pain, indigestion, acid reflux [48.59% (86/177)]. In the HGMUE group, the occurrence rate of clearing throat was the highest [42.57% (43/101)], then foreign body sensations of throat accounted for 33.66% (34/101), and gastroesophageal reflux symptoms was 27.72% (28/101). In the HGUME+GERD group, the most common symptom was gastroesophageal reflux symptoms [76.32% (58/76)], then clearing throat [69.74% (53/76)] and foreign body sensations of throat [68.42% (52/76)]. Under gastroscopy, 177 heterotopic gastric lesions were found under gastroscopy with orange-red round, oval or elongated island like ones, most of which were flat and a few slightly protruded from the peripheral plane. There were 132 (74.58%) single-lesion cases, 38 (21.47%) 2-lesion, and 7 (3.95%) 3- or more-lesion cases; there were 37 (20.90%) small lesions (maximum diameter <0.5 cm), and 74 (41.81%) median-size lesions (maximum diameter of 0.5-1.0 cm), and 66 (37.3%) larger lesions (maximum diameter >1.0 cm). Among the 30 [16.95% (30/177)] samples of mucosal tissue, 15 [50.00% (15/30)] were mainly cardia gland, 8 [26.67% (8/30)] were mainly pyloric gland, 6 [20.00% (6/30)] were mixed type, and 1 [3.33% (1/30)] was squamous epithelium. In the immunohistochemical test, 20 cases [66.67% (20/30)] showed positive of H +/K +-ATPase, and 10 cases [33.33% (10/30)] were negative. Conclusion:HGMUE is more common in male patients, and may be combined with GERD. Among them, patients with combined GERD are more likely to develop laryngopharyngeal reflux. The heterotopic gastric mucosas lesions are orange-red round, oval or elongated island-like under gastroscopy, and most of them are flat, single and median- or large-sized. Histological types are mostly fundic glands, and H +/K +-ATPase positive is more common. It is speculated that acid secretion may be an important factor leading to throat symptoms.

OBJECTIVE: To report the clinical manifestation and genetic characteristics of a child with Thiamine metabolism dysfunction syndrome 5. METHODS: Clinical data and genetic results were collected and analyzed. Peripheral blood samples of the child and their parents were collected for whole exome sequencing, and the functional effect of the variants on the TPK1 enzyme activity was verified by an in vitro assay. RESULTS: A four-year-old boy presented with preschool onset of ataxia were characterized. High-throughput sequencing identified a novel homozygous variant of TPK1 gene c.382G>A (p.Leu128Phe). His father and mother were both found carrying the variant. The variant protein showed a 30.9% reduction in TPK1 enzyme activity compared with the wildtype. CONCLUSION A novel pathogenic variant has been identified in a boy with thiamine metabolic dysfunction syndrome type 5.
Child, Preschool ; Genetic Testing ; Homozygote ; Humans ; Male ; Mutation ; Thiamine ; Whole Exome Sequencing

To investigate cerebral autoregulation(CA)in patients with severe unilateral carotid artery stenosis by near infrared spectroscopy. Thirty patients who underwent general anesthesia in our hospital from January 2015 to February 2017 were enrolled in this study.The stenosis group included 15 patients with severe unilateral internal carotid artery stenosis,and the control group included 15 patients without carotid artery stenosis.Both groups were matched in sex and age.Cerebral tissue oxygenation index(TOI)and mean arterial pressure were recorded continuously under stable general anesthesia.The Pearson correlation coefficient()was calculated to judge the CA status. TOI was not significantly different between the stenosis side and the non-stenosis side in the stenosis group(66.52±6.50 65.23±4.50;=0.93, =0.368)or between the stenosis side in the stenosis group and the stenosis side in the control group(66.52±6.50 64.22±3.87;=1.18, =0.248).The values of stenosis side and non-stenosis side in the stenosis group were 0.36±0.12 and 0.17±0.11,respectively,and the values of the stenosis side in the stenosis group and the stenosis side of the control group were 0.36±0.12 and 0.13±0.08,respectively.In the stenosis group,5 patients had transient ischemic attack and 2 patients had a history of stroke within 3 months before operation.When an value of 0.342 was used as the judgment point of CA abnormality,the sensitivity and specificity were 0.625 and 0.909,respectively. Within the range of normal blood pressure fluctuation,cerebral blood flow is linked to blood pressure at the stenosis side in patients with severe unilateral carotid artery stenosis.
Blood Pressure ; Carotid Stenosis ; Cerebrovascular Circulation ; Homeostasis ; Humans ; Ischemic Attack, Transient

Objective:To analyze the CT and MRI features of primary hepatic sarcomatoid carcinoma.Methods:A retrospective study was conducted on 16 patients with primary hepatic sarcomatoid carcinoma who presented to Wenzhou People's Hospital of Zhejiang Province and the Second Affiliated Hospital of Wenzhou Medical University from January 2009 to June 2019. There were 8 males and 8 females, with age ranging from 35 to 71 years (average 56.8 years). The site, size, shape, margin, density of signal, adjacent tissue changes and degree enhancement of tumor were analyzed.Results:Tumors in the liver in the 16 patients were all solitary, with 11 in the right and 5 in the left liver. The maximum diameter of tumor ranged from 3 to 16cm (average 8.5cm). On plain CT scanning ( n=16), the tumors were round or oval in 6, and lobulated or irregular in 10 patients. The margins of the tumors were clear in 10 and unclear in 6 patients. All tumors showed low density, with 15 tumors showing uneven density, with necrosis and liquefaction of different sizes in the center, while 1 tumor showing uniform density. On plain MRI scanning ( n=4), four tumors had clear margins, with necrosis and liquefaction seen in the center of the tumors. The solid part showed a slightly lower signal on T 1 weighted imaging and a slightly higher signal on T 2 weighted imaging. The liquefaction focus of central necrosis showed higher signal intensity on T 2 weighted imaging. Enhanced scanning ( n=12 on CT enhancement and n=4 on MRI enhancement), the margins of the tumors were enhanced in the arterial phase. The enhancement was continued into the portal venous and delayed phases in 7 patients. Strip septate and margin enhancement in the tumor were enhanced in the arterial phase. The enhancement was continued into the portal venous and delayed phases in 7 patients. Inhomogeneous strengthening in the tumor was enhanced in the arterial phase. The enhancement was continued into the portal venous and delayed phases in 1 patient. Inhomogeneous strengthening in the tumor was enhanced in the arterial phase. The enhancement was continued into the portal venous phase. In the delayed phase, enhancement in the tumor decreased, but there was continuous enhancement of the margin and interval of the tumor in 1 patient. Conclusions:Hepatic sarcomatoid carcinoma showed dual imaging characteristics of sarcoma and cancer. The imaging features of hepatic sarcomatoid carcinoma depended on the proportion of sarcomatoid components. Large intrahepatic tumors showed necrotic cystic degeneration, moderate or significant persistent enhancement in striped septum and margin of tumor.

Objective To observe the expression of protein AQP5 and CC16 in lung after hemorrhagic shock resuscitation in rats in order to explore the mechanism of acute lung injury.Methods Thirty-two healthy and clean male SD rats were randomly (random number) divided into two groups:control group and hemorrhagic shock resuscitation group (n =16 in each).Besides,each group was further divided into two subgroups according to the experiment done at 12 h and 24 h after hemorrhagic shock resuscitation (n =8).The hemorrhagic shock model was made by using Wiggers' modified method.Resuscitation was done by transfusing the autologous blood and the equal volume of Ringer's solution.Blood samples were obtained from abdominal aorta at each given interval to measure the level of plasma endotoxin,and assay the CC16 and AQP5 by using ELISA.After the rats were sacrificed,the left lung tissue was taken to measure lung water content and the dry/wet ratio,and to examine the levels of CC16 and AQP5 in lung tissue by immunohistochemical method.Results ①The level of plasma endotoxin in the experimental group was significantly higher than that in the control group (P ＜ 0.01).②The content of plasma CC16 in the experimental group was higher than that in the control group (P ＜ 0.05).③Compared with the control group,the content of pulmonary homogenate AQP5 in the experimental group was significantly lower (P ＜0.05).④The lung water content (the dry/wet ratio) of the experimental group was obviously higher than that of the control group (P ＜ 0.05).⑤Hislogogical observation with HE staining showed in the control group,the alveolar structure was complete,the alveolar sacs were clear,and the alveolar septum was intact;but in the experimental group,the alveolar septum was widened,and there were obvious hemorrhage and neutrophil infiltration in the alveolar space.⑥ The level of lung tissue CC16 in control group was significantly higher compared with experimental group (P ＜ 0.05).⑦ The level of lung tissue AQP5 was significantly higher in control group compared with experimental group (P ＜ 0.05).Conclusions The proteins of AQP5 and CC16 were involved in the process of acute lung injury after hemorrhagic shock resuscitation in rats,and their levels were positively correlated with length of time after hemorrhagic shock.