Discovery of New Isotopes

Using the fusion-evaporation reaction ^{106}Cd(^{58}Ni,4n)^{160}Os and the gas-filled recoil separator SHANS, two new isotopes _{76}^{160}Os and _{74}^{156}W have been identified. The α decay of ^{160}Os, measured with an α-particle energy of 7080(26) keV and a half-life of 201_{-37}^{+58} µs, is assigned to originate from the ground state. The daughter nucleus ^{156}W is a ß^{+} emitter with a half-life of 291_{-61}^{+86} ms. The newly measured α-decay data allow us to derive α-decay reduced widths (δ^{2}) for the N=84 isotones up to osmium (Z=76), which are found to decrease with increasing atomic number above Z=68. The reduction of δ^{2} is interpreted as evidence for the strengthening of the N=82 shell closure toward the proton drip line, supported by the increase of the neutron-shell gaps predicted in theoretical models.

[Construction of natural population cohort on telephone follow-up management quality control system and discussion regarding critical issues by REDCap system].

With completing a baseline survey of a large natural population cohort, conducting regular follow-up has become a key factor in further improving the quality of cohort construction and ensuring its sustainable development. Typical cohort follow-up methods include repeat surveys, routine monitoring, and community-oriented surveillance. However, in practical applications, there are often issues such as high costs, difficulty, and high error rates. Telephone follow-up is an important supplementary method to the methods mentioned above, as it has the characteristics of low cost, fast response, and high quality. However, the with difficult organization, quality control is challenging, response rates are low, and management levels vary widely, which limits its widespread use in large-scale population cohort studies. Given the above problems, this study draws on customer relationship management based on the actual needs of the China Northwest Cohort follow-up. It relies on the REDCap electronic data collection platform to build a telephone follow-up management and quality control system. Targeted solutions are provided for key issues in telephone follow-up implementation, including organizational structure, project management, data collection, and process quality control, to improve the quality control level of telephone follow-up comprehensively and thereby enhance the quality and efficiency of follow-up. We hope to provide standardized follow-up programs and efficient quality control tools for newly established and existing cohort studies.

[Clinical effects of antibiotic bone cement combined with free anterolateral thigh flap in sequential treatment of diabetic foot ulcer].

Objective: To investigate the clinical effects of antibiotic bone cement combined with free anterolateral thigh flap in sequential treatment of diabetic foot ulcer (DFU) wounds. Methods: A retrospective observational study was conducted. From August 2018 to August 2021, 15 patients with DFU who met the inclusion criteria were admitted to the Affiliated Hospital of Zunyi Medical University, including 12 males and 3 females, aged 42-65 years, with a history of type 2 diabetes for 5-19 years. All the wounds of patients were complicated with local bone, muscle, or tendon defects or exposure. The wounds were covered with antibiotic bone cement after debridement in stage Ⅰ+free anterolateral thigh chimeric perforator flap (perforator flap+muscle flap) or simple free anterolateral thigh flap grafting in stage Ⅱ. The defect area of the wound after bone cement removal and debridement was 9.0 cm×5.0 cm-20.0 cm×7.0 cm, the incision area of the flap was 10.0 cm×5.0 cm-22.0 cm×7.0 cm, and the incision area of the muscle flap was 5.0 cm×3.0 cm-8.0 cm×4.0 cm. The donor sites of flaps were sutured directly. During follow-up, the situations of donor site healing and flap survival were observed. At the last follow-up, the texture and shape of the flap, the presence of new ulcers on both limbs, and the walking ability of the patient were observed. Results: During the follow-up of 8 to 21 months after operation in stage Ⅱ, the donor sites healed well with only residual linear scar; flaps in 14 patients survived completely, and the flap in 1 patient developed partial necrosis at 3 weeks after stage Ⅱ surgery, which was healed after debridement and skin grafting. At the last follow-up, the flaps were good in texture and appearance, there were no new ulcers in the affected limb or opposite limb, and the patients had no obvious impairment in daily walking function. Conclusions: To repair DFU wounds with antibiotic bone cement combined with free anterolateral thigh flap can rapidly control the infection, achieving a high survival rate of flap after operation with no obvious impairment in daily walking function of patients.

[Robotic-assisted laparoscopic modified ventral onlay lingual mucosal graft in complex ureteral stricture construction: experience of eight cases].

Objective: To examine the efficacy of robot-assisted laparoscopic modified ventral onlay lingual mucosal graft for complex ureteral stricture. Methods: The clinical data of 8 patients with ureteral stricture admitted to the Department of Urology, General Hospital of Southern Theater Command from May to October 2022 were retrospectively analyzed. There were 6 males and 2 females, aged (45.1±10.2) years (range: 34 to 64 years), body mass index (24.6±2.0) kg/m2 (range: 20.7 to 26.6 kg/m2). Five cases on the left side, 3 cases on the right side, the length of the ureteral structure was (3.1±0.7) cm (range: 2.2 to 4.5 cm). The value of preoperative serum creatinine was (113.8±22.3) µmol/L (range: 96 to 15 µmol/L). Before excising the structure segment, the titched anastomosed part of the dorsal wall of the ureter, and then the posteriorly augmented anastomotic, the remaining ventral side was augmented with a onlay lingual mucosa graft, then the omentum flap was used to wrap the reconstructed ureteral segment. The lingual mucosa graft with a length of 2.5 to 5.0 cm and a width of 1.0 to 1.5 cm was cut according to the actual structure. The surgery information of the patient, complications, and recent follow-up were recorded. Results: The operation under robot-assisted laparoscopy was performed successfully in the 8 patients without conversion to open surgery. The duration of the operation was (226.9±22.8) minutes (range: 210 to 255 minutes), estimated blood loss was (93.8±25.9) ml (range: 75 to 150 ml), the retention time of the postoperative drainage tube was (4.8±1.3) days (range: 3 to 7 days), and the duration of postoperative hospitalization was (11.1±3.6) days (range: 9 to 14 days). One week after the operation, the patient could pronounce correctly, enunciate clearly, and eat normally. Double J tubes were removed 4 to 8 weeks after the operation. The follow-up time in this group was 3 to 9 months, the follow-up patients underwent imaging and other examinations, which showed a significant improvement in hydronephrosis on the affected side, and the value of renal pelvic separation on the affected side was (1.4±0.8) cm (range: 0 to 2.3 cm). The serum creatinine value was (100.1±24.9) µmol/L (range: 76 to 155 µmol/L). Three months after the operation, the ureteroscopy showed that the ureter was smooth and the mucosa was normal. Conclusions: Robot-assisted laparoscopic ureteroplasty with a lingual mucosal graft is a safe and feasible operation for complex ureteral stricture without serious complications, which provides a surgical option for repairing ureteral stricture.

22q11.2 deletion syndrome complicated with pulmonary alveolar proteinosis in a child: a case report.

BACKGROUND: To analyze the clinical data and next generation sequencing (NGS) results from a child with 22q11.2 deletion syndrome (22q11DS) complicated with pulmonary alveolar proteinosis (PAP) who was admitted to the Department of Pediatrics of Fuyang People's Hospital and to present a review of the literature. CASE PRESENTATION: A 9-year-old male child, whose face had a small mandible and high-arched palate, but lacked a cleft palate, had repeated respiratory tract infections and bronchiectasis. Clinical examination, computer tomography, and electronic bronchoscopy were performed. Genetic testing via NGS was undertaken. PAP was confirmed by Periodic Acid Schiff staining of milky white alveolar lavage fluid isolated by electronic bronchoscopy. A deletion of approximately 2.46 Mbp on chromosome 22q11.2 was confirmed by NGS. During hospitalization, anti-infection, nebulization, alveolar lavage, and regular application of thymosin were administered to the patient. The condition of the patient stabilized following treatment. CONCLUSIONS: 22q11DS and PAP are both rare diseases, and the manifestation of 22q11DS combined with PAP has not been previously reported. The diagnosis and treatment of this case will be a reference for future clinical work.

[Surgical treatment of large and giant recurrent meningiomas near the middle and posterior third part of the superior sagittal sinus with extracranial invading].

OBJECTIVE: To investigate the surgical strategy for large and giant recurrent meningiomas near the middle and posterior third part of the superior sagittal sinus with extracranial invading. METHODS: The clinical data of 16 patients with large and giant recurrent meningioma in the middle and posterior third part of the superior sagittal sinus with extracranial invasion who underwent surgery in the Department of Neurosurgery of Peking University Third Hospital from May 2019 to May 2022 were retrospectively analyzed. All the patients underwent brain-enhanced magnetic resonance imaging (MRI), magnetic resonance venography (MRV), computed tomography angiography (CTA) and three-dimensional skull computed tomography (CT) before, to evaluate the extent of tumor invasion, the edema of brain tissue, the degree of skull damage, the blood supply of the tumor, and the degree of compression of the superior sagittal sinus, etc, and to formulate an individualized surgical plan. The neurological function of the patients was evaluated 1 week, 1 month, and 3 months after the operation, and the tumor condition was evaluated by brain-enhanced MRI 3 months, 6 months, and 1 year after the operation. RESULTS: The tumors in the 16 patients were all located in the middle and posterior 1/3 part of the superior sagittal sinus and invaded extracranially. Among them, 8 cases were operated for the second time, 6 cases for the third time, and 2 cases for the fourth time; In the last operation, the bone flap was used to repair the skull in 4 cases, and the titanium mesh was used in 12 cases; Tumor arterials of 3 cases were embolized under digital subtraction angiography (DSA). Tumors of 10 cases were resected at Simpson grade Ⅰ, and 6 cases at Simpson grade Ⅱ; 2 cases underwent decompressive craniectomy during operation, and 14 cases underwent cranioplasty at the same time; scalp incisions of 14 cases were directly sutured, and flap transposition was used in 14 cases. When evaluating nerve function after operation, the limb muscle strength was improved compared with that before operation, and the Karnofsky performance scale (KPS) score reached 100 points 3 months after operation. During the follow-up, 1 patient's tumor recurred after 1 year and received Gamma Knife treatment, and the rest of the patients had no recurrence during the follow-up period. CONCLUSION: Surgical treatment is the first choice for large and giant recurrent meningiomas near the middle and posterior third part of the superior sagittal sinus with extracranial invading. It is a safe and effective surgical method to take individualized surgical plan after detailed preoperative assessment of cerebral edema, tumor blood supply, venous sinus compression, and scalp invasion.

[Risk assessment of internal mammary lymph node metastasis and choice of irradiation of internal mammary lymphatic drainage area in breast cancer patients with negative internal breast lymph nodes on imaging].

Objective: To explore the independent risk factors of internal mammary lymph nodes (IMN) metastasis and the risk assessment method of IMN metastasis preoperatively in breast cancer patients with negative IMN in imaging examination, and guide the radiotherapy of IMN in patients with different risk stratification of IMN metastasis. Methods: The clinical and pathological data of 301 breast cancer patients who underwent internal mammary sentinel node biopsy(IM-SLNB) and/or IMN dissection in Shandong Cancer Hospital with negative IMN on CT and/or MRI from January 2010 to October 2019 were analyzed retrospectively. The independent risk factors were analyzed by univariate and multivariate logistic regression, and the independent risk factors of IMN metastasis were used to risk stratification. Results: Among the 301 patients, 43 patients had IMN metastasis, and the rate of IMN metastasis was 14.3%. Univariate analysis showed that vascular tumor thrombus, progesterone receptor (PR) expression, T stage and N stage were associated with IMN metastasis. Multivariate logistic regression analysis showed that tumor located in medial quadrant, positive PR and axillary lymph node metastasis were independent risk factors for IMN metastasis. The risk of IMN metastasis was assessed according to the independent risk factors of the patients: low-risk group is including 0 risk factor, medium-risk group is including 1 risk factor, and high-risk group is including 2-3 risk factors. According to this evaluation criteria, 301 patients with breast cancer were divided into low-risk group (with 0 risk factors), medium-risk group (with 1 risk factor) and high-risk group (with 2-3 risk factors). The IMN metastasis rates were 0 (0/34), 4.3% (6/140) and 29.1% (37/127), respectively. Conclusions: The risk stratification of IMN metastasis according to three independent risk factors of IMN metastasis including tumor located in medial quadrant, positive PR and axillary lymph node metastasis in breast cancer patients can guide the radiotherapy of IMN in newly diagnosed breast cancer patients. For N1 patients, radiotherapy of IMN is strongly recommended when the primary tumor is located in the medial quadrant and/or PR positive.

[Clinical characteristics and risk factors of pericardial effusion after hematopoietic stem cell transplantation in children with thalassemia major].

Objective: To investigate the characteristics, risk factors and outcomes of thalassemia major (TM) children with pericardial effusion (PE) after allo-geneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Clinical data of 446 TM children received allo-HSCT at Shenzhen Children's Hospital between January 2012 and December 2020 were analyzed retrospectively. Patients were divided into PE and non-PE group according to the occurrence of PE. Chi-square tests were used to investigate the risk factors that were associated with the development of PE. Kaplan-Meier method was used for survival analysis of the 2 groups. Results: Twenty-five out of 446 patients (5.6%) developed PE at a time of 75.0 (66.5, 112.5) days after allo-HSCT. Among these patients, 22 cases (88.0%) had PE within 6 months after allo-HSCT and 19 patients (76.0%) had PE within 100 days after allo-HSCT. The diagnoses of PE were confirmed using echocardiography. Pericardial tamponade was observed in only 1 patient, who later undergone emergency pericardiocentesis. The rest of patients received conservative managements alone. PE disappeared in all patients after treatment. Risk factors that were associated with the development of PE after allo-HSCT included the gender of patients, the type of transplantation, the number of mononuclear cells (MNC) infuse, pulmonary infection after HSCT and transplantation associated thrombotic microangiopathy (TA-TMA) (χ²=3.99, 10.20, 14.18, 36.24, 15.03, all P<0.05). In 239 patients that received haploidentical HSCT, the development of PE was associated with the gender of patients, pulmonary infection after HSCT and TA-TMA (χ²=4.48, 20.89, 12.70, all P<0.05). The overall survival rates of PE and non-PE groups were 96.0% (24/25) and 98.6% (415/421). The development of PE was not associated with the overall survival of TM children after allo-HSCT (χ²=1.73, P=0.188). Conclusions: PE mainly develop within 100 days after allo-HSCT in pediatric TM recipients. Haploidentical grafts, female gender, pulmonary infection after HSCT and TA-TMA are the main risk factors associated with PE development after transplant. However, the presence of PE don't have a significant impact on the outcomes of pediatric TM patients after allo-HSCT.

[Clinical application effects of two longitudes three transverses method in perforator location of thoracodorsal artery perforator flap and deep wound repair].

Objective: To explore the clinical application value of two longitudes three transverses method in the location of the perforator of thoracodorsal artery perforator and deep wound repair. Methods: The retrospectively observational study was conducted. From December 2018 to June 2020, 17 patients with deep wounds who were admitted to the Affiliated Hospital of Zunyi Medical University met the inclusion criteria and were included in this study, including 7 males and 10 females, aged 12 to 72 years. The wound areas of patients after debridement were 7 cm×3 cm to 11 cm×7 cm. Two longitudinal lines were located through the midpoint of the armpit, the posterior superior iliac spine, and the protruding point of the sacroiliac joint, and three transverse lines were located 5, 10, and 15 cm below the midpoint of the armpit between the two longitudinal lines, i.e. two longitudes three transverses method, resulting in two trapezoidal areas. And then the thoracodorsal artery perforators in two trapezoidal areas were explored by the portable Doppler blood flow detector. On this account, a single or lobulated free thoracodorsal artery perforator flap or flap that carrying partial latissimus dorsi muscle, with an area of 7 cm×4 cm to 12 cm×8 cm was designed and harvested to repair the wound. The donor sites were all closed by suturing directly. The number and location of thoracodorsal artery perforators, and the distance from the position where the first perforator (the perforator closest to the axillary apex) exits the muscle to the lateral border of the latissimus dorsi in preoperative localization and intraoperative exploration, the diameter of thoracodorsal artery perforator measured during operation, and the flap types were recorded. The survivals of flaps and appearances of donor sites were followed up. Results: The number and location of thoracodorsal artery perforators located before operation in each patient were consistent with the results of intraoperative exploration. A total of 42 perforators were found in two trapezoidal areas, with 2 or 3 perforators each patient. The perforators were all located in two trapezoid areas, and a stable perforator (the first perforator) was located and detected in the first trapezoidal area. There were averagely 1.47 perforators in the second trapezoidal area. The position where the first perforator exits the muscle was 2.1-3.1 cm away from the lateral border of the latissimus dorsi. The diameters of thoracodorsal artery perforators were 0.4-0.6 mm. In this group, 12 cases were repaired with single thoracodorsal artery perforator flap, 3 cases with lobulated thoracodorsal artery perforator flap, and 2 cases with thoracodorsal artery perforator flap carrying partial latissimus dorsi muscle. The patients were followed up for 6 to 16 months. All the 17 flaps survived with good elasticity, blood circulation, and soft texture. Only linear scar was left in the donor area. Conclusions: The two longitudes three transverses method is helpful to locate the perforator of thoracodorsal artery perforator flap. The method is simple and reliable. The thoracodorsal artery perforator flap designed and harvested based on this method has good clinical effects in repairing deep wound, with minimal donor site damage.

New α-Emitting Isotope

A new α-emitting isotope ^{214}U, produced by the fusion-evaporation reaction ^{182}W(^{36}Ar,4n)^{214}U, was identified by employing the gas-filled recoil separator SHANS and the recoil-α correlation technique. More precise α-decay properties of even-even nuclei ^{216,218}U were also measured in the reactions of ^{40}Ar, ^{40}Ca beams with ^{180,182,184}W targets. By combining the experimental data, improved α-decay reduced widths δ^{2} for the even-even Po-Pu nuclei in the vicinity of the magic neutron number N=126 are deduced. Their systematic trends are discussed in terms of the N_{p}N_{n} scheme in order to study the influence of proton-neutron interaction on α decay in this region of nuclei. It is strikingly found that the reduced widths of ^{214,216}U are significantly enhanced by a factor of two as compared with the N_{p}N_{n} systematics for the 84≤Z≤90 and N<126 even-even nuclei. The abnormal enhancement is interpreted by the strong monopole interaction between the valence protons and neutrons occupying the π1f_{7/2} and ν1f_{5/2} spin-orbit partner orbits, which is supported by the large-scale shell model calculation.

Phosphatase and tensin homolog (PTEN) suppresses triacylglycerol accumulation and monounsaturated fatty acid synthesis in goat mammary epithelial cells.

Phosphatase and tensin homolog (PTEN) is a well-known tumor suppressor in nonruminants and regulates various cellular processes including growth through dephosphorylation of phosphoinositide substrates. Although studies with bovine mammary tissue suggested a role for PTEN during lactation, its potential role in lipid metabolism remains unknown. Objectives of the present study were to determine PTEN abundance in goat mammary tissue at 2 stages of lactation (n = 6 Xinong Saanen dairy goats per stage), and to use gene-silencing and adenoviral transfections in vitro with isolated goat mammary epithelial cells (GMEC) to evaluate the role of PTEN abundance of lipid metabolism-related genes. Abundance of PTEN decreased by 51.5% at peak lactation compared with the dry period. The PTEN was overexpressed in isolated GMEC through adenoviral transfection using an adenovirus system with Ad-GFP (recombinant adenovirus of green fluorescent protein) as control, and silenced via targeted small interfering RNA (siRNA) transfection with a scrambled small interfering RNA as a negative control. Cell culture was performed for 48 h before RNA extraction, triacylglycerol (TAG) analysis, and fatty acid analysis. Overexpression of PTEN downregulated abundance of acetyl-coenzyme A carboxylase α (ACACA), fatty acid synthase (FASN), sterol regulatory element binding transcription factor1 (SREBF1), stearoyl-coenzyme A desaturase 1 (SCD1), diacylglycerol acytransferase 1 (DGAT1), 1-acylglycerol-3-phosphate O-acyltransferase 6 (AGPAT6) coupled with an increase in patatin-like-phospholipase domain containing 2 (PNPLA2), hormone-sensitive lipase (LIPE), and carnitine palmitoyltransferase 1 ß (CPT1B). Furthermore, overexpressing PTEN in vitro resulted in a significant decrease in TAG concentration and concentration of C16:1. In contrast, interference of PTEN led to an opposite effect on lipid metabolism in GMEC. These changes suggested a shift from lipogenesis and esterification to lipolysis and fatty acid oxidation. Collectively, PTEN seems to play a role in monounsaturated fatty acids synthesis and lipid accumulation in GMEC.

Expressions of SAA, CRP, and FERR in different severities of COVID-19.

OBJECTIVE: To explore the expression and significance of SAA, CRP and FERR in patients diagnosed with COVID-19. PATIENTS AND METHODS: A total of 225 patients diagnosed with COVID-19 who were admitted to the North Hospital of First Hospital in Changsha, China, from 9th February 2020 to 7th March 2020 were enrolled. Their general data, laboratory test results and levels of SAA, CRP and FERR were extracted from electronic medical records. RESULTS: Age was an important risk factor for the severity of COVID-19 in the patients. Compared with the non-severe group, the severe group showed statistical significance in the levels of total protein, albumin, ALT and AST in liver function, UA in renal function, myocardial enzyme CK-MB and LDH, and immunoglobulin IgG and IgM. The levels of SAA, CRP, and FERR were significantly increased in patients with severe COVID-19. ROC curve analysis results showed that the AUC, from small to large, was as follows: SAA+CRP+FERR, CRP + FERR, SAA + CRP, SAA + FERR, SAA, FERR, and CRP, which indicated the benefit of the combination of the three indicators. The sensitivity and specificity of the combined detection of the three indicators were higher than those of the detection of any single indicator or two combined indicators. A Spearman correlation analysis of the data showed that the initial CRP/SAA, SAA/FERR, and CRP/FERR were positively correlated. The continuous results of SAA, CRP and FERR throughout the study period showed that the values of the severe group on a given day were higher than those of the non-severe group; the values of the two groups peaked on the 5th or 7th day and then decreased, and the decreasing trend of the severe group was more evident. CONCLUSIONS: SAA, CRP and FERR are sensitive serological indicators used to evaluate the severity of COVID-19. The combined detection of serum SAA, FERR, and CRP, which are positively related to COVID-19 infection, offers guiding significance for the occurrence of COVID-19 infection and the severity of the disease. Such detection provides effective detection indicators for the progress and prognosis of COVID-19; these indicators will enable effective intervention measures to be implemented in time and the rates of severe illness and mortality to be reduced.

Short-Lived α-Emitting Isotope

A new, very short-lived neutron-deficient isotope ^{222}Np was produced in the complete-fusion reaction ^{187}Re(^{40}Ar,5n)^{222}Np, and observed at the gas-filled recoil separator SHANS. The new isotope ^{222}Np was identified by employing a recoil-α correlation measurement, and six α-decay chains were established for it. The decay properties of ^{222}Np with E_{α}=10016(33) keV and T_{1/2}=380_{-110}^{+260} ns were determined experimentally. The α-decay systematics of Np isotopes is improved by adding the new data for ^{222}Np, which validates the N=126 shell effect in Np isotopes. The evolution of the N=126 shell closure is discussed in the neutron-deficient nuclei up to Np within the framework of α-decay reduced width.

Coronavirus disease 2019: a clinical review.

In December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in Wuhan, China, and it subsequently spread in many countries around the world. Many efforts have been applied to control and prevent the spread of COVID-19, and many scientific studies have been conducted in a short period of time. Here we present an overview of the viral structure, pathogenesis, diagnosis, and clinical features of COVID-19 based on the current state of knowledge, and we compare its clinical characteristics with SARS and Middle East Respiratory Syndrome (MERS). Current researches on potentially effective treatment alternatives are discussed. We hope this review can help medical workers and researchers around the world contain the current COVID-19 pandemic.

New Isotope

A new short-lived neutron-deficient isotope ^{220}Np was synthesized in the fusion-evaporation reaction ^{185}Re(^{40}Ar,5n)^{220}Np at the gas-filled recoil separator SHANS. Based on the measurement of the correlated α-decay chains, the decay properties of ^{220}Np with E_{α}=10040(18) keV and T_{1/2}=25_{-7}^{+14} µs were determined, which are in good agreement with theoretical predictions. From the new experimental results coupled with the recently reported α-decay data of ^{219,223}Np, the α-decay systematics for Np isotopes around N=126 was established, which allows us for the first time to test the robustness of the N=126 shell closure in Z=93 Np isotopes. The results also indicate that, in the region of nuclei with Z≥83, the proton drip line has been reached for all odd-Z isotopes up to Np.

[Effects of combined transplantation of rat Schwann cells and fibroblasts on nerve regeneration of denervated perforator flaps in rats and the mechanism].

Objective: To explore the effects of combined transplantation of the rat Schwann cells and fibroblasts (Fbs) on the nerve regeneration of denervated perforator flaps in rats and the mechanism. Methods: (1) Fbs were isolated from the trunk of 2 Sprague-Dawley (SD) rats embryos of 14-16 days' pregnancy and cultured, and the morphology of the cells was observed. The third passage of cells were used for subsequent experiments. The protein expressions of fibronectin and Ephrin-B2 were observed by immunohistochemical method. The mRNA expression of Ephrin-B2 was detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction (n=3). (2) Schwann cells were isolated from the bilateral sciatic nerves and brachial plexus nerves of 45 SD rats born for 1-3 days and cultured, and the morphology of the cells was observed. The third passage of cells were used for subsequent experiments. The rate of S100 positive cells was detected by immunofluorescence method and flow cytometer, with sample numbers of 9 and 3 respectively. (3) In Dulbecco's modified Eagle medium (DMEM) high glucose medium, 1 mL Fbs and 1 mL Schwann cells both in the concentration of 1×10(5) cells/mL were co-cultured as Schwann cells+ Fbs co-culture group, and 2 mL Schwann cells in the concentration of 1×10(5) cells/mL were cultured alone as Schwann cells alone culture group, with 5 wells in each group. The clusters of Schwann cells in the two groups were observed and counted under inverted phase contrast microscope at post culture hour (PCH) 6 and 24 respectively. The clusters of Schwann cells in Schwann cells+ Fbs co-culture group were observed by immunofluorescence method at PCH 24 too. The protein expressions of EphB2, Sox2, and N-cadherin in Schwann cells of two groups at PCH 24 were detected by Western blotting (n=20). (4) Totally 100 8-week-old male SD rats were selected, and an in situ replanted peritoneal denervated perforator flap was made in each rat. According to the random number table, the rats were divided into simple flap group, Fbs alone transplantation group, Schwann cells alone transplantation group, Schwann cells+ Fbs co-transplantation group, with 25 rats in each group. Flaps of rats in Fbs alone transplantation group and Schwann cells alone transplantation group were injected with 0.4 mL Fb and 0.4 mL Schwann cells respectively (2×10(6) cells each). Flaps of rats in Schwann cells+ Fbs co-transplantation group were injected with 0.4 mL Fbs and Schwann cells mixed cells (totally 2×10(6) cells, cell number ratio: 1∶1), and flaps of rats of simple flap group were injected with the same volume of DMEM high glucose medium. On post injection day (PID) 2, 5, 7, 9, and 14, 5 rats in each group were selected respectively according to the random number table. The flap tissue was collected, and the number, diameter, and arrangement of regenerated nerves were observed by immunofluorescence method. Data were processed with completely random designed t test, analysis of variance for repeated measurement, t test, and Bonferroni correction. Results: (1) The third passage of cells isolated and cultured from the rat embryo trunks were uniform in size and shape, long spindle-shaped, with a large proportion of nuclei. Strong positive expressions of fibronectin and Ephrin-B2 protein in cells were observed, and the mRNA expression of Ephrin-B2 was 0.004 1±0.000 8. The cells were identified as Fbs. (2) After 5 days of culture, the primary cells isolated from the sciatic nerves and brachial plexus nerves of neonatal rats were elongated in cell bodies and grew in nest, fence, or vortex-like shape. The third passage of cells were detected by immunofluorescence method and flow cytometer, and the corresponding S100 positive cell rates were (95.9±1.0)% and (95.8±1.1)% respectively. The cells were identified as Schwann cells. (3) At PCH 6 and 24, the cluster numbers of Schwann cells in Schwann cells+ Fbs co-culture group were significantly higher than those of Schwann cells alone culture group (t=6.500, 10.614, P<0.01). At PCH 24, the Schwann cells in Schwann cells+ Fbs co-culture group aggregated into clusters, Fbs dispersed around the Schwann cell clusters, and the protein expressions of EphB2, N-cadherin, and Sox2 in Schwann cells were significantly higher than those in Schwann cells alone culture group (t=2.975, 19.717, 11.159, P<0.05 or P<0.01). (4) On PID 2, a small number of scattered, disordered, short, and thin nerve fibers were observed in the flap tissue of rats in the four groups. From PID 5 to 14, the number of nerve fibers in the flap tissue of rats of Schwann cells+ Fbs co-transplantation group increased gradually, and the nerve fibers were with long diameter and arranged orderly. The number of nerve fibers in the flap tissue of rats of Schwann cells alone transplantation group increased, but the nerve fibers were with short diameter and arranged disorderly, and the number was smaller than that of Schwann cells+ Fbs co-transplantation group. In simple flap group and Fbs alone transplantation group, the nerve fibers in the flap tissue of rats gradually degenerated with gradually decreased number or even disappeared. Conclusions: The combined transplantation of Fbs and Schwann cells in rats can regulate Schwann cells migration and clustering by activating Ephrin/Eph-Sox2-N-cadherin signaling pathway, thus promoting the orderly nerve regeneration of denervated perforator flaps in rats.

Question 3: Can we diagnose asthma in children under the age of 5 years?

The diagnosis of asthma in children under five years has been controversial due to changing concepts of what true asthma is in this age group. Previous diagnostic algorithms that used clinical indices to predict the persistence of asthma symptoms or phenotypes based on asthma triggers do not predict which children will benefit from asthma medication. A pragmatic approach to asthma diagnosis in this age group is based on identifying signs and symptoms of reversible airflow obstruction and documenting their response to asthma medication. Hopefully, this approach will provide clearer guidance to clinicians and improve asthma morbidity in these young children.

RETRACTED: Modulation of macrophage phenotype through controlled release of interleukin-4 from gelatine coatings on titanium surfaces.

Pro-inflammatory phenotype (M1) macrophages initiate angiogenesis, while their prolonged activation can induce chronic inflammation. Anti-inflammatory phenotype (M2) macrophages promote vessel maturation and tissue regeneration. Biomaterials which can promote M2 polarisation after appropriate inflammation should enhance angiogenesis and wound healing. Herein, Interleukin-4 (IL-4), an anti-inflammatory cytokine, was adsorbed onto a titanium surface. Then, a genipin cross-linked gelatine hydrogel was coated onto the surface to delay IL-4 release. The cross-linking degree of the hydrogel was modulated by the different amount of genipin to control release of IL-4. When 0.7 wt% (weight %) genipin was used as a cross-linker, the sample (GG07-I) released less IL-4 within the first several days, followed by a sustained release time to 14 d. Meanwhile, the release rate of IL-4 in GG07-I reached a peak between 3 d and 7 d. In culture with macrophages in vitro, GG07-I and GG07 exhibited good cytocompatibility. The phenotypical switch of macrophages stimulated by the samples was determined by FACS, ELISA and PCR. Macrophages cultured with GG07-I, GG07 and PT were firstly activated to the M1 phenotype by interferon-gamma (IFN-γ). Then, due to the release of IL-4 in 5 to 7 d, GG07-I enhanced CD206, increased the secretion and gene expression of M2 marker, such as interleukin-10 (IL-10), arginase-1 (ARG-1) and platelet derived growth factor-BB (PDGF- BB). GG07-I prompted the switch from M1 to M2 phenotype. Those appropriate secretion of cytokines would benefit both vascularisation and osseointegration. Thus, the biomaterial directing inflammatory reaction has good prospects for clinical treatments.