Inflammatory factors mediated the effect of air pollution on ischemic stroke: a two-step, mediation Mendelian randomization study.

OBJECTIVE: Numerous investigations have indicated a correlation between air pollution (AP) and an elevated ischemic stroke (IS) likelihood. The existing literature does not provide a consensus about the possible link between AP and IS. A two-sample Mendelian randomization (MR) analysis was utilized to systematically measure the causal link between AP and ischemic stroke. Furthermore, the mediating impact of inflammatory factors was also performed by a two-step MR. MATERIALS AND METHODS: A two-sample MR analysis was utilized to examine the AP impact on the incidence of IS. Additionally, a two-step MR approach was carried out to account for possible mediating variables. The indirect impact was determined by employing the product approach, which included multiplying the AP impact on inflammatory factors by the inflammatory factors' impacts on IS. The MR effect was identified through inverse variance-weighted (IVW) meta-analysis of each Wald Ratio. Additionally, complementary studies were conducted using the weighted median and MR-egger approaches. RESULTS: The IVW method with random effects showed that the per unit increase in genetically predicted PM2.5 was linked to the 0.362-fold elevated ischemic stroke risk (OR: 1.362, 95% CI: 1.032-1.796, p=0.029). Furthermore, the IVM technique, incorporating random effects, demonstrated that the per unit increase in genetically predicted PM2.5 was related to an elevated Interleukin (IL)-1ß risk (OR: 1.529, 95% CI: 1.191-1.963, p=0.001), IL-6 (OR: 1.498, 95% CI: 1.094-2.052, p=0.012) and IL-17 (OR: 1.478, 95% CI: 1.021-2.139, p=0.038). IL-1ß, IL-6, and IL-17 modulated the PM2.5 impact on ischemic stroke, while the proportion mediated by them was 59.5%. CONCLUSIONS: A positive correlation between genetically predicted PM2.5 levels and elevated ischemic stroke risk is mediated by IL-1ß, IL-6, and IL-17.

[Clinical efficacy of antibiotic bone cement combined with vacuum sealing drainage in treating diabetes mellitus complicated with necrotizing fasciitis].

Objective: To explore the clinical efficacy of antibiotic bone cement combined with vacuum sealing drainage (VSD) in treating diabetes mellitus complicated with necrotizing fasciitis. Methods: The retrospective observational study approach was used. From January 2020 to March 2022, 12 patients with type 2 diabetes complicated with necrotizing fasciitis who met the inclusion criteria were admitted to Wuxi Ninth People's Hospital, including 7 males and 5 females, aged 27 to 76 years. The initial diagnosis of lesions was in the lower limbs. After admission, bedside incision and drainage were performed timely, and a sample of wound exudate was collected for microbial cultivation. At the same time, the comprehensive supportive treatment was performed. At stage Ⅰ, debridement was performed, and the skin and soft tissue defect area was 40 cm×15 cm to 80 cm×25 cm after debridement. The dead space was filled with bone cement containing gentamicin and vancomycin and VSD was performed. After there was no obvious infection on the wound, the antibiotic bone cement was removed and wound repair surgery was performed at stage Ⅱ. The times of debridement, amputation, infection control, wound treatment method and wound healing at stage Ⅱ, total hospitalization day, and recurrence of necrotizing fasciitis during follow-up after the stage Ⅱ surgery. At the last follow-up, the walking function of patients was evaluated according to the scoring standards of American Orthopedic Foot and Ankle Association (AOFAS). Results: Eleven patients had wound infection control with one debridement surgery and did not undergo amputation surgery; one patient had significant foot gangrene, and the infection was controlled after one debridement and amputation of the gangrenous limb. Blood routine and infection indicators gradually returned to normal within 7 days after surgery. At stage Ⅱ, the wounds in 4 patients were sutured directly, the wounds in 6 patients were repaired with full-thickness inguinal skin graft, while the wounds in 2 patients were repaired with pedicled or tongue-shaped flaps at the wound edge. The wounds healed well after surgery, with no ulceration. The total hospitalization day of patients was 20 to 45 days. Follow-up for 3 to 24 months after stage Ⅱ surgery showed no recurrence of necrotizing fasciitis in any patient. At the last follow-up, the walking function was evaluated as excellent in 10 cases and good in 2 cases according to the AOFAS scoring standard. Conclusions: Antibiotic bone cement combined with VSD used in treating type 2 diabetes complicated with necrotizing fasciitis can effectively control infection and reduce the times of debridement, with good wound healing and walking function after surgery.

[Effects of pedicled flap combined with membrane induction technique in repairing foot and ankle wounds in diabetic patients].

Objective: To explore the effects of pedicled flap combined with membrane induction technique in repairing foot and ankle wounds in diabetic patients. Methods: A retrospective observational study was conducted. From March 2019 to July 2021, 12 patients with diabetic foot and ankle wounds who met the inclusion criteria were admitted to Wuxi Ninth People's Hospital, including 7 males and 5 females, aged 20 to 92 years. The wound area before debridement was 4.0 cm×2.5 cm to 16.0 cm×12.5 cm. The patients underwent debridement+antibiotic cement tamponade in stage Ⅰ; according to the wound site, peroneal artery perforator flap or posterior tibial artery perforator flap was chosen to repair the wound in stage Ⅱ, with the area of the resected flap ranging from 4.5 cm×3.0 cm to 18.5 cm×14.0 cm. The donor site was directly closed in 4 patients or covered by full-thickness inguinal skin graft in 8 patients. After the operation of stage Ⅱ, the survival of flap and skin graft, the scar in donor and recipient sites of flap, the appearance of flap, and the function of ankle joint of affected extremity were followed up. The recovery of foot and ankle function was evaluated and rated by the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scoring System at the last follow-up. Results: During the follow-up of 4 to 15 months after the operation of stage Ⅱ, both the flap and skin graft survived, without obvious infection recurrence. Linear scars were left in donor and recipient sites of flap, with good appearance in flap. The function of ankle joint in the affected extremity was nearly normal. At the last follow-up, the AOFAS scores of patients were 79 to 93, with excellent in 8 cases and good in 4 cases. Conclusions: The pedicled flap combined with membrane induction technique for repairing foot and ankle wounds in diabetic patients has the advantage of simple operation, preserved ankle joint function, and less postoperative infection recurrence, which is worth popularizing in clinical practice.

[Risk factors of occult lymph node metastasis of levels â ¢ and â £ in papillary thyroid carcinoma].

Objective: To investigate the potential risk factors for occult lateral cervical lymph node metastasis (LNM) to levels Ⅲ and Ⅳ in patients with papillary thyroid carcinoma (PTC) and the necessity of super-selective lateral lymph node dissection for patients harboring these metastases. Methods: This prospective study included PTC patients who were operated by the same surgeon in the Department of Head and Neck Surgery of Cancer Hospital, Chinese Academy of Medical Sciences from October 2015 through October 2019. Preoperative ultrasound and enhanced Computer Tomography (CT) did not denote suspected enlarged lymph nodes in the lateral neck. All patients underwent lymph node dissection in levels Ⅲ and Ⅳ on the basis of original thyroid collar incision after LNM to level Ⅵ was confirmed by preoperative fine needlebiopsy or intraoperative frozen pathology. Results: Of all 143 patients, 74 (51.7%) had occult LNM in levels Ⅲ and Ⅳ confirmed by postoperative pathology. The average number of metastasized lymph nodes in levels Ⅲ and Ⅳ was 2.64±1.80, and that in level Ⅵ was 3.77±3.27. There was a significant linear positive correlation between the number of metastasized lymph nodes in level Ⅵ and that in levels Ⅲ and Ⅳ (r=0.341, P<0.001). That the metastasized lymph nodes in level Ⅵ equals three was the best predictor of occult lateral LNM to levels Ⅲ and Ⅳ. Univariate analysis showed that age <55 years, tumor size ≥2.0 cm, number of metastasized lymph nodes in level Ⅵ ≥3, and percentage of metastasized lymph nodes in the total number of dissected lymph nodes in level Ⅵ >50% were associated with occult LNM in levels Ⅲ and Ⅳ (P<0.05). Multivariate analysis showed that number of metastasized lymph nodes in level Ⅵ≥3 was an independent risk factor for occult LNM in levels Ⅲ and Ⅳ (P=0.006). Conclusions: Age, tumor size and LNM in level Ⅵ were associated with occult lateral LNM in PTC patients. Lymph node dissection in levels Ⅲ and Ⅳ could be considered for selective patients, since it will help to avoid secondary operation for residual tumor or recurrence resulted from insufficient treatment without increasing the incidence of complications or affecting patients' appearances.

Metagenomic next-generation sequencing vs. conventional detection methods for detecting the pulmonary infections.

OBJECTIVE: The absence of proper pathogen treatment in the early stages can result in missing out on treatment chances or the overuse of antibiotics, both of which are the primary factors behind fatalities caused by lung infections. In this study, we aimed to investigate the efficacy of metagenomic next-generation sequencing (mNGS) in comparison to conventional detection methods in detecting infectious pathogens. PATIENTS AND METHODS: In this retrospective study, the infection pathogens of 104 patients were examined, and 86 bronchoalveolar lavage fluid (BALF), eight pleural effusions, and ten sputum samples were collected. The conventional detection approaches and mNGS analysis were used to determine the infection pathogen profiles and their detection rates were analyzed. RESULTS: Our study showed that mNGS was more sensitive (89.42%) than the conventional detection methods (56.73%) (p < 0.001), with a 32.69% improvement in sensitivity. The efficacy of mNGS in detecting mixed infections was significantly higher than that of conventional detection methods, with a detection rate of 85.29% compared to 17.65% (p < 0.001). The study demonstrated that mNGS had a higher sensitivity than the conventional detection methods when it came to diagnosing pulmonary infections, making it a potentially useful tool for clinical diagnosis. CONCLUSIONS: Combining mNGS with other pathogenic detection techniques can be an effective way to increase the rate of detecting pulmonary infections, as well as to provide guidance for treatment adjustments. Furthermore, the timing of sample collection and antibiotic administration can influence the effectiveness of mNGS when used on BALF specimens.

[Analysis of success rate of organoid construction of nasopharyngeal carcinoma by first-day suspension method].

Objective: To investigate the efficacy of the first-day suspension method for improving the success rate of construction of nasopharyngeal carcinoma-patient derived organoids (NPC-PDO). Methods: The tumor samples of 14 nasopharyngeal carcinoma(NPC) patients, i.e.,13 males and 1 female, with a mean age of 43.0±12.0 years old, were collected from the Affiliated Tumor Hospital of Guangxi Medical University and the First Affiliated Hospital of Guangxi Medical University from January 2022 to July 2022. The tumor samples of 3 patients were digested into single cell suspension and divided into 2 groups, for comparing the efficacy of NPC-PDO construction by the direct inoculation method and the first-day suspension method. The remaining 11 patients were randomized to receive either the direct inoculation method or the first-day suspension method for NPC-PDO construction. The diameter and the number of spheres of NPC-PDO constructed by the two methods were compared by optical microscope; the 3D cell viability detection kit was used to compare the cell viability; the survival rates were compared by trypan blue staining; the success rates of the two construction methods were compared; the number of cases which could be successfully passaged for more than 5 generations and were consistent with the original tissue by pathological examination was counted; and the dynamic changes of cells in suspension overnight were observed by live cell workstation. The independent sample t-test was applied to compare the measurement data of the two groups, and the chi-square test was used to compare the classification data. Results: Compared with the direct inoculation, the diameter and the number of spheres of NPC-PDO constructed by the first-day suspension method were increased, with a higher cell activity, and the success rate of construction was obviously improved (80.0% vs 16.7%, χ2=4.41, P<0.05). In the suspension state, some of the cells aggregated and increased their ability to proliferate. Conclusion: The first-day suspension method can improve the success rate of NPC-PDO construction, especially for those whose original tumor sample size is small.

[Active surveillance for thyroid micro-malignant nodules].

Objective: To evaluate the effect of ultrasound diagnosis of thyroid micro-malignant nodules and accumulate practical experience for the management of active surveillance for them, so as to avoid overtreatment. Methods: A total of 949 patients who were diagnosed with thyroid malignant nodules using ultrasonography, with the nodules being less than 1 cm in size and without regional lymph node metastasis or distant metastasis, were included. They were treated by the same surgeon of the Department of Head and Neck Surgery, Cancer Hospital, Chinese Academy of Medical Sciences from February 2014 to December 2020. 112 patients chose immediate surgery. The rest patients were asked to accept ultrasound examination every 6 months to 1 year. Follow-up endpoints: tumor size growth of 3 mm, tumor volume increase greater than 50%, lymph node metastasis or distant metastasis. Results: The median follow-up time was 19 months. 713 patients underwent surveillance for more than 6 months. Of the 713 patients, 570 (79.9%) were women, with mean age at 43.5 years old. Tumor progression was observed in 47 (6.6%) patients with a cumulative incidence of 2.7% (1 year), 7.2% (2 years) and 9.5% (3 years). In multivariate analysis, patient age [HR=0.508, 95%CI: 0.275-0.939, P=0.031], lesion number [HR=2.945, 95%CI: 1.593-5.444, P=0.001] and tumor size [HR=2.245, 95%CI: 1.202-4.192, P=0.011] at the beginning of observation were independent risk factors for tumor progression in patients with minimal thyroid malignant nodules during follow-up. During a median (range) active surveillance of 19 (6-80) months, 74 patients chose surgery during the surveillance. Among the 186 patients who underwent surgery, only 3 patients were diagnosed with fibrotic nodules in pathology, while the rest were papillary thyroid carcinoma. The ultrasound accuracy reached 98.4%(183/186). Conclusions: Ultrasonography is an effective method of diagnosing malignant thyroid nodules. Thyroid micro-malignant nodules progress slowly. As a result, it is safe to observe them instead of taking immediate surgery. Patient age, lesion number and tumor size at the beginning of observation are independent risk factors for the tumor progression of malignant nodules.

Visible imaging system with changeable field of view on the HL-2A tokamak.

A new visible imaging system characterizing a flexible optical design and delivering high resolution frames is established on the HL-2A tokamak. It features a modular configuration, consisting of a front-end imaging lens, a set of bilateral telecentric relay lenses, and a camera. To avoid the effects of plasma radiation (x and gamma-rays) and magnetic field variation on the camera, it should be away from the coils. Therefore, the length of the relay lenses determines the total size of the imaging system. The main feature of this imaging system is to realize the variation of field of view (FOV) by interchanging the front-end prime lenses or by using a zoom lens directly rather than designing the optical system afresh, which lowers the cost drastically. The primary purpose of varying FOV is to enrich the versatility of this system, i.e., focusing on a narrow FOV such as gas puff imaging or a wide FOV such as the plasma cross sections. During the HL-2A experiments, this visible imaging system is used to provide high quality pictures of the plasma-wall interaction, divertor detachment, pellet injections, and so on. The frames confirmed that a strong radiation close to the X point is correlated with the completely detached inner target.

[Death-related risk factors analysis of surgical treatment of myocardial infarction combined with ventricular septal rupture].

Objective: To in vestigate the death-related risk factors of surgical treatment of myocardial infarction (MI) combined with ventricular septal rupture (VSR). Methods: The clinical data of patients (68 cases) with ventricular septal rupture after myocardial infarction (PI-VSR) from January 2008 to December 2020 in Beijing Anzhen Hospital were retrospectively selected and analyzed. We followed up the surviving patients and divided them into the survival group and the death group according to the perioperative and follow-up results. The univariate analysis was performed on various indicators, and the Cox regression analysis was used to analyze the risk factors related to postoperative death. Results: A total of 68 patients (42 were male and 26 were female, with age 44-82 (64.3±8.2) years after surgical treatment of myocardial infarction combined with ventricular septal rupture were enrolled, 9 patients died during the perioperative period, 59 surviving patients were followed up for 0.1-10.5 years(mean, 4 years), and 7 deaths during follow-up. Based on this, 52 patients were selected as the survival group while 16 patients as the death group. The results of univariate analysis showed that age, VSR to operation time less than 7 days, killip grade ≥ grade 3, cardiogenic shock, preoperative use of IABP, emergent surgery were related to postoperative death. The factors with P<0.2 factors in univariate analysis were selected into the multivariate Cox regression analysis. Age ([OR=1.110(1.012-1.217), P=0.026], platelet count [OR=0.990(0.981-0.999), P=0.031], D dimer (OR=1.002[1.001-1.003], P=0.003), cardiogenic shock (OR=6.084[1.729-21.405], P=0.005) were independent risk factors for postoperative death. All patients were followed up, the survival rate of 2-year, 4-year, 6-year, 8-year, and 10-year was 77.5%, 77.5%, 71.0%, 71.0%, and 71.0%, respectively. Conclusions: Age, platelet count, D-dimer, and cardiogenic shock are risk factors for death after surgical treatment of myocardial infarction combined with ventricular septal rupture. Surgery is an effective method for the treatment of myocardial infarction combined with ventricular septal rupture. Long-term prognosis of the surviving patients during perioperative are relatively better.

[Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development].

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.

[Prospects and reflections on the research and development of next-generation malaria vaccines].

Vaccination is one of the most effective intervention for the containment and elimination of infectious diseases. Recently, the world's first malaria vaccine RTS, S/AS01 was approved by WHO for use among children living in moderately and highly malaria endemic areas of Africa, which brings a hope for the research and development of malaria vaccines. Here, we review the current status of malaria vaccines development and provide a perspective on the development of next-generation malaria vaccines, so as to provide insights into the successful development of malaria vaccines.

Effects of maternal and progeny dietary selenium supplementation on growth performance and antioxidant capacity in ducklings.

This study evaluated the effects of selenium (Se) supplementation in maternal and offspring diets on performance and antioxidant capacity of ducklings aged from 0 to 2 wk. A total of 144 female Longyan duck breeders aged 22-wk were allotted into 2 treatments and fed a control diet or a 0.16 mg Se/kg supplemented diet. At 40-wk, 120 offspring from each treatment were divided into 2 groups, with 6 replicates of 10 birds. Using a 2 × 2 factorial design, ducklings from each maternal dietary treatment were assigned to a control diet or a 0.16 mg Se/kg supplemented diet from hatch to 2-wk. Compared with Se-deficient diet, maternal diet supplemented with 0.16 mg Se/kg increased the BW of hatchlings (P < 0.01). There were interactions between maternal and progeny diet with 0.16 mg Se/kg in BW of ducklings aged 2 wk and BW gain (BWG) as ducklings from maternal Se/progeny none treatment had the lightest BW and BWG (P < 0.01). Maternal diet with 0.16 mg Se/kg decreased plasma concentration of uric acid and insulin-like growth factor 1 (P < 0.01), and progeny diet supplemented with 0.16 mg Se/kg increased the activities of glutathione peroxidase 3 (GPx3) in plasma and glutathione peroxidase 1 in erythrocyte (P < 0.01). Maternal diet with 0.16 mg Se/kg increased (P < 0.05) the hepatic activity of total superoxide dismutase (T-SOD). Progeny diet supplemented with 0.16 mg Se/kg increased (P < 0.01) hepatic activity of GPx3 and decreased (P < 0.01) the hepatic concentration of malondialdehyde. Interactions were detected between maternal and progeny diet with 0.16 mg Se/kg in hepatic activity of T-SOD and maternal and progeny diet supplemented with Se displayed the highest hepatic activity of T-SOD (P < 0.05). Overall, Se supplementation in the diet of duck breeders and offspring increased the antioxidant capacity of ducklings. Maternal Se supplementation increased the BW of hatchlings, whereas maternal and progeny dietary Se supplementation did not affect the BWG of ducklings aged from 0 to 2 wk. Se supplementation with additional 0.16 mg/kg in the diet of duck breeders and offspring displayed beneficial effects particularly on the antioxidant capacity in ducklings.

[Effect analysis on endoscopic transnasal resection of epidural cholesteatoma at paracentral skull base].

Objective: To indicate the clinical features of endoscopic transnasal resection of epidural cholesteatoma at paracentral skull base and to analyze its efficacy. Methods: The total excision rate, postoperative complications and postoperative curative effect of 7 patients (4 males and 3 females, aging from 32 to 63 years old) who underwent middle skull base surgery for epidural cholesteatoma resection under transnasal endoscope at Tianjin Huanhu Hospital between August 2017 and August 2020 were retrospectively reviewed. All patients were followed up for 6 to 36 months. The postoperative MRI, clinical symptoms and recurrence were reviewed. Descriptive statistical methods were used for analysis. Results: Among the 7 patients, there were total resection (complete resection of cyst contents and capsule) in 4 patients, near-total resection (complete resection of cyst contents, incomplete resection of cyst capsule) in 1 patient, and subtotal resection (incomplete resection of cyst contents and capsule) in 2 patients. The clinical symptoms of all patients were improved postoperatively with 1 patient who had no clinical symptoms. One case had postoperative cerebrospinal fluid rhinorrhea, which was cured after lumbar drainage and nasal iodoform gauge packing. Up to now, 7 patients (including patients with partial resection) had no recurrence. Conclusion: Endoscopic transnasal approaches may be effectively used for resection of epidural cholesteatoma in the paracentral skull base in carefully selected cases.

[Evaluation of the fresh air purification system in the classroom under heavy pollution weather].

Evaluate the effect of the fresh air purification system on the improvement of indoor PM2.5 levels in a primary school classroom in Jinan City, Shandong Province. Our purpose is to explore the optimal operating time of the fresh air system and the main factors that affect the fresh air purification system to improve indoor air quality. From December 9, 2019 to December 10, 2019, two classrooms of the same area on the third floor of a primary school building in Jinan City, Shandong Province were selected as monitoring points. During the operation of the fresh air purification system, the PM2.5 concentration in the classroom is reduced by an average of 48.1%-61.5% compared to the outdoor PM2.5 concentration. After running for about 2 hours, the indoor PM2.5 concentration decreased to a relatively stable concentration level. The operating time of the fresh air purification system, student activities between classes, indoor temperature, indoor relative humidity, and outdoor PM2.5 concentration are important factors that affect the indoor particulate removal rate. In the case of a certain amount of fresh air and indoor area, closing doors and windows and appropriately extending the operation time of the fresh air purification system can improve the air quality in the classroom to a certain extent and protect the health of students.