[Silent pulmonary shadows].

An elderly woman with a 1-year history of pulmonary shadows was admitted because of intermittent cough and sputum production for 2 months. Chest computed tomography (CT) scans showed bilateral consolidations and ground-glass opacities, with areas of low attenuation inside consolidative opacities on the mediastinal window. Previous history of radiotherapy for nasopharyngeal carcinoma and long-term use of a compound menthol nasal drops provided were important clues to the diagnosis. CT scan-guided needle lung biopsy and bronchoalveolar lavage were performed, and lipid-laden macrophages were confirmed in both bronchoalveolar lavage and lung tissue. Final diagnosis of exogenous lipoid pneumonia was made on the basis of her risk factors for aspiration, history of oil exposure, and classic radiological and histopathological features. Symptoms improved after discontinuation of causative exposure. It is important for clinicians to raise awareness of exogenous lipoid pneumonia and other aspiration lung diseases.

Engineered CRISPR-Cas12a for higher-order combinatorial chromatin perturbations.

Multiplexed genetic perturbations are critical for testing functional interactions among coding or non-coding genetic elements. Compared to double-stranded DNA cutting, repressive chromatin formation using CRISPR interference (CRISPRi) avoids genotoxicity and is more effective for perturbing non-coding regulatory elements in pooled assays. However, current CRISPRi pooled screening approaches are limited to targeting one to three genomic sites per cell. We engineer an Acidaminococcus Cas12a (AsCas12a) variant, multiplexed transcriptional interference AsCas12a (multiAsCas12a), that incorporates R1226A, a mutation that stabilizes the ribonucleoprotein-DNA complex via DNA nicking. The multiAsCas12a-KRAB fusion improves CRISPRi activity over DNase-dead AsCas12a-KRAB fusions, often rescuing the activities of lentivirally delivered CRISPR RNAs (crRNA) that are inactive when used with the latter. multiAsCas12a-KRAB supports CRISPRi using 6-plex crRNA arrays in high-throughput pooled screens. Using multiAsCas12a-KRAB, we discover enhancer elements and dissect the combinatorial function of cis-regulatory elements in human cells. These results instantiate a group testing framework for efficiently surveying numerous combinations of chromatin perturbations for biological discovery and engineering.

[Application of V-Y advancement flap with facial artery perforator for the repair of midface skin defects].

Objective: To investigate the efficacy of V-Y advancement flap with facial artery perforator for the repair of midface skin defects. Methods: A retrospective analysis was performed on 18 patients with facial skin cancer, including 11 males and 7 females, aged 65-83 years, who underwent the repair of midface skin defects using V-Y advancement flap with facial artery perforator in the Department of Head and Neck Surgery, Affiliated Cancer Hospital of Nantong University from January 2020 to April 2023. Medium, large or complex midface skin defects developed after surgical resections of the primary lesions. According to the defect site, size, location information of facial vessels, a V-Y advancement flap with appropriate shape was designed for each case. During the operation, the facial vessels and their perforators were retained in the pedicle of the flap, the facial nerve branches were dissected and protected, and the further denuded pedicle was determined according to actual amount of advancement. After the flap was advanced, the facial defect area was repaired without tension, and the anatomical positions and functions of the eyes, nose and mouth were restored as far as possible. Postoperative follow-ups were conducted to observe the survival rate of the flaps, postoperative complications, recurrences and metastases of tumors. Results: Midface defects of 3.0 cm×3.5 cm-6.5 cm×7.5 cm were observed after tumor resections, which involved one or more subregions. The sizes of the flaps were 3.5 cm×9.0 cm-7.0 cm×18.0 cm. All flaps were completely alive except for one with temporary local bruising. With following-up of 4-40 months, 5 of the 12 patients with lower eyelid and inner canthus invasions had lower eyelid ectropion, but no exposed keratitis was found; one case with poorly differentiated squamous cell carcinoma had lymph node metastasis in the submandibular region and underwent neck dissection again; no recurrence or metastasis occurred in the remaining cases. Conclusion: The V-Y advancement flap with facial artery perforator can be used to repair medium, large or complex midface skin defects, with a high survival rate, and the operation method is safe and reliable.

[Diffuse thickening of bronchial walls with multiple nodular mucosal protrusions].

A 58-year-old woman presented with a six-month history of nasal congestion, sore throat and cough, and a five-month history of dyspnea. She had a history of xerostomia for one year. On examination, the bilateral submandibular gland and parotid glands were enlarged. Parotid and anterior cervical lymph nodes were palpable. There were rales in both lungs. The rest of the physical examination was unremarkable. Sialographic analysis showed normal caliber in the main duct, stenosis in secondary ducts, and dilation in the proximal ducts. Minor salivary gland biopsy demonstrated periductal lymphocytic infiltration. Chest computed tomography (CT) showed diffuse thickening of the tracheal and bilateral bronchial walls. Bronchoscopy revealed macroscopic multiple nodules mainly in the trachea and bilateral main bronchus. Endobronchial biopsy showed lymphocytic infiltration in the bronchial submucosa. She was diagnosed with Sjögren's syndrome and treated with glucocorticoids. The dose of prednisone was started at 30 mg/d and tapered gradually. Following treatment, the patient's clinical condition improved dramatically, with shrinkage of the enlarged lymph nodes, bilateral submandibular and parotid glands. A repeated chest CT scan revealed improvement of the tracheal and bilateral bronchial thickening. Multiple nodules in the airway regressed, as evidenced by repeated bronchoscopic examination. The final diagnosis was a large-airway disease associated with Sjögren's syndrome.Among airway diseases in Sjögren's syndrome, peripheral airway diseases including bronchiolitis and bronchiectasis are common; however, central airway lesions in Sjögren's syndrome, especially with macroscopic nodules, are rare. In this case, we demonstrated tracheal and endobronchial nodules in Sjögren's syndrome as determined by clinical features, CT scan, bronchoscopy, and response to therapy.

[Efficacy evaluation of short-term personalized vestibular rehabilitation in the treatment of acute unilateral vestibulopathy].

Objective: To explore the efficacy and effective node of short-term personalized vestibular rehabilitation (ST-PVR) in treating acute unilateral vestibulopathy (AUVP). Methods: A randomized controlled trial was carried out. The AUVP patients who were admitted to the First Affiliated Hospital of Zhengzhou University from July 2022 to March 2023 were selected and randomized to the vestibular rehabilitation (VR) group and control group via computer-generated randomization. Standard care was the medical treatment with betahistine and prednisolone. Meanwhile, the VR group received ST-PVR. All the patients completed the baseline assessment and underwent follow-up assessments at 1 month and 3 months after the treatment. The assessments were consisted of spontaneous nystagmus (NYS), Romberg test (ROM), head thrust test (HTT), visual analogue scale (VAS) for vertigo, dizziness handicap inventory scale (DHI), activities-specific balance confidence scale (ABC), caloric test using video-electronystagmograph (VNG), and video-head impulse test (vHIT). The measurement data that did not conform to normal distribution were represented by M (Q1, Q3). Generalized estimating equation (GEE) was used to analyze the influence of the ST-PVR on the values of these clinical indicators and the VR grading score. The values of clinical indicators and the VR grading score were compared between the two groups at each follow-up point. Results: Seventy-one AUVP patients were included, with 35 cases in the VR group [14 males and 21 females, aged 51 (33, 55) years] and 36 cases in control group [17 males and 19 females, aged 46 (34, 59) years]. There were statistically significant differences in the impact of ST-PVR on the values of clinical indicators between the two groups (ABC: ß=10.89, P<0.001; VAS: ß=-1.64, P<0.001; DHI: ß=-8.70, P<0.001; NYS: ß=26.73, P<0.001; vHIT: ß=1.41, P=0.047; the VR grading score: ß=1.03, P=0.045). The assessments of the VR group in the positive rate of NYS [14.3% (5/35) vs 50.0% (18/36), P<0.001], ROM [48.6% (17/35) vs 55.6% (20/36), P<0.001], directional preponderance (DP) [34.3% (12/35) vs 75.0% (27/36), P<0.001] and DHI [26 (22, 32) vs 36 (30, 60), P=0.001] were significantly lower than that of the control group at 1 month after the treatment. The results showed a statistically significant difference in ABC [88 (80, 90) vs 76 (61, 88), P<0.001], VAS [2 (1, 3) vs 3 (2, 5), P<0.001] at 3-months after the treatment. The VR grading score of the VR group was improved significantly than those of the control group at 1 month after treatment [21 (17, 21) vs 16 (13, 20), P=0.001]. Conclusion: ST-PVR could improve the results of clinical indicators and VR grading score of the AUVP patients effectively after 1 month of the systematical treatment, and alleviate the symptoms and signs of dizziness in the acute phase as early as possible.

[Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation in the treatment of secondary acute myeloid leukemia].

Objective: To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with secondary acute myeloid leukemia (sAML) . Methods: In this multicenter, retrospective clinical study, adult patients aged ≥18 years who underwent allo-HSCT for sAML at four centers of the Zhejiang Hematopoietic Stem Cell Transplantation Collaborative Group from January 2014 to November 2022 were included, and the efficacy and prognostic factors of allo-HSCT were analyzed. Results: A total of 95 patients were enrolled; 66 (69.5%) had myelodysplastic syndrome-acute myeloid leukemia (MDS-AML) , 4 (4.2%) had MDS/MPN-AML, and 25 (26.3%) had therapy-related AML (tAML) . The 3-year CIR, LFS, and overall survival (OS) rates were 18.6% (95% CI 10.2%-27.0%) , 70.6% (95% CI 60.8%-80.4%) , and 73.3% (95% CI 63.9%-82.7%) , respectively. The 3-year CIRs of the M-AML group (including MDS-AML and MDS/MPN-AML) and the tAML group were 20.0% and 16.4%, respectively (P=0.430) . The 3-year LFSs were 68.3% and 75.4%, respectively (P=0.176) . The 3-year OS rates were 69.7% and 75.4%, respectively (P=0.233) . The 3-year CIRs of the groups with and without TP53 mutations were 60.0% and 13.7%, respectively (P=0.003) ; the 3-year LFSs were 20.0% and 76.5%, respectively (P=0.002) ; and the 3-year OS rates were 40.0% and 77.6%, respectively (P=0.002) . According to European LeukmiaNet 2022 (ELN2022) risk stratification, the 3-year CIRs of patients in the low-, intermediate-, and high-risk groups were 8.3%, 17.8%, and 22.6%, respectively (P=0.639) . The three-year LFSs were 91.7%, 69.5%, and 65.6%, respectively (P=0.268) . The 3-year OS rates were 91.7%, 71.4%, and 70.1%, respectively (P=0.314) . Multivariate analysis revealed that advanced disease at allo-HSCT and TP53 mutations were independent risk factors for CIR, LFS, and OS. Conclusion: There was no significant difference in the prognosis of patients who underwent allo-HSCT among the MDS-AML, MDS/MPN-AML, and tAML groups. Advanced disease at transplantation and TP53 mutations were poor prognostic factors. ELN2022 risk stratification had limited value for predicting the prognosis of patients with sAML following allo-HSCT.

[Blastic plasmacytoid dendritic cell tumor treated with DVT regimen: a case report and literature review].

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive hematological malignancy, there is no standard treatment and the prognosis is very poor. Affiliated Zhongshan Hospital of Dalian University report a case of 85-year-old BPDCN male patient treated with DVT regimen (decitabine combined with Venetoclax and thalidomide) and achieved complete remission. The patient with skin nodules and the pathology diagnosed BPDCN, the next generation sequencing of skin nodules showed mutations of IDH2 and ASXL1. DVT (decitabine combined with Venetoclax and thalidomide) has significant efficacy with rapid and deep remission for BPDCN, and the adverse effects is less, especially suitable for elderly patients who cannot tolerate intense chemotherapy.

[Adiponectin improves endometrial receptivity in rats with polycystic ovary syndrome by upregulating the PPARα/HOXA10 pathway].

OBJECTIVE: To explore the role of the PPARα/HOXA10 signaling pathway in mediating the effect of adiponectin (APN) for improving endometrial receptivity in a rat model of polycystic ovary syndrome (PCOS). METHODS: Forty female SD rat models with letrozole-induced PCOS were randomized, with 10 normal rats as the control, into 4 equal groups for treatment with APN alone, APN combined with GW6471 (a specific PPARα inhibitor) or the vehicle for 20 days, or no further treatment (PCOS model group). GW6471 treatment (daily dose of 1 mg/kg) and vehicle treatment were initiated on the 11th day following the start of APN treatment, all administered via intraperitoneal injection. The rats were observed for changes in estrous cycle, body weight, ovarian index and morphology, uterine index and morphology, serum hormone levels and lipid metabolism parameters. Endometrial expressions of PPARα and HOXA10 were detected with immunohistochemistry and Western blotting. The development of endometrial pinopodes was observed under electron microscope, and pregnancies of the rats were recorded. RESULTS: The rat models of PCOS exhibited obvious estrous cycle disorders with significantly prolonged estrous interval, increased body weight and ovarian index, decreased uterine index, disordered serum hormones and lipid metabolism (P < 0.05), and polycystic ovarian changes, and these changes were significantly improved by APN treatment. Endometrial expressions of PPARα and HOXA10 were significantly lowered in PCOS rats and effectively up-regulated after APN treatment, but GW6471 treatment obviously blocked the effect of APN (P < 0.05). APN showed strong protective effect against PCOS-induced impairment of endometrial pinopode development, and this effect was obviously attenuated by GW6471. APN also significantly increased the pregnancy rate and embryo number in PCOS rats, while GW6471 obviously reduced the embryo number and caused developmental retardation of the embryos. CONCLUSION: APN can improve endometrial receptivity in PCOS rats by upregulating the PARα/HOXA10 pathway.

[A case of follicular lymphoma with recurrent fever and pulmonary infiltrates].

We reported a case of a 65-year-old male who had been treated with obinutuzumab and chemotherapy for follicular lymphoma. He was infected with SARS-CoV-2 after the second course of therapy. He developed fever, cough and bilateral pulmonary infiltrates. His nasopharyngeal swab became negative only temporarily after repeated courses of antiviral therapy, and the symptoms and pulmonary infiltrates waxed and waned. He presented to our hospital with exertional dyspnea and hypoxemia after his nasopharyngeal swab was positive for SARS-CoV-2 for the fourth time. He had an elevated serum lactate dehydrogenase and a positive 1, 3-ß-D-glucan test. The PCR test for Pneumocystis jirovecii in the sputum was positive. The patient was diagnosed with persistent COVID-19 and Pneumocystis jirovecii pneumonia. He responded well to the combination treatment of antiviral medication, convalescent plasma, trimethoprim-sulfamethoxazole and corticosteroids.

Predictive effect of net water uptake on futile recanalisation in patients with acute large-vessel occlusion stroke.

AIM: To determine whether net water uptake (NWU) based on automated software evaluation could predict futile recanalisation in patients with acute anterior circulation large-vessel occlusion (LVO). MATERIALS AND METHODS: Patients with acute anterior circulation LVO undergoing mechanical thrombectomy in Jinling Hospital were evaluated retrospectively. NWU and other baseline data were evaluated by performing univariate and multivariate analyses. The primary endpoint was 90-day modified Rankin scale score ≥3. A nomogram to predict poor clinical outcomes was developed based on multivariate logistic regression analysis. RESULTS: Overall, 135 patients who underwent thrombectomy with a TICI grade ≥2b were enrolled. In multivariate logistic regression analysis, the following factors were identified as independent predictors of futile recanalisation: age (odds ratio [OR]: 1.055, 95 % confidence interval [CI]: 1.004-1.110, p=0.035), female (OR: 0.289, 95 % CI: 0.098-0.850, p=0.024), hypertension (OR: 3.182, 95 % CI: 1.160-8.728, p=0.025), high blood glucose level (OR: 1.36, 95 % CI: 1.087-1.701, p=0.007), admission National Institutes of Health Stroke Scale score (OR: 1.082, 95 % CI: 1.003-1.168, p=0.043), and NWU (OR: 1.312, 95 % CI: 1.038-1.659, p=0.023). CONCLUSIONS: NWU based on Alberta Stroke Program Early Computed Tomography (CT) Score (ASPECTS) could be used to predict the occurrence of futile recanalisation in patients with acute anterior circulation LVO ischaemic stroke.

[High expression of CPNE3 correlates with poor long-term prognosis of gastric cancer by inhibiting cell apoptosis via activating PI3K/AKT signaling].

OBJECTIVE: To explore the correlation of CPNE3 expression with long-term prognosis of patients with gastric cancer (GC) and the possible mechanism. METHODS: We retrospectively collected the data of 104 GC patients undergoing radical surgery in our hospital from February, 2013 to October, 2017. TCGA database and immunohistochemistry were used to analyze CPNE3 expression level in GC tissues and its effects on tumor progression and long-term prognosis of the patients. GO analysis was performed to predict the biological role of CPNE3 in GC. We also conducted cell experiments with MGC803 cells and observed the effects of CPNE3 knockdown, CPNE3 overexpression and LY294002 (a PI3K/AKT inhibitor) treatment on cell apoptosis and cellular expressions of apoptotic proteins using flow cytometry and Western blotting. RESULTS: TCGA analysis and immunohistochemistry both showed high expressions of CPNE3 in GC (P < 0.05). The patients with high CPNE3 expressions had a reduced 5-year survival (P < 0.01), and a high CPNE3 expression, CEA level≥5 µg/L, CA19-9 level ≥37 kU/L, T3-T4 stage, and N2-N3 stage were all independent risk factors for a lowered 5-year survival rate after surgery. The sensitivity and specificity of CPNE3 for predicting 5-year mortality was 79.59% and 74.55%, respectively (P < 0.05). GO analysis predicted that CPNE3 negatively regulated GC cell apoptosis. In MGC803 cells, CPNE3 knockdown significantly increased cell apoptosis, enhanced Bax and Cleaved Caspase-3 expressions and decreased Bcl-2 expression, while CPNE3 overexpression produced the opposite results (P < 0.05). The cellular expressions of p-PI3K and p-AKT were significantly decreased following CPNE3 knockdown and increased following CPNE3 overexpression (P < 0.05). Treatment with LY294002 obviously attenuated the inhibitory effect of CPNE3 overexpression on apoptosis of MGC803 cells (P < 0.05). CONCLUSION: CPNE3 is highly expressed in GC tissues and affects the long-term prognosis of the patients possibly by inhibiting GC cell apoptosis through activation of PI3K/AKT signaling.

[Cost-effectiveness of pharmaceutical smoking cessation intervention in China primary cancer prevention].

Objectives: To evaluate the cost-effectiveness of typical pharmaceutical smoking cessation intervention strategies in China in the context of primary cancer prevention. Methods: Markov cohort simulation models were established to simulate the burden of 12 smoking caused cancer, including lung cancer, oral cancer, nasopharyngeal cancer, laryngeal cancer, esophageal cancer, gastric cancer, pancreatic cancer, liver cancer, kidney cancer, bladder cancer, cervical cancer, and acute myeloid leukemia. Taking incremental cost effectiveness ratio (ICER) as the main indicator, the model sets one year as the cycling period for 50 periods and simulates the cohort of 10 000 thirty-five-year-old current smokers with various smoking cessation strategies. To ensure the robustness of conclusion, univariate sensitivity analysis, probability sensitivity analysis, and age-group sensitivity analysis were conducted. Results: The results showed that varenicline intervention was the most cost-effective intervention. Compared to the next most effective option, incremental cost of each additional quality-adjusted life year is 11 140.28 yuan, which is below the threshold of willingness to pay (1 year GDP per capita). The value of ICER increased as the increasing age group of adopting intervention, but neither exceeded the threshold of willingness to pay. One-way sensitivity analysis showed that the value of discount rate, the hazard ratio and cost of intervention strategy had a greater impact on the result of ICER. Conclusion: In China, the use of varenicline to quit smoking is highly cost effective in the context of cancer primary prevention, especially for younger smokers.

China Alzheimer's Disease and Neurodegenerative Disorder Research (CANDOR) -A Prospective Cohort Study for Alzheimer's Disease and Vascular Cognitive Impairment.

BACKGROUND: Alzheimer's disease (AD) and vascular cognitive impairment (VCI) are the two main causes of dementia. AD and VCI share similar symptoms of cognitive decline and may be attributable to similar risk factors. Establishing a prospective cohort to compare VCI and AD would help to understand vascular risk factors related to dementia. OBJECTIVES: China Alzheimer's disease and Neurodegenerative Disorder Research (CANDOR) study is a prospective multicenter cohort study. It aims to study the similarities and differences between AD and post stroke cognitive impairment (PSCI) in neuroimaging changes, disease progression, and multiple omics studies. DESIGN: This is an ongoing study. From July 31, 2019, to August 1, 2022, we recruited 1449 participants with ages between 40 and 100 years. The cohort included three groups: AD group, PSCI group, and normal cognitive (NC) group. Data were collected in face-to-face interviews at baseline, and will be followed up every year for 4 years. The PSCI group had additional follow-ups at 3-month and 6-month after enrollment. Brain Magnetic Resonance Imaging (MRI) included high-resolution sequences for intracranial arteries. Cognitive assessments and follow-up information will be prospectively collected. Biological specimens including blood and urine at baseline were collected and tested. PARTICIPANTS: The targeted sample size of PSCI group was 500, AD group with 600 and NC group with 2000. There were 1449 participants enrolled. Include 508 participants were in NC group, 387 in AD group and 554 in PSCI group. MEASUREMENTS: Demographics, clinical parameters, and medical examinations were collected and performed. Cognitive assessment was performed to assess all cognitive domains including memory, language, executive function, and orientation function. CONCLUSIONS: The CANDOR study is a prospective cohort study. Data from this cohort provide us an opportunity to investigate the contribution of vascular factors to dementia pathogenesis.

[Pathogenic characteristics and influence factors of bloodstream infection-induced severe sepsis in pediatric intensive care unit].

Objective: To summarize the pathogenic characteristics of bloodstream infection (BSI)-induced severe sepsis and analyze the influence factors in pediatric intensive care unit (PICU). Methods: Pediatric patients who were diagnosed with severe sepsis caused by BSI in the PICU of Children's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2016 to December 2021 were retrospectively selected and divided into survival group and death group according to their discharge outcomes. Clinical characteristics, laboratory parameters, pathogenic characteristics and drug resistance of the patients were collected. The characteristics of pathogens, clinical and laboratory indicators were summarized, and the influencing factors of death in children with severe sepsis caused by BSI were analyzed based on binary multivariate logistic regression. Results: A total of 132 patients, aged [M (Q1, Q3)] 36 (10, 119) months, with BSI-induced severe sepsis were enrolled in this study, including 81 males and 51 females. There were 38 cases aged 36 (15, 120) months in the death group, including 23 males and 15 females. There were 94 cases, aged 36 (8, 108) months, in the survival group, including 58 males and 36 females. A total of 132 strains of pathogens were isolated, including 87 strains (65.9%) of Gram-negative bacteria. The top 5 pathogens were Klebsiella pneumoniae (24 cases, 18.2%), Escherichia coli (17 cases, 12.9%), Acinetobacter baumannii (13 cases, 9.8%), Pseudomonas aeruginosa (10 cases, 7.6%) and Staphylococcus aureus (10 cases, 7.6%). The proportion of multi-drug resistant bacteria in hospital-acquired BSI was higher than that in community-acquired BSI [52.9% (36/68) vs 15.6% (10/64), P=0.001]. The proportions of community-acquired infection were 58.5% (55/94) and 23.7% (9/38) in the survival and death groups, respectively, the difference was statistically significant (P<0.001). The proportion of central venous catheter insertion before bloodstream infection in the death group was higher than that in the survival group [63.2% (24/38) vs 42.6% (40/94), P=0.034]. According to the binary multivariate logistic regression analysis, hospital-acquired infection (OR=4.80, 95%CI: 1.825-12.621, P=0.001), absolute neutrophil count (ANC) (OR=0.93, 95%CI: 0.863-0.993, P=0.030) and decreased albumin (OR=0.89, 95%CI: 0.817-0.977, P=0.014) were risk factors for death. Conclusions: The common pathogen of BSI-induced severe sepsis in PICU is Gram-negative bacteria. The proportion of multi-drug resistant organisms of BSI obtained in hospitals is high. Children with severe sepsis due to BSI with nosocomial acquired infection, ANC and decreased albumin have a high risk of death.

Mandibular reconstruction using an iliac bone flap with perforator-supported external oblique abdominal muscle island: a pilot study.

The deep circumflex iliac artery (DCIA) flap is one of the bone flaps commonly used for mandibular reconstruction. Observation of the skin paddle and Doppler ultrasound are methods that are usually used to monitor DCIA flaps after mandibular reconstruction surgery. The aim of this study was to introduce a novel DCIA flap with a perforator-supported external oblique abdominal muscle (EOAM) island for postoperative flap monitoring. This study included five patients who underwent mandibular reconstruction using this modified technique. The DCIA flap and the EOAM island supplied by the ascending branch of the DCIA were harvested during the surgery. After mandibular reconstruction, the EOAM island was placed in the submandibular region to monitor the blood supply to the DCIA flap after surgery. The blood supply to the DCIA flap was monitored by observing the colour, texture, and bleeding condition of the EOAM island. After the monitoring period, the EOAM was removed and the ascending branch of the DCIA was ligated. The outcome was successful in all patients. The EOAM island supported by the ascending branch of the DCIA is reliable and safe, thus providing a robust option to monitor the blood supply to the DCIA flap.

Acupuncture and its ability to restore and maintain immune homeostasis.

Immune homeostasis is a steady immune state that not only protects the host from pathogens but also prevents the emergence of pathological self-reactive immune cells. The disruption of immune homeostasis leads to the development of various diseases, such as cancer and autoimmune diseases. An emerging paradigm for the treatment of these diseases with dysfunctional immune systems is the restoration and maintenance of immune homeostasis. However, currently available drugs exert a unidirectional influence on immunity whereby they either augment or inhibit it. This strategy is associated with the drawback of potential adverse effects arising from uncontrolled activation or suppression of the immune system. Fortunately, evidence suggests that acupuncture can bidirectionally regulate the immune system to maintain immune homeostasis. In cases of immunosuppressive diseases (e.g. cancer), acupuncture has an enhancing effect on immunity. Conversely, in autoimmune diseases (e.g. rheumatoid arthritis), acupuncture has been observed to have an immunosuppressive effect, which helps restore normal immune tolerance. However, there is no publication systematically summarizing the bidirectional regulatory effects of acupuncture on the immune system in the literature. Here, our review provides a comprehensive overview of the various mechanisms through which acupuncture modulates the immune system in a bidirectional manner. These mechanisms include the augmentation of NK and CD8+ T cell function, as well as the restoration of Th1/Th2, Th17/Treg and M1/M2 balance. Thus, we propose the concept that acupuncture has the potential to alleviate illnesses through the facilitation of immune normalization. Moreover, we further highlight the therapeutic potential of acupuncture.

Effect of occlusal stabilisation splint with or without arthroscopic disc repositioning on condylar bone remodelling in adolescent patients.

The aim of this study was to investigate the treatment effects of a stabilisation splint (SS) with and without arthroscopic disc repositioning (ADR) on condylar bone remodelling in adolescent patients with anterior disc displacement without reduction (ADDwoR). Cone beam computed tomography and magnetic resonance imaging were used to analyse condylar bone remodelling, condyle position, and disc position. Twenty-two temporomandibular joints of 14 patients who underwent ADR (age range 12-20 years; mean follow-up 12.5 ± 7.8 months) and 21 temporomandibular joints of 14 patients who did not undergo ADR (age range 13-20 years; mean follow-up 11.1 ± 5.1 months) were included. The change in bone volume (P < 0.001), rate of bone volume change (P < 0.001), and change in condyle height (P = 0.031) were significantly greater in patients with ADR than in those without ADR. The changes in posterior joint space (P = 0.013), superior joint space (P = 0.020), and ratio of condyle sagittal position (P = 0.013) were significantly greater in patients with ADR than in those without ADR. All discs in patients who underwent ADR and one disc in those who did not undergo ADR were backward repositioned. In conclusion, in adolescent patients with ADDwoR, ADR with SS therapy achieved better condyle and disc position than SS therapy alone, and also induced bone generation.

Higher-order combinatorial chromatin perturbations by engineered CRISPR-Cas12a for functional genomics.

Multiplexed genetic perturbations are critical for testing functional interactions among coding or non-coding genetic elements. Compared to double-stranded DNA cutting, repressive chromatin formation using CRISPR interference (CRISPRi) avoids genotoxicity and is more effective for perturbing non-coding regulatory elements in pooled assays. However, current CRISPRi pooled screening approaches are limited to targeting 1-3 genomic sites per cell. To develop a tool for higher-order ( > 3) combinatorial targeting of genomic sites with CRISPRi in functional genomics screens, we engineered an Acidaminococcus Cas12a variant -- referred to as mul tiplexed transcriptional interference AsCas12a (multiAsCas12a). multiAsCas12a incorporates a key mutation, R1226A, motivated by the hypothesis of nicking-induced stabilization of the ribonucleoprotein:DNA complex for improving CRISPRi activity. multiAsCas12a significantly outperforms prior state-of-the-art Cas12a variants in combinatorial CRISPRi targeting using high-order multiplexed arrays of lentivirally transduced CRISPR RNAs (crRNA), including in high-throughput pooled screens using 6-plex crRNA array libraries. Using multiAsCas12a CRISPRi, we discover new enhancer elements and dissect the combinatorial function of cis-regulatory elements. These results instantiate a group testing framework for efficiently surveying potentially numerous combinations of chromatin perturbations for biological discovery and engineering.

Rationale and Design of a Phase II Trial of Combined Serplulimab and Chemotherapy in Patients with Histologically Transformed Small Cell Lung Cancer: a Prospective, Single-arm and Multicentre Study.

AIMS: Transformed small cell lung cancer (T-SCLC) is a highly aggressive clinical disease with a notably poor prognosis. It most often arises from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) following treatment. To date, no standard treatment has been established for T-SCLC. Platinum-etoposide was the most commonly used regimen, but progression-free survival remains unsatisfactory. Therefore, there is an urgent unmet need to develop novel and effective strategies for this population. Our study, a multicentre, open-label, single-arm phase II clinical trial (NCT05957510), aims to evaluate the efficacy and safety of serplulimab plus chemotherapy in untreated T-SCLC patients after histological transformation. MATERIALS AND METHODS: In total, 36 eligible participants experiencing SCLC transformation from EGFR-mutant NSCLC will be enrolled to receive combination therapy of serplulimab, etoposide and carboplatin for four to six cycles, followed by maintenance therapy with serplulimab for up to 2 years. The primary endpoint is progression-free survival; secondary endpoints include objective response rate, overall survival and safety. RESULTS: Enrolment started in July 2023 and is ongoing, with an estimated completion date of December 2025. CONCLUSIONS: This study aims to provide valuable insights into the efficacy and safety of combining serplulimab with chemotherapy for treating patients with T-SCLC originating from EGFR-mutant NSCLC.

[Outcomes and care practices of extremely preterm infants at 22-25 weeks' gestation age from the Chinese Neonatal Network].

Objective: To describe the current status and trends in the outcomes and care practices of extremely preterm infants at 22-25 weeks' gestation age from the Chinese Neonatal Network (CHNN) from 2019 to 2021. Methods: This cross-sectional study used data from the CHNN cohort of very preterm infants. All 963 extremely preterm infants with gestational age between 22-25 weeks who were admitted to neonatal intensive care units (NICU) of the CHNN from 2019 to 2021 were included. Infants admitted after 24 hours of life or transferred to non-CHNN hospitals were excluded. Perinatal care practices, survival rates, incidences of major morbidities, and NICU treatments were described according to different gestational age groups and admission years. Comparison among gestational age groups was conducted using χ2 and Kruskal-Wallis tests. Trends by year were evaluated by Cochran-Armitage and Jonckheere-Terpstra tests for trend. Results: Of the 963 extremely preterm infants enrolled, 588 extremely preterm infants (61.1%) were male. The gestational age was 25.0 (24.4, 25.6) weeks, with 29 extremely preterm infants (3.0%), 88 extremely preterm infants (9.1%), 264 extremely preterm infants (27.4%), and 582 extremely preterm infants (60.4%) at 22, 23, 24, and 25 weeks of gestation age, respectively. The birth weight was 770 (680, 840) g. From 2019 to 2021, the number of extremely preterm infants increased each year (285, 312, and 366 extremely preterm infants, respectively). Antenatal steroids and magnesium sulfate were administered to 67.7% (615/908) and 51.1% (453/886) mothers of extremely preterm infants. In the delivery room, 20.8% (200/963) and 69.5% (669/963) extremely preterm infants received noninvasive positive end-expiratory pressure support and endotracheal intubation. Delayed cord clamping and cord milking were performed in 19.0% (149/784) and 30.4% (241/794) extremely preterm infants. From 2019 to 2021, there were significant increases in the usage of antenatal steroids, antenatal magnesium sulfate, and delivery room noninvasive positive-end expiratory pressure support (all P<0.05). Overall, 349 extremely preterm infants (36.2%) did not receive complete care, 392 extremely preterm infants (40.7%) received complete care and survived to discharge, and 222 extremely preterm infants (23.1%) received complete care but died in hospital. The survival rates for extremely preterm infants at 22, 23, 24 and 25 weeks of gestation age were 10.3% (3/29), 23.9% (21/88), 33.0% (87/264) and 48.3% (281/582), respectively. From 2019 to 2021, there were no statistically significant trends in complete care, survival, and mortality rates (all P>0.05). Only 11.5% (45/392) extremely preterm infants survived without major morbidities. Moderate to severe bronchopulmonary dysplasia (67.3% (264/392)) and severe retinopathy of prematurity (61.5% (241/392)) were the most common morbidities among survivors. The incidences of severe intraventricular hemorrhage or periventricular leukomalacia, necrotizing enterocolitis, and sepsis were 15.3% (60/392), 5.9% (23/392) and 19.1% (75/392), respectively. Overall, 83.7% (328/392) survivors received invasive ventilation during hospitalization, with a duration of 22 (10, 42) days. The hospital stay for survivors was 97 (86, 116) days. Conclusions: With the increasing number of extremely preterm infants at 22-25 weeks' gestation admitted to CHNN NICU, the survival rate remained low, especially the rate of survival without major morbidities. Further quality improvement initiatives are needed to facilitate the implementation of evidence-based care practices.