AAV9-based PMM2 gene replacement augments PMM2 expression and improves glycosylation in primary fibroblasts of patients with phosphomannomutase 2 deficiency (PMM2-CDG).

Inherited deficiency of phosphomannomutase 2 (PMM2) (aka PMM2-CDG) is the most common congenital disorders of glycosylation (CDG) and has no cure. With debilitating morbidity and significant mortality, it is imperative to explore novel, safe, and effective therapies for the disease. Our Proof-of-Concept study showed that AAV9-PMM2 infection of patient fibroblasts augmented PMM2 expression and improved glycosylation. Thus, AAV9-PMM2 gene replacement is a promising therapeutic strategy for PMM2-CDG patients.

[Strengthen multidisciplinary diagnosis and treatment and collaborative research on chronic cough].

Chronic cough is the most common complaint in respiratory specialist clinics. The causes of chronic cough are related to respiratory system, otorhinolaryngology, gastroenterology, psychiatry and other systems. Cough hypersensitivity is the most important clinical and pathophysiological feature. Many patients with chronic cough are misdiagnosed and treated inappropriately. To improve the diagnosis and treatment of chronic cough, we should establish a multidisciplinary team and strengthen collaborative study, including cough laboratory, multidisciplinary clinic, and chronic cough ward.

[Advances in clinical studies of chronic cough].

Chronic cough is a common complaint in respiratory specialist clinics, with a significant impact on cough-specific quality of life and psychophysiological health. The diagnosis, treatment and management of chronic cough remains a major challenge. We summarized a series of recent advances from clinical studies in the epidemiology, diagnosis and management of chronic cough over the past year.

CREB3L2 Regulates Hemidesmosome Formation during Epithelial Sealing.

The long-term success rate of dental implants can be improved by establishing a favorable biological sealing with a high-quality epithelial attachment. The application of mesenchymal stem cells (MSCs) holds promise for facilitating the soft tissue integration around implants, but the molecular mechanism is still unclear and the general application of MSC sheet for soft tissue integration is also relatively unexplored. We found that gingival tissue-derived MSC (GMSC) sheet treatment significantly promoted the expression of hemidesmosome (HD)-related genes and proteins in gingival epithelial cells (GECs). The formation of HDs played a key role in strengthening peri-implant epithelium (PIE) sealing. Further, high-throughput transcriptome sequencing showed that GMSC sheet significantly upregulated the PI3K/AKT pathway, confirming that cell adhesion and HD expression in GECs were regulated by GMSC sheet. We observed that the expression of transcription factor CREB3L2 in GECs was downregulated. After treatment with PI3K pathway inhibitor LY294002, CREB3L2 messenger RNA and protein expression levels were upregulated. Further experiments showed that overexpression or knockdown of CREB3L2 could significantly inhibit or promote HD-related genes and proteins, respectively. We confirmed that CREB3L2 was a transcription factor downstream of the PI3K/AKT pathway and participated in the formation of HDs regulated by GMSC sheet. Finally, through the establishment of early implant placement model in rats, we clarified the molecular function of CREB3L2 in PIE sealing as a mechanical transmission molecule in GECs. The application of GMSC sheet-implant complex could enhance the formation of HDs at the implant-PIE interface and decrease the penetration distance of horseradish peroxidase between the implant and PIE. Meanwhile, GMSC sheet reduced the length of CREB3L2 protein expression on PIE. These findings elucidate the potential function and molecular mechanism of MSC sheet regulating the epithelial sealing around implants, providing new insights and ideas for the application of stem cell therapy in regenerative medicine.

[Investigation on cognition, diagnosis and treatment status of chest tightness variant asthma among Chinese pediatricians].

Objective: To evaluate the awareness, diagnosis and treatment of chest tightness variant asthma (CTVA) among pediatricians in China. Methods: The survey was conducted by convenient sampling method. Pediatricians with professional title of attending physician and above from different grades hospitals in 30 provinces were invited to conduct online questionnaire surveys through WeChat, pediatricians scan QR codes to complete electronic questionnaires in the mini program from January 16th to February 4th, 2021. The contents of questionnaire included the awareness, diagnosis and treatment of CTVA, and comparing the differences between pediatricians in secondary hospitals and tertiary hospitals. Results: A total of 1 529 pediatricians participated in the survey, and 1 484 (97.06%) pediatricians completed the questionnaire and included in the analysis, including 420 males (28.30%). The awareness rate of CTVA among pediatricians was 77.83 % (1 155/1 484). Pediatricians in tertiary hospitals had higher rates of awareness of CTVA than pediatricians in secondary hospitals [81.86% (898/1 097) vs 66.41% (257/387), P<0.001] and had better execution of the guidelines [89.15% (978/1 097) vs 79.59% (308/387), P<0.001]. A total of 93.06 % (1 381/1 484) of pediatricians' first-line treatment included inhaled corticosteroids (ICS) for CTVA. Among them, a higher proportion of pediatricians in tertiary hospitals used ICS included regimens for first-line treatment of CTVA compared with pediatricians in secondary hospitals [94.90% (1 041/1 097) vs 87.86% (340/387), P<0.001]. The reported well control rate of CTVA was 32.08% (476/1 484), which was significantly lower in secondary hospitals than that in tertiary hospitals [17.31% (67/387) vs 37.28% (409/1 097), P<0.001]. Conclusion: Most pediatricians are well aware of CTVA, among which there is a certain gap in clinical practice between pediatricians in secondary hospitals and tertiary hospitals in terms of understanding, diagnosis, and treatment of CTVA.

Combining Unimanual and Bimanual Therapies for Children with Hemiparesis: Is There an Optimal Delivery Schedule?

Constraint-induced movement therapy (CIMT) and bimanual therapy (BT) are among the most effective hand therapies for children with unilateral cerebral palsy (uCP). Since they train different aspects of hand use, they likely have synergistic effects. The aim of this study was to examine the efficacy of different combinations of mCIMT and BT in an intensive occupational therapy program for children with uCP. Children (n = 35) participated in intensive modified CIMT (mCIMT) and BT, 6 weeks, 5 days/week, 6 h/day. During the first 2 weeks, children wore a mitt over the less-affected hand and engaged in functional and play activities with the affected hand. Starting in week 3, bimanual play and functional activities were added progressively, 1 hour/week. This intervention was compared to two different schedules of block interventions: (1) 3 weeks of mCIMT followed by 3 weeks of BT, and (2) 3 weeks of BT followed by 3 weeks of mCIMT. Hand function was tested before, after, and two months after therapy with the Assisting Hand Assessment (AHA), Pediatric Evaluation of Disability Inventory (PEDI), and Canadian Occupational Performance Measure (COPM). All three groups of children improved in functional independence (PEDI; p < 0.031), goal performance (COPM Performance; p < 0.0001) and satisfaction (COPM Satisfaction; p < 0.0001), which persisted two months post-intervention. All groups showed similar amounts of improvement, indicating that the delivery schedule for mCIMT and BT does not significantly impact the outcomes.

Cocaine screening in patients undergoing nasal reconstructive surgery: a cross-sectional, survey-based study of UK rhinology consultants.

OBJECTIVE: This study aimed to explore the current practices of the UK rhinology consultant body in regard to cocaine screening in nasal reconstructive surgery. METHOD: A 12-question online survey was distributed to rhinology consultants (October 2021 to February 2022) currently practising in the UK. RESULTS: A total of 55 consultants responded. Fifty-three per cent asked patients about cocaine use prior to consideration of surgery, and 45 per cent performed cocaine testing prior to consideration of surgery. Of these, the majority employed urine testing alone (60 per cent), with hair testing being less common as a single screening modality (4 per cent). Sixteen per cent opted for both urine and hair testing. The most common reasons for not performing cocaine testing included patient history or clinical examination that was not suggestive of cocaine use (44 per cent), lack of formal guidelines (33 per cent) and lack of testing availability (27 per cent). Sixty-four per cent were in favour of a national policy for cocaine screening. CONCLUSION: There is marked variation in cocaine screening practices for nasal reconstructive surgery among UK rhinologists.

[Eosinophilic bronchitis: update and review].

Eosinophilic bronchitis (EB) is a common cause of chronic cough, which shares similar airway eosinophilic inflammation with asthma, however, there is no airway hyperresponsiveness and airflow obstruction. The mechanism of the different phenotype between EB and asthma remains unclear. The differences in the location of airway inflammation, the level of inflammatory mediators, the imbalance of important metabolic pathways, and the degree of airway remodeling may result in different pathogenesis between EB and asthma. EB response well to inhaled corticosteroids but recurrence of EB is still high after treatment. The longer duration of treatment with inhaled corticosteroids could decrease the relapse rate. On the prognosis of EB, a long-term follow-up study suggested that EB should be a distinct entity rather than an early stage of asthma or chronic obstructive pulmonary disease.

Fat necrosis in the breast: a multimodality imaging review of its natural course with different aetiologies.

Fat necrosis of the breast is a commonly encountered condition in daily practice. It is a benign pathology, but it can have variable manifestations and patterns that may sometimes mimic malignancy, depending on its stage of evolution and its underlying cause. This review demonstrates the wide spectrum of appearances of fat necrosis on mammography, digital breast tomosynthesis (DBT), ultrasound, magnetic resonance imaging (MRI), computed tomography (CT), and positron-emission tomography (PET). Sequential follow-up images are included in some cases to illustrate the temporal change of the findings. The typical location and distribution of fat necrosis from a comprehensive list of aetiologies are discussed. Improved knowledge of the multimodality imaging features of fat necrosis could enhance diagnostic accuracy and clinical management, thus avoiding unnecessary invasive investigations.

Vitamin D and smell impairment: a systematic literature review.

OBJECTIVE: Smell impairment affects 60-80 per cent of individuals aged over 80 years. This review aimed to identify any association between vitamin D deficiency and smell impairment, and determine the efficacy of vitamin D to treat smell impairment. METHODS: A literature search was conducted across four databases between the years 2000 and 2022. The literature screen was performed by two independent reviewers. RESULTS: Seven articles were included in this review. Four studies examined the association between vitamin D deficiency and smell impairment, with three studies identifying a significant relationship. Three studies investigated the use of vitamin D as treatment for smell impairment, which found complete resolution or significant symptom improvement after vitamin D deficiency was treated. CONCLUSION: This review identified limited studies on this topic. As vitamin D supplementation is relatively cost-efficient, further large-scale studies should be carried out to investigate the efficacy of vitamin D for treating anosmia.

Semi-automatic method for pre-surgery scoliosis classification on X-ray images using Bending Asymmetry Index.

PURPOSE: Bending Asymmetry Index (BAI) has been proposed to characterize the types of scoliotic curve in three-dimensional ultrasound imaging. Scolioscan has demonstrated its validity and reliability in scoliosis assessment with manual assessment-based X-ray imaging. The objective of this study is to investigate the ultrasound-derived BAI method to X-ray imaging of scoliosis, with supplementary information provided for the pre-surgery planning. METHODS: About 30 pre-surgery scoliosis subjects (9 males and 21 females; Cobb: 50.9 ± 19.7°, range 18°-115°) were investigated retrospectively. Each subject underwent three-posture X-ray scanning supine on a plain mattress on the same day. BAI is an indicator to distinguish structural or non-structural curves through the spine flexibility information obtained from lateral bending spinal profiles. BAI was calculated semi-automatically with manual annotation of vertebral centroids and pelvis level inclination adjustment. BAI classification was validated with the scoliotic curve type and traditional Lenke classification using side-bending Cobb angle measurement (S-Cobb). RESULTS: 82 curves from 30 pre-surgery scoliosis patients were included. The correlation coefficient was R2 = 0.730 (p < 0.05) between BAI and S-Cobb. In terms of scoliotic curve type classification, all curves were correctly classified; out of 30 subjects, 1 case was confirmed as misclassified when applying to Lenke classification earlier, thus has been adjusted. CONCLUSION: BAI method has demonstrated its inter-modality versatility in X-ray imaging application. The curve type classification and the pre-surgery Lenke classification both indicated promising performances upon the exploratory dataset. A fully-automated of BAI measurement is surely an interesting direction to continue our endeavor. Deep learning on the vertebral-level segmentation should be involved in further study.

Can hemifacial spasm lead to glaucomatous changes?

PURPOSE: To evaluate the association between hemifacial spasm (HFS) patients and glaucoma as a function of the Botox dosage required. METHODS: A retrospective review of clinical documents and procedure records. RESULTS: Information of 76 consecutive patients (58 females) with HFS who received Botox treatment were reviewed. The age at onset of HFS was 66±11 (32-85) years, and all manifested unilaterally. Ten (13%, 95% confidence interval: 6.5-22.9%) patients were diagnosed with glaucoma, including 8 primary open-angle glaucoma (POAG) (4 unilateral and ipsilateral to the HFS), and 2 bilateral chronic angle-closure glaucoma (CACG). Nine of the 10 patients developed glaucoma after the onset of the HFS. The Botox dosage was significantly higher among those diagnosed with glaucoma (31+/8 vs. 26+/7units, P<0.05). There was a positive relationship between the presenting intraocular pressure (IOP) and the Botox dosage required (R=0.31, P=0.0116). However, there was a weak relationship between the Botox dosage required and the vertical cup to disc ratio (R=0.076, P=0.525). The presenting IOP of the HFS-affected eyes in those diagnosed with glaucoma was higher than those without glaucoma (19±3.5 vs. 13±3.2mmHg, P=<0.05). The presenting IOP between the HFS-affected and unaffected eyes was similar (16±4.8 vs. 15+/4.6mmHg, P=0.430). Smoking status, history of diabetes mellitus, hypertension, hyperlipidemia and obstructive sleep apnea were not different between HFS patients with or without glaucoma. CONCLUSIONS: Hemifacial spasm patients with glaucoma were associated with a higher Botox dosage. We found a positive relationship between the Botox dosage required and the presenting IOP. Whether hemifacial spasm can result in fluctuation of IOP, eventually causing glaucomatous damage, remains to be studied further.

[Chronic cough in China: progress and perspectives].

Great progress has been made in regard of mechanism, etiological diagnosis and treatment of chronic cough since the beginning of the 20th century, and Chinese guidelines of diagnosis, management of cough was developed. Moreover, Chinese experts also participated in the formulation of international cough guidelines. Through the promotion of the guidelines, the level of diagnosis and treatment of chronic cough has been significantly improved in China. In the future, we should strengthen the studies on the epidemiology of chronic cough, the central regulation of chronic cough, and the treatment of refractory chronic cough, and promote the cough guidelines in primary community hospitals.

[Epidemiology of chronic cough in China: current status and future perspective].

Chronic cough is one of the most common major complaints in medical outpatient. Chronic cough not only seriously affects quality of personal life, but also burdens public health. Large-scale and high-quality epidemiological study on chronic cough has not been carried out in China, and relevant reviews are also lacking. Therefore, based on the studies concerning epidemiology of chronic cough in China, we reviewed the prevalence, risk factors, etiology, quality of life and economic burden. In addition, future perspectives and reasonable suggestions for the development of epidemiology of chronic cough were also proposed.