Lens placode modulates extracellular matrix formation during early eye development.

The role extracellular matrix (ECM) in multiple events of morphogenesis has been well described, little is known about its specific role in early eye development. One of the first morphogenic events in lens development is placodal thickening, which converts the presumptive lens ectoderm from cuboidal to pseudostratified epithelium. This process occurs in the anterior pre-placodal ectoderm when the optic vesicle approaches the cephalic ectoderm and is regulated by transcription factor Pax6 and secreted BMP4. Since cells and ECM have a dynamic relationship of interdependence and modulation, we hypothesized that the ECM evolves with cell shape changes during lens placode formation. This study investigates changes in optic ECM including both protein distribution deposition, extracellular gelatinase activity and gene expression patterns during early optic development using chicken and mouse models. In particular, the expression of Timp2, a metalloprotease inhibitor, corresponds with a decrease in gelatinase activity within the optic ECM. Furthermore, we demonstrate that optic ECM remodeling depends on BMP signaling in the placode. Together, our findings suggest that the lens placode plays an active role in remodeling the optic ECM during early eye development.

Improved small vessel visibility in diabetic foot arteriography using dual-energy CT.

AIM: To test the feasibility and performance of dual-energy computed tomography (DECT) in foot arteriography of diabetic patients, where contrast medium is largely reduced within the small vessels. MATERIALS AND METHODS: A total of 50 diabetic patients were enrolled prospectively, where DECT was acquired immediately after the CT angiography (CTA, group A) of the lower extremity. Two images were derived from the DECT data, one optimal virtual monochromatic image (VMI, group B) and one fusion image (group C), both of which were compared against the CTA image for visualising the foot arteries. The contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) were evaluated. The arterial course and contrast were graded each using a five-point scale. The clarity of small vessel depiction was quantified by comparing the number of plantar metatarsal arteries found in the maximum intensity projection image. RESULTS: The median CNRs and SNRs obtained in group B were approximately 45% and 20% higher than those in groups A and C, respectively (p<0.05). Group B also received higher subjective scores on the posterior tibial artery and the foot arteries (all >3) than groups A and C. The number of visible branches of the plantar metatarsal arteries was found to be substantially higher (p<0.05) in group B (median=6) than in groups A (median=2) and C (median=4). CONCLUSION: DECT was found to be superior to conventional CTA in foot arteriography, and beyond the lower extremity, it might be a general favourable solution for imaging regions with small vessels and reduced contrast medium.

May Measurement Month 2021: an analysis of blood pressure screening results from Ecuador.

Arterial hypertension is a growing burden worldwide, leading to over 10.8 million deaths each year. Before the outbreak of the COVID-19 pandemic, cardiovascular diseases were the main cause of death in Ecuador. Hypertension is the main risk factor for the major cause of death, coronary and cerebrovascular disease. The 2021 May Measurement Month Campaign (MMM21) is a global initiative by the International Society of Hypertension aimed at raising awareness of high blood pressure (BP) and to provide a temporary solution for opportunistic screening until more systematic approaches can be established. A cross-sectional survey was carried out in May 2021 across 22 health centres in Ecuador. The average age of participants was 44.7 ± 15.8 years. Blood pressure measurement, the definition of hypertension (mean of the 2nd and 3rd BP measurements ≥ 140/90 mmHg or on medication for high BP), and statistical analysis followed the standard MMM protocol. In total, 1326 volunteers participated in MMM21. After multiple imputation of missing BP readings, 423 (31.9%) had hypertension. Of those, 70.5% were receiving antihypertensive medication. Of individuals receiving antihypertensive medication, 50.0% had uncontrolled BP. Overall, of 423 participants with hypertension, only 35.2% had their BP controlled (<140/90 mmHg). MMM21 demonstrated a high prevalence of hypertension in Ecuador during the COVID-19 pandemic. It was the largest BP screening campaign done in Ecuador thus far. The high percentage of persons untreated or with uncontrolled hypertension while on pharmacologic treatment suggests that appropriate screening can help to identify a significant number of people with elevated BP and those inadequately treated. These data should attract the attention of doctors and health care providers in Ecuador.

[Clinical characteristics and prognostic factors of breast cancer patients with tumor deposits in the ipsilateral axillary region].

Objective: To investigate the clinicopathologic features and prognostic factors of breast cancer patients with tumor deposits in the ipsilateral axillary region. Methods: We retrospectively analyzed the clinicopathologic data and follow-up results of 155 patients with breast cancer diagnosed for the first time and complicated with tumor deposits in the ipsilateral axillary region in the Department of Thyroid-Breast-Vascular Surgery of Xijing Hospital from January 2008 to September 2018. Kaplan-Meier method was used for survival analysis. Log rank test was used for the univariate analysis of prognostic factors, and Cox regression was used for multivariate analysis. Results: The median disease free survival (DFS), median distant metastasis free survival (DMFS), and median overall survival (OS) of the 155 patients were 52.0 months, 66.6 months, and 102.2 months, respectively. The 5-year and 10-year DFS rates were 45.7% and 23.1%, the 5-year and 10-year DMFS rates were 56.9% and 28.9%, and the 5-year and 10-year OS rates were 79.3% and 46.0%, respectively. Multivariate Cox regression analysis showed that family tumor history (HR=0.362, 95% CI: 0.140-0.937), clinical T stage (T3: HR=3.508, 95% CI: 1.380-8.918; T4: HR=2.220, 95% CI: 1.076-4.580), estrogen/progesterone receptor status (HR=0.476, 95% CI: 0.261-0.866), number of tumor deposits (HR=1.965, 95% CI:1.104-3.500) and neoadjuvant chemotherapy (HR=1.961, 95% CI: 1.032-3.725) were independent influencing factors for DFS. Molecular subtype [human epidermal growth factor receptor-2(HER-2) positive and hormone receptor negative: HR=7.862, 95% CI: 3.189-19.379], number of tumor deposits (HR=2.155, 95% CI: 1.103-4.212), neoadjuvant chemotherapy (HR=5.002, 95% CI: 2.300-10.880) and radiotherapy (HR=2.316, 95% CI: 1.005-5.341) were independent influencing factors of DMFS. Histological grade (HR=4.362, 95% CI: 1.932-9.849), estrogen/progesterone receptor expression (HR=0.399, 95% CI: 0.168-0.945), HER-2 expression (HR=2.535, 95% CI: 1.114-5.768) and neoadjuvant chemotherapy (HR=4.080, 95% CI: 1.679-9.913) were independent influencing factors of OS. Conclusions: The presence of tumor deposits weakens the influence of axillary lymph node status and distant metastases on the prognosis of breast cancer patients. Therefore, a clinicopathological staging system taking into account tumor deposits should be developed. Since the number of tumor deposits affects the risk of recurrence and metastasis of breast cancer patients, we recommend that the number of tumor deposits should be reported in detail in the pathological report after breast cancer surgery.

[Effect of sirolimus combined with anti-CD20 monoclonal antibody desensitization on the prognosis of patients underwent haploidentical stem cell transplantation].

Objective: To investigate the effects of sirolimus combined with anti-CD20 monoclonal antibody desensitization on the prognosis of patients with haploidentical stem cell transplantation (haplo-SCT). Methods: Fifteen consecutive patients who received haplo-SCT and pre-transplant donor specific anti-human leukocyte antigen (HLA) antibody (DSA) positive [mean fluorescence intensity (MFI)≥2 000] in the Institute of Hematological Diseases from November 2021 to March 2023 were retrospectively recruited into the desensitized group. There were 4 males and 11 females, with a median age [M(Q1, Q3)] of 48 (37, 59) years. All patients were desensitized with sirolimus combined with anti-CD20 monoclonal antibody. The non-desensitized group included 29 patients with haplo-SCT who had not received desensitization treatment from August 2012 to June 2016. There were 12 males and 17 females with a median age of 42 (26, 50) years. Up to October 1, 2023, the median follow-up time was 13 (9, 18) months in the study group and 23 (14, 29) months in the control group. The changes of MFI before and after desensitization treatment and the prognosis of patients in the desensitized group were compared, including the incidence of primary implantation failure (pGF), neutrophil implantation time, platelet implantation time, grade Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) and chronic GVHD incidence, non-recurrence related mortality, event-free survival rate, disease-free survival rate and overall survival rate. The survival curve was drawn by Kaplan-Meier method, and the survival rate between groups was compared with Log-rank test. Results: After desensitization treatment, the level of DSA MFI in the desensitized group decreased from 8 879 (7 544, 11 495) to 3 781 (1 638, 4 165) after desensitization treatment (P<0.01). All of the patients achieved hematopoietic recovery, and the median time for neutrophil and platelet engraftment were 14 (11, 15) and 20 (18, 25) days, respectively. The incidence of pGF in the desensitized group was 0, which was lower than that in the non-desensitized group (34.5%, 10/29) (P=0.011). The expected 1-year disease-free survival rate and overall survival rate in the desensitized group were 100% (15/15) and 100% (15/15) respectively, while those in the non-desensitized group were 75.9% (22/29) and 75.9% (22/29) respectively, the difference was not statistically significant (both P>0.05). The one-year event-free survival rate in the desensitized group was expected to be 100% (15/15), which was higher than that in the non-desensitized group (51.3%, 15/29) (P=0.002). Conclusion: Sirolimus combined with anti-CD20 monoclonal antibody desensitization therapy can reduce the DSA level of haplo-SCT recipients, promote hematopoietic engraftment after transplantation, and avoid the occurrence of pGF after transplantation.

CXCR2 expression during melanoma tumorigenesis controls transcriptional programs that facilitate tumor growth.

BACKGROUND: Though the CXCR2 chemokine receptor is known to play a key role in cancer growth and response to therapy, a direct link between expression of CXCR2 in tumor progenitor cells during induction of tumorigenesis has not been established. METHODS: To characterize the role of CXCR2 during melanoma tumorigenesis, we generated tamoxifen-inducible tyrosinase-promoter driven BrafV600E/Pten-/-/Cxcr2-/- and NRasQ61R/INK4a-/-/Cxcr2-/- melanoma models. In addition, the effects of a CXCR1/CXCR2 antagonist, SX-682, on melanoma tumorigenesis were evaluated in BrafV600E/Pten-/- and NRasQ61R/INK4a-/- mice and in melanoma cell lines. Potential mechanisms by which Cxcr2 affects melanoma tumorigenesis in these murine models were explored using RNAseq, mMCP-counter, ChIPseq, and qRT-PCR; flow cytometry, and reverse phosphoprotein analysis (RPPA). RESULTS: Genetic loss of Cxcr2 or pharmacological inhibition of CXCR1/CXCR2 during melanoma tumor induction resulted in key changes in gene expression that reduced tumor incidence/growth and increased anti-tumor immunity. Interestingly, after Cxcr2 ablation, Tfcp2l1, a key tumor suppressive transcription factor, was the only gene significantly induced with a log2 fold-change greater than 2 in these three different melanoma models. CONCLUSIONS: Here, we provide novel mechanistic insight revealing how loss of Cxcr2 expression/activity in melanoma tumor progenitor cells results in reduced tumor burden and creation of an anti-tumor immune microenvironment. This mechanism entails an increase in expression of the tumor suppressive transcription factor, Tfcp2l1, along with alteration in the expression of genes involved in growth regulation, tumor suppression, stemness, differentiation, and immune modulation. These gene expression changes are coincident with reduction in the activation of key growth regulatory pathways, including AKT and mTOR.

[Prevalence of colorectal cancer in 2020: a comparative analysis between China and the world].

Objective: To demonstrate the disease burden and epidemiological characteristics of colorectal cancer in different regions by analyzing the incidence and mortality data in China and worldwide in 2020. Methods: Estimation of the incidence and mortality data of colorectal cancer were obtained from the GLOBOCAN 2020 database. The incidence, death, age standardized incidence rate (ASIR) and age standardized mortality rate (ASMR) of colorectal cancer in China and 20 regions in the world were compared. The correlation between the Human Development Index (HDI) and ASIR/ASMR was analyzed. Results: In 2020, the number of new cases of colorectal cancer in the world reached 1 931 600, and the number of deaths reached 935 200. The incidence and mortality in all regions of the world continued to rise in the age group above 50 years old. The morbidity and mortality in male were higher than those in female. East Asia ranked the highest number of incidence cases and deaths in the world, which were 740 000 and 360 100 respectively. There were significant differences in incidence and mortality among regions in the world. The highest ASIR and ASMR were observed in Northern Europe (33.61/100 000) and Eastern Europe (14.53/100 000), whereas the lowest ASIR and ASMR were both observed in South-Central Asia (5.46/100 000 and 3.16/100 000). HDI had significant exponential relationship with ASIR (r(2)=0.59, P<0.001) and ASMR (r(2)=0.38, P<0.001). There were 555 500 new cases and 286 200 death cases of colorectal cancer in China, accounting for about 30% of the world and more than 75% of East Asia. The ASIR of China was 24.07/100 000, ranking at the medium level, while the ASMR was 12.07/100 000, ranking at the high level of world. Conclusion: The incidence and mortality of colorectal cancer are highly correlated with HDI. China is one of the countries with the heaviest disease burden of colorectal cancer in the world.

[Clinical characteristics of patients with human adenovirus infection undergoing allogeneic hematopoietic stem cell transplantation].

Objective: To investigate the clinical characteristics and prognosis of human adenovirus (HAdV) infection in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: This is a retrospective case series study. Patients who received allo-HSCT and had symptoms of HAdV infection were tested in the Hematology Department at Perking University People's Hospital from August 2015 to October 2019. Real-time quantitative PCR was used to detect HAdV DNA from 2 728 patients with potential infection. HAdV DNA-positive patients were defined as having HAdV infection. The clinical features of these patients were analyzed, and a case-pair method was used to select patients without HAdV infection as the control group in a 1∶3 ratio. The clinical results of the two groups were compared using Kaplan-Meier and Log-rank testing. Results: A total of 7 119 samples were tested for HAdV, of which 99 samples from 36 patients were positive. Of these patients, 22 developed HAdV viremia, and 24 patients had concurrent infection with another virus. Nineteen patients had fever (53%), 25 had gastrointestinal symptoms (69%), 11 had respiratory symptoms (31%), nine had reduced liver function (25%), and six had nervous system symptoms (17%). Twenty-three patients developed acute graft-versus-host disease of grade 2 or higher. Of all the patients with HAdV infection, nine were treated with cidofovir, seven of whom became HAdV negative and two had invalid treatment. The median follow-up time was 496 (216, 940) d post-HSCT. The overall survival at 5 years post HSCT was 48.4%±9.2% vs. 91.3%±3.5% (χ2=65.03, P<0.001) in patients with and without HADV, respectively. The non-relapse mortality at 5 years post-HSCT was 40.8%±8.8% vs. 4.0%±2.0% (χ2=34.17, P<0.001) in patients with and without HADV, respectively. Conclusions: After allo-HSCT, HAdV-infected patients are dominated by gastrointestinal and respiratory symptoms and have an increased risk of combined acute graft-versus-host disease of >2 degrees. Patients with HAdV infection have poor overall survival and high non-relapse mortality.

[Safety and survival analysis of haplo-identical hematopoietic stem cell transplantation in patients with severe aplastic anemia who had previous failure to antithymoglobulin treatment].

Objective: To investigate the safety and efficacy of haplo-identical hematopoietic stem cell transplantation (haplo-HSCT) conditioning with the same dosage form of antithymoglobulin (ATG) in patients with severe aplastic anemia (SAA) failure to ATG. Methods: This was a retrospective cohort study. A total of 65 patients with SAA who failed ATG treatment and received haplo-HSCT conditioning with the same dosage of ATG at the Institute of Hematology, Peking University People's Hospital between July 2008 and October 2020 were included as the ATG treatment failure group. An additional 65 SAA patients who applied ATG for the first time during haplo-HSCT were randomly selected by stratified sampling as the first-line haplo-HSCT group. Baseline clinical data and follow-up data of the two groups were collected. Conditioning-related toxicity within 10 days after ATG application and long-term prognosis were analyzed. The Kaplan-Meier was used to calculate the overall survival rate, and the Log-rank test was applied to compare the rates of the two groups. Results: In the ATG treatment failure group, there were 36 males and 29 females, and the age at the time of transplantation [M (Q1, Q3)] was 16 (8, 25) years. In the first-line haplo-HSCT group, there were 35 males and 30 females, with a median age of 17 (7, 26) years. Within 10 days of ATG application, the incidence of noninfectious fever, noninfectious diarrhea, and liver injury in the ATG treatment failure group was 78% (51 cases), 45% (29 cases), and 28% (18 cases), respectively, and in the first-line haplo-HSCT group was 74% (48 cases), 54% (35 cases), and 25% (16 cases), respectively; the difference between the two groups was not statistically significant for any of these three parameters (all P>0.05). For graft-versus-host disease (GVHD), there was no significant difference between the ATG treatment failure group and the first-line haplo-HSCT group in the development of 100 day Ⅱ to Ⅳ acute GVHD (29.51%±0.35% vs. 25.42%±0.33%), Ⅲ to Ⅳ acute GVHD (6.56%±0.10% vs. 6.78%±0.11%), and 3-year chronic GVHD (26.73%±0.36% vs. 21.15%±0.30%) (all P>0.05). Three-year overall survival (79.6%±5.1% vs. 84.6%±4.5%) and 3-year failure-free survival (79.6%±5.1% vs. 81.5%±4.8%) were also comparable between these two groups (both P>0.05). Conclusions: Compared with no exposure to ATG before HSCT, similar early adverse effects and comparable survival outcomes were achieved in patients with SAA who failed previous ATG treatment and received haplo-HSCT conditioning with the same dosage form of ATG. This might indicate that previous failure of ATG treatment does not significantly impact the efficacy and safety of salvaging haplo-HSCT in patients with SAA.

[Clinical analysis of the usefulness of letermovir for prevention of cytomegalovirus infection after haploidentical hematopoietic stem cell transplantation].

Objective: To analyze the efficacy and safety of letermovir in primary prophylaxis of cytomegalovirus (CMV) reactivation in patients receiving haploidentical hematopoietic stem cell transplantation. Methods: This retrospective, cohort study was conducted using data of patients who underwent haploidentical transplantation at Peking University Institute of Hematology and received letermovir for primary prophylaxis between May 1, 2022 and August 30, 2022. The inclusion criteria of the letermovir group were as follows: letermovir initiation within 30 days after transplantation and continuation for≥90 days after transplantation. Patients who underwent haploidentical transplantation within the same time period but did not receive letermovir prophylaxis were selected in a 1∶4 ratio as controls. The main outcomes were the incidence of CMV infection and CMV disease after transplantation as well as the possible effects of letermovir on acute graft versus host disease (aGVHD), non-relapse mortality (NRM), and bone marrow suppression. Categorical variables were analyzed by chi-square test, and continuous variables were analyzed by Mann-Whitney U test. The Kaplan-Meier method was used for evaluating incidence differences. Results: Seventeen patients were included in the letermovir prophylaxis group. The median patient age in the letermovir group was significantly greater than that in the control group (43 yr vs. 15 yr; Z=-4.28, P<0.001). The two groups showed no significant difference in sex distribution and primary diseases, etc. (all P>0.05). The proportion of CMV-seronegative donors was significantly higher in the letermovir prophylaxis group in comparison with the control group (8/17 vs. 0/68, χ2=35.32, P<0.001). Three out of the 17 patients in the letermovir group experienced CMV reactivation, which was significantly lower than the incidence of CMV reactivation in the control group (3/17 vs. 40/68, χ2=9.23, P=0.002), and no CMV disease development observed in the letermovir group. Letermovir showed no significant effects on platelet engraftment (P=0.105), aGVHD (P=0.348), and 100-day NRM (P=0.474). Conclusions: Preliminary data suggest that letermovir may effectively reduce the incidence of CMV infection after haploidentical transplantation without influencing aGVHD, NRM, and bone marrow suppression. Prospective randomized controlled studies are required to further verify these findings.

[Clinical and genetic analysis of tyrosine hydroxylase deficiency of six cases].

The clinical and molecular genetic data of 6 patients with genetically confirmed tyrosine hydroxylase deficiency(THD) diagnosed in Department of Neurology, Qilu Hospital of Shandong University from March 2017 to February 2022 were retrospectively collected and analyzed. The 6 patients were from 5 families. Among them, 5 patients had persistent or paroxysmal abnormal walking posture, 4 patients had dystonia of head and face, including spasm of perioral and oculopharyngeal muscles, hyperactivity, and binocular upvision, 4 patients showed obvious morning light and evening heavy phenomenon, 2 patients had postural tremor of limbs, 2 patients had psychomotor retardation from childhood, 1 patient only had limb and cervical muscle weakness, 1 patient had epileptic seizures. Of the 6 patients, only 1 was adult-onset, and the rest were child-onset. Four patients had good response to low-dose dopa preparation, 2 patients from the same family had poor response to dopamine treatment, requiring extremely low dose initiation and multi-frequency titration treatment. However, the long-term treatment effect was poor with obvious abnormalities. Gene testing of 5 families revealed 8 mutations in the TH gene, with c.698G>A (p.R233H) being the hot spot mutation site. The clinical manifestations of THD are complex. Besides paroxysmal or persistent dystonia, it can also be accompanied by eye movement crisis, muscle weakness, epilepsy, and delayed mental and motor development. Most patients respond well to low-dose dopamine preparations, but a small number of patients require titration treatment with extremely low-dose dopamine preparations, and the long-term effect is not satisfactory.

[Analysis on epidemiological characteristics of allergens with allergic skin diseases in a hospital in Beijing City from 2017 to 2021].

Objectives: In order to provide valuable information for the diagnosis and treatment of dermatitis, the prevalence rate and trend changes of common allergens in patients with allergic skin diseases in Beijing City were investigated and analyzed. Methods: This study was a retrospective data collection study. A total of 2 822 patients diagnosed with moderate to severe atopic dermatitis with allergen examinations were collected from Peking University First Hospital from 2017 to 2021, most of them were adults, and 83%(2 340/2 822) were over 18 years old. The ImmunoCAP fluorescent enzyme-linked immunoassay system was used to quantify specific IgE. The positive rate of each allergen was counted according to age, gender and year. The epidemiological characteristics and trends were analyzed. Results: In the past five years, 22 503 allergen-specific IgE test data were collected, and the positive rate of allergens in 40%(1 122/2 822) of the 2 822 patients was mainly multiple sensitization, the positive rate of allergens and multiple sensitization rates were the highest in people aged 13-18 years old. The 2 822 patients were dominated by inhaled allergens, and the highest positive rate was inhaled mixture (29.3%). The top five positive rates of inhaled allergens were Dermatophagoides farina (26.7%), Dermatophagoides pteronyssinus (25.5%), Mugwort (23.9%), Birch pollen (19.2%) and Siberian cocklebur (18.2%). The top five positive rates of food allergens were shrimp (15.2%), peanut (14.8%), sesame (14.7%), wheat (13.2%) and milk (13.1%). Analysis of the positive rate of allergens in different age groups showed except for the positive rate of birch pollen peaked at 3-12 years old, other inhaled allergens were the highest food allergens in 13-18 years old. Among food allergens, the positive rates of fx5, milk, egg and wheat were the highest in <3 years old, the positive rate decreased gradually with age, and the positive rate of other food allergens peaked at 13-18 years old, and the shrimp and crab was the highest in adult. The positive rate of various allergens in the 2 822 patients showed little difference between male and female and the male was slightly higher than female. In the past five years, the positive rate of allergens has been on the rise. The changes of inhaled allergens in cat/dog hair dander, Dermatophagoides farina and cicadas were large, while the positive rate of food allergens was stable. Conclusions: The etiology of the allergic skin diseases is complex, which may be related to allergen exposure, heredity, immunity, environmental factors, abnormal skin barrier function, etc. This study showed the distribution of allergens in patients with allergic skin diseases in Beijing City to a certain extent. It provided epidemiological data and clinical evidence for the prevention and treatment of allergic diseases.

[Promote the high-quality development of gastrointestinal surgery with technological concept innovation].

In the past 30 years, gastrointestinal surgery in China has made significant progress, which is reflected in the gradual standardization of clinical diagnosis and treatment, significant improvement in surgical quality, improvement in short-term and long-term postoperative outcomes, and continuous development of high-quality clinical research. At present, the spectrum of disease in gastrointestinal surgery has changed from traditional benign diseases to malignant diseases represented by gastric cancer and colorectal cancer, metabolic diseases represented by obesity and diabetes, and immune diseases represented by inflammatory bowel disease. It is necessary to carry out full-cycle management for patients. In the new era full of opportunities and challenges, surgeons must be driven by innovation in surgical technology, guided by high-quality clinical research and guaranteed by standardized diagnosis and treatment of diseases, to continue to promote the high-quality development of gastrointestinal surgery in China.

The COVANOS trial - insight into post-COVID olfactory dysfunction and the role of smell training.

BACKGROUND: Olfactory dysfunction is a cardinal symptom of COVID-19 infection, however, studies assessing long-term olfactory dysfunction are limited and no randomised-controlled trials (RCTs) of early olfactory training have been conducted. METHODOLOGY: We conducted a prospective, multi-centre study consisting of baseline psychophysical measurements of smell and taste function. Eligible participants were further recruited into a 12-week RCT of olfactory training versus control (safety information). Patient-reported outcomes were measured using an electronic survey and BSIT at baseline and 12 weeks. An additional 1-year follow-up was open to all participants. RESULTS: 218 individuals with a sudden loss of sense of smell of at least 4-weeks were recruited. Psychophysical smell loss was observed in only 32.1%; 63 participants were recruited into the RCT. The absolute difference in BSIT improvement after 12 weeks was 0.45 higher in the intervention arm. 76 participants completed 1-year follow-up; 10/19 (52.6%) of participants with an abnormal baseline BSIT test scored below the normal threshold at 1-year, and 24/29 (82.8%) had persistent parosmia. CONCLUSIONS: Early olfactory training may be helpful, although our findings are inconclusive. Notably, a number of individuals who completed the 1-year assessment had persistent smell loss and parosmia at 1-year. As such, both should be considered important entities of long-Covid and further studies to improve management are highly warranted.

Characterization of embryonic surface ectoderm cell protrusions.

BACKGROUND: During embryonic development, complex changes in cell behavior generate the final form of the tissues. Extension of cell protrusions have been described as an important component in this process. Cellular protrusions have been associated with generation of traction, intercellular communication or establishment of signaling gradients. Here, we describe and compare in detail from live imaging data the dynamics of protrusions in the surface ectoderm of chick and mouse embryos. In particular, we explore the differences between cells surrounding the lens placode and other regions of the head. RESULTS: Our results showed that protrusions from the eye region in mouse embryos are longer than those in chick embryos. In addition, protrusions from regions where there are no significant changes in tissue shape are longer and more stable than protrusions that surround the invaginating lens placode. We did not find a clear directionality to the protrusions in any region. Finally, we observed intercellular trafficking of membrane puncta in the protrusions of both embryos in all the regions analyzed. CONCLUSIONS: In summary, the results presented here suggest that the dynamics of these protrusions adapt to their surroundings and possibly contribute to intercellular communication in embryonic cephalic epithelia.

[Incidence and cause of abnormal cholesterol in children aged 2-18 years in a single center].

OBJECTIVE: To investigate the abnormality and distribution of plasma cholesterol levels in single-center hospitalized children. METHODS: The blood lipid levels of children aged 2-18 years who had blood lipid test results in Peking University First Hospital from June 2016 to June 2019 were etrospectively analyzed. Cholesterol oxidase method was used for total cholesterol, and high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were detected by clearance method. The counting data were compared with chi-square test. RESULTS: The survey had involved 11 829 children (7 087 were boys and 4 742 were girls). 1 822 (15.4%) children were with elevated total cholesterol, 1 371 (11.6%) children with elevated low-density lipoprotein cholesterol, and 2 798 (23.7%) children with high-density lipoprotein cholesterol reduction. The total number of the children with abnormal cholesterol levels was 4 427 (37.4%). Among the 7 835 children who visited hospital due to the disease not commonly inducing dyslipidemia, 731 (9.3%) had elevated TC, 561 (7.2%) had elevated LDL-C, 1 886 (24.1%) had decreased HDL-C, and 2 576 (32.9%) had abnormal cholesterol levels. Among the children with different diseases, the difference in the incidence of abnormal cholesterol was statistically significant. The top three main groups of the children with increased total cholesterol and low-density lipoprotein cholesterol were "dyslipidemia", "urinary tract disease", and "nutritional disease"; The top three main groups of the children with reduced high-density lipoprotein cholesterol were "respiratory diseases", "dyslipidemia", "hematological diseases and malignant tumors". Among the 1 257 blood li-pid test results sent by other departments, 300 cases had abnormal cholesterol levels (23.8%). Among them, there were 70 children with hypercholesterolemia (5.6%), 44 children with increased low-density lipoprotein cholesterol (3.5%), and 224 children with reduced high-density lipoprotein cholesterol (17.8%). There were 365 (4.6%) children with low-density lipoprotein cholesterol ≥140 mg/dL (3.6 mmol/L) who needed to further exclude familiar hypercholesterolemia among the children who visited hospitals due to the disease not commonly inducing dyslipidemia. CONCLUSION: Children in hospitals have a high incidence of cholesterol abnormalities. Doctors need to pay more attention to the cholesterol diagnosis and management regardless of the discipline, which not only helps to control secondary hypercholesterolemia, but also provides the possibility of detecting familial hypercholesterolemia in time.

[Relationship between treatment and prognosis in patients with late-onset severe pneumonia after allogeneic hematopoietic stem cell transplantation].

OBJECTIVE: To explore the relationship between drug treatment and outcomes in patients with late-onset severe pneumonia (LOSP) after allogeneic stem cell transplantation (allo-SCT). METHODS: We retrospectively analyzed the effects of the initiation time of treatment drugs, especially antiviral drugs and glucocorticoids on the clinical outcomes in 82 patients between January 2016 and August 2021 who developed LOSP after allo-SCT in Peking University People's Hospital. Univariate analysis was performed by Mann-Whitney U test and χ2 test, and multivariate analysis was performed by Logistic regression. When multiple groups (n>2) were involved in the χ2 test, Bonferroni correction was used for the level of significance test. RESULTS: Of all 82 patients in this study, the median onset time of LOSP was 220 d (93-813 d) after transplantation, and the 60-day survival rate was 58.5% (48/82). The median improvement time of the survival patients was 18 d (7-44 d), while the median death time of the died patients was 22 d (2-53 d). Multivariate analysis showed that the initiation time of antiviral drugs from the onset of LOSP (< 10 d vs. ≥10 d, P=0.012), and the initiation time of glucocorticoids from antiviral drugs (< 10 d vs. ≥10 d, P=0.027) were the factors affecting the final outcome of the patients with LOSP at the end of 60 d. According to the above results, LOSP patients were divided into four subgroups: group A (antiviral drugs < 10 d, glucocorticoids ≥10 d), group B (antiviral drugs < 10 d, glucocorticoids < 10 d), group C (antiviral drugs ≥10 d, glucocorticoids ≥10 d) and group D (antiviral drugs ≥10 d, glucocorticoids < 10 d), the 60-day survival rates were 91.7%, 56.8%, 50.0% and 21.4%, respectively. CONCLUSION: Our study demonstrated that in patients who developed LOSP after allo-SCT, the initiation time of antiviral drugs and glucocorticoids were associated with the prognosis of LOSP, and the survival rate was highest in patients who received antiviral drugs early and glucocorticoids later. It suggested that for patients with LOSP of unknown etiology should be highly suspicious of the possibility of a secondary hyperimmune response to viral infection.

[Green channel construction mode and development of stroke center in China].

Stroke poses a social and economic burden worldwide.Intravenous thrombolytic therapy and endovascular interventional therapy are recommended as early as possible for patients with acute ischemic stroke in many national and international guidelines, however, their clinical applications are limited due to their strong time dependence.To date, the treatment of acute stroke in China has many problems, such as backward development of hospital treatment process and shortage of stroke professionals.Establishing a complete stroke green channel and maintaining its smooth operation contributes to the most important and effective way to promote thrombolytic therapy, which requires setting a clear target time, appropriately adjusting the hospital layout and hardware and software investment, attaching importance to team building and clear job responsibilities.Moreover, the most important task is to improve the green channel process through replacing the "serial mode" with the "parallel mode", making full use of the first aid map of stroke, bridging the gap between pre-hospital and in-hospital treatment, and popularizing stroke-related knowledge.In recent years, considerable progress has been made in the construction of stroke green channel in China.The implementation of the above-mentioned reform mode may minimize pre-hospital and in-hospital delays, expand the benefit population of stroke and thus improve the early treatment rate of acute ischemic stroke.

[Contrastive study on MRI signs of intestinal and pancreatobiliary-type periampullary carcinoma].

Objective: The magnetic resonance imaging (MRI) features of intestinal-type periampullary carcinoma (IPAC) and pancreatobiliary-type periampullary carcinoma (PPAC) were compared and analyzed to discuss the optimal diagnosis scheme. Method: Preoperative MRI images of 59 patients (32 males, 27 females, aged 37-80 years) diagnosed with periampullary carcinoma (PAC) confirmed by surgery and pathology in Nanjing Drum Tower Hospital from January 2017 to July 2020 were retrospectively analyzed. The patients were divided into 21 cases in the IPAC group (11 males, 10 females) and 38 cases in the PPAC group (21 males, 17 females) according to histopathological results. The conventional MRI plain scan signs included in the analysis include lesion morphology, the largest diameter of the lesion, lesion location, duodenal papilla morphology, plain scan lesion signal (with the normal pancreatic signal as reference), diffusion weighted imaging (DWI) signal. Magnetic resonance cholangiopancreatography (MRCP) image signs include the dilatation of common bile duct and main pancreatic duct and quantitative analysis of their diameter, the presence of a round filling defect in the distal end of the common bile duct, the morphology of common bile duct stenosis, the dilatation of lateral branches around the obstructed pancreatic duct, the ductal sign, the distance from the end of the obstructed common bile duct to the duodenal papilla, the distance from the end of the obstructed pancreatic duct to the duodenal papilla, and the angle of the pancreaticobiliary duct. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of single meaningful factors. The MRI features of PAC were summarized according to the significant single factor indicators and were classified into 5 image types. And the diagnostic efficacy of the classification criteria for pathological subtypes of PAC was evaluated by the ROC curve. The DeLong test was used to compare the area under the ROC curve (AUC) of multiple diagnostic methods. Results: In univariate analysis, there were statistically significant differences between IPAC and PPAC in lesion location, duodenal papilla morphology, the circular filling defect in the distal end of the common bile duct, the distance from the obstructed pancreatic duct to the duodenal papilla, the angle of the pancreaticobiliary duct, and lesion signal characteristics on plain T2WI fat suppressant images (all P<0.05). Among the 5 types of MRI images, IPAC is mostly manifested as duodenal papillary nodules(15/21,71.4%), while PPAC is more manifested as pancreatic mass type(18/38,47.4%), thickened common bile duct wall type(9/38,23.7%) or ampullary mass type(9/38,23.7%). Both IPAC(2/21,9.5%) and PPAC(0,0) rarely showed the nodular type of common bile duct lumen. In the DeLong test of the significant univariate index(lesion location, duodenal papilla morphology, the circular filling defect in the distal end of the common bile duct, the distance from obstructed pancreatic duct to duodenal papilla, the angle of the pancreaticobiliary duct, and lesion signal characteristics on plain T2WI fat suppressant images) and the 5 classification of MRI images, the AUC of the 5 classifications of MRI images was 0.932(95%CI:0.867-0.997), which was higher than that of any of the significant univariate indexes (all P<0.05). In addition, the 5 classifications of MRI images have the same high diagnostic power as the logistic regression analysis model(P>0.05). Conclusions: The 5 classification of MRI images can improve the accuracy of differential diagnosis of IPAC and PPAC before surgery, and the diagnostic efficiency is better than any single factor meaningful index and comparable to that of the logistic regression analysis model.

[Keratoconus after transepithelial photorefractive keratectomy: a case report].

A 24-year-old male was treated with transepithelial photorefractive keratectomy for myopia in both eyes 5 years ago. He had allergic conjunctivitis for 3 years. The night vision of both eyes was decreased for 2 years. The clinical diagnosis was keratoconus binoculus. Therefore, corneal collagen cross-linking was performed in both eyes, and the follow-up was 6 months. Confocal microscopy showed that the cross-linking of riboflavin and fiber amino was successful, and the keratoconus did not progress during the follow-up. Although there have been few case reports of keratoconus after transepithelial photorefractive keratectomy at home and abroad, great importance should be attached to the early and comprehensive screening of keratoconus in the candidates of refractive surgery in order to improve the long-term safety.