Nowadays,the prevalence of nonalcoholic fatty liver disease(NAFLD)is constantly rising in China and globally,and its incidence rate is increasing year by year,which has seriously affected human life and health.Lipophagy is molecular chaperone-mediated autophagy and has the functions of promoting lipolysis,maintaining the lipid homeostasis of hepatocytes,and alleviating hepatocyte fatty degeneration.Lipophagy has three main processes of lipid droplet catabolism,lipid droplet autophagy,and fatty acid β-oxidation,which are regulated by key genes,receptors,and enzymes.Currently,important advances have been achieved for the intervention methods of traditional Chinese medicine,Western medicine,diet,and exercise in the research on lipophagy,which provides new perspectives for the prevention and treatment strategies for NAFLD.

Objective:To analyze the clinical phenotype and the associated pathogenic genes in a family exhibiting autosomal dominant inherited optic atrophy (ADOA).Methods:A pedigree analysis was conducted on a Han Chinese family with ADOA comprising two generations and four individuals from Henan Province.The family with two ADOA patients was recruited at Henan Eye Hospital between July and October 2023.Detailed medical histories were collected for the proband and family members.Comprehensive ophthalmologic evaluations were performed, including assessments of visual acuity, visual field, fundus photography, electroretinogram (ERG), visual evoked potential (VEP), and optical coherence tomography.Additionally, hearing, electromyography, and magnetic resonance imaging were performed on the proband to assess the presence of systemic symptoms.Peripheral blood samples were collected from four family members, and whole exome sequencing (WES) was performed on the proband, with subsequent validation via Sanger sequencing for the other family members.The pathogenicity and protein struture of the novel variant were analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[15]).Written informed consent was obtained from each subject.Results:The proband was a 15-year-old female with a 4-year history of vision loss in the left eye and optic atrophy, mild thinning of central macular foveal thickness, locally mild thinning of ganglion cell complex layer thickness, low VEP amplitude, and partial visual field defects in both eyes, and no significant hearing impairment or dystonia on systemic examination.The proband's mother had partial optic nerve atrophy and slightly decreased central macular foveal thickness in both eyes, and mild ERG abnormalities, but no significant VEP abnormalities.WES identified a heterozygous nonsense variant c. 676C>T (p.Gln226Ter) in exon 6 of the OPA1 gene of the proband and her mother.This variant has not been previously reported in the literature, nor is it listed in the Human Gene Mutation Database, the Thousand Genomes Project, or the Genome Aggregation Database, which results in a premature termination codon at glutamine position 226.Protein structure analysis showed that p. Gln226Ter of the OPA1 protein induces alterations in the hydrogen bonding of the protein binding to surrounding residues, which in turn leads to protein function alterations.The variant was classified as potentially pathogenic according to the ACMG standards and guidelines. Conclusions:Patients in this ADOA family present with adolescent-onset optic atrophy in both eyes, with a predominance in the left eye.The c. 676C>T variant in OPA1 gene might be the causative variant in this ADOA family.Notably, this is the first report of this specific variant.

Objective:To compare the detection rate and time cost of different imaging methods for retinal and optic disc neovascularization in proliferative diabetic retinopathy (PDR).Methods:A cross-sectional study was conducted.Thirty-eight patients (48 eyes) with PDR were enrolled in Henan Eye Hospital from October 2019 to February 2021, including 22 males (28 eyes) and 16 females (20 eyes). The average age of the patients was (51.08±13.35) years.All patients underwent ultra-widefield imaging (UWFI), fundus fluorescein angiography (FFA), optical coherence tomography angiography (OCTA), en face optical coherence tomography (OCT), near-infrared fundus imaging (IR) combined with spectral domain OCT (SD-OCT). Wide field swept-source OCTA (WF-SS-OCTA) was performed in the patients who were unsuitable for FFA.The time required for each examination in one eye and the detection rate of neovascularization at the optic disc (NVD) and retinal neovascularization elsewhere (NVE) were recorded.This study adhered to the Declaration of Helsinki.The study protocol was approved by Henan Eye Hospital (No.HNEECKY-2021[22]). All patients were informed about the method and purpose of the study and voluntarily signed the informed consent form.Results:The mean monocular examination time costs of UWFI, IR+ SD-OCT, OCTA+ en face OCT, FFA and WF-SS-OCT was (0.51±0.13), (2.08±0.57), (5.79±0.68), (17.66±1.83) and (13.38±1.23)min, respectively.There was a significant overall difference in the mean monocular examination time among the five methods ( F=2 077.960, P<0.001). The detection rates of UWFI, IR+ SD-OCT, OCTA+ en face OCT, FFA+ WF-SS-OCT for NVE and NVD were 52.1%(25/48) and 12.5%(6/48), 81.3%(39/48) and 20.8%(10/48), 83.3%(40/48) and 27.1%(13/48), 93.8%(45/48) and 29.2%(14/48), respectively.There were significant differences in the detection rates of NVE ( χ2=26.460, P<0.001) but not in the detection rates of NVD ( χ2=4.645, P=0.200) among the various methods.Five neovascular buds were detected by OCTA in 3 eyes, but not by FFA. Conclusions:UWFI and IR+ SD-OCT are faster and non-invasive methods for the screening of NVD and NVE in PDR eyes.Compared with FFA, OCTA and en face OCT can show the shape of neovascularization more clearly.FFA provides a wide-range retinal image, but it is time-consuming and invasive.WF-SS-OCTA extends the examination range of OCTA and detects neovascularization non-invasively and faster than FFA.

Objective:To investigate the clinical efficacy in one stage reconstruction of composite defects of Achilles tendon and surrounding soft tissues with a flap transfer combined with allogeneic tendon transplantation.Methods:From July 2018 to August 2022, a total of 12 patients, including 9 males and 3 females, with a mean age of 31.5(ranged 8 to 56) years old, had surgery with flap transfer combined with transplantation of allogeneic tendon in one stage reconstruction for compound defects of Achilles tendon and soft tissue at the Department of Orthopaedics of First Affiliated Hospital of Nanchang University. The defects of Achilles tendons ranged from 4.0 to 9.0 cm, and the soft tissue defects sized from 3.0 cm × 4.0 cm to 14.0 cm × 6.0 cm. Of the 12 patients, 6 received transfers of sural neurovascular flaps, 3 with peroneal perforator flaps and 3 with free anterolateral thigh flaps(ALTF). The flaps sized from 4.0 cm × 4.5 cm to 15.0 cm×7.0 cm, and in addition, allogeneic tendon grafts were used to reconstruct the defects of Achilles tendons in all patients. All the flap donor sites were either directly sutured or covered with skin grafts. Follow-up was carried out by visits of outpatient clinic or telephone or WeChat distant interviews. The flap survival and recovery of ankle function and Achilles tendon were observed.Results:During the 3 months to 2 years of follow-up, none of the patient showed obvious immunological rejection against the transplanted allogeneic tendon. All 12 flaps survived well with the colour and texture close to the surrounding skin. No ulceration occurred in both of the donor and recipient sites. There was no re-rupture of the transplanted allogeneic tendon. At the final follow-up, ankle movement was measured at 13.4°±2.6° in dorsal extension and 33.6°±3.2° in plantar flexion. According to American Orthopaedic Foot and Ankle Society (AOFAS) ankle and hind foot function score, a score of 88.7±5.6 was achieved with 7 patients in excellent, 4 in good and 1 was acceptable.Conclusion:In patients with a composite defect of Achilles tendon and surrrounding soft tissue, the application of a flap transfer combined with a homogeneous allograft tendon transplantation in an one stage surgery is a feasible surgical procedure. It can achieve a satisfactory outcome with less trauma and fewer complications.

Objective:To investigate the imaging features of iris fluorescein angiography (IFA) combined with fluorescein fundus angiography (FFA) in diabetic iridopathy.Methods:A cross-sectional study was conducted.Sixty-five eyes of 44 patients with proliferative diabetic retinopathy (PDR) combined with diabetic iridopathy (DI) were enrolled in Henan Eye Hospital from May 2013 to May 2020.Patients were divided into non-proliferative diabetic iridopathy (NPDI) group and rubeosis iridis group according to the imaging results.Ophthalmic examinations including visual acuity, intraocular pressure, slit lamp miacroscopy, IFA and FFA were carried out in all patients.IFA was used to detect the iris imaging characteristics and the regression time of fluorescein in anterior chamber, and FFA was used to observe the retinal image characteristics and the incidence of optic disc neovascularization.To avoid the statistical error of recording the IFA examination time of the contralateral eye, only the relevant data of the affected eyes were analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2020[06]). Written informed consent was obatined from all patients before any medical examination.Results:Among the patients, 30 cases (50 eyes) were with NPDI and 14 cases (15 eyes) were with rubeosis iridis.The fluorescein regression time in anterior chamber of NPDI group was (3.37±0.11) minutes, which was significantly shorter than (6.02±0.29) minutes of rubeosis iridis group ( t=8.541, P<0.001). Strong fluorescence of retinal neovascularization was observed in both groups.The incidence of optic disc neovascularization in NPDI group was 20% (6/30), which was significantly lower than 50% (7/14) in rubeosis iridis group ( P=0.04). Conclusions:Diabetic rubeosis iridis can be diagnosed by the imaging features of IFA and the fluorescein regression time in anterior chamber.PDR combined with optic disc neovascularization should be evaluated by FFA combined with IFA.

Objective:To study the correlation between the acute-phase characteristics of motor evoked potential (MEP) and severities of spinal cord injury in patients with acute cervical hyperextension injury and central cord syndrome (CCS).Methods:Retrospectively analyzed were the data of 45 patients with acute cervical hyperextension injury and CCS (observation group) who had been admitted to Department of Orthopedics, Tongji Hospital Affiliated to Tongji University from December 2018 to July 2021 and 20 healthy controls. Examination of transcranial magnetic stimulation-induced MEP was performed in patients with CCS and healthy controls using a magpro x100 magnetic stimulator, and recording was conducted in bilateral abductor pollicis brevis (APB). The characteristics of MEP waveform latency, amplitude and motor threshold were described and compared between the healthy control and observation groups; the correlations were analyzed between the MEP latency and the severity of spinal cord injury [American Spinal Injury Association (ASIA) total score and motor function of Upper Extremity Motor Subscores (UEMS)] in the observation group. According to different MEP-induced states, the patients in the observation group were divided into a resting group ( n=19), a facilitation group ( n=18), and a no-waveform group ( n=8). The severity of spinal cord injury (ASIA total score) and the functional independence of the spinal cord (SCIM-Ⅲ score) were compared among the 3 groups to analyze the correlation between the MEP-induced state and the severity of spinal cord injury (ASIA total score). Results:The observation group had a significantly longer MEP latency [(30.16±6.32) ms], a significantly smaller amplitude [(0.54±0.30) mV] and a significantly higher motor threshold [(65%±11%)] than the healthy control group (all P<0.05). The MEP latency in the observation group was significantly correlated with ASIA total score ( r=-0.730, P<0.001) and UEMS ( r=-0.740, P<0.001). The ASIA total score and SCIM-Ⅲ score were significantly different among the 3 groups ( P<0.05), and the MEP-induced state was significantly correlated with the severity of spinal cord injury (ASIA total score) ( r=0.668, P<0.001). Conclusions:In patients with acute cervical hyperextension injury and CCS, the MEP latency is prolonged, the amplitude lowered, and the motor threshold enhanced. The MEP latency is strongly correlated with the severity of spinal cord injury and upper limb motor function. The MEP-induced state is also closely related to the severity of spinal cord injury.

【Objective】 To explore the relationship between climate factors and the number of street voluntary blood donors in Beijing and develop a reliable predictive model, so as to provide reference for donor recruitment. 【Methods】 The data of weather and the number of street blood donors from January 2018 to October 2019 were collected to formulate generalized additive model(GAM) and autoregressive integrated moving average model(ARIMA), and the predicative accuracy of the two models was assessed using data from November to December 2019. 【Results】 GAM indicated that the number of donors decreased when the wind force was 4 to 5 (95%CI: 0.805, 0.995), and the number on weekends and official holidays was 1.562 (95% CI: 1.510, 1.617) and 1.779 (95%CI: 1.035, 3.055) times that of the working day respectively. The number of blood donors increased with the elevation of temperature until 25℃, then declined with temperature increasing slowly. The two-day predictive accuracy of GAM and ARIMA was 92.14% and 90.55%, with overall accuracy at (84.46±11.12)% and (87.65±9.3)%, respectively. 【Conclusion】 Considering official holiday, strong wind and temperature, etc, the ARIMA model runs stable overall, while GAM is good at short-term prediction. The comprehensive use of two predictive models is helpful in guiding the recruitment of blood donors.

The coronavirus disease 2019 (COVID-19) pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spread primary via respiratory droplets and infects the lungs. Currently widely used cell lines and animals are unable to accurately mimic human physiological conditions because of the abnormal status of cell lines (transformed or cancer cells) and species differences between animals and humans. Organoids are stem cell-derived self-organized three-dimensional culture in vitro and model the physiological conditions of natural organs. Here we showed that SARS-CoV-2 infected and extensively replicated in human embryonic stem cells (hESCs)-derived lung organoids, including airway and alveolar organoids which covered the complete infection and spread route for SARS-CoV-2 within lungs. The infected cells were ciliated, club, and alveolar type 2 (AT2) cells, which were sequentially located from the proximal to the distal airway and terminal alveoli, respectively. Additionally, RNA-seq revealed early cell response to virus infection including an unexpected downregulation of the metabolic processes, especially lipid metabolism, in addition to the well-known upregulation of immune response. Further, Remdesivir and a human neutralizing antibody potently inhibited SARS-CoV-2 replication in lung organoids. Therefore, human lung organoids can serve as a pathophysiological model to investigate the underlying mechanism of SARS-CoV-2 infection and to discover and test therapeutic drugs for COVID-19.
Adenosine Monophosphate/therapeutic use* ; Alanine/therapeutic use* ; Alveolar Epithelial Cells/virology* ; Antibodies, Neutralizing/therapeutic use* ; COVID-19/virology* ; Down-Regulation ; Drug Discovery ; Human Embryonic Stem Cells/metabolism* ; Humans ; Immunity ; Lipid Metabolism ; Lung/virology* ; RNA, Viral/metabolism* ; SARS-CoV-2/physiology* ; Virus Replication/drug effects*

Objective:To observe the incidence of diabetic iridopathy and optic disc neovascularization in the contralateral eyes of proliferative diabetic retinopathy (PDR) with proliferative diabetic iridopathy (PDI).Methods:A retrospective case-control study. From February 2014 to May 2020, 72 eyes of 36 patients with PDR and PDI who underwent iris fluorescein angiography (IFA) combined with fluorescein fundus angiography(FFA) at the Henan Eye Institute were enrolled in the study. Among them, there were 34 eyes in 17 males and 38 eyes in 19 females; the average age was 62.3±4.7 years. All patients underwent best corrected visual acuity(BCVA), intraocular pressure, IFA combined with FFA examination. The BCVA examination was performed using the international standard visual acuity chart, which was converted into logarithm of the minimum angle of resolution BCVA for statistic analysis. According to PDI staging, patients were divided into early rubeosis iridis(RI) group and neovascular glaucoma (NVG) group, with 28 and 8 cases respectively. Compared with NVG group, RI group had better BCVA and intraocular pressure, and the difference was statistically significant( t=6.433, 10.619; P=0.000, 0.011). The incidence of PDI and the incidence of binocular optic disc neovascularization in the two groups were compared, and Fisher's exact probability method was used for comparison. Results:The results of the IFA examination showed that in the RI group, the pupil border and the iris surface of the iris of the affected eyes had strong neovascular bud-like or patchy fluorescence; the pupil border and the middle of the iris of the patients in the NVG stage had strong neovascular cluster-like fluorescence. Among the contralateral eyes in the RI group, 6 eyes (21.4%, 6/28) were with PDI (stage RI), 21 eyes (75.0%, 21/28) were with non-PDI (NPDI), and 1 eye (1/ 28, 3.6%) were absence of diabetic iris disease. Among the contralateral eyes in the NVG group, there were 5 eyes with PDI (62.5%, 5/8), including 4 eyes with RI stage, 1 eye with NVG stage (12.5%, 1/8); 3 eyes with NPDI. The image of IFA in patients with NPDI early showed as punctate fluorescence in the local small blood vessels of the iris itself. The incidence of PDI in the contralateral eye of the RI group was lower than that of the NVG group, and the difference was statistically significant ( P=0.040). The results of FFA examination showed that 9 (32.1%, 9/28) and 8 (28.6%, 8/28) eyes of the affected eye and the contralateral eye in the RI group were combined with optic disc neovascularization. In NVG group, there were seperately 6 eyes (75.0%, 6/8) in the affected eyes and the contralateral eyes with optic disc neovascularization. The differences in the incidence of optic disc neovascularization between the two groups of the affected eyes and the contralateral eye were statistically significant ( P=0.046, 0.040). Conclusion:The incidence of PDI and optic disc neovascularization in the contralateral eye of PDR and PDI, RI is lower than that of NVG.

Objective:To investigate the clinical efficacy of laparoscopic sleeve gastrec-tomy (LSG) in the treatment of obesity associated nonalcoholic fatty liver disease (NAFLD).Methods:The retrospective and descriptive study was conducted. The clinical data of 40 patients with obesity associated NAFLD who were admitted to Xijing Hospital of Digestive Diseases of Air Force Medical University from January 2018 to June 2019 were collected. There were 19 males and 21 females, aged (27±8)years. Patients underwent LSG after preoperative examinations and evaluations. Observation indicators: (1) surgical and postoperative conditions; (2) follow-up. Follow-up was conducted by telephone interview, WeChat, and outpatient review to detect the liver function, glucose and lipid metabolism-related status as well as the relief of comorbidities of patients at 6 and 12 months after LSG. The follow-up was up to June 2020. Measurement data with normal distribu-tion were represented as Mean± SD. Repeated measurement data were analyzed by the repeated measures ANOVA. Count data were represented as absolute numbers, and chi-square test was used for comparison between groups. Results:(1) Surgical and postoperative conditions: 40 patients underwent LSG successfully, without intraoperative conversion to laparotomy or death. The operation time, volume of intraoperative blood loss, and duration of postoperative hospital stay were (83±12)minutes, (19±7)mL and (3.7±0.7)days. Among the 40 patients, 1 case had fat liquefac-tion after LSG and 2 had abdominal distension within a month, who were improved after symp-tomatic and supportive treatment. (2) Follow-up: 40 patients were followed up at postoperative 6 and 12 months. The body mass of 40 patients was (112±17)kg, (85±16)kg, (73±11)kg before operation, at postoperative 6 and 12 months, respectively. The body mass index was (39.7±4.2)kg/m 2, (30.0±4.5)kg/m 2, (25.9±2.9)kg/m 2 before operation, at postoperative 6 and 12 months, respectively. The alanine aminotransferase was (56.40±39.51)U/L, (30.15±17.93)U/L, (26.45±9.44)U/L before operation, at postoperative 6 and 12 months, respectively. The aspartate amino-transferase was (34.03±19.62)U/L, (28.20±10.27)U/L, (24.90±8.44)U/L before operation, at post-operative 6 and 12 months, respectively. The gamma-glutamyltransferase was (48.68±28.45)U/L, (43.30±18.56)U/L, (32.80±12.09)U/L before operation, at postoperative 6 and 12 months, respectively. The fasting blood-glucose was (6.51±2.38)mmol/L, (5.64±1.51)mmol/L, (4.98±0.91)mmol/L before operation, at postoperative 6 and 12 months, respectively. The triglyceride was (1.81±0.95)mmol/L, (1.48±0.57)mmol/L, (1.17±0.44)mmol/L before operation, at postoperative 6 and 12 months, respectively. The total cholesterol was (4.77±0.98)mmol/L, (4.58±0.75)mmol/L, (4.10±0.68)mmol/L before operation, at postoperative 6 and 12 months, respectively. The low density lipoprotein cholesterin was (2.99±0.81)mmol/L, (2.79±0.54)mmol/L, (2.48±0.40)mmol/L before operation, at postopera-tive 6 and 12 months, respectively. The high density lipoprotein cholesterin increased was (1.08±0.20)mmol/L, (1.15±0.18)mmol/L, (1.45±0.21)mmol/L before operation, at postoperative 6 and 12 months, respectively. Compared with preoperative indicators, there were significant differences in postoperative body mass, body mass index, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, fasting blood-glucose, triglyceride, total cholesterol and low density lipoprotein cholesterin ( F=472.439, 533.730, 26.791, 11.029, 25.545, 27.994, 27.534, 36.220, 18.596, P<0.05), showing a downward trend. There was a significant difference between preoperative and postoperative high density lipoprotein cholesterin ( F=68.974, P<0.05), showing a upward trend. The excess weight loss of 40 patients at 6 months and 12 months after LSG were 61%±18% and 85%±15%. The preoperative ultrasonography of 40 patients showed no, mild, moderate and severe fatty liver in 0, 2, 15 and 23 cases, respectively. The above indicators were 8, 9, 12, 11 cases at post-operative 6 months, and 23, 11, 6, 0 cases at postoperative 12 months, respectively. There was a significant difference of the grade of NAFLD between patients before and after surgery ( χ2=68.210, P<0.05). Conclusion:LSG has an accurate short-term clinical efficacy for obesity associated NAFLD, which can reduce body mass, improve liver function, alleviat the disorders of glucose and lipid metabolism and the severity of medium-severe fatty liver.