Objective:This study targets students enrolled in the Sino-foreign joint clinical medicine program collaboratively run by Chongqing Medical University, China and the University of Leicester, UK, aiming to propose suggestions and improvement measures on optimizing students' learning experiences and promoting the high-quality development of Sino-foreign cooperative education through questionnaire survey analysis.Methods:This study utilized convenience sampling and a self-designed questionnaire to collect feedback on the curriculum system and teaching methods, the adaptability of the educational system to the Chinese clinical practitioner examination, and the approaches and benefits of studying abroad. The data were presented as percentages.Results:Among the 75 respondents, 32 (42.67%) students expressed overall satisfaction or high satisfaction with the curriculum system and teaching methods. Specifically, 22 (29.33%) students were satisfied or very satisfied with the teaching methods of the Sino-foreign joint medical courses. Regarding the educational system's adaptability to the Chinese clinical practitioner examination, 74 (98.67%) students felt that the medical education provided by the joint program needed further adjustments or improvements, of whom 53 (70.67%) students believed that the content of the joint program was somewhat or not well aligned with the requirements of the Chinese practitioner examination, and 55 (73.33%) students thought that the joint program's discipline structure was not sufficiently comprehensive for training medical professionals. In terms of studying abroad, 57 (76.00%) students felt that overseas study had a positive impact on enhancing their overall quality.Conclusions:The joint clinical medicine program at our university draws on British educational principles to improve overall student quality. In response to students' needs regarding the curriculum system, teaching methods, and practitioner examination, the university plans to refine its teaching content and methods by implementing innovative training concepts, focusing on interdisciplinary integration, streamlining the curriculum, increasing tutoring, and promoting case-based group discussions to improve classroom teaching quality.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective:To analyze the pathogenicity and clinical characteristics of patients with Cohen syndrome caused by a compound heterozygous variation of VPS13B gene. Methods:A pedigree investigation was conducted.A Chinese Han family with Cohen syndrome was recruited from Henan Eye Hospital in September 2021.There were three members of two generations in this family, including one patient.The clinical data of the proband and his parents were collected, and the relevant ophthalmic and general examinations were performed to evaluate the clinical phenotype.The peripheral venous blood samples of the family members were collected to extract whole genomic DNA, and the whole exome sequencing was performed.Sanger sequencing and pedigree co-segregation analysis were performed among the family members.According to the ACMG guidelines, the pathogenicity of the selected variants was evaluated and the online tools were used to predict the pathogenicity of the variants.Relevant literature of Cohen syndrome were retrieved in Online Mendelian Inheritance in Man (OMIM) and PubMed, China National Knowledge Infrastructure and Wanfang databases by taking Cohen syndrome and VPS13B gene as the searching keywords.The clinical manifestations and pathogenic variants of patients in the literature were summarized, and the relationship between genotype and clinical phenotype was analyzed.This study protocol adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[15]). Both the subject and the patient's guardian were aware of the study purpose and method.Written informed consent was obtained. Results:The family was consistent with autosomal recessive inheritance.The proband, a 5-year-old male, had bilateral night blindness with photophobia, ptosis, lower eyelid entropion, and trichiasis; high myopia in both eyes; osteoblastoid pigmentation in the peripheral retina, atrophy and thinning of the outer layer of the peripheral retina, extinguished flashing electroretinogram; global growth retardation, typical facial features, slender fingers and toes, flatfoot, foot valgus, dystonia, no cardiac abnormalities; excessively cheerful personality.The clinical manifestations of the proband were consistent with Cohen syndrome.No obvious abnormality was found in the clinical phenotype and the auxiliary examination of the proband's parents.Whole exon sequencing revealed that the proband carried two heterozygous variations, a nonsense variation c. 11713C>T(p.Gln3905*) and a splicing variation c. 6940+ 1G>T.Sanger sequencing confirmed that the above variations were co-segregated in this family.c.11713C>T(p.Gln3905*) was a novel variant, which prematurely terminated the protein encoded by it and affected the normal function of the protein.The two variations were pathogenic variants according to the ACMG guidelines.A total of 12 articles on variants and clinical characteristics of Cohen syndrome in China were retrieved.Combined with the results of this study, a total of 24 VPS13B variants were found in Chinese patients, of which the incidence of frameshift variation was 41.7%(10/24), missense variation 20.8%(5/24), splicing variation 20.8%(5/24) and nonsense variation 16.7%(4/24), respectively.The onset age of patients with Cohen syndrome was from 28 days to 12 years old.The symptoms such as nerve system, eye, brain, and bone were sporadic, and the clinical manifestations were highly heterogeneous. Conclusions:A novel pathogenic variation c. 11713C>T is found in the VPS13B gene of the Cohen syndrome pedigree in this study, and expands the pathogenic variation spectrum of the VPS13B gene.The clinical manifestations of Cohen syndrome are highly heterogeneous.

Objective:To investigate the diagnostic value of independent and combined subtests of the psychometric hepatic encephalopathy score (PHES) in mild hepatic encephalopathy(MHE) of patients with liver cirrhosis, so as to optimize the PHES.Methods:This was a prospective, multicenter and real-world study which was sponsored by the National Clinical Research Center of Infectious Diseases and the Portal Hypertension Consortium. Twenty-six hospitals from 13 provinces, autonomous regions and municipalities countrywide participated in this study, induding Tianjin Third Central Hospital, the Fourth People′s Hospital of Qinghai Province, the Second Affiliated Hospital of Baotou Medical College, the Third People′s Hospital of Taiyuan, the Fifth Medical Center of PLA General Hospital and so on. From October 2021 to February 2022, outpatients and hospitalized patients with liver cirrhosis and no obvious hepatic encephalopathy were consecutively enrolled. All patients received 5 PHES subjects in the same order: number connection test(NCT)-A, NCT-B, digit symbol test(DST), line tracing test(LTT) and serial dotting test(SDT), and the scores were calculated. The total score of PHES <-4 was taken as the cut-off value for diagnosing MHE. Compare the differences in each subtest between MHE group and non-MHE group. Receiver operating characteristic curve(ROC) and area under the curve(AUC) was performed to assess the diagnostic value of independent and combined subtests in MHE. Mann-Whitney U test and DeLong test were used for statistical analysis. Results:A total of 581 patients with liver cirrhosis were enrolled, 457 were diagnosed as MHE, and the incidence of MHE was 78.7%. The results of NCT-A, NCT-B, SDT, LTT, DST of MHE group were 60.00 s(47.01 s, 88.00 s), 90.45 s(69.32 s, 125.35 s), 74.00 s(57.65 s, 96.60 s), 74.72(60.00, 98.61) and 27.00(20.00, 36.00), respectively. Compared those of non-MHE group(34.00 s(29.15 s, 44.48 s), 50.00 s(40.98 s, 60.77 s), 50.00 s(41.07 s, 63.03 s), 46.23(38.55, 59.42) and 42.00(34.00, 50.75)), the differences were statistically significant( Z=12.37, 12.98, 9.83, 11.56, 10.66; all P<0.001). The AUC(95% confidence interval(95% CI)) of subtests of PHES NCT-B, NCT-A, LTT, DST and SDT alone in MHE diagnosis were 0.880(0.849 to 0.910), 0.862(0.828 to 0.896), 0.838(0.799 to 0.877), 0.812(0.772 to 0.851) and 0.788(0.743 to 0.832), respectively. The combination of 2 PHES subtests significantly increased the diagnostic efficacy. Among them the diagnostic efficacy of the combination of NCT-B and LTT was the best, the AUC(95% CI) was 0.924(0.902 to 0.947), the specificity was 91.9% and the sensitivity was 79.2%, which was better than a single PHES subtest (NCT-A, NCT-B, SDT, LTT and DST) and the combination of NCT-A and DST(AUC was 0.879, 95% CI0.847 to 0.910) which was recommended by guidelines on the management of hepatic encephalopathy in cirrhosis, the differences were statistically significant ( Z=3.78, 3.83, 5.57, 5.51, 5.38, 2.93; all P<0.01). Furthermore, compared between the combination of NCT-B and LTT and the combination of 3 subests of PHES, only the diagnostic efficacy of combination of NCT-B, LTT and SDT (AUC was 0.936, 95% CI 0.916 to 0.956) was better than that of the combination of NCT-B and LTT, the difference was statistically significant( Z=2.32, P=0.020). Conclusion:Based on the diagnostic efficacy and clinical feasibility of PHES subtests and their combinations, the combination of NCT-B and LTT is recommended for the diagnosis of MHE.

Objective:The clinical phenotypes and pathogenicity of isolated cone-rod dystrophy (CORD) caused by two novel complex heterozygous variants of the CEP290 gene were analyzed using high-resolution multi-mode imaging and gene detection techniques. Methods:A retrospective study. Two patients and two family members from a CORD family who were diagnosed by genetic testing at Henan Provincial People's Hospital in December 2021 were included in the study. All subjects underwent best-corrected visual acuity (BCVA), color fundus photography, autofluorescence, swept-source optical coherence tomography (SS-OCT), adaptive optics fundus imaging, static threshold field, full field and multiple electroretinogram (ERG) examination, as well as other systemic examinations throughout the body. The peripheral venous blood of the subjects was collected, and the whole genome DNA was extracted. DNA sequencing was performed using the Inherited Retinal Disease Kit PS400, and Sanger verification and pedigree co-segregation analysis were performed on the suspected pathogenic mutation sites. Validation was performed by Sanger sequencing, pathogenicity analysis was performed in accordance with the American College of Medical Genetics and Genomics (ACMG) guidelines. Conservation of variation among different species was analyzed by GERP++, Clustal Omega and Weblogo.Results:Both patients were male, and their ages were 21 and 29 years old, respectively. The right eye and left eye about BCVAs were 0.7, 0.4 and 0.3, 0.4, respectively. The full field and multiple electroretinogram ERG showed a decreased function of cones and rods, especially cones. SS-OCT showed thinning of the outer nuclear layer of macular, and attenuation of ellipsoid zone reflectivity in B-scan. Adaptive optics fundus imaging examination showed that the arrangement of cone cells in the fovea of the fovea was disordered and the density decreased, and the retinal pigment epithelial cells were seen through the atrophy of cone cells in some areas at 10°visual angle. No obvious abnormality was found in other systemic examinations of the whole body. Genetic testing showed that 2 novel compound heterozygous variants c.950T >A (p.Leu317*) (M1) and c.4144_4149del (p.Tyr1382_Glu1383del) (M2) in CEP290 were found in two patients. The first variant was predicted to be harmful in MutationTaster and CADD. GERP++ showed highly conserved among different species. The pathogenicity of the variant was suspected to be likely pathogenic according to ACMG guidelines. The pathogenicity of the second variant was uncertain significance. The parents of the proband had no similar ocular abnormalities. Verified by Sanger sequencing, it was consistent with co-separation in the family. Conclusions:Patients with pure CORD caused by CEP290 gene mutation still retain better vision when the cone structure is abnormal, the density is decreased, and the function of cone and rod cells is decreased. CEP290 M1 and M2 are newly discovered nonsense mutations and newly discovered deletion mutations, which expanded the causative gene spectrum of pure CORD.

Objective:To explore the sensitivity of the normal population to nasolabial subunits.Methods:From 2016 to 2017, we took frontal photos of 25 (20 to 40 years old) people with basically normal nasolabial subunits in West China Hospital of Stomatology. The lip subunits were adjusted at 1.1, 1.2, and 1.3 times magnification or translation to obtain photos of different degrees of malformation of the nasal and lip subunits. A total of 189 young healthy people [96 males, 93 females; age (20.00±1.32) years old] without correction surgery and no maxillofacial deformities were selected to judge the facial aesthetic visual effect of their vision on the nasolabial subunit.Results:The peak sensitivity of nasolabial subunits is the nostril symmetry and columella deviation followed by lip symmetry.Conclusions:Young healthy people have high aesthetic visual effects on nostril symmetry and nasal column translation facial translation, average facial visual effects on lip symmetry and the lowest facial aesthetic visual effects on lip peak symmetry.

Objective The purpose of this study was to investigate the differential expression of circRNAs in human blood, as a diagnostic marker for pre-diabetes and type 2 diabetes mellitus( T2DM). Methods Microarray analysis was used to select several differentially expressed circRNAs from three normal patients and three T2DM patients. Enlarge the sample size(normal controls,n=20;subjects with impaired glucose regulation,n=20;and type 2 diabetes mellitus,n=20) to determine a circRNA which the most evident differentially expressed by fluorescence quantitative PCR( Q-PCR). Then they were verified with expanded samples ( normal controls, n= 50; impaired glucose regulations,n=50;type 2 diabetes mellitus, n=50) by Q-PCR. Results A total of 2 953 differentially expressed circRNAs were found in microarray analysis, of which 1 439 were up-regulated and 1 514 were down-regulated. Nine differentially expressed circRNAs were selected from the 1 439 circRNAs that were up-regulated(hsa-circ-103838, hsa-circ-103965, hsa-circ-104227, hsa-circ-002117, hsa-circ-000094, hsa-circ-101226, hsa-circ-101720, hsa-circ-400029, and hsa-circ-100633). The Q-PCR results of the expanded sample( n=60) showed that the difference expression of hsa-circ-000094(Alias:has-circ-0000247) in the nine circRNAs was the most obvious one among the 3 groups, the area under the maximum curve was found by ROC curve analysis, SIGR=0. 802 5[ 95% confidence interval (0.665 5-0.939 5), P=0.001]; ST2DM=0.77[95% confidence interval (0.624-0.916), P=0.003]. In order to verify the clinical diagnostic ability of hsa-circ-000094, the experiment was conducted to further expand the sample ( n=150). The results showed that the expression of hsa-circ-000094 in the three groups was different, the difference and ROC curve analysis were statistically significant, SIGR=0. 673 3 [ 95% confidence interval (0.575 7-0. 771 0), P＜0. 01]; ST2DM=0. 723 1 [ 95% confidence interval ( 0. 632 7-0. 813 4), P＜ 0.01]. Conclusion The higher expression of hsa-circ-000094 in peripheral blood provides a certain diagnostic basis for pre-diabetes as well as type 2 diabetes mellitus.

Hypercalcemia is an abnormal calcium metabolism, which can be caused by many diseases. Hypercalcemia caused by sarcoidosis is unusual. Sarcoidosis is a systemic granulomatous disease, it is lack of specificity in initial manifestations and easy to be misdiagnosed. In this paper, we report a patient with hypercalcemia and mediastinal lymphadenectasis, which the first diagnosis was misdiagnosed as tumour. Finally, sarcoidosis was diagnosed by mediastinal lymph node biopsy, and the patient was subsequently treated with glucocorticoid. Prednisone treatment improved symptoms of sarcoidosis, normalised serum calcium and mediastinal lymph nodes were diminished. This case suggests that clinicians need to raise awareness of sarcoidosis to identify and diagnose it correctly.

Objective To observe the effect of qixiantang decoction on asthma model mice and to explore its mechanism of phosphatase gene ( PTEN)-up-regulation. Methods A total of 28 healthy female BALB/c mice were divided into 4 groups according to the random number table ( n=7 ): normal control group, model control group, qixiantang decoction group, and dexamethasone group. The mice were sensitized with ovalbumin ( OVA) for asthma model. Qixiantang decoction group was treated with drug after OVA sensitization. Hematoxylin-eosin ( H-E) staining was applied to observe the pulmonary inflammation in mice, and periodic acid Schiff ( PAS) staining was used to examine airway mucus secretion. ELISA was used to detect the concentration of serum IgE. Real-time quantitative PCR was used to examine IL-13 and IL-5 gene expression changes in lung tissues of mice. Western blotting was used to detect the expression of PTEN and SIRT1 protein in lung tissues. Results The lung tissue inflammatory infiltration and mucus secretion in model control group were higher than normal control group (P<0. 01), and that in the qixiantang decoction group. The level of serum IgE in model control group [(6. 67 ± 2. 59) pg·mL-1)] was significantly higher than normal control group [(0.27 ± 0.05) pg·mL-1, P <0.01] ,and that in the qixiantang decoction group [(3.52 ±1.44) pg·mL-1,P<0.05]. The expression of PTEN and SIRT1 in lung tissue of model control group were significantly lower than normal control group, and that of qixiantang decoction group. The expression of IL-5 and IL-13 mRNA of qixiantang decoction group was significantly lower (P<0. 05). Conclusion Qixiantang decoction could significantly ameliorate inflammation in asthmatic mice by regulate IgE、IL-5、IL-13 expression, and might up-regulate PTEN expression via SIRT1 signal.

Objective To explore the in vitro antibacterial effect of tanreqing injection combined with cefuroxime sodium injection against staphylococcus aureus. Methods The MIC of tanreqing injection or cefuroxime sodium injection against staphylococcus aureus was detected by microamount dilution method.The antibacterial activity of tanreqing injection combined with cefuroxime sodium injection was determined by a chess board dilution method and assessed according to FIC index. Results The MIC of tanreqing injection and cefuroxime sodium injection against staphylococcus aureus was 1∶256 and 2 μg . mL-1 , respectively. While combined with each other, the MIC of tanreqing injection and cefuroxime sodium injection against staphylococcus aureus was 1∶4 096 and 0. 125 μg . mL-1 , respectively. The FIC index of tanreqing injection combined with cefuroxime sodium injection against staphylococcus aureus was 0. 125. Conclusion Tanreqing injection has a synergistic antibacterial effect against staphylococcus aureus when it was combined with cefuroxime sodium injection.