Objective: To establish a real-time quality control scheme based on the median (MD-IC) of internal control cycle threshold value in negative samples (NEG-IC-CT), so as to monitor anomalies such as progressive drift in nucleic acid testing system not covered by conventional internal quality control (IQC) in blood center nucleic acid laboratories, and to verify its feasibility. Methods: The internal control CT values of 54 426 negative samples were retrospectively collected. These samples were from four reagent batches of the two new and old equipment sets during the operation of the Wantai nucleic acid testing system in our blood center. The daily median of NEG-IC-CT values was used as the research indicator. Control limits were calculated using median absolute deviation (MAD) to construct the Median-MAD quality control chart. The monitoring performance of this scheme for the operation status of the testing system was simultaneously evaluated. Results: Statistical analysis showed significant differences in NEG-IC-CT value distribution between the new and old equipment sets, as well as between the two different reagent batches of the old equipment (P<0.000 1). The NEG-IC-CT value performance of the two different reagent batches of the new equipment was no significant difference in distribution (P>0.05). This scheme identified three typies of distinct anomalies. The out-of-control events observed with the old equipment in both the O1 and O2 reagent batches suggested potential performance decay due to equipment aging. The unreported change of reagent batch in time of Phase B with new equipment caused a stepwise drift on the quality control chart. In the later stage of Phase A with the new equipment, an alert was triggered, indicating potential quality risks associated with practices such as the mixed use of the remaining reagents and extremely long operator working hours. Conclusion: The realtime quality control scheme based on NEG-IC-CT value established in this study has been preliminarily validated for its monitoring effectiveness in nucleic acid testing in our blood center. This scheme performed well in detecting differences among testing systems and reagent batches, serving as an effective supplement to routine internal quality control. It can provide an intuitive and effective evaluation method for monitoring the performance of the nucleic acid testing process at blood center.

Objective To evaluate the association of different obesity phenotypes and their components with the risk of cognitive impairment in older Chinese adults,and to assess the association between obesity and cognitive impairment in different cognition-related genetic backgrounds.Methods A cross-sectional study based on the West China Health and Aging Cohort was conducted.Logistic regression was applied to estimate the association of obesity phenotypes and components with cognitive impairment in older Chinese adults stratified by APOE gene and polygenic risk scores.Results A total of 7 316 participants were enrolled,of whom 1 820 had cognitive impairment.Weight gains were associated with a reduced risk of cognitive impairment(odds ratio[OR]=0.96,95%CI,0.95-0.97).Being overweight with a normal waist-to-hip ratio was a protective factor for cognition(OR=0.74,95%CI,0.61-0.90),whereas the coexistence of elevated waist-to-hip ratio and overweight did not increase the risk of cognitive impairment.Sarcopenia was associated with an elevated risk of cognitive impairment.This association was found in both overweight(OR=2.03,95%CI,1.71-2.41)and non-overweight older adults(OR=1.86,95%CI,1.58-2.20),and was significant across all polygenic risk score strata.Conclusion Increasing body mass may serve as a key protective factor against cognitive decline in older adults.Having sarcopenia and obesity is associated with an elevated risk of cognitive impairment,independent of genetic susceptibility.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

BACKGROUND:Oral and maxillofacial bone tissue defects can seriously affect the physical and mental health of patients.When bone defects occur in diabetic patients,bone metabolism disorders caused by abnormal blood sugar make it more difficult to repair and treat. OBJECTIVE:To attempt to apply AOPDM1,a polypeptide with potential bioactivity to the osteogenic treatment of diabetic patients. METHODS:In normal or high-glucose environment,different concentrations of AOPDM1 were used to interfere with mouse bone marrow mesenchymal stem cells,and cell proliferation,alkaline phosphatase activity,mineralization nodules formation and osteogenic differentiation gene expression were detected.The polycaprolactone scaffold was prepared by electrospinning technology,and the scaffold was modified by polydopamine to prepare the polycaprolactone-polydopamine composite scaffold.Finally,the scaffolds were placed in AOPDM1 solution to prepare polycaprolactone-polydopamine-AOPDM1 scaffolds.The water contact angle and mechanical properties of the scaffolds were tested in the three groups.In normal or high-glucose environment,the three groups of scaffolds were co-cultured with mouse bone marrow mesenchymal stem cells,respectively,and cell adhesion,alkaline phosphatase activity and osteopontin expression were detected. RESULTS AND CONCLUSION:(1)Compared with normal environment,high-glucose environment inhibited the proliferation of bone marrow mesenchymal stem cells.In the same environment,AOPDM1 could promote the proliferation of mouse bone marrow mesenchymal stem cells.When AOPDM1 concentration was the same,alkaline phosphatase activity,mineralization ability and mRNA expression of type Ⅰ collagen,osteopontin,alkaline phosphatase,and Runx2 of bone marrow mesenchymal stem cells were decreased in high-glucose environment compared with normal environment.Under the same environment,AOPDM1 could improve the alkaline phosphatase activity,mineralization ability,and mRNA expression of type Ⅰ collagen,osteopontin,alkaline phosphatase and Runx2 of bone marrow mesenchymal stem cells.(2)The hydrophilicity of polycaprolactone-polydopamine scaffold and polycaprolactone-polydopamine-AOPDM1 scaffold was higher than that of polycaprolactone scaffold(P<0.001),and there was no significant difference in tensile strength and elastic modulus among the three groups(P>0.05).Compared with the other two groups of scaffolds,the cells on the polycaprolactone-polydopamine-AOPDM1 scaffold had better adhesion morphology.When the scaffolds were identical,compared with normal environment,high-glucose environment inhibited alkaline phosphatase activity and osteopontin expression of bone marrow mesenchymal stem cells.When the environment was the same,the alkaline phosphatase activity and osteopontin expression of bone marrow mesenchymal stem cells on the polycaprolactone-polydopamine-AOPDM1 scaffold were higher than those on the other two scaffolds.(3)The above results prove that polycaprolactone-polydopamine-AOPDM composite scaffold can promote the osteogenic properties of bone marrow mesenchymal stem cells in high-glucose environment.

Objective:To investigate the early auditory discrimination of vowels, consonants and lexical tones in prelingually-deafened children with cochlear implants (CI) using auditory event-related potentials.Methods:Nineteen prelingually-deafened CI children and 19 normal hearing (NH) children were recruited in this study. A multi-deviant oddball paradigm was constructed using the monosyllable/ta1/as the standard stimulus and monosyllables/tu1/,/te1/, /da1/,/ra1/,/ta4/and/ta2/as the deviant stimuli. The event-related potentials evoked by vowel, consonant and lexical tone contrasts were recorded and analyzed in the two groups.Results:NH children showed robust mismatch negativities (MMNs) to vowel, consonant and lexical tone contrasts ( P<0.05), whereas CI children only showed positive mismatch responses (pMMRs) and P3a responses to the vowel ( P<0.05) and consonant contrasts ( P<0.05) and no significant event-related potential to the lexical tone contrasts ( P>0.05). The longer pMMR and P3a peak latencies ( P<0.01) but similar amplitudes ( P>0.05) were found in CI children than in NH children. CI children showed weaker phase synchronization of θ oscillations than NH children ( P<0.05). The duration of CI use was positively correlated with the scores of Categories of Auditory Performance (CAP) ( P=0.004), Speech Intelligibility Rate (SIR) ( P=0.044) and Meaningful Auditory Integration Scale (MAIS) ( P=0.001) in CI children. Conclusions:Prelingually-deafened CI children can process vowels and consonants at an early stage. However, their ability of processing speech, especially lexical tones, is still more immature compared with their NH peers. The event-related potentials could be objective electrophysiological indicators reflecting the maturity of CI children′s auditory speech functions. Long-term CI use is beneficial for prelingually-deafened children to improve auditory and speech performance.

The purpose of this study was to reveal the resistance mechanism of Mycoplasma bovis from Xizang yaks to macrolide antibiotics and provide theoretical basis for clinical medication.In this study,10 strains of Mycoplasma bovis from Xizang yaks were tested for drug sensitivity to macrolide antibiotics using the micromethod,and sensitive strains were induced to be highly resist-ant in vitro.The results showed that all 10 strains of Mycoplasma bovis exhibited varying degrees of resistance to macrolide antibiotics.However,through methylation enzyme and inactivation en-zyme gene detection and analysis,it was found that there was no methylation enzyme encoded by the methylation enzyme gene and no resistance mechanism mediated by macrolide inactivation en-zymes,indicating that there were no mutations in the target gene loci of the sensitive and resistant strains.However,highly resistant strains in vitro have mutations at the domain Ⅱ,L22,and even L4 target gene loci,indicating that if two or more target gene amino acid loci undergo mutations,highly resistant strains can be produced.After testing with active efflux systems,it was found that there were no active efflux systems using macrolide antibiotics as substrates.It can be seen that the strain of Mycoplasma bovis from Xizang yaks is prone to mutation under the pressure of high con-centrations of macrolides,and there are mutations in two or more target gene amino acid sites,which is prone to produce highly resistant strains.

Objective:To investigate the relationship between the mechanism of clonidine preventing sevoflurane-induced neurotoxicity and Tau phosphorylation in neonatal mice.Methods:Seventy-two SPF healthy newborn C57BL/6 wild-type mice, aged 6 days, were divided into 4 groups ( n=18 each) using a random number table method: normal control group (C group), clonidine control group (CC group), sevoflurane-induced neurotoxicity group (S group) and prevention with clonidine group (SC group). Mice inhaled 3% sevoflurane for 2 h daily on postnatal days 6, 9 and 12, and normal saline or clonidine 1 mg/kg was intraperitoneally injected before anesthesia in S group and SC group. Six mice were randomly selected from each group after the end of anesthesia on postnatal day 12, and the hippocampal tissues were removed for determination of the expression of the phosphorylated Tau protein (AT8) and total Tau protein (Tau46) at Tau-PS202 and Tau-PT205 sites by Western blot. The ratio of AT8 expression to Tau 46 expression (AT8/Tau46 ratio) was calculated. Another 12 mice in each group underwent novel object recognition test on postnatal days 29-30 (the discrimination ratio of novel objects was observed), and the Morris water maze test was performed on postnatal days 31-37 (the escape latency and the times of crossing the platform were observed). After the end of the behavioral testing, the hippocampal tissues were harvested under anesthesia to detect the expression of postsynaptic density-95 (PSD-95) by Western blot. Results:Compared with group C, the expression of AT8 was significantly up-regulated, the ratio of AT8/Tau46 was increased, the expression of PSD-95 was down-regulated, and the number of crossing platforms and novel object discrimination ratio were decreased in group S ( P<0.05). Compared with group S, the expression of AT8 was significantly down-regulated, the ratio of AT8/Tau46 was decreased, the expression of PSD-95 was up-regulated, and the number of crossing platforms and novel object discrimination ratio were significantly increased in group SC ( P<0.05). There was no significant difference in the expression of Tau46 and escape latency among the four groups ( P>0.05). Conclusions:The mechanism by which clonidine prevents sevoflurane-induced neurotoxicity in neonatal mice is related to the inhibition of Tau phosphorylation.

OBJECTIVE: To explore the feasibility and early effectiveness of computer-simulated osteotomy based on the health-side combined with guide plate technique in the treatment of cubitus varus deformity in adolescents. METHODS: The clinical data of 23 patients with cubitus varus deformity who met the selection criteria between June 2019 and February 2023 were retrospectively analyzed. There were 17 males and 6 females, ranging in age from 4 to 16 years with an average of 8.5 years. The time from injury to operation was 1-4 years. The angle of distal humerus rotation was defined by humeral head posterior inclination angle using low radiation dose CT to scan the patient's upper extremity data at one time, and the preoperative rotation of the distal humerus on the affected side was (33.82±4.39)°. The CT plain scan data were imported into 9yuan3D digital orthopaedic system (V3.34 software) to reconstruct three-dimensional images of both upper extremities. The simulated operation was performed with the healthy upper extremity as the reference, the best osteotomy scheme was planned, overlapped and compared, and the osteotomy guide plate was prepared. The patients were followed up regularly after operation, and the formation of callus in the osteotomy area was observed by X-ray examination. Before and after operation, the carrying angle of both upper extremities (the angle of cubitus valgus was positive, and the angle of cubitus varus was negative) and anteversion angle were measured on X-ray and CT images. At the same time, the flexion and extension range of motion of elbow joint and the external rotation range of motion of upper extremity were measured, and Mayo score was used to evaluate the function of elbow joint. RESULTS: The operation time ranged from 34 to 46 minutes, with an average of 39 minutes. All patients were followed up 5-26 months, with a mean of 14.9 months. All the incisions healed by first intention after the operation; 2 patients had nail path irritation symptoms after Kirschner wire fixation, which improved after dressing change; no complication such as breakage and loosening of internal fixators occurred after regular X-ray review. Continuous callus formed at the osteotomy end at 4 weeks after operation, and the osteotomy end healed at 8-12 weeks after operation. At last follow-up, the carrying angle, anteversion angle, external rotation range of motion, and extension and flexion range of motion of the elbow joint of the affected side significantly improved when compared with preoperative ones ( P<0.05). Except for the extension range of motion of the healthy elbow joint ( P<0.05), there was no significant difference in other indicators between the two sides ( P>0.05). At last follow-up, the Mayo elbow score was 85-100, with an average of 99.3; 22 cases were excellent, 1 case was good, and the excellent and good rate was 100%. CONCLUSION Computer-simulated osteotomy based on health-side combined with guide plate technique for treating cubitus varus deformity in adolescents can achieve precise osteotomy, which has the advantages of short operation time and easy operation, and the short-term effectiveness is satisfactory.
Male ; Female ; Humans ; Adolescent ; Child, Preschool ; Child ; Elbow ; Humeral Fractures/surgery* ; Retrospective Studies ; Joint Deformities, Acquired/surgery* ; Elbow Joint/surgery* ; Limb Deformities, Congenital ; Osteotomy/methods* ; Humeral Head ; Range of Motion, Articular ; Computers ; Treatment Outcome

As confusion mounts over RNA isoforms involved in phenotypic plasticity, aberrant CpG methylation-mediated disruption of alternative splicing is increasingly recognized as a driver of intratumor heterogeneity (ITH). Protease serine 3 (PRSS3), possessing four splice variants (PRSS3-SVs; PRSS3-V1-V4), is an indispensable trypsin that shows paradoxical effects on cancer development. Here, we found that PRSS3 transcripts and their isoforms were divergently expressed in lung cancer, exhibiting opposing functions and clinical outcomes, namely, oncogenic PRSS3-V1 and PRSS3-V2 versus tumor-suppressive PRSS3-V3, by targeting different downstream genes. We identified an intragenic CpG island (iCpGI) in PRSS3. Hypermethylation of iCpGI was mediated by UHRF1/DNMT1 complex interference with the binding of myeloid zinc finger 1 (MZF1) to regulate PRSS3 transcription. The garlic-derived compound diallyl trisulfide cooperated with 5-aza-2'-deoxycytidine to exert antitumor effects in lung adenocarcinoma cells through site-specific iCpGI demethylation specifically allowing MZF1 to upregulate PRSS3-V3 expression. Epigenetic silencing of PRSS3-V3 via iCpGI methylation (iCpGIm) in BALF and tumor tissues was associated with early clinical progression in patients with lung cancer but not in those with squamous cell carcinoma or inflammatory disease. Thus, UHRF1/DNMT1-MZF1 axis-modulated site-specific iCpGIm regulates divergent expression of PRSS3-SVs, conferring nongenetic functional ITH, with implications for early detection of lung cancer and targeted therapies.