ObjectiveMagnetoencephalography (MEG), a non-invasive neuroimaging technique, meticulously captures the magnetic fields emanating from brain electrical activity. Compared with MEG based on superconducting quantum interference devices (SQUID), MEG based on optically pump magnetometer (OPM) has the advantages of higher sensitivity, better spatial resolution and lower cost. However, most of the current studies are clinical studies, and there is a lack of animal studies on MEG based on OPM technology. Pain, a multifaceted sensory and emotional phenomenon, induces intricate alterations in brain activity, exhibiting notable sex differences. Despite clinical revelations of pain-related neuronal activity through MEG, specific properties remain elusive, and comprehensive laboratory studies on pain-associated brain activity alterations are lacking. The aim of this study was to investigate the effects of inflammatory pain (induced by Complete Freund’s Adjuvant (CFA)) on brain activity in a rat model using the MEG technique, to analysis changes in brain activity during pain perception, and to explore sex differences in pain-related MEG signaling. MethodsThis study utilized adult male and female Sprague-Dawley rats. Inflammatory pain was induced via intraplantar injection of CFA (100 μl, 50% in saline) in the left hind paw, with control groups receiving saline. Pain behavior was assessed using von Frey filaments at baseline and 1 h post-injection. For MEG recording, anesthetized rats had an OPM positioned on their head within a magnetic shield, undergoing two 15-minute sessions: a 5-minute baseline followed by a 10-minute mechanical stimulation phase. Data analysis included artifact removal and time-frequency analysis of spontaneous brain activity using accumulated spectrograms, generating spectrograms focused on the 4-30 Hz frequency range. ResultsMEG recordings in anesthetized rats during resting states and hind paw mechanical stimulation were compared, before and after saline/CFA injections. Mechanical stimulation elevated alpha activity in both male and female rats pre- and post-saline/CFA injections. Saline/CFA injections augmented average power in both sexes compared to pre-injection states. Remarkably, female rats exhibited higher average spectral power 1 h after CFA injection than after saline injection during resting states. Furthermore, despite comparable pain thresholds measured by classical pain behavioral tests post-CFA treatment, female rats displayed higher average power than males in the resting state after CFA injection. ConclusionThese results imply an enhanced perception of inflammatory pain in female rats compared to their male counterparts. Our study exhibits sex differences in alpha activities following CFA injection, highlighting heightened brain alpha activity in female rats during acute inflammatory pain in the resting state. Our study provides a method for OPM-based MEG recordings to be used to study brain activity in anaesthetized animals. In addition, the findings of this study contribute to a deeper understanding of pain-related neural activity and pain sex differences.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

ObjectiveTo explore the establishment and evaluation methods of the rat model of acute myocardial infarction （AMI） in coronary heart disease with the syndrome of Qi and Yin deficiency by sleep deprivation （SD） combined with isoproterenol （ISO） and preliminarily explore its biological basis. MethodForty SD rats were assigned into normal （no treatment）， SD （treatment in modified multi-platform water environment for 96 h）， ISO （subcutaneous injection of ISO at 100 mg·kg^-1 once every other day for a total of 2 times）， and SD+ISO （injection of 100 mg·kg^-1 ISO after SD for 72 h and 96 h） groups. The cardiac function was detected by small animal echocardiography. The serum levels of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， and cardiac troponin T （cTnT） were measured by biochemical methods. The pathological changes of the myocardial tissue were observed by hematoxylin-eosin staining. The general state， body weight， grip strength， body temperature， behaviors in open field test， serum levels of cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， cAMP/cGMP ratio， red （R）， green （G）， blue （B） values of the tongue surface， and pulse amplitude were observed and measured to evaluate the modeling results. Enzyme-linked immunosorbent assay was employed to determine the serum levels of interleukin-18 （IL-18）， tumor necrosis factor-α （TNF-α）， superoxide dismutase （SOD）， malondialdehyde （MDA）， corticotropin-releasing factor （CRF）， adrenocorticotropic hormone （ACTH）， triiodothyronine （T3）， tetraiodothyronine （T4）， cluster of differentiation 4 （CD4）， and cluster of differentiation 8 （CD8）. ResultIn terms of disease indicators， the ISO and SD+ISO groups had lower cardiac function indicators than the normal group （P<0.01）. The levels of CK， CM-MB， LDH and cTnT elevated in each model group compared with the normal group （P<0.01）. The pathological changes of myocardial tissue were obvious in the ISO and SD+ISO groups. In terms of syndrome indicators， compared with the normal group， the SD and SD+ISO groups showed decreased body weight at each time point （P<0.01）， and the ISO group showed decreased body weight at the time points of 48 h and 72 h （P<0.05， P<0.01）. The paw temperature and rectal temperature increased in the SD group （P<0.01）. The model groups showed weakened grasp strength， lowered R， G， and B values of the tongue surface （P<0.01）， prolonged immobility time （P<0.01）， reduced total distance and number of entering the central area （P<0.01）， decreased average speed （P<0.05， P<0.01）， and increased cAMP and cGMP （P<0.05， P<0.01）. The cAMP/cGMP ratio was increased in the SD+ISO group （P<0.01）， and the pulse amplitude was decreased in the SD and SD+ISO groups （P<0.01）. In terms of serological indicators，compared with the normal group， the levels of IL-18， TNF-α， SOD and MDA were significantly increased in the ISO and SD+ISO groups （P<0.01）， the CRF， ACTH， CORT， T3， T4， CD4 and CD8 in the model groups were increased （P<0.05， P<0.01）. ConclusionSleep deprivation for 96 h combined with high-dose ISO can successfully establish a rat model of acute myocardial infarction in coronary heart disease with the syndrome of Qi and Yin deficiency. The model evaluation system can be built with disease indicators of western medicine， histopathological indicators， macroscopic indicators of traditional Chinese medicine， and serological indicators.

Objective To observe the application effect and safety of continuous adductor canal block(ACB)with different doses of dexmedetomidine(DEX)combined with ropivacaine in postoperative analgesia of total knee arthroplasty(TKA).Methods Patients with TKA were enrolled as the research subjects and were divided into low-dose group,middle-dose group and high-dose group by the random number table method.At 10 min before induction of general anesthesia,all the groups were given 20 mL of 0.5％ropivacaine loading dose for ACB,placed nerve block indwelling catheter,and started ACB analgesia pump after the end of surgery.Low-dose group,middle-dose group and high-dose group were given 0.5,1.0 and 1.5 μg·kg-1 DEX+0.25％ropivacaine for a total of 100 mL,with a background dose of 4 mL·h-1and a control dose of 4 mL,and they locked for 30 min and continuously treated for 48 h.The surgical parameters and postoperative recovery quality of the two groups were compared.Visual analogue scale(VAS)was used to evaluate the pain status in resting state and motion state at 2,6,12,24 and 48 h after surgery.The number of effective compressions of self-controlled analgesia pump and the dosage of remedial analgesics at 48 h after surgery were counted and the safety evaluation was performed.Results No cases dropped out during treatment,and finally 30 cases were included in low-dose,middle-dose and high-dose groups,respectively.The first ambulation times in low-dose,middle-dose and high-dose groups were(54.22±8.37),(47.68±7.65)and(52.79±8.74)h;the time of active knee flexion 90° were(8.90±3.10),(7.20±2.70)and(8.60±2.40)d;the motion VAS scores were(3.86±0.59),(3.57±0.51)and(3.48±0.52)points at 48 h after surgery;the times of first analgesia pump compression within 48 h after surgery were(10.57±3.87),(12.45±3.63)and(13.36±3.56)h;the number of effective compressions of self-controlled analgesia pump were(6.11±2.18),(3.76±1.14)and(3.24±1.07)times;the remedial analgesia rates were 13.33％,0 and 0;at 6 h after surgery,quadriceps muscle strength scores were(4.81±0.21),(4.75±0.23)and(4.61±0.26)points,and the incidence rates of adverse drug reactions were 20.00％,6.67％and 6.67％,respectively.There were statistically significant differences in the above indicators between low-dose group and middle-dose group except for the incidence of adverse drug reactions(all P＜0.05).There were statistical differences between low-dose group and high-dose group except for the incidence of adverse drug reactions(all P＜0.05),but there were no statistical differences between middle-dose group and high-dose group(all P＞0.05).Conclusion The use of 1.0 μg·kg-1DEX combined with ropivacaine for ACB in TKA patients can achieve good postoperative analgesia effect and it has small impact on muscle strength and has good safety,thus this dose can be used as a clinical recommended dose.

BACKGROUND:After the internal fixation of cannulated screws in femoral neck fractures,because the affected limb is often unable to bear weight in the short term and the implants with high stiffness have a stress shielding effect on the fracture end,it is easy to cause osteoporosis of the affected limb and changes in the biomechanical distribution of the proximal femur,the incidence of osteonecrosis of the femoral head is high after surgery.At present,few studies have been conducted on the biomechanical effects of osteoporosis at the proximal end of the femur occurring after femoral neck fracture surgery on femoral neck fracture treated with cannulated screws. OBJECTIVE:Using finite element analysis,to investigate the biomechanical effects of osteoporosis occurring after femoral neck fracture surgery on femoral neck fracture treated with cannulated screws and explore the role of biomechanical factors in osteonecrosis of the femoral head. METHODS:Based on the obtained CT scan data of the femur in a patient with a femoral neck fracture,a proximal femoral model for internal fixation for femoral neck fracture was established by Mimics 19.0,3-Matic,UG 11.0,Hypermesh 14.0,and Abaqus software.One finite element model of the proximal femur without osteoporosis and three finite element models of the proximal femur with osteoporosis were analyzed using Abaqus software.The stress,contact pressure,displacement peak and cloud map under different components of the four models were measured and analyzed,and the internal stress changes and distribution of the femoral head were compared and analyzed. RESULTS AND CONCLUSION:The stresses and contact pressures of the femoral head and lower anterior cannulated screws varied more with the degree of osteoporosis.The peak displacement of the four models increased slowly with the degree of osteoporosis.By one-way analysis of variance,there was no significant effect of the degree of osteoporosis on the peak stress,contact pressure,and displacement of the different components.The internal stress distribution of the femoral head changed with the degree of osteoporosis.Changes in the biomechanical environment of the proximal femur have an important impact on osteonecrosis of the femoral head.

【Objective】 To objectively evaluate the quality control level of blood testing process in blood banks through quantitative monitoring and trend analysis, and to promote the homogenization level and standardized management of blood testing laboratories in blood banks. 【Methods】 A quality monitoring indicator system covering the whole process of blood collection and supply, including blood donation service, blood component preparation, blood testing, blood supply and quality control was established. The questionnaire Quality Monitoring Indicators for Blood Collection and Supply Process with clear definition of indicators and calculation formulas was distributed to 17 blood banks in Shandong province. Quality monitoring indicators of each blood bank from January to December 2022 were collected, and 31 indicators in terms of blood testing were analyzed using SPSS25.0 software. 【Results】 The proportion of unqualified serological tests in 17 blood bank laboratories was 55.84% for ALT, 13.63% for HBsAg, 5.08% for anti HCV, 5.62% for anti HIV, 18.18% for anti TP, and 1.65% for other factors (mainly sample quality). The detection unqualified rate and median were (1.23±0.57)% and 1.11%, respectively. The ALT unqualified rate and median were (0.74±0.53)% and 0.60%, respectively. The detection unqualified rate was positively correlated with ALT unqualified rate (r=0.974, P<0.05). The unqualified rate of HBsAg, anti HCV, anti HIV and anti TP was (0.15±0.09)%, (0.05±0.04)%, (0.06±0.03)% and (0.20±0.05)% respectively. The average unqualified rate, average hemolysis rate, average insufficient volume rate and the abnormal hematocrit rate of samples in 17 blood bank laboratories was 0.21‰, 0.08‰, 0.01‰ and 0.02‰ respectively. There were differences in the retest concordance rates of four HBsAg, anti HCV and anti HIV reagents, and three anti TP reagents among 17 blood bank laboratories (P<0.05). The usage rate of ELISA reagents was (114.56±3.30)%, the outage rate of ELISA was (10.23±7.05) ‰, and the out of range rate of ELISA was (0.90±1.17) ‰. There was no correlation between the out of range rate, outrage rate and usage rate (all P>0.05), while the outrage rate was positively correlated with the usage rate (r=0.592, P<0.05). A total of 443 HBV DNA positive samples were detected in all blood banks, with an unqualified rate of 3.78/10 000; 15 HCV RNA positive samples were detected, with an unqualified rate of 0.13/10 000; 5 HIV RNA positive samples were detected, with an unqualified rate of 0.04/10 000. The unqualified rate of NAT was (0.72±0.04)‰, the single NAT reaction rate [(0.39±0.02)‰] was positively correlated with the single HBV DNA reaction rate [ (0.36±0.02) ‰] (r=0.886, P<0.05). There was a difference in the discriminated reactive rate by individual NAT among three blood bank laboratories (C, F, H) (P<0.05). The median resolution rate of 17 blood station laboratories by minipool test was 36.36%, the median rate of invalid batch of NAT was 0.67%, and the median rate of invalid result of NAT was 0.07‰. The consistency rate of ELISA dual reagent detection results was (99.63±0.24)%, and the median length of equipment failure was 14 days. The error rate of blood type testing in blood collection department was 0.14‰. 【Conclusion】 The quality monitoring indicator system for blood testing process in Shandong can monitor potential risks before, during and after the experiment, and has good applicability, feasibility, and effectiveness, and can facilitate the continuous improvement of laboratory quality control level. The application of blood testing quality monitoring indicators will promote the homogenization and standardization of blood quality management in Shandong, and lay the foundation for future comprehensive evaluations of blood banks.

【Objective】 To establish an effective quality monitoring indicator system for blood quality control in blood banks, in order to analyze the quality control indicators for blood collection and supply, and evaluate blood quality control process, thus promoting continuous improvement and standardizing management of blood quality control in blood banks. 【Methods】 A quality monitoring indicator system covering the whole process of blood collection and supply, including blood donation services, component preparation, blood testing, blood supply and quality control was established. The Questionnaire of Quality Monitoring Indicators for Blood Collection and Supply Process was distributed to 17 blood banks in Shandong, which clarified the definition and calculation formula of indicators. The quality monitoring indicator data from January to December 2022 in each blood bank were collected, and 20 quality control indicators data were analyzed by SPSS25.0 software. 【Results】 The average pass rate of key equipment monitoring, environment monitoring, key material monitoring, and blood testing item monitoring of 17 blood banks were 99.47%, 99.51%, 99.95% and 98.99%, respectively. Significant difference was noticed in the pass rate of environment monitoring among blood banks of varied scales(P<0.05), and the Pearson correlation coefficient (r) between the total number of blood quality testing items and the total amount of blood component preparation was 0.645 (P<0.05). The average discarding rates of blood testing or non-blood testing were 1.14% and 3.36% respectively, showing significant difference among blood banks of varied scales (P<0.05). The average discarding rate of lipemic blood was 3.07%, which had a positive correlation with the discarding rate of non testing (r=0.981 3, P<0.05). There was a statistically significant difference in the discarding rate of lipemic blood between blood banks with lipemic blood control measures and those without (P<0.05). The average discarding rate of abnormal color, non-standard volume, blood bag damage, hemolysis, blood protein precipitation and blood clotting were 0.20%, 0.14%, 0.06%, 0.06%, 0.02% and 0.02% respectively, showing statistically significant differences among large, medium and small blood banks(P<0.05).The average discarding rates of expired blood, other factors, confidential unit exclusion and unqualified samples were 0.02%, 0.05%, 0.003% and 0.004%, respectively. The discarding rate of blood with air bubbles was 0.015%, while that of blood with foreign body and unqualified label were 0. 【Conclusion】 The quality control indicator system of blood banks in Shandong can monitor weak points in process management, with good applicability, feasibility, and effectiveness. It is conducive to evaluate different blood banks, continuously improve the quality control level of blood collection and supply, promote the homogenization and standardization of blood quality management, and lay the foundation for comprehensive evaluation of blood banks in Shandong.