Objective: To delineate the epidemiologic profile of rifampicin resistant pulmonary tuberculosis (RR-PTB) among students in Chongqing, so as to provide evidence for effectively controlling RR-PTB outbreaks in schools. Methods: Individual level surveillance records of 395 student RR-PTB cases reported from 2015 to 2024 were extracted from the China Information System for Disease Control and Prevention. The Joinpoint regression analysis was employed to quantify temporal trends in the registration rate of student RR-PTB cases, and the comparison of RR-PTB registration rates with different demographic characteristics and different regions was performed using Chi-square test. Results: From 2015 to 2024, a total of 395 student RR-PTB cases were identified, with the registration rate ranged from 0.07 per 100 000 to 1.47 per 100 000, showed a fluctuating upward trend ( AAPC= 35.22%, t =4.13, P <0.01). A turning point was detected in 2017, rates rose during 2015-2017 (APC=295.23%， t =4.62， P < 0.01 ) and plateaued thereafter (APC=-0.47%， t =-0.12， P =0.91). The proportion of RR-PTB cases occurring among students increased both among all RR-PTB cases (1.54% in 2015, 7.48% in 2024) and all student pulmonary tuberculosis cases (0.20% in 2015, 7.17% in 2024), with significant linear trends ( χ 2 trend =33.55,159.98, both P <0.01). The majority of cases were enrolled in senior high school (50.38%), classified as retreatment (53.92%), of Han ethnicity (75.95%), and diagnosed with multidrug resistant tuberculosis(53.16%). There were significant differences in the composition of different ethnicity, registration category and resistance pattern between different years( χ 2=23.47, 17.23, 59.64，all P <0.05). The South-Eastern Wuling Mountainous Region exhibited the highest notification rate (3.96 per 100 000), whereas the western region had the lowest rate ( 0.47 per 100 000). County level jurisdictions reported higher rates than district level ones (2.16 per 100 000 vs 0.63 per 100 000 ). Statistically significant differences were observed in the RR-PTB reported rates among students across different districts and counties( χ 2=418.05,167.05,both P <0.01). Conclusions From 2015 to 2024, the registration rate of detected student RR-PTB cases in Chongqing showed an increasing trend. Students have become one of the key populations for drug resistant TB prevention and control. Intensified health education and active case finding should be implemented to enhance proactive surveillance capabilities.

OBJECTIVE To analyze the results of speech-evoked auditory brainstem response(s-ABR)tests in patients with presbycusis and explore the mechanisms of speech coding in these patients.METHODS Thirty patients with presbycusis(presbycusis group),30 elderly individuals with normal hearing(elderly normal group),and 30 young adults with normal hearing(young control group)were recruited.The s-ABR was elicited using a 40 ms duration complex speech stimulus/da/,and the characteristics of s-ABR were analyzed in each group.RESULTS The latencies of waves V and A in the presbycusis group were significantly prolonged compared to both the elderly normal group and the young control group(P<0.05).However,there was no statistically significant difference in the latencies of waves between the elderly normal group and the young control group(P>0.05).The amplitude of wave A and the slope of the V-A complex wave in the presbycusis group were significantly lower than those in the young control group(P<0.05),while no statistically significant differences were observed in the amplitudes of other waves.CONCLUSION The characteristics of s-ABR in patients with presbycusis suggest that these patients have poor synchronization in response to stimulus timing and deficiencies in coding high-frequency and rapidly changing auditory information,which may be one of the mechanisms underlying the decline in speech abilities in patients with presbycusis.

Objective:To investigate the correlation between cerebral blood flow (CBF) in different brain regions and gait disorder (GD) in patients with cerebral small vessel disease (CSVD).Methods:Patients with CSVD visited the Department of Neurology, the Second Affiliated Hospital of Xuzhou Medical University from November 2023 to October 2024 were included prospectively. They were divided into GD group (<0.8 m/s) and non-GD group (≥0.8 m/s) based on their step speed. CBF was measured using 3D pseudo-continuous arterial spin labeling (3D-pCASL) perfusion imaging. Gait parameters were quantitatively evaluated using a wearable gait analyzer. Multivariate logistic regression analysis was used to determine independent factors associated with GD in patients with CSVD. Partial correlation analysis was used to determine the correlation between gait parameters and CBF in different brain regions. Results:A total of 52 patients with CSVD were enrolled, including 26 males and 26 females, aged 67.00±6.84 years. Thirty-eight cases (73.1%) had mild overall burden of CSVD, and 14 cases (26.9%) had a moderate to severe overall burden of CSVD. There were 17 patients (32.7%) in the GD group and 35 (67.3%) in the non-GD group. Compared with the non-GD group, the body mass index was significantly higher, the CBF of the left occipital lobe and bilateral cerebellum decreased significantly, the step speed, step length, stride length, step frequency, swing phase, peak arm angular velocity, arm swing amplitude, maximum calf anterior/posterior swing angle, peak calf angular velocity, foot swing speed, and peak sagittal plane angular velocity in the torso decreased significantly, while the number of steps, stance phase, step length asymmetry, stride length, and step length variability increased significantly in the GD group (all P<0.05). Multivariate logistic regression analysis showed that left cerebellar CBF was an independent protective factor for GD in patients with CSVD (odds ratio 0.902, 95% confidence interval 0.827-0.982; P=0.019). For every 1 ml/(100 g.min) decreased in left cerebellar CBF, the patients with CSVD had an increased risk of developing GD by approximately 9.8%. Partial correlation analysis showed that left occipital lobe CBF was significantly positively correlated with step speed ( r=0.305, P=0.032), maximum calf back swing angle ( r=0.314, P=0.026), and peak calf angular velocity ( r=0.356, P=0.011). The left cerebellar CBF was significantly positively correlated with step speed ( r=0.295, P=0.037) and significantly negatively correlated with step length variability ( r=-0.335, P=0.017); the right cerebellar CBF was significantly positively correlated with step speed ( r=0.309, P=0.029) and significantly negatively correlated with step length variability ( r=-0.344, P=0.014). Conclusion:GD in patients with CSVD is associated with decreased CBF in the left occipital lobe and bilateral cerebellum, and decreased CBF in the left cerebellum significantly increased the risk of GD in patients with CSVD.

Objective To explore the application of case-based learning(CBL)approach in the basic medical stage for eight-year clinical medical program.Methods A total of 320 students from the eight-year clinical medicine pro-gram at Peking Union Medical College in the grades of 2014-2015 and 2019-2020 were selected as the study subjects.These students were divided into two groups,162 students in the classes of 2014 and 2015 as the control group,and 158 students in the classes of 2019 and 2020 as the experimental group.The students in the control group received classic teaching in the basic medicine stage characterized by traditional lectures as the main teaching method.The students in the experimental group received traditional lectures supplemented by CBL.In this study,the cardiovascular system was taken as an example,and the assessment scores and questionnaires of the two groups of students were collected in order to evaluate the teaching effectiveness and to obtain timely teaching feedback.Results Traditional lecture combined with CBL method significantly improved the theory assessment scores of students in the experimental group,stimulated learning interest and intrinsic motivation,and enhanced team learn-ing and problem-solving ability.Students believed that CBL teaching could effectively improve the ability to link theory to clinical practice.In addition,CBL teaching method encouraged the interaction between teachers and students and improved teaching efficiency.Conclusions Well-designing and well-organized CBL teaching from multiple levels,including teachers,students,and curricula,can be better accepted and acknowledged by students from eight-year clinical medical program at the stage of basic medical education.

Objective:To explore the association between sublingual microcirculatory perfusion vessel proportion (PPV), high mobility group protein B1 (HMGB1), and sepsis-induced coagulopathy (SIC), and to identify early predictive markers for clinical intervention.Methods:A total of 66 septic patients admitted to the Respiratory Intensive Care Unit (RICU) between November 2021 and May 2024 were enrolled. Based on SIC diagnosis within 24 hours of admission, patients were categorized into SIC ( n=36) and non-SIC ( n=30) groups. Clinical parameters, including prothrombin time (PT), activated partial thromboplastin time (APTT), sublingual PPV, and serum HMGB1 levels (measured at 0 h and 6 h), were analyzed. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to identify independent predictors. Results:Compared with the non-SIC group, the SIC group demonstrated significantly prolonged PT ( P<0.05) and APTT ( P<0.05), elevated 0 h lactate levels, and increased 6 h HMGB1. Spearman analysis revealed a positive correlation between 6 h PPV and platelet count ( P<0.05), while an inverse correlation was observed with 6 h PT ( P<0.05). Multivariate regression identified APTT, 6 h PPV, and 6 h HMGB1 as independent predictors of SIC. ROC analysis yielded AUC values of 0.732 for APTT, 0.802 for 6 h PPV, and 0.765 for 6 h HMGB1. The combination of 6 h PPV and HMGB1 further improved predictive accuracy (AUC=0.873). Conclusions:Prolonged APTT, decreased 6 h PPV, and elevated 6h HMGB1 are key indicators of SIC. Integrated assessment of these markers enhances early risk stratification in septic patients, facilitating timely clinical intervention.

ObjectiveMolecular docking and animal experiments were employed to explore the protective effect and mechanism of Da Chengqitang （DCQD） on intestinal barrier in septic mice. MethodText mining method was used to screen the active ingredients in DCQD. AutoDock Tools and Discovery Studio were used to study the interactions of active components with the core target proteins ［claudin-1， tumor necrosis factor （TNF）-α， interleukin （IL）-6， endogenous antimicrobial peptide mCRAMP， Toll-like receptor 4 （TLR4）， and myeloid differentiation primary response gene 88 （MyD88）］ in sepsis. Fifty C57BL/6 mice were randomized into sham， model， low- and high-dose （4 g∙kg^-1 and 8 g∙kg^-1） DCQD， and ulinastatin groups （n=10）. Before， during， and after the day of modeling surgery， each group was administrated with corresponding drugs. The mice in other groups except the model group were subjected to modeling by cecal ligation and puncture. Enzyme-linked immunosorbent assay （ELISA） was used measure the serum level of D-lactic acid to assess intestinal mucosa permeability. Hematoxylin-eosin staining was employed to observe the histopathological changes in the ileum and assess the intestinal mucosal damage and inflammatory infiltration. Western blotting was employed to determine the expression levels of tight junction proteins claudin-1 and occludin in the ileal tissue， which were indicative of the bowel barrier function. The TNF-α and IL-6 levels were measured by ELISA to assess the intestinal inflammation. The expression of mCRAMP in the ileal tissue was observed by immunohistochemistry. The mRNA levels of mCRAMP， TLR4， and MyD88 in mouse ileal tissue were determined by Real-time polymerase chain reaction， on the basis of which the mechanism of DCQD in protecting the intestinal barrier of septic mice was explored. ResultMolecular docking results showed that most of the 10 active ingredients of DCQD that were screened out by text mining could bind to sepsis targets by van der Waals force， hydrogen bonding， and other conjugated systems. The results of animal experiments showed that compared with the model group， low- or high-dose DCQD lowered the D-lactic acid level in the serum （P<0.01）， alleviated damage to the ileal tissue and mucosal edema， protected the small intestine villus integrity， reduced inflammatory cell infiltration， promoted the expression of claudin-1 （P<0.01）， lowered the IL-6 level （P<0.01）， up-regulated the mRNA and protein levels of mCRAMP （P<0.01）， and down-regulated the mRNA and protein levels of TLR4 and MyD88 （P<0.01） in the ileal tissue. In addition， high-dose DCQD lowered the TNF-α level and promoted the expression of occludin in the ileum tissue （P<0.01）， and low-dose DCQD up-regulated the protein level of occludin in the ileum tissue （P<0.05）. ConclusionDCQD has a protective effect on intestinal barrier in septic mice. It can reduce intestinal inflammation， repair intestinal mucosal damage， improve the tight junction protein level， and reduce intestinal mucosal permeability by up-regulating the mRNA and protein levels of mCRAMP and the down-regulating the expression of genes in the TLR4/MyD88 pathway.

Objective:To investigate the molecular biological mechanism of Bw07 allele and its transferase alteration carried by a proband of ABw07 subtype.Methods:A 2-year-old male child was selected as the research object. The peripheral blood of the proband and his parents was identified for ABO blood type by the test tube method, and the ABO subgroup PCR-SSP detection and ABO gene sequencing were performed on the three individuals to determine their blood type genotypes. Finally, the effect of the p.Arg352Gln mutation on Bw07 transferase was verified by virtual mutation, DUET structure prediction, molecular dynamics analysis, and in vitro cellular experiments.Results:The serological phenotypes of the proband and his mother were ABw and Bw, respectively, while his father was normal A. The ABO subgroup PCR-SSP assay identified the three genotypes as Bw07/A, Bw07/O, and A/A, respectively.Sanger sequencing further verified that the proband and his mother carried the Bw07 gene, and virtual mutation showed that the intermolecular forces were weakened by the R352Q mutation. DUET predicted that this p.Arg352Gln mutation could affect the thermodynamic stability of Bw07 transferase. Molecular dynamics analysis confirmed that the alteration of thermodynamic stability was mainly related to the appearance of large fluctuations in the amino acid backbone atoms in the 125-133, 193-198 and 336-354 regions, and in vitro cellular experiments further verified the weakened antigen synthesis of Bw07 transferase.Conclusion:The formation of the ABw07 phenotype is associated with the mutation of the highly conserved Arg352 to Gln in Bw07 transferase.

Objective To statistically analyze the perioperative results of patients with ABO-incompatible kidney trans-plantation(ABOi-KT),in order to explore the changes in blood group antibody of type-A/B recipients.Methods A total of 33 cases of blood group A/B ABOi-KT recipients in our hospital from January 2021 to October 2023 were recruited and divided into two groups of group A(n=18)and group B(n=15)according to the different blood types of recipient.The effects of preoperative plasmapheresis on antibody titer,antibody rebound and renal function after operation(serum urea ni-trogen,creatinine and estimated glomerular filtration rate on the 1st,3rd,7th and 14th day)were analyzed between the two groups.According to the postoperative rebound of blood type antibodies,33 recipients were divided into antibody rebound group(n=7)and non rebound group(n=26),and the differences in initial blood type antibody titers between the two groups were analyzed.Results There was no significant difference in the clearance rate of IgM with preoperative plasma ex-change between the two groups(Z=-0.26,P＞0.05);Levels of serum urea nitrogen and creatinine on the 1st,3rd,7th and 14th day after operation between group A and group B were not statistically significant(P＞0.05),the same as eGFR.Group B was more prone to rebound antibody compared with group A(P＜0.05).There was a significant difference in the in-itial IgM antibody titer between the blood type antibody rebound group and the non rebound group(Z=-2.127,P＜0.05),but no statistically significant difference in the initial IgG antibody titer(Z=-1.835,P＞0.05)between the two groups was found.Conclusion The patients type B receiving type AB kidney donors are more prone to rebound antibody after ABOi-KT operation compared to the the patients type A receiving type AB.

Objective:To explore the molecular basis for an individual with Bel subtype of the ABO blood type due to a novel c. 620T>C variant gene, and assess its impact on the structure of GTB transferase.Methods:An individual who had visited the First Affiliated Hospital of Zhengzhou University on February 11, 2023 was selected as the study subject. ABO phenotyping was initially conducted with serological methods, which was followed by direct sequencing of 7 exons of the ABO gene. Subsequently, single-strand sequencing was carried out by using allele-specific primers, and the variant in the B transferase was homology-modeled using the Modeller software. The impact of the variant on the transferase′s spatial structure was analyzed with the PyMOL software. Results:The serological phenotype of the patient was identified as the Bel subtype. Direct sequencing revealed that she has harbored a novel c. 620T>C variant, resulting in a p. Leu207Pro substitution in the polypeptide chain. Combined with single-strand sequencing, her genotype was ultimately determined as ABO* BELnew/ ABO* O.01.02. Three-dimensional protein structure modeling showed that, compared with the wild type, the distance of one hydrogen bond between Proline and Glycine at position 272 has increased, along with disappearance of another hydrogen bond. Conclusion:The novel c. 620T>C (p.Leu207Pro) variant of B allele may affect the structural stability of the glycosyltransferase. The weakened enzyme activity in turn may lead to reduced B antigen expression, manifesting as the Bel subtype by serological analysis.