ObjectiveTo observe the clinical efficacy and safety of Huatan Quyu formula in treating cerebral small vessel disease （CSVD） with phlegm and blood stasis blocking collateral pattern via randomized controlled trial， and explore its mechanism of improving CSVD by regulating glymphatic system （GS） circulation. MethodsSixty-eight CSVD patients with phlegm and blood stasis blocking collateral pattern in the Department of Encephalopathy， Affiliated Hospital of Shaanxi University of Chinese Medicine from April to December 2024 were selected and randomly divided into an experimental group （34 cases） and a control group， with 34 cases in each group. Both groups received basic Western medicine treatment， while the experimental group additionally received Huatan Quyu formula. After a course of 12 weeks， the following parameters were compared between the two groups before and after treatment. Clinical outcomes were assessed using the Tinetti performance-oriented mobility assessment （POMA）， Montreal Cognitive Assessment （MoCA）， Scales for Outcomes in Parkinson's Disease-Autonomic （SCOPA-AUT）， and traditional Chinese medicine （TCM） syndrome scores of phlegm and blood stasis blocking collateral pattern. Perivascular space （PVS） in the frontal lobe/basal ganglia and cerebrospinal fluid （CSF） flow parameters in the cerebral aqueduct were evaluated by 3.0T brain MRI， cerebrospinal fluid flow imaging， and phase-contrast magnetic resonance imaging （PC-MRI）. Then， safety indicators were monitored， and SPSS 25.0 was used for statistical analysis. ResultsSixty-four patients completed the study （32 in each group）. ①Baseline data： No statistically significant difference was found between the two group. ②Efficacy indicators： After treatment， the experimental group exhibited significantly improved total POMA， SCOPA-AUT， and TCM syndrome scores （P<0.01）， outperforming the control group （P<0.05）. No significant change was observed in MoCA scores between the two groups. ③Imaging indicators： The experimental group showed a reduced PVS area alongside significantly increased CSF flow parameters （including downward flow during the systolic period， and upward flow during the diastolic period） （P<0.01）， which were superior to the control group （P<0.01）. ④Safety： The laboratory indicators were normal in both groups， with no drug-related adverse reactions. ConclusionFor CSVD patients with phlegm and blood stasis blocking collateral pattern， Huatan Quyu formula can safely and effectively improve motor function， autonomic nerve function， and TCM syndromes， with potential mechanisms related to pulsatile CSF flow enhancement and GS circulation efficiency improvement.

ObjectiveTo investigate the possible mechanism by which Zhiqiao Gancao Decoction （枳壳甘草汤， ZGD） delays intervertebral disc degeneration （IDD） based on the Hippo-yes-associated protein （YAP）/transcriptional co-activator with PDZ-binding motif （TAZ） signaling pathway. MethodsA total of 50 SD rats were randomly divided into sham surgery group， model group， low-dose ZGD group， high-dose ZGD group， and high-dose ZGD + inhibitor group， with 10 rats in each group. In the sham surgery group， the rats were pierced in the skin and muscle at the Co6/7/8 segments of the tail with a 21G needle （depth approximately 2 mm） without damaging the intervertebral disc. In the other groups， rats were injected with a 21G needle at the Co6/7/8 segments of the tail to establish an IDD model by piercing the tail intervertebral disc 5 mm. One week after modeling， rats in the low-dose and high-dose ZGD groups were given 6.24 and 12.24 g/（kg·d） of the decoction via gastric gavage， respectively. The high-dose ZGD + inhibitor group was given 12.24 g/（kg·d） of the decoction and an intraperitoneal injection of YAP/TAZ inhibitor Verteporfin 10 mg/kg. The sham surgery and model groups were given 5 ml/（kg·d） of normal saline via gavage. The gavage was given once a day， and the intraperitoneal injection was given every other day. After 4 weeks of continuous intervention， the pathological changes of the tail intervertebral discs were observed using HE staining， Oil Red O-Green staining， and Toluidine Blue staining. Immunohistochemistry was used to detect the expression of aggrecan and MMP3 in the nucleus pulposus. TUNEL fluorescence staining was performed to detect apoptosis in the nucleus pulposus， and the apoptosis rate was calculated. Western blot was used to detect the Hippo-YAP/TAZ signaling pathway， including YAP， phosphorylated YAP （p-YAP）， phosphorylated MST1/2 （p-MST1/2）， phosphorylated TAZ （p-TAZ） and apoptosis-related proteins， such as Cleaved Caspase 3， P53， Bcl-2 and Bax. ResultsCompared with sham surgery group， the rats in the model group showed significant degenerative changes in the intervertebral disc. The levels of aggrecan， Bcl-2， and YAP proteins in the nucleus pulposus decreased， while the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and the apoptosis rate increased （P < 0.01）. Compared with the model group， the drug intervention groups showed partial recovery in intervertebral disc degeneration. The levels of aggrecan， Bcl-2， and YAP proteins increased， while the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and the apoptosis rate decreased （P＜0.05 or P＜0.01）. The high-dose ZGD group showed more significant recovery in intervertebral disc degeneration compared to the low-dose ZGD group， with a decrease in the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and apoptosis rate， and an increase in the levels of aggrecan， Bcl-2， and YAP proteins （P＜0.05 or P＜0.01）. Compared with the high-dose ZGD group， the high-dose ZGD + inhibitor group showed a reduced recovery in intervertebral disc degeneration， with an increase in the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and apoptosis rate， and a decrease in the levels of aggrecan， Bcl-2， and YAP proteins （P＜0.05 or P＜0.01）. ConclusionZGD may delay intervertebral disc degeneration by inhibiting the phosphorylation of YAP in the nucleus pulposus， maintaining the function of the Hippo-YAP/TAZ signaling pathway， and reducing apoptosis of nucleus pulposus cells.

As the most common phenotype of type 1 neurofibromatosis(NF1),plexiform neurofibromas(pNF)exhibit early asymptomatic presentation but multisite involvement,with a risk of progression.Imaging serves as vital tool for evaluation and management of NF1-associated pNF.The progresses of imaging for evaluating NF1-related pNF were reviewed in this article.

Objective:To explore the application effects of a method combining progressive case study and fishbone diagram in clinical teaching of interns in general surgery, and evaluate its impact on medical students' theoretical knowledge mastery, clinical practice ability development, and systematic thinking cultivation.Methods:Sixty undergraduate clinical medicine students who interned in the Department of General Surgery from July 2022 to December 2023 were selected as the research subjects and randomly divided into a control group ( n=30) and an observation group ( n=30). The control group received traditional case-based teaching through centralized lectures, group discussions, and review/Q&A sessions. The observation group received an integrated teaching approach combining progressive case study and fishbone diagram through the design of progressive cases and fishbone diagrams. Teaching effectiveness was evaluated through theoretical assessment, practical assessment, and teaching satisfaction survey. SPSS 22.0 was used for t-test and χ2 test. Results:The total score of theoretical assessments for the observation group interns was higher than that of the control group [(86.97±4.60) vs. (66.06±5.96), t=-17.79, P<0.001]. The differences in scores of diagnosis and treatment standards [(17.03±1.82) vs. (14.07±2.35)] and differential diagnosis [(12.85±1.42) vs. (8.92±2.37)] were particularly significant. In the practical assessments, the total score of the observation group interns [(90.19±5.04) vs. (68.63±4.30), t=-17.82, P<0.001] and their scores in individual assessments were higher than those of the control group, especially in acute abdomen evaluation [(18.23±1.72) vs. (14.37±2.05)], laparoscopic spatial positioning [(8.83±0.95) vs. (5.92±1.38)], and intraoperative emergency management [(8.95±0.97) vs. (6.05±1.23)]. The satisfaction scores of the observation group interns were higher than those of the control group ( P<0.001), with the greatest improvement in clinical thinking [(4.65±0.61) vs. (3.10±0.71)] and teacher-student interaction quality [(4.72±0.53) vs. (3.11±0.63)]. Conclusions:The teaching method combining progressive case study and fishbone diagram significantly improved interns' theoretical assessment scores, practical operation ability, and clinical decision-making level through the dynamic presentation of case evolution processes and the application of structured analysis tools, and also enhanced the teaching satisfaction.

Objective:To understand the coverage and information consistency rate of National Immunization Program (NIP) vaccines among children born during 2020-2021 in Zhejiang Province, Chongqing City, and Shanxi Province (3 provinces) of China .Methods:A simple random sampling method was used to randomly select 3 counties (districts) from each of the 3 provinces, 5 townships from each county (district), and 5 villages from each township. Vaccination information for seven NIP vaccines was collected for children born between 2020 and 2021 in each village. The vaccination coverage, timely coverage, and consistency rates between the survey data and the Immunization Planning Information System data were analyzed.Results:A total of 1 117 children were investigated. The vaccination coverage for each dose of NIP vaccine ranged from 99.10% to 100.00%, with those in Zhejiang Province, Chongqing City, and Shanxi Province ranging from 99.19% to 100.00%, 98.92% to 100.00%, and 99.20% to 100.00%, respectively. The timely coverage of each dose of NIP vaccine ranged from 89.79% to 99.82%, with those in Zhejiang Province, Chongqing City, and Shanxi Province ranging from 94.09% to 99.73%, 89.52% to 99.73%, and 78.55% to 100.00%, respectively. The consistency rate of information on each dose of NIP vaccine ranged from 94.36% to 99.91%, with those in Zhejiang Province, Chongqing City, and Shanxi Province ranging from 97.85% to 99.73%, 98.92% to 100.00%, and 86.06% to 100.00%, respectively.Conclusions:Coverage of NIP vaccines was generally high among children born during 2020-2021 in the 3 provinces of China, but there were regional differences in the timely coverage of some vaccine doses and the vaccination information consistency rate. It is necessary to strengthen the timely vaccination of children's vaccine booster doses and optimize the management of vaccination services.

Objective:To investigate the anemia conditions and characteristics of iron metabolism during different stages of pregnancy in women with different genotypes of thalassemia.Methods:This cohort study selected 3 303 singleton pregnant women who underwent regular prenatal examinations and genetic tests of thalassemia and were delivered at Maternal & Child Health Hospital of Guangxi Zhuang Autonomous Region from January 2019 to December 2023. According to the results of thalassemia gene testing, the women were divided into groups: those without thalassemia genes served as the control group (1 539 cases), and those with thalassemia genes (1 764 cases) were further divided based on genotype into the -α/αα group (326 cases), --/αα or -α/-α group (649 cases), point mutation α-thalassemia group (201 cases), β 0-thalassemia group (368 cases), β +-thalassemia group (91 cases), and α combined with β-thalassemia group (129 cases). Hemoglobin (Hb) and serum ferritin (SF) levels were measured in the first, second, and third trimester of pregnancy. Differences in anemia and iron reserves among the groups at different pregnancy stages were compared using repeated measures analysis of variance, LSD test, Kruskal-Wallis rank-sum test, and Bonferroni correction. Results:Compared to the first trimester, Hb levels decreased in the second and third trimester across all groups (LSD test, all P<0.05), and the severity of anemia increased (Bonferroni correction, all P<0.017). The severity of anemia varied among the groups at the same pregnancy stage ( Hfirst trimester=918.20, Hsecond trimester=1 224.50, Hthird trimester=980.19; all P<0.001), and Hb levels also differed ( Ffirst trimester=282.54, Fsecond trimester=352.31, Fthird trimester=239.02; all P<0.001). The β 0-thalassemia group had higher rates of moderate anemia in the first, second, and third trimester of pregnancy [38.6% (142/368), 85.3% (314/368), and 73.6% (271/368)] compared to other groups (Bonferroni correction, all P<0.002), and lower Hb levels [(102.1±8.9), (92.0±7.3), and (94.6±7.7) g/L] than other groups (LSD test, all P<0.05). As pregnancy progresses, SF levels in each group of pregnant women gradually decreased (LSD test, all P<0.05), and the degree of iron deficiency worsened (Bonferroni correction, all P<0.05). The iron deficiency rate in thalassemia pregnant women during the third trimester ranges from 21.5% (79/368) to 46.0% (150/326). The degree of iron deficiency varies among groups within the same gestational period ( Hfirst trimester=79.13, Hsecond trimester=203.98, Hthird trimester=130.55; all P<0.001), and SF levels also differ ( Ffirst trimester=17.28, Fsecond trimester=44.60, Fthird trimester=31.87; all P<0.001). Among them, the β 0-thalassemia group had the lowest iron deficiency rates in the second, and third trimesters [9.8% (36/368), and 21.5% (79/368)] (Bonferroni correction, all P<0.002). SF levels in the β 0-thalassemia and β +-thalassemia groups were higher than those in other groups during each gestational period (LSD test, all P<0.05). Conclusions:Pregnant women with thalassemia may experience varying degrees of iron deficiency during pregnancy, with the severity of iron deficiency and anemia increasing with gestational age. The degree of iron deficiency and anemia during pregnancy varies among pregnant women with different genotypes of thalassemia. Clinically, individualized management should be provided for pregnant women with thalassemia based on their genotypes, with dynamic monitoring of anemia and iron metabolism changes.

Objective:To investigate the effects of sampling methods on pathological assessment of resected non-small cell lung cancer (NSCLC) specimen with tumor maximum diameter >3 cm after neoadjuvant therapy.Methods:NSCLC patients with a large tumor (diameter >3 cm) that were resected after neoadjuvant therapy from June 2020 to July 2023 were retrospectively collected in the Department of Pathology, Shanghai Pulmonary Hospital, Shanghai, China. Sampling methods of the tumor bed were performed in accordance with the international and Chinese experts recommendations for resection specimens following neoadjuvant therapy (recommended sampling method, RSM), and all remaining tumor bed lesions were completely sampled after recommended sampling (complete sampling method, CSM). The difference of pathological response assessment of residual viable tumor (RVT) between RSM and CSM was examined.Results:A total of 90 cases were identified and analyzed, including 39 cases of squamous cell carcinoma and 51 cases of adenocarcinoma, treated with neoadjuvant therapy including chemotherapy in 22 cases (24.4%), targeted therapy in 14 cases (15.6%), and chemoimmunotherapy in 54 cases (60.0%). There were 62 males and 28 females with an average age of (62.7±17.9) years. The average tumor maximum diameter was 4.3 cm (range, 3.1-8.0 cm). The average number of sampled blocks was 8 blocks (range, 5 to 16) and 15 blocks (range, 8 to 36) per case by RSM and CSM, respectively. According to the definition of major pathological response (MPR) in which RVT is ≤10%, the numbers of patients with MPR were 34 cases by RSM and 30 cases by CSM, respectively. Four cases showed inconsistent RVT between the two methods, including one case of squamous cell carcinoma and three cases of adenocarcinoma. The RVT of the four inconsistent cases was 7%, 7%, 5% and 9% (MPR by RSM), and 15%, 15%, 15% and 20% (non-MPR by CSM), respectively. The kappa values of MPR consistency evaluated by the two sampling methods were 0.893 for all cases, 0.906 for squamous cell carcinoma cases and 0.751 for adenocarcinoma cases. According to MPR cut-off of 65% for invasive primary adenocarcinoma, 24 cases and 20 cases achieved MPR by RSM and CSM, respectively. Of the four inconsistent cases, the RVT by RSM was 60% in three cases and 65% in one case (MPR), whereas the RVT by CSM was 70% in three cases and 75% in one case (non-MPR). The kappa value of the two sampling methods was 0.741.Conclusions:There is high consistency between RSM and CSM in the pathological assessment of post-treatment responses in resected NSCLC specimens with tumor maximum diameter larger than 3 cm. When the percentage of RVT cells is close to MPR, re-evaluation of the specimen is required and CSM may be necessary to accurately evaluate the degree of pathological remission, assist in clinical postoperative treatment, and predict patient prognosis.

Objective To investigate the protective effects of Ligilactobacillus salivarius Li01(L.salivarius Li01)against DNA damage induced by Helicobacter pylori(Hp),Benzo(a)pyrene(BaP),and Hp+BaP,and to evaluate the probiotic properties of L.salivarius Li01.Methods After 1 week of adaptive feeding,specific pathogen-free male Mongolian gerbils were randomly assigned to groups and subjected to intragastric administration of Hp,BaP,and Hp+BaP for model induction.At week 32 post model establishment,therapeutic L.salivarius Li01 was administered intragastrically.At week 36,peripheral blood samples were collected from each group for the comet assay,while liver tissues were collected and tested for Cyp1a1 gene expression levels.Results Compared with those in the control group,the comet tail length,％tail DNA,and hepatic Cyp1a1 expression levels were significantly increased in the Hp,BaP,and Hp+BaP groups(P＜0.0001).Among these,the comet tail length,olive tail moment,％tail DNA,and hepatic Cyp1a1 expression levels were significantly higher in the Hp+BaP group than in the Hp and BaP groups(P＜0.05).Following intervention with L.salivarius Li01,the comet tail length,olive tail moment,％tail DNA,and hepatic Cyp1a1 expression levels were significantly reduced in each group(P＜0.001).Conclusions Hp infection,BaP exposure,and the Hp+BaP combination induced DNA damage in the peripheral lymphocytes of Mongolian gerbils,with the Hp+BaP combination showing synergistic damage.L.salivarius Li01 had a protective effect against DNA damage caused by Hp,BaP,and Hp+BaP.

Objective:To investigate the effects of sampling methods on pathological assessment of resected non-small cell lung cancer (NSCLC) specimen with tumor maximum diameter >3 cm after neoadjuvant therapy.Methods:NSCLC patients with a large tumor (diameter >3 cm) that were resected after neoadjuvant therapy from June 2020 to July 2023 were retrospectively collected in the Department of Pathology, Shanghai Pulmonary Hospital, Shanghai, China. Sampling methods of the tumor bed were performed in accordance with the international and Chinese experts recommendations for resection specimens following neoadjuvant therapy (recommended sampling method, RSM), and all remaining tumor bed lesions were completely sampled after recommended sampling (complete sampling method, CSM). The difference of pathological response assessment of residual viable tumor (RVT) between RSM and CSM was examined.Results:A total of 90 cases were identified and analyzed, including 39 cases of squamous cell carcinoma and 51 cases of adenocarcinoma, treated with neoadjuvant therapy including chemotherapy in 22 cases (24.4%), targeted therapy in 14 cases (15.6%), and chemoimmunotherapy in 54 cases (60.0%). There were 62 males and 28 females with an average age of (62.7±17.9) years. The average tumor maximum diameter was 4.3 cm (range, 3.1-8.0 cm). The average number of sampled blocks was 8 blocks (range, 5 to 16) and 15 blocks (range, 8 to 36) per case by RSM and CSM, respectively. According to the definition of major pathological response (MPR) in which RVT is ≤10%, the numbers of patients with MPR were 34 cases by RSM and 30 cases by CSM, respectively. Four cases showed inconsistent RVT between the two methods, including one case of squamous cell carcinoma and three cases of adenocarcinoma. The RVT of the four inconsistent cases was 7%, 7%, 5% and 9% (MPR by RSM), and 15%, 15%, 15% and 20% (non-MPR by CSM), respectively. The kappa values of MPR consistency evaluated by the two sampling methods were 0.893 for all cases, 0.906 for squamous cell carcinoma cases and 0.751 for adenocarcinoma cases. According to MPR cut-off of 65% for invasive primary adenocarcinoma, 24 cases and 20 cases achieved MPR by RSM and CSM, respectively. Of the four inconsistent cases, the RVT by RSM was 60% in three cases and 65% in one case (MPR), whereas the RVT by CSM was 70% in three cases and 75% in one case (non-MPR). The kappa value of the two sampling methods was 0.741.Conclusions:There is high consistency between RSM and CSM in the pathological assessment of post-treatment responses in resected NSCLC specimens with tumor maximum diameter larger than 3 cm. When the percentage of RVT cells is close to MPR, re-evaluation of the specimen is required and CSM may be necessary to accurately evaluate the degree of pathological remission, assist in clinical postoperative treatment, and predict patient prognosis.

Objective To explore the feasibility and value of synthetic MRI combined with reduced field of view(r FOV)intravoxel incoherent motion diffusion weighted imaging(IVIM-DWI)in preoperative predicting TN stage of rectal cancer.Methods The ima-ging and clinical data of 40 patients with rectal cancer confirmed by operation and pathology were collected and divided into low T stage group(T1-T2 stage)and high T stage group(T3-T4 stage),N0 stage group and N1-N2 stage group according to postoperative pathological staging as the golden standard.Independent sample t-tests were conducted to compare the parameter differences of synthetic MRI[T1,T2,and proton density(PD)values]and IVIM-DWI(D,D*,and f values)between the two groups.Receiver operating charac-teristic(ROC)curves were used to evaluate the efficacy of each parameter with statistically significant differences.Results Signifi-cant differences were observed in the T2 values of synthetic MRI and the D and f values of IVIM-DWI between high and low T stage groups,as well as between N0 and N1-N2 stage groups(P<0.05).The D value showed the highest area under the curve(AUC)(AUC=0.888)in predicting T stage group,and the T2 value was predominant(AUC=0.790)for N stage group prediction.The combination models of T2,D,and f values yielded superior predictive capability for TN stage in preoperative predicting rectal cancer,with AUC of 0.890 and 0.807,respectively.Conclusion Synthetic MRI combined with r FOV IVIM-DWI is feasible in preoperative prediction of TN stage of rectal cancer,which shows a higher efficacy,and is a useful supplement to conventional MRI technology.