Single-cell analysis reveals a unique microenvironment in peri-implantitis.

AIM: This study aimed to reveal the unique microenvironment of peri-implantitis through single-cell analysis. MATERIALS AND METHODS: Herein, we performed single-cell RNA sequencing (scRNA-seq) of biopsies from patients with peri-implantitis (PI) and compared the results with healthy individuals (H) and patients with periodontitis (PD). RESULTS: Decreased numbers of stromal cells and increased immune cells were found in the PI group, which implies a severe inflammatory infiltration. The fibroblasts were found to be heterogeneous and the specific pro-inflammatory CXCL13+ sub-cluster was more represented in the PI group, in contrast to the PD and H groups. Furthermore, more neutrophil infiltration was detected in the PI group than in the PD group, and cell-cell communication and ligand-receptor pairs revealed most neutrophils were recruited by CXCL13+ fibroblasts through CXCL8/CXCL6-CXCR2/CXCR1. Notably, our study demonstrated that the unique microenvironment of the PI group promoted the differentiation of monocyte/macrophage lineage cells into osteoclasts, which might explain the faster and more severe bone resorption in the progression of PI than PD. CONCLUSIONS: Collectively, this study suggests a unique immune microenvironment of PI, which may explain the differences between PI and PD in the clinic. These outcomes will aid in finding new specific and effective treatments for PI.

[Analysis of clinical characteristic of pediatric with progressive familial intrahepatic cholestasis type 3].

Objective: To analyze the clinical manifestations, pathology, and gene variant characteristics in children with progressive familial intrahepatic cholestasis type 3 (PFIC3). Methods: This retrospective study assessed the clinical manifestations, pathological features, gene variants, and prognosis data of 11 children with PFIC3 hospitalized in the Department of Hepatology, Fifth Medical Center, PLA General Hospital, from January 2015 to December 2022. Panel or whole exome sequencing was performed on the probands, followed by Sanger sequencing for verification within the family. Detected pathogenic variants were compared with known disease databases. Additionally, the new variants were predicted the deleteriousness and protein structure using relevant software to evaluate their pathogenicity. Results: Among the 11 PFIC3 children, 8 were boys and 3 were girls. The age of onset was 3.1 (0.2, 15.6) years. The main complaint of onset was different in the 11 patients;5 of them were abnormal liver function, 3 of them were liver and spleen enlargement, 2 of them were abdominal distension, and 1 of them was jaundice. alanine aminotransferase, asparate aminotransferase and r-glutamyltransferase increased in all the patients, which were(113±40), (150±44) and (270±156) U/L respectively. Moreover, direct bilirubin increased in 9 patients, and cholestasis was showed in 8 patients. All patients showed liver fibrosis on imaging, and 8 patients had cirrhosis. The pathological features of 8 cases by liver biopsy were as follows: 8 cases of fibrosis in the portal area, 7 cases of small bile duct hyperplasia, 4 cases of positive copper staining, and 5 cases of cirrhosis. A total of 17 ABCB4 gene variants were detected, including 9 new variants: c.589C>T(p.Q197X), c.1230+1G>A(Splicing), c.2914G>A(P.D972N), c.1058G>A(p.C353Y), c.956G>T(p.G319V), c.473T>A(p.L158Q), c.164T>C(p.L55S), c.2493G>C(p.R831S), and c.1150G>C(p.G384R). All 11 patients were treated with ursodeoxycholic acid and followed up for 5.1(0.6, 7.4) years. Among them, 4 cases of cirrhosis progressed continuously, 3 cases had liver transplantations, and the remaining 4 cases were stable after medical treatment. Conclusions: Children with PFIC3 have early onset, diverse clinical manifestations, rapid progression of fibrotic and cholestasis, as well as poor prognosis. Genetic testing helps to confirm the diagnosis.

[The effect of glucose-6-phosphate dehydrogenase deficiency on allogeneic hematopoietic stem cell transplantation in patients with hematological disorders].

Objectives: To determine the effect of glucose-6-phosphate-dehydrogenase (G6PD) deficiency on patients' complications and prognosis following allogeneic stem cell hematopoietic transplantation (allo-HSCT) . Methods: 7 patients with G6PD deficiency (study group) who underwent allo-HSCT at Peking University People's Hospital from March 2015 to January 2021 were selected as the study group, and thirty-five patients who underwent allo-HSCT during the same period but did not have G6PD deficiency were randomly selected as the control group in a 1∶5 ratio. Gender, age, underlying diseases, and donors were balanced between the two groups. Collect clinical data from two patient groups and perform a retrospective nested case-control study. Results: The study group consisted of six male patients and one female patient, with a median age of 37 (range, 2-45) years old. The underlying hematologic diseases included acute myeloid leukemia (n=3), acute lymphocytic leukemia (n=2), and severe aplastic anemia (n=2). All 7 G6PD deficiency patients achieved engraftment of neutrophils within 28 days of allo-HSCT, while the engraftment rate of neutrophils was 94.5% in the control group. The median days of platelet engraftment were 21 (6-64) d and 14 (7-70) d (P=0.113). The incidence rates of secondary poor graft function in the study group and control group were 42.9% (3/7) and 8.6% (3/35), respectively (P=0.036). The CMV infection rates were 71.4% (5/7) and 31.4% (11/35), respectively (P=0.049). The incidence rates of hemorrhagic cystitis were 57.1% (4/7) and 8.6% (3/35), respectively (P=0.005), while the bacterial infection rates were 100% (7/7) and 77.1% (27/35), respectively (P=0.070). The infection rates of EBV were 14.3% (1/7) and 14.3% (5/35), respectively (P=1.000), while the incidence of fungal infection was 14.3% (1/7) and 25.7% (9/35), respectively (P=0.497). The rates of post-transplant lymphoproliferative disease (PTLD) were 0% and 5.7%, respectively (P=0.387) . Conclusions: The findings of this study indicate that blood disease patients with G6PD deficiency can tolerate conventional allo-HSCT pretreatment regimens, and granulocytes and platelets can be implanted successfully. However, after transplantation, patients should exercise caution to avoid viral infection, complications of hemorrhagic cystitis, and secondary poor graft function.

Study of association between corneal shape parameters and axial length elongation during orthokeratology using image-pro plus software.

BACKGROUND: The aim was to validate the correlation between corneal shape parameters and axial length growth (ALG) during orthokeratology using Image-Pro Plus (IPP) 6.0 software. METHODS: This retrospective study used medical records of myopic children aged 8-13 years (n = 104) undergoing orthokeratology. Their corneal topography and axial length were measured at baseline and subsequent follow-ups after lens wear. Corneal shape parameters, including the treatment zone (TZ) area, TZ diameter, TZ fractal dimension, TZ radius ratio, eccentric distance, pupil area, and pupillary peripheral steepened zone(PSZ) area, were measured using IPP software. The impact of corneal shape parameters at 3 months post-orthokeratology visit on 1.5-year ALG was evaluated using multivariate linear regression analysis. RESULTS: ALG exhibited significant associations with age, TZ area, TZ diameter, TZ fractal dimension, and eccentric distance on univariate linear regression analysis. Multivariate regression analysis identified age, TZ area, and eccentric distance as significantly correlated with ALG (all P < 0.01), with eccentric distance showing the strongest correlation (ß = -0.370). The regressive equation was y = 1.870 - 0.235a + 0.276b - 0.370c, where y represents ALG, a represents age, b represents TZ area, and c represents eccentric distance; R2 = 0.27). No significant relationships were observed between the TZ radius ratio, pupillary PSZ area, and ALG. CONCLUSIONS: IPP software proves effective in capturing precise corneal shape parameters after orthokeratology. Eccentric distance, rather than age or the TZ area, significantly influences ALG retardation.

Frequency Transmission of Oscillation from External Whole-Body Vibration Platform to the Larynx.

PURPOSE: This study investigates (1) the presence of frequency transmission of oscillation from an external whole-body vibration (WBV) platform to the larynx; and (2) the factors that influence this frequency transmission. METHODS: Thirty participants (mean age=22.3years) with normal voice were exposed to four frequency-intensity levels of WBV (10 Hz-10%, 10 Hz-20%, 20 Hz-10%, 20 Hz-20%) and were instructed to produce the natural vowel /a/ three times during each WBV setting. The frequency was extracted from the middle 1-second of each electroglottographic (EGG) signal after passing through a Hann band filter with a range of 6-24 Hz. Linear mixed-effects models were applied to determine the factors that influenced the absolute deviation of the frequency transmission. RESULTS: All participants exhibit an extracted EGG frequency that aligns with the external WBV frequency, deviating by - 0.6 to 1.2 Hz. The absolute deviation of WBV frequency transmission is consistent for both sexes across various WBV settings, except the 10 Hz-10% setting where men tend to exhibit significantly higher deviations (P = 0.018). CONCLUSION: Oscillations at a specific frequency are transmitted from an external WBV platform to the larynx. This study proposes the use of a "spring" system to investigate the effect of WBV on the larynx, and recommends further research to explore the potential of WBV in managing voice disorders.

[Evaluation of differences in quality of life in patients with chronic graft-versus-host disease].

Objective: To evaluate the status of, differences in, and factors influencing quality of life (QoL) in patients with chronic graft-versus-host disease (GVHD). Methods: From September 2021 to February 2023, a cross-sectional study of 140 patients with chronic GVHD was conducted at our center. Symptom burden was assessed by the Lee Symptomatology Scale (LSS), and QoL was assessed by the Medical Outcome Study 36-Item Short-Form Health Survey (SF-36) (version 1) and five-level EuroQoL five-dimensional questionnaire (EQ-5D-5L). Results: Data from 140 respondents, including 32 (22.9%) with mild chronic GVHD, 87 (62.1%) with moderate chronic GVHD, and 21 (15.0%) with severe chronic GVHD, were analyzed. Of the respondents, 61.4% were male, and the median transplantation age was 34 (15-68) years. The primary diagnoses were acute myeloid leukemia (50.0%), acute lymphoblastic leukemia (20.0%), and myelodysplastic syndrome (15.0%). The common chronic GVHD-affected organs included the skin in 74 patients (52.9%), the eyes in 57 patients (40.7%), and the liver in 50 patients (35.7%). Among the whole cohort, the eye (20.48±23.75), psychological (16.13±17.00), and oral (13.66±20.55) scores were highest in the LSS group. The physiological function (36.07±11.13), social function (36.10±10.68), and role-emotional functioning (38.36±11.88) scores were lowest in the SF-36 group. The EQ-5D index was 0.764. The total LSS scores for mild, moderate, and severe chronic GVHD were 6.51±6.15, 10.07±5.61, and 20.90±10.09, respectively. The SF-36 physical component scores (PCSs) were 43.12±6.38, 40.73±7.14, and 36.97±6.97, respectively, and the mental component scores (MCSs) were 43.00±8.47, 38.90±9.52, and 28.96±9.63, respectively. The EQ-5D values were 0.810±0.124, 0.762±0.179, and 0.702±0.198, respectively. The multivariate analysis showed that the overall symptom burden (ß=-0.517), oral symptom burden (ß=-0.456), National Institute of Health (NIH) criteria for the eyes (ß=-0.376), and nutrition-related symptom burden (ß=-0.211) were significantly negatively correlated with the PCS. The NIH score (ß=-0.260) was negatively correlated with the MCS score. Oral symptom burden (ß=-0.400), joint/fascia NIH criteria (ß=-0.332), number of involved systems (ß=-0.253), overall NIH criteria (ß=-0.205), and number of immunosuppressants taken (ß=-0.171) were significantly negatively correlated with the EQ-5D score (all P<0.05). Medium to strong correlations were found between the EQ-5D score and the SF-36 score (|r|=0.384-0.571, P<0.001). Conclusions: The QoL of patients with chronic GVHD is impaired, and the more severe the disease, the poorer the QoL. Overall symptom burden, severity of eyes, and oral symptom burden were the most important factors affecting QoL.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with gastric cancer.

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with gastric cancer (GC), published in late 2022 and the updated ESMO Gastric Cancer Living Guideline published in July 2023, were adapted in August 2023, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with GC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with GC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), coordinated by ESMO and the Japanese Society of Medical Oncology (JSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian regions represented by the 10 oncological societies. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with GC across the different regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling and age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different regions of Asia.

Non-KAM classical chaos topology for electrons in superlattice minibands determines the inter-well quantum transition rates.

We investigate the quantum-classical correspondence for a particle tunnelling through a periodic superlattice structure with an applied bias voltage and an additional tilted harmonic oscillator potential. We show that the quantum mechanical tunnelling rate between neighbouring quantum wells of the superlattice is determined by the topology of the phase trajectories of the analogous classical system. This result also enables us to estimate, with high accuracy, the tunnelling rate between two spatially displaced simple harmonic oscillator states using a classical model, and thus gain new insight into this generic quantum phenomenon. This finding opens new directions for exploring and understanding the quantum-classical correspondence principle and quantum jumps between displaced harmonic oscillators, which are important in many branches of natural science.

[Clinical features and risk factors for invasive fungal sinusitis after allogeneic hematopoietic stem cell transplantation].

Objective: To analyze the clinical characteristics and outcomes of patients with invasive fungal sinusitis (invasive fungal rhinosinusitis, IFR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and explored the risk factors for IFR after allo-HSCT. Methods: Nineteen patients with IFR after allo-HSCT at Peking University People's Hospital from January 2012 to December 2021 were selected as the study group, and 95 patients without IFR after allo-HSCT during this period were randomly selected as the control group (1:5 ratio) . Results: Nineteen patients, including 10 males and 9 females, had IFR after allo-HSCT. The median age was 36 (10-59) years. The median IFR onset time was 68 (9-880) days after allo-HSCT. There were seven patients with acute myeloid leukemia, five with acute lymphoblastic leukemia, two with myelodysplastic syndrome, two with chronic myeloid leukemia, one with acute mixed-cell leukemia, one with multiple myeloma, and one with T-lymphoblastic lymph node tumor. There were 13 confirmed cases and 6 clinically diagnosed cases. The responsible fungus was Mucor in two cases, Rhizopus in four, Aspergillus in four, and Candida in three. Five patients received combined treatment comprising amphotericin B and posaconazole, one patient received combined treatment comprising voriconazole and posaconazole, nine patients received voriconazole, and four patients received amphotericin B. In addition to antifungal treatment, 10 patients underwent surgery. After antifungal treatment and surgery, 15 patients achieved a response, including 13 patients with a complete response and 2 patients with a partial response. Multivariate analysis revealed that neutropenia before transplantation (P=0.021) , hemorrhagic cystitis after transplantation (P=0.012) , delayed platelet engraftment (P=0.008) , and lower transplant mononuclear cell count (P=0.012) were independent risk factors for IFR after allo-HSCT. The 5-year overall survival rates in the IFR and control groups after transplantation were 29.00%±0.12% and 91.00%±0.03%, respectively (P<0.01) . Conclusion: Although IFR is rare, it is associated with poor outcomes in patients undergoing allo-HSCT. The combination of antifungal treatment and surgery might be effective.

[Study based on the acetaldehyde dehydrogenase 2 gene polymorphism and acetaminophen-induced liver injury].

Objective: To explore the association between aldehyde dehydrogenase 2 (ALDH2) gene polymorphisms and abnormal liver function-induced by acetaminophen (APAP) drugs. Methods: An ALDH2 gene knockout mouse model was constructed using CRISPR/Cas9 gene editing technology. The obtained heterozygous mice were mated with opposite sex of heterozygotes. Genomic DNA was extracted from the tail of the offspring mouse. The polymerase chain reaction (PCR) method was used to determine the ALDH2 genotype. APAP was further used to induce acute drug-induced liver injury models in wild-type and ALDH2 knockout mice. Blood and liver tissues of mice were collected for liver function index, HE staining, F4/80 immunohistochemistry, and other detections. The intergroup mean was compared using a one-way ANOVA. The LSD- t test was used for pairwise comparison. Results: ALDH2 knockout mice were bred successfully. The genotyping of the offspring was segregated into the wild-type (ALDH2(+/+)), heterozygous mutant (ALDH2(+/-)), and homozygous mutant (ALDH2(-/-)), respectively. Biochemical and histological results after APAP modeling showed that the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil) was not significantly increased in the blank control group (P < 0.05), while the ALT, AST,ALP, and TBil were all elevated in the APAP experimental group. The levels of ALT (P  = 0.004), AST (P = 0.002), and TBil (P = 0.012) were significantly elevated among the mutant group compared to those in the wild-type group, and the expression levels of these indicators were also significantly elevated among the homozygous mutant group compared to those in the heterozygous mutant group (P = 0.003, 0 and 0.006). In addition, the ALP levels were higher in the heterozygous mutation group than those in the homozygous mutant group (P = 0.085) and wild-type group mice, but the difference was only statistically significant compared to wild-type mice (P = 0.002). HE staining results showed that mice in the APAP experimental group had hepatocyte degeneration, necrosis, and increased inflammatory cell infiltration, which was mostly evident in mutant mice. Simultaneously, the F4/80 immunohistochemical staining results showed that brown granules were visible in the liver tissue of APAP experimental group mice, and its expression levels were significantly enhanced compared to the blank control group. Conclusion: APAP-induced liver function abnormalities were associated with the ALDH2 gene polymorphism. The liver injury symptoms were increased in ALDH2 mutant mice following APAP modeling, and the ALDH2 gene defect may alleviate, to some extent, APAP-induced liver function abnormalities.

[Analysis of transfusion effect of different platelet matching schemes in patients with platelet transfusion refractoriness].

Objective: To analyze the transfusion effect of different platelet matching schemes in patients with platelet transfusion refractoriness (PTR). Methods: A total of 94 patients with PTR received by Taiyuan Blood Center from January to December 2021 were retrospectively analyzed, including 26 males and 68 females, aged 53(34,66) years. Platelet antibody screening was performed by enzyme-linked immunosorbent assay (ELISA). For patients with positive human leukocyte antigen (HLA) class Ⅰ antibodies, Luminex platform liquid chip assay was used to identify the specificity of antibodies, and platelets with missing allelic expression antigen corresponding to their specific antibodies were found in the platelet donor gene database established in our laboratory. For patients with negative class HLA-Ⅰ antibody screening, medium and high-resolution HLA-A and B alleles were genotyped by polymerase chain reaction restriction sequence specific oligonucleotide (PCR-SSO), and the compatible platelets were searched from the platelet donor gene database by HLA cross-reactive group genotype matching scheme or directly selected by serological cross-matching. The PCI compliance rate and total transfusion effective rate of different mismatch site groups and different matching scheme groups were statistically analyzed. Results: Platelet antibody was detected in 39 of 94 PTR patients with a positive rate of 41.5%, and all of them were HLA-Ⅰ antibodies, and 1 case was accompanied by human platelet antigen (HPA) antibody. A total of 134 times of compatible platelets were supplied to 39 patients with HLA-Ⅰ antibody positive by using antibody avoidance matching method. And the total effective rate of transfusion was 97.8% (131/134); The PCI compliance rates of HLA-A antigen mismatch, HLA-B antigen mismatch and HLA-A and B antigen mismatch groups were 81.6% (31/38), 86.5% (32/37) and 78.6% (22/28), respectively. The total effective rate of transfusion was 97.4% (37/38), 94.6% (35/37) and 100% (28/28), respectively, with no statistical significance (all P>0.05). A total of 118 times of compatible platelets were provided by HLA antigen cross-reaction group genotype matching and serological cross-matching, 90 transfusion effects were collected during follow-up, and the total effective rate was 76.7% (69/90). Conclusion: The combination of different platelet matching schemes can improve the PCI compliance rate and the total effective rate of transfusion in PTR patients.

[Effect of sirolimus combined with anti-CD20 monoclonal antibody desensitization on the prognosis of patients underwent haploidentical stem cell transplantation].

Objective: To investigate the effects of sirolimus combined with anti-CD20 monoclonal antibody desensitization on the prognosis of patients with haploidentical stem cell transplantation (haplo-SCT). Methods: Fifteen consecutive patients who received haplo-SCT and pre-transplant donor specific anti-human leukocyte antigen (HLA) antibody (DSA) positive [mean fluorescence intensity (MFI)≥2 000] in the Institute of Hematological Diseases from November 2021 to March 2023 were retrospectively recruited into the desensitized group. There were 4 males and 11 females, with a median age [M(Q1, Q3)] of 48 (37, 59) years. All patients were desensitized with sirolimus combined with anti-CD20 monoclonal antibody. The non-desensitized group included 29 patients with haplo-SCT who had not received desensitization treatment from August 2012 to June 2016. There were 12 males and 17 females with a median age of 42 (26, 50) years. Up to October 1, 2023, the median follow-up time was 13 (9, 18) months in the study group and 23 (14, 29) months in the control group. The changes of MFI before and after desensitization treatment and the prognosis of patients in the desensitized group were compared, including the incidence of primary implantation failure (pGF), neutrophil implantation time, platelet implantation time, grade Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) and chronic GVHD incidence, non-recurrence related mortality, event-free survival rate, disease-free survival rate and overall survival rate. The survival curve was drawn by Kaplan-Meier method, and the survival rate between groups was compared with Log-rank test. Results: After desensitization treatment, the level of DSA MFI in the desensitized group decreased from 8 879 (7 544, 11 495) to 3 781 (1 638, 4 165) after desensitization treatment (P<0.01). All of the patients achieved hematopoietic recovery, and the median time for neutrophil and platelet engraftment were 14 (11, 15) and 20 (18, 25) days, respectively. The incidence of pGF in the desensitized group was 0, which was lower than that in the non-desensitized group (34.5%, 10/29) (P=0.011). The expected 1-year disease-free survival rate and overall survival rate in the desensitized group were 100% (15/15) and 100% (15/15) respectively, while those in the non-desensitized group were 75.9% (22/29) and 75.9% (22/29) respectively, the difference was not statistically significant (both P>0.05). The one-year event-free survival rate in the desensitized group was expected to be 100% (15/15), which was higher than that in the non-desensitized group (51.3%, 15/29) (P=0.002). Conclusion: Sirolimus combined with anti-CD20 monoclonal antibody desensitization therapy can reduce the DSA level of haplo-SCT recipients, promote hematopoietic engraftment after transplantation, and avoid the occurrence of pGF after transplantation.

[Diagnostic value of high frequency oscillation in localization of type â ¡ focal cortical dysplasia epilepsy].

Retrospective analysis was conducted on 9 patients with type Ⅱ focal cortical dysplasia (FCD) who underwent stereo-electroencephalography (SEEG) implantation in the Department of Neurosurgery of the First Affiliated Hospital of Fujian Medical University from November 2020 to February 2023. The onset area, onset time, and frequency of high-frequency oscillations (HFO) were analyzed and the correlation of HFOs with interictal, preictal, and ictal periods. SEEG recordings of 80-500 Hz HFOs were observed in both interictal and ictal periods in 9 patients, with 6 patients exhibiting fast ripples (FR) in the range of 250-500 Hz. Surgical resection of the seizure onset area and FR-generating electrodes was performed, and postoperative follow-up for over 2 years indicated Engel I in 5 cases. 6 patients showed continuous discharge during the preictal period, and the distribution index of continuous discharge was positively correlated with seizure frequency. HFOs in the range of 80-500 Hz were present in all four seizure onset patterns during the ictal period. The onset area and FR-emitting electrode were surgically removed in 6 patients with continuous discharge and overlapping HFOs during the preictal period, with 5 cases of Engel I. Type Ⅱ FCD discharges exhibited complexity, high discharge indices, and a close association with HFOs. Compared with the spike wave, the electrode range of HF is more limited, and the incidence of HF before attack is significantly increased, which is closely correlated with the onset area. The simultaneous occurrence of HFO and the spike waves has higher diagnostic value than the individual occurrence, effectively enhancing surgical efficacy.

Efficacy and safety of intrathecal pemetrexed for TKI-failed leptomeningeal metastases from EGFR+ NSCLC: an expanded, single-arm, phase II clinical trial.

BACKGROUND: This study aimed to evaluate the efficacy and safety of intrathecal pemetrexed (IP) for treating patients with leptomeningeal metastases (LM) from non-small-cell lung cancer (NSCLC) who progressed from epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment in an expanded, prospective, single-arm, phase II clinical study (ChiCTR1800016615). PATIENTS AND METHODS: Patients with confirmed NSCLC-LM who progressed from TKI received IP (50 mg, day 1/day 5 for 1 week, then every 3 weeks for four cycles, and then once monthly) until disease progression or intolerance. Objectives were to assess overall survival (OS), response rate, and safety. Measurable lesions were assessed by investigator according to RECIST version 1.1. LM were assessed according to the Response Assessment in Neuro-Oncology (RANO) criteria. RESULTS: The study included 132 patients; 68% were female and median age was 52 years (31-74 years). The median OS was 12 months (95% confidence interval 10.4-13.6 months), RANO-assessed response rate was 80.3% (106/132), and the most common adverse event was myelosuppression (n = 42; 31.8%), which reversed after symptomatic treatment. The results of subgroup analysis showed that absence of brain parenchymal metastasis, good Eastern Cooperative Oncology Group score, good response to IP treatment, negative cytology after treatment, and patients without neck/back pain/difficult defecation had longer survival. Gender, age, previous intrathecal methotrexate/cytarabine, and whole-brain radiotherapy had no significant influence on OS. CONCLUSIONS: This study further showed that IP is an effective and safe treatment method for the EGFR-TKI-failed NSCLC-LM, and should be recommended for these patients in clinical practice and guidelines.

[Psychological problems in breast cancer patients should be taken seriously].

With the transformation of the biopsychosocial medical model, psychological problems and related interventions for breast cancer patients have received more and more attention. Patients often have various psychological problems, in diagnosis, treatment, and even in the state of disease-free survival, such as anxiety and depression, which not only seriously reduces the quality of life, but also affects the follow-up treatment and increases the risk of recurrence and metastasis. Therefore, physicians should perform routine psychological screening and appropriate intervention for patients. In recent years, psychological intervention has gradually become an important part of comprehensive breast cancer treatment, in which cognitive behavior therapy can alleviate patients' anxiety and sleep disorders, mindfulness therapy can treat patients' anxiety, depression and fear of cancer recurrence, and psychoeducational support is mainly used to address patients' mood disorders and sexual dysfunction. Improving patients' compliance with treatment and quality of life is the main goal of psychological intervention for breast cancer patients.

[Echocardiographic two-dimensional strain evaluation of right ventricular function in healthy adults].

Objective: To explore the feasibility of using two-dimensional speckle tracking echocardiography for measuring right ventricular strain and function in healthy adults, and to analyze the impact of age and gender. Methods: This study is a cross-sectional study. Healthy adults who underwent physical examination in the Physical Examination Center of Beijing Hospital from January 1, 2020 to January 1, 2021 were included. Two researchers independently measured various right ventricular longitudinal strain indices using the Echopac software, including (global longitudinal strain (GLS), apical longitudinal strain (ALS), midventricle longitudinal strain (MLS), basal longitudinal strain (BLS), free wall GLS (FWGLS), free wall ALS (FWALS), free wall MLS (FWMLS) and free wall BLS (FWBLS)) as well as tricuspid annular plane systolic excursion (TAPSE) and right ventricle-fraction of area change (RVFAC). The above indicators were taken as the average of two physicians. The consistency of the measurements by two physicians was evaluated by the within-group correlation coefficient (ICC). Results: A total of 233 subjects were included, including 137 males, aged (58.5±14.2) years. ICC values was all above 0.8 with excellent agreement. The values of FWGLS and GLS in healthy adults were -26.63% and -21.89%, respectively. There was no statistically significant difference in TAPSE ((2.06±0.41)cm vs. (2.10±0.39)cm, P=0.510) and RVFAC ((51.17±9.91)% vs. (50.89±8.65)%, P=0.826) between males and females. The values of various right ventricular long axis strain indicators (GLS, ALS, MLS, BLS, FWGLS, FWMLS, FWMLS, FWBLS) in females aged 18 to 40 and 41 to 65 years were higher than those in males of the same age (all P<0.05), while there was no statistically significant difference in the values of various right ventricular long axis strain indicators between the sexes in subjects aged 65 years and above (all P>0.05). In females, the right ventricular GLS, ALS, MLS, FWGLS, FWALS, FWMLS, and FWBLS values in the groups aged 18 to 40 and 41 to 65 years were significantly higher than those in the group aged 65 years and above (all P<0.05). In contrast, no significant differences were found in these indices among different age groups in males (all P>0.05). Conclusions: Using two-dimensional speckle tracking technology in echocardiography to measure right ventricular strain indicators is feasible and highly reproducible. Gender and age have an impact on right ventricular strain indicators.

[Correlation analysis between Pirani score and talo-navicular angle,calcaneo-cuboid angle and tibio-calcaneall angle of infant clubfoot under ultrasound].

Objective: To explore the evaluation effect of ultrasonography and Pirani score on tarsal deformity, treatment effect and pseudo-correction of congenital clubfoot in infants and young children, and the correlation between the two methods. Methods: This is a retrospective case series study. The clinical data of 26 children (40 feet) with congenital clubfoot who were evaluated by ultrasonography in the Third Affiliated Hospital of Zhengzhou University from January 2020 to January 2023 were retrospectively collected. There were 16 males and 10 females. The age at the first ultrasound examination was (M(IQR)) 9.0 (18.0) days (range: 1 to 46 days). All patients were treated with Ponseti method by the same physician. The Pirani scores before and after treatment and at the last examination, and the talonavicular angle, calcaneocuboid angle and tibiocalcaneal angle measured by ultrasound were collected, and the treatment and follow-up were recorded. Paired sample t test, repeated measures analysis of variance or Kruskal-Wallis test were used for data comparison, and Spearman correlation analysis was used for correlation analysis. The receiver operating characteristic curve was used to calculate the efficacy of ultrasound in evaluating different Pirani scores. Results: The number of plaster fixation in 26 children was 4.0 (1.0) times (range: 2 to 8 times). The medial talonavicular angle and posterior tibiocalcaneal angle were significantly improved after treatment and at the last follow-up compared with those before treatment, and the differences were statistically significant (all P<0.01). There was no difference in lateral calcaneocuboid angle before and after treatment and at the last follow-up (F=1.971, P>0.05). Pseudo-correction occurred in 2 cases (2 feet) during the treatment, with an incidence of 5%. Correlation analysis showed that there was a moderate positive correlation between talonavicular angle and Pirani midfoot score (r=0.480, P<0.01). There was no correlation between calcaneocuboid angle and Pirani midfoot score (r=0.114, P=0.105). There was a moderate negative correlation between tibial heel angle and Pirani hindfoot score (r=-0.566, P<0.01). The cut-off point of Pirani midfoot score of 1.5 was 38.78°, the sensitivity was 0.90, the specificity was 0.56, and the area under the curve was 0.75. The cut-off value of angle was 27.51 °, the sensitivity was 0.16, the specificity was 0.92, and the area under the curve was 0.44.The cut-off points of Pirani midfoot score of 3.0 were 45.08°and 9.96°, the sensitivity was 0.94 and 0.91, the specificity was 0.37 and 0.42, and the area under the curve was 0.59 and 0.62, respectively. The cut-off values of Pirani hindfoot score of 2.0 and 3.0 were 167.46° and 160.15°, respectively. The sensitivity was 0.75 and 0.67, the specificity was 0.81 and 0.83, and the area under the curve was 0.78 and 0.71, respectively. Conclusion: Ultrasound can complement with Pirani score, visually and dynamically observe the morphology and position changes of talonavicular joint, calcaneocuboid joint and tibiotalocalcaneal joint, monitor the recovery and pseudo-correction of tarsal bones, and better evaluate the therapeutic effect.

[Clinical efficacy of modified Yokoyama procedure with extraocular muscle transposition for high myopic eyes with restrictive esotropia].

Objective: To investigate the clinical efficacy of the modified Yokoyama procedure with extraocular muscle transposition for high myopic eyes with restrictive esotropia. Methods: A retrospective case series study was conducted. Clinical data were collected from patients who underwent the modified Yokoyama procedure with extraocular muscle transposition for high myopic eyes with restrictive esotropia at Eye Hospital of Shandong First Medical University from February 2017 to February 2022. During the procedure, the superior rectus and lateral rectus muscles were fully separated. A longitudinal blunt incision was made in the central muscle belly extending posteriorly to 12-14 mm from the muscle insertion. The temporal half of the superior rectus muscle and the upper half of the lateral rectus muscle belly were transposed and secured to the contralateral muscle insertion. Simultaneously, medial rectus muscle recession was performed. Follow-up visits were conducted at 1 week, 1 month, 3 months, and 6 months postoperatively. Patients' ocular alignment, eye movements, improvement in compensatory head posture, objective degrees of strabismus using synoptophore, changes in extraocular muscles and globe position on orbital CT scan were recorded. Surgical complications were also documented. Results: Five patients (8 eyes) were included in this study, including 4 females (7 eyes) and 1 male (1 eye), with an average age of (63±11) years and an average axial length of (34.58±2.25) mm. The medial rectus muscle recession during surgery was (7.6±2.3) mm. Preoperatively, all patients had esotropia with a horizontal range of+15°to+45° and a vertical range of+15°to+45°. Significant limitations in lateral and upward gaze were observed, with a degree of restriction ranging from-3 (-4 to-1). Three patients with bilateral involvement and one patient with unilateral involvement exhibited significant compensatory head postures. One patient with unilateral involvement had no compensatory head posture. Preoperative orbital CT scans indicated nasal displacement of the superior rectus muscle and inferior displacement of the lateral rectus muscle, with the eyeball herniating from the muscle cone. At the 6-month follow-up, all patients achieved nearly orthophoric alignment. Objective degrees of horizontal strabismus ranged from-4°to+7°, and vertical strabismus ranged from 0°to +6°, as determined by synoptophore examination. Eye movements significantly improved, with a degree of restriction of-1 (-2 to-1) for lateral gaze and-2 (-3 to-1) for upward gaze. Compensatory head postures disappeared, and orbital CT scans indicated the eyeball was located within the muscle cone. There were no severe complications such as anterior segment ischemia, muscle adhesions, disease recurrence, secondary glaucoma, or globe penetration. Conclusion: The preliminary clinical outcomes of the modified Yokoyama procedure with extraocular muscle transposition for high myopic eyes with restrictive esotropia are promising.

[Prevalence of Helicobacter pylori infection and risk factors among family members in Qinghai Province, China].

Objective: To investigate the prevalence of Helicobacter pylori infection among family members, and analyze associated risk factors. Methods: The current investigation was a cross-sectional study. The Qinghai region was stratified into urban areas, agricultural areas, and pastoral areas. The urban areas of Xining City, the agricultural areas of Haidong City, and the pastoral areas of Haibei Tibetan Autonomous Prefecture were selected. A total of 396 resident families (1 131 people) who underwent health checkups from 2021 to 2022 in the above areas were included in the survey study. Questionnaires were administered and H. pylori infection was detected using the 13C-urea breath test. Numerical data were expressed as cases and percentages, and the Chi-square test was used to compare differences in H. pylori infection rates in the populations and families in each group. Multifactorial logistic regression was used to analyze risk factors for H. pylori infection, and P<0.05 was considered statistically significant. Results: The prevalence of H. pylori infection in Qinghai province was 52.8% (597/1 131) and the prevalence of H. pylori infection in households was 80.6% (319/396). In H. pylori-positive households with at least 1 infected spouse, 40.4% (36/89) had only 1 infected spouse, and in 59.6% (53/89) both spouses were infected. In analysis of children infected by parents with H. pylori, 20.0% (9/45) of households had fathers and children infected, 48.9% (22/45) had mothers and children infected, and 31.1% (14/45) had both parents and children infected. In univariate analysis there was a statistically significant difference in the overall comparison of H. pylori infection rates among families with different numbers of people living together (χ2=11.12, P=0.004), and between-group comparisons suggested that H. pylori infection rates were higher in families with 4 or 5 people and more than 5 people living together than in families with 2 or 3 people living together. The H. pylori infection rate was higher in families that did not use serving chopsticks and spoons during family meals than in families that did use serving chopsticks and spoons (χ2=6.12, P=0.013). In multifactorial logistic regression analyses the number of people living together in a family and whether or not serving chopsticks and spoons were used at family meals were associated with H. pylori infection (P<0.05). Conclusion: The H. pylori infection rate in families in Qinghai Province is high, and there is a clear association with family aggregation. It is more common for both members of a couple to be infected, and H. pylori infection of a mother has a greater effect on the children's infection status than H. pylori infection of a father. The infection rate of H. pylori was lower in families that used serving chopsticks and spoons during dinner gatherings, and the fewer the number of people living together in the family, the lower the H. pylori infection rate.