Objective To explore the incidence and prognosis of citrin deficiency in Maoming,and to understand mutation types and frequency of SLC25A13 gene.Methods A total of 88 322 newborns born in Maoming from April 2022 to January 2025 were selected as research subjects.These specimens were screened using tandem mass spectrometry.Newborns with elevated citrulline levels or suspected clinical symptoms of citrin deficiency were recalled immediately for further genetic confirmation,and treated confirmed cases were followed up.Results Among 88 322 newborns,53 cases were positive for citrulline by tandem mass spectrometry,43 cases were recalled with positive initial screening,23 cases were still positive for citrulline after re-examination.Finally,1 case of neonatal intrahepatic cholestasis caused by citrin deficiency(NICCD)was clinically diagnosed,and 10 cases were diagnosed with SLC25A13 gene,of which 1 case was false negative.Therefore,the total positive predictive value was 18.87％(10/53),and the prevalence rate of NICCD in Maoming was 1/8029(11/88 322).A total of 5 mutation sites were detected in 10 neonates with NICCD gene diagnosis,and the top 3 mutation sites in the order of proportion were:c.852-855delTATG accounted for 65.0％(13/20),c.615+5G>A accounted for 15.0％(3/20),IVS16ins3kb accounted for 10.0％(2/20).Among the 11 cases,1 case refused treatment and died of liver failure,while the remaining 10 cases were developing well after standardized treatment.Conclusion The incidence of neonatal citrin deficiency in Maoming is significantly higher than in other areas.Tandem mass spectrometry enables rapid early detection of citrin deficiency,though false-negative results may occur in individual cases.Combining genetic sequencing can improve diagnostic accuracy,and achieve precise management of inherited metabolic diseases.

Objective To explore the incidence and prognosis of citrin deficiency in Maoming,and to understand mutation types and frequency of SLC25A13 gene.Methods A total of 88 322 newborns born in Maoming from April 2022 to January 2025 were selected as research subjects.These specimens were screened using tandem mass spectrometry.Newborns with elevated citrulline levels or suspected clinical symptoms of citrin deficiency were recalled immediately for further genetic confirmation,and treated confirmed cases were followed up.Results Among 88 322 newborns,53 cases were positive for citrulline by tandem mass spectrometry,43 cases were recalled with positive initial screening,23 cases were still positive for citrulline after re-examination.Finally,1 case of neonatal intrahepatic cholestasis caused by citrin deficiency(NICCD)was clinically diagnosed,and 10 cases were diagnosed with SLC25A13 gene,of which 1 case was false negative.Therefore,the total positive predictive value was 18.87％(10/53),and the prevalence rate of NICCD in Maoming was 1/8029(11/88 322).A total of 5 mutation sites were detected in 10 neonates with NICCD gene diagnosis,and the top 3 mutation sites in the order of proportion were:c.852-855delTATG accounted for 65.0％(13/20),c.615+5G>A accounted for 15.0％(3/20),IVS16ins3kb accounted for 10.0％(2/20).Among the 11 cases,1 case refused treatment and died of liver failure,while the remaining 10 cases were developing well after standardized treatment.Conclusion The incidence of neonatal citrin deficiency in Maoming is significantly higher than in other areas.Tandem mass spectrometry enables rapid early detection of citrin deficiency,though false-negative results may occur in individual cases.Combining genetic sequencing can improve diagnostic accuracy,and achieve precise management of inherited metabolic diseases.

Objective:To evaluate the value of 18F-FDG PET/CT for preoperative localization of epileptogenic foci in refractory epilepsy patients with negative MRI. Methods:Clinical data (550 lobes) of 55 epilepsy patients (38 males, 17 females, age (20.0±8.1) years) with negative MRI who underwent preoperative 18F-FDG PET/CT-MRI between January 2014 and June 2020 at the First Affiliated Hospital of Jinan University were retrospectively analyzed. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of 18F-FDG PET/CT, video electroencephalogram (VEEG), PET/CT+ VEEG and PET/CT-VEEG for localizing epileptogenic foci were calculated using stereoelectroencephalography (SEEG) and the outcomes of at least 1 year of postoperative follow-up as reference standards. χ2 test was used to compare the efficiencies of different examination modalities for unilobar, multilobar and all patients. Results:The correct lateralization rate of epileptogenic foci was 92.6%(25/27) using PET/CT. The sensitivity, specificity, accuracy, PPV and NPV of PET/CT for localization of epileptogenic foci were 65.1%(54/83), 77.9%(364/467), 76.0%(418/550), 34.4%(54/157) and 92.6%(364/393), respectively. The sensitivities of PET/CT-VEEG for localization of epileptogenic foci in all patients and patients with multilobar epilepsy were higher than those of VEEG alone (75.9%(63/83) vs 45.8%(38/83), 68.6%(35/51) vs 31.4%(16/51); χ2 values: 15.80, 14.16, both P<0.001). The specificities of PET/CT+ VEEG for localization of epileptogenic foci in all patients and patients with unilobar epilepsy were higher than those of VEEG alone (97.6%(456/467) vs 94.6%(442/467), 97.9%(282/288) vs 94.1%(271/288); χ2 values: 5.66, 5.48; P values: 0.017, 0.019). The sensitivity of PET/CT-VEEG (PET/CT and VEEG concordance) for localization of epileptogenic foci was higher than that of PET/CT+ VEEG (PET/CT and VEEG discordance) (8/9 vs 28.4%(21/74); χ2=10.40, P=0.001), and its specificity and accuracy were higher than those of PET/CT-VEEG (PET/CT and VEEG discordance) (93.4%(57/61) vs 71.7%(291/406), 92.9%(65/70) vs 72.1%(346/480); χ2 values: 13.23, 13.96; both P<0.001). Conclusions:18F-FDG PET/CT can localize and lateralize epileptogenic foci in patients with negative MRI. The combination of 18F-FDG PET/CT and VEEG improves the sensitivity, specificity, and accuracy for epileptogenic foci detection. 18F-FDG PET/CT is more accurate in detecting epileptogenic foci when it is concordant with VEEG.

Objective:To predict the short-term postoperative recurrence status of patients with refractory temporal lobe epilepsy (TLE) by analyzing preoperative 18F-FDG PET images and patients′ clinical characteristics based on deep residual neural network (ResNet). Methods:Retrospective analysis was conducted on preoperative 18F-FDG PET images and clinical data of 220 patients with refractory TLE (132 males and 88 females, age 23.0(20.0, 30.2) years)) in the First Affiliated Hospital of Jinan University between January 2014 and June 2020. ResNet was used to perform high-throughput feature extraction on preprocessed PET images and clinical features, and to perform a postoperative recurrence prediction task for differentiating patients with TLE. The predictive performance of ResNet model was evaluated by ROC curve analysis, and the AUC was compared with that of classical Cox proportional risk model using Delong test. Results:Based on PET images combined with clinical feature training, AUCs of the ResNet in predicting 12-, 24-, and 36-month postoperative recurrence were 0.895±0.073, 0.861±0.058 and 0.754±0.111, respectively, which were 0.717±0.093, 0.697±0.081 and 0.645±0.087 for Cox proportional hazards model respectively ( z values: -3.00, -2.98, -1.09, P values: 0.011, 0.018, 0.310). The ResNet showed best predictive effect for recurrence events within 12 months after surgery. Conclusion:The ResNet model is expected to be used in clinical practice for postoperative follow-up of patients with TLE, helping for risk stratification and individualized management of postoperative patients.

Objective:To evaluate the optimization effect of transcutaneous electrical acupoint stimulation (TEAS) combined with moderate sedation with propofol (TEAS-propofol balanced anesthesia) for gastrointestinal endoscopy.Methods:This was a single-blind randomized controlled trial. American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ patients, aged 18-64 yr, undergoing elective gastrointestinal endoscopy at the Endoscopic Diagnosis and Treatment Center of the Affiliated Hospital of Qingdao University from May to August 2022, were divided into 2 groups using the block random allocation method: conventional anesthesia group (group C) and TEAS-propofol balanced anesthesia group (group TPB). Patients received moderate sedation with propofol plus routine anesthesia with fentanyl 50 μg in group C. In TPB group, TEAS was performed at bilateral Neiguan, Hegu and Zusanli acupoints before surgery until the end of surgery, and patients received propofol for moderate sedation (Modified Observer′s Assessment of Alertness/Sedation scale score was 3). The efficacy and safety of anesthesia and parameters related to outcomes were observed and recorded.Results:In this study, 66 patients were recruited, with 33 in each group, the failure rate of anesthesia in both groups was 3%, and no reflux or aspiration was found. Compared with group C, no significant changes were found in the patients′ satisfaction on the same day, intraoperative pain response score, incidence of intraoperative adverse reactions (tachycardia, hypertension, bucking and body movement), awake time, consumption of propofol, rate of intraoperative awareness and rate of patients hoping to receive the same anesthesia method again postoperatively ( P>0.05), the patients′ satisfaction was significantly increased on the next day ( P<0.05), the incidence of intraoperative respiratory depression, physician satisfaction, and degree of postoperative dizziness and nausea were significantly reduced ( P<0.05), and the discharge time and time to the complete recovery of normal behavior function was significantly shortened in group TPB ( P<0.05). Conclusions:The combination of TEAS at bilateral Neiguan, Hegu and Zusanli acupoints with moderate sedation using propofol for gastrointestinal endoscopy is not only safe and effective, but also beneficial to the postoperative outcome of patients, and the effect is better than that of conventional anesthesia with propofol and fentanyl.

Recurrence and metastasis remain the leading cause of death in breast cancer patients due to the lack of effective treatment. A microenvironment suitable for cancer cell growth, referred to as pre-metastatic niche (PMN), is formed in distant organs before metastasis occurs. Myeloid-derived suppressor cells (MDSCs) are a heterogenous population of immature myeloid cells with immunosuppressive effects. They can expand in large numbers in breast cancer patients and participate in the formation of PMN. MDSCs can remodel the extracellular matrix of pulmonary vascular endothelial cells and recruit cancer stem cells to promote the lung metastasis of breast cancer. Furthermore, MDSCs facilitate immune evasion of breast cancer cells to impact the efficacy of immunotherapy. It is proposed that MDSCs represent a potential therapeutic target for the inhibition of recurrence and metastasis in breast cancer. Therapeutic strategies targeting MDSCs have shown promising efficacy in preclinical studies and clinical trials. This review presents a summary of the principal factors involved in the recruitment and activation of MDSCs during the formation of PMN, and outlines MDSCs functions such as immunosuppression and the current targeted therapies against MDSCs, aiming to provide new ideas for the treatment of distant metastases in breast cancer.
Humans ; Myeloid-Derived Suppressor Cells/immunology* ; Breast Neoplasms/immunology* ; Female ; Tumor Microenvironment ; Disease Progression ; Immunotherapy/methods* ; Neoplasm Metastasis ; Neoplastic Stem Cells

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive non-Hodgkin’s lymphoma that affects the brain, eyes, cerebrospinal fluid, or spinal cord without systemic involvement. The outcome of patients with PCNSL is worse compared to patients with systemic diffuse large B-cell lymphoma. Given potential mortality associated with severe immune effector cell-associated neurotoxicity syndrome (ICANS), patients with PCNSL have been excluded from most clinical trials involving chimeric antigen receptor T-cell (CAR-T) therapy initially. Here, we report for the first time to apply decitabine-primed tandem CD19/CD22 dual-targeted CAR-T therapy with programmed cell death-1 (PD-1) and Bruton’s tyrosine kinase (BTK) inhibitors maintenance in one patient with multiline-resistant refractory PCNSL and the patient has maintained complete remission (CR) for a 35-month follow-up period. This case represents the first successful treatment of multiline resistant refractory PCNSL with long-term CR and without inducing ICANS under tandem CD19/CD22 bispecific CAR-T therapy followed by maintenance therapy with PD-1 and BTK inhibitors. This study shows tremendous potential in the treatment of PCNSL and offers a look toward ongoing clinical studies.

Objective:To explore the influencing factors of bowel preparation quality in hospitalized elderly patients, and to find the appropriate waiting time from the end of bowel preparation to the beginning of colonoscopy.Methods:Baseline and clinical data of elderly patients over 60 years old who underwent colonoscopy in the Tenth People′s Hospital, Tongji University from February 2021 to August 2021 were collected. Multivariate analysis was used to screen the factors that might affect the quality of bowel preparation in hospitalized elderly patients. Patients were grouped according to waiting time before colonoscopy. After eliminating confounding factors using propensity matching analysis, the difference of bowel preparation quality among groups was compared.Results:251 patients were included in the study. Multivariate analysis revealed that, hypertension ( OR=3.530, 95% CI 1.295-9.618), chronic constipation ( OR=3.302,95% CI 1.132-9.632), dietary compliance ( OR=0.161, 95% CI 0.070-0.371), medication and drinking water compliance ( OR=0.167, 95% CI 0.070-0.397), exercise compliance after medication ( OR=2.245, 95% CI 1.040-4.845), The frequency of defecation after medication ( OR=0.446, 95% CI 0.308-0.647) and waiting time ( OR=0.537, 95% CI 0.387-0.745) were important factors affecting the quality of bowel preparation in hospitalized elderly patients ( P<0.05). There were differences in bowel preparation quality between groups of waiting times. The overall quality of bowel preparation in 120-180 min group was significantly better than that in 241-300 min group, 301-360 min group and>360 min group ( P<0.05). The overall quality of bowel preparation in 181-240 min group was better than that in >360 min group ( P<0.05). There were no significant differences among other groups( P>0.05). The scores of cecum and ascending colon were the best in 120-180 min group, and the cleanliness of descending colon, sigmoid colon and rectum was significantly higher in 241-300 min group, 301-360 min group and > 360 min group. The scores of descending colon, sigmoid colon and rectum showed that the intestinal preparation quality of 181-240 min group was better than that of 301-360 min group and > 360 min group. Conclusions:The best examination time for elderly patients is about 180 minutes after bowelpreparation. Medical workers should flexibly guide the medication time to ensure that patients are in the best clean state of intestinal tract during examination.

Objective: To investigate the effect of chrysotile exposure on ribosomal DNA (rDNA) copy number and DNA damage response, so as to provide insights into the mechanism of asbestos-induced carcinogenesis. Methods: Human pleural mesothelial MeT-5A cells were treated with chrysotile suspensions at doses of 1.25, 2.5 and 5 μg/cm2 (low-, medium-, high-dose group), while PBS served as controls. MeT-5A cells were harvested 6, 24, 48 and 72 h post-treatment, and the rDNA copy numbers and the BIRC5, HRAS, GINS4 and RRM2 mRNA expression were determined using a quantitative real-time PCR (qPCR) assay. The apoptosis of MeT-5A cells and DNA damage were detected using Muse cell analyzer. The rDNA copy numbers, DNA damage responses and BIRC5, HRAS, GINS4 and RRM2 mRNA expression were compared in MeT-5A cells treated with different doses of chrysotile suspensions. Results: There were significant differences in 45S rDNA copy numbers among low-, medium-, high-dose groups and the control groups 6, 48 and 72 h post-treatment with chrysotile suspensions, and significantly lower 45S rDNA copy numbers were measured in low-, medium- and high-dose groups than in the control group 6 h post-treatment, while significantly higher 45S rDNA copy numbers were found in the high-dose group than in low- and medium-dose groups 48 and 72 h post-treatment (all P<0.05). There were significant differences in 5S rDNA copy numbers among low-, medium-, high-dose groups and the control groups 24, 48 and 72 h post-treatment with chrysotile suspensions, and significantly lower 5S rDNA copy numbers were measured in medium- and high-dose groups than in the control group 24 and 48 h post-treatment, while significantly lower 5S rDNA copy numbers were found in medium- and high-dose groups than in the low-dose group 24, 72 h post-treatment (all P<0.05). There were significant differences in the overall apoptotic rate of MeT-5A cells among groups at different time points, and the overall apoptotic rate of MeT-5A cells were significantly higher in medium- and high-dose groups than in the control group (all P<0.05), with late-stage apoptosis predominantly detected. There were significant differences in the rates of ATM activation and DNA double-strand break in MeT-5A cells among groups 72 h post-treatment, and higher rates of ATM activation and DNA double-strand break were measured in medium- and high-dose groups than in the control group (all P<0.05). In addition, there were significant differences in the relative mRNA expression of BIRC5, HRAS, GINS4 and RRM2 genes among groups 24 and 48 h post-treatment, and significantly lower BIRC5, HRAS, GINS4 and RRM2 mRNA expression was quantified in medium- and high-dose groups than in the control group (all P<0.05). Conclusion Exposure to chrysotile may induce rDNA copy number variations and altered expression of nucleolar proteins in human pleural mesothelial cells, which may be involved in the regulation of DNA damage responses.

Objective:To investigate the application value of advance care planning among patients with chronic heart failure, so as to provide reference for the clinical practice of advance care planning.Methods:A total of 62 chronic heart failure patients from October 2017 to November 2019 in Fuwai Central China Cardiovascular Hospital were assigned to control group and experimental group according to the enrolled time, with 31 cases in each group. The patients in the control group from October 2017 to October 2018 recieved routine nursing, the experimental group from November 2018 to November 2019 carried out advance care planning based on the routine care. Before and after 3 weeks of intervention, the fatigue symptom and psychological condition were assessed by the Multidimensional Fatigue Inventory (MFI-20) and Symptom Checklist 90 (SCL-90), respectively.Results:There was no significant difference in the score of MFI-20 and SCL-90 before intervention between the two groups( P>0.05). After 3 weeks of intervention, the mental fatigue scores and total scores in MFI-20 were (8.23 ± 2.77), (51.00 ± 5.03) points in the experimental group, significantly lower than those in the control group (10.23 ± 2.58), (54.06 ± 5.50) points, the differences were statistically significant ( t=2.94, 2.29, all P<0.05). After 3 weeks of intervention, the somatization, obsessive symptoms, depression, anxiety, hostility scores and total score of SCL-90 were (1.28 ± 0.14), (1.43 ± 0.09), (1.19 ± 0.12), (1.13 ± 0.08), (1.33 ± 0.07), (121.00 ± 3.68) points in the experimental group, significantly lower than those in the control group (1.82 ± 0.44), (1.73 ± 0.58), (1.69 ± 0.12), (1.78 ± 0.13), (1.39 ± 0.10), (144.69 ± 9.09) points, the differences were statistically significant ( t values were 2.76-23.06, all P<0.05). Conclusions:Advance care planning can effectively alleviate fatigue symptom and improve psychological condition of patients with chronic heart failure.