BACKGROUND: Peripheral helper T (T PH ) cells are uniquely positioned within pathologically inflamed non-lymphoid tissues to stimulate B-cell responses and antibody production. However, the phenotype, function, and clinical relevance of T PH cells in hepatocellular carcinoma (HCC) are currently unknown. METHODS: Blood, tumor, and peritumoral liver tissue samples from 39 HCC patients (Sep 2016-Aug 2017) and 101 HCC patients (Sep 2011-Dec 2012) at the Third Affiliated Hospital of Sun Yat-sen University were used. Flow cytometry was used to quantify the expression, phenotype, and function of T PH cells. Log-rank tests were performed to evaluate disease-free survival and overall survival in samples from 39 patients and 101 patients with HCC. T PH cells, CD19 + B cells, and T follicular helper (T FH ) cells were cultured separately in vitro or isolated from C57/B6L mice in vivo for functional assays. RESULTS: T PH cells highly infiltrated tumor tissues, which was correlated with tumor size, early recurrence, and shorter survival time. The tumor-infiltrated T PH cells showed a unique ICOS hi CXCL13 + IL-21 - MAF + BCL-6 - phenotype and triggered naïve B-cell differentiation into regulatory B cells. Triggering programmed cell death protein 1 (PD-1) induced the production of C-X-C motif chemokine ligand 13 (CXCL13) by T PH cells, which then suppressed tumor-specific immunity and promoted disease progression. CONCLUSION Our study reveals a novel regulatory mechanism of T PH cell-regulatory B-cell-mediated immunosuppression and provides an important perspective for determining the balance between the differentiation of protumorigenic T PH cells and that of antitumorigenic T FH cells in the HCC microenvironment.
Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Humans ; T-Lymphocytes, Helper-Inducer/metabolism* ; Animals ; Mice ; Male ; Female ; Mice, Inbred C57BL ; Middle Aged ; B-Lymphocytes, Regulatory/metabolism* ; Flow Cytometry ; Interleukin-21 ; Aged ; Chemokine CXCL13/metabolism*

Objective:To investigate and evaluate the clinical efficacy and safety of a modified anterior approach for transpupillary silicone oil removal combined with phacoemulsification and intraocular lens (IOL) implantation.Methods:A retrospective case-control study. A total of 148 patients (148 eyes) who underwent silicone oil removal combined with cataract surgery at the Department of Ophthalmology, Guangdong Provincial People's Hospital between January 2020 and November 2024 were included in the study. All affected eyes underwent preoperative examinations including best-corrected visual acuity (BCVA), intraocular pressure, corneal topography, and optical coherence tomography (OCT). Based on the method of silicone oil removal, the eyes were divided into two groups: group A (modified anterior approach transpupillary silicone oil removal combined with phacoemulsification and IOL implantation, 99 eyes) and group B (standard pars plana vitrectomy for silicone oil removal combined with phacoemulsification and IOL implantation, 49 eyes). The surgical duration, changes in BCVA and intraocular pressure at 1 day, 7 days, and 1 month postoperatively, as well as the incidence of complications such as corneal edema and its resolution, conjunctival congestion, iris prolapse, posterior capsule rupture, nucleus drop, IOL position, residual silicone oil in the vitreous cavity or anterior chamber, vitreous hemorrhage, recurrent retinal detachment (RD), and choroidal detachment or hemorrhage, were compared between the two groups. The independent sample t-test was used for the comparison of measurement data between the two groups, and the χ2 test was used for the comparison of count data. Results:The operation time of group A and group B was (17.01±1.28) min and (31.62±2.32) min, respectively. The operation time of group A was significantly shorter than that of group B, and the difference was statistically significant ( t=?41.002, P<0.001). The comparison of BCVA ( t =?0.561, ?0.833, ?1.386) and IOP ( t=?0.055, 1.375, ?0.507) between the two groups of affected eyes before surgery and at 1 day and 7 days after surgery showed no statistically significant differences ( P>0.05). There was no silicone oil residual in group A, while 3 eyes in group B were observed with silicone oil residual (6.1%, 3/49). Neovascular glaucoma was observed in one eye. Compared to group A, group B exhibited a statistically significant increase in the incidence of postoperative conjunctival congestion, silicone oil retention, and posterior capsular opacification ( χ2=10.600, 6.187, 92.617; P<0.05). In contrast, no statistically significant differences were observed between the groups in the incidence of corneal edema or recurrent retinal detachment (RD) ( χ2=0.272, 1.557; P>0.05). No intraoperative complications, such as iris prolapse, posterior capsular rupture, nucleus drop, zonular dehiscence, choroidal detachment, or hemorrhage, occurred in any of the operated eyes. Furthermore, no postoperative complications, including corneal endothelial decompensation, IOL displacement, or endophthalmitis, were observed during the follow-up period. Conclusion:Compared to the conventional pars plana approach for silicone oil removal combined with cataract surgery, the modified anterior perfusion transpupillary approach demonstrated significantly shorter surgical duration and a reduced incidence of postoperative complications.

BACKGROUND:Skeletal muscle insulin resistance is the key pathological link of type 2 diabetes.The traditional Chinese medicine compound Roujishuncuiyin can effectively improve skeletal muscle insulin resistance,but its mechanism has not been clarified.OBJECTIVE:To explore the mechanism of Roujishuncuiyin on skeletal muscle insulin resistance in type 2 diabetes mice.METHODS:Forty db/db mice with type 2 diabetes mellitus were randomized into a model group,a low-dose Roujishuncuiyin group,a high-dose Roujishuncuiyin group,and a positive drug group,with 10 mice in each group.The latter three administration groups were given 157.5 mg/g and 630 mg/g Roujishuncuiyin and 200 mg/g metformin hydrochloride aqueous solution by gavage once a day,respectively.In addition,10 db/dm mice were selected as the blank control group.Mice in the model and blank control groups were given the same dose of 0.9％NaCl solution by gavage.After 12 weeks of intervention,fasting blood glucose was measured in each group of mice,and oral glucose tolerance test was performed to calculate the area under the blood glucose curve.ELISA was used to detect serum insulin level and calculate the resistance index.Mitochondrial structure of skeletal muscle tissue was observed under transmission electron microscopy.Western blot was used to detect the expression levels and phosphorylation levels of protein kinase B(AKT)and glycogen synthase kinase 3β(GSK-3β)proteins in skeletal muscle.RESULTS AND CONCLUSION:(1)Compared with the blank control group,fasting blood glucose,fasting insulin and insulin resistance index were significantly higher in the model group(P＜0.05),the area under the curve of the oral glucose tolerance test was significantly increased(P＜0.05),the expression of p-AKT and p-GSK3β proteins in tibialis anterior muscle was significantly decreased(P＜0.05),and there was a large amount of mitochondrial damage in tibialis anterior muscle and a large number of lipid droplets in the interstitium.(2)Compared with the model group,fasting blood glucose,fasting insulin,and insulin resistance index were significantly reduced in the low-and high-dose Roujishuncuiyin groups and the positive control group(P＜0.05),the area under the curve of the oral glucose tolerance test was reduced(P＜0.05),the expression of p-AKT and p-GSK3β proteins in the tibialis anterior muscle was significantly elevated(P＜0.05),and mitochondrial damage in the tibialis anterior muscle was significantly ameliorated,with decreased lipid droplets in the interstitium.(3)The above indexes were better in the high-dose Roujishuncuiyin group than the low-dose Roujishuncuiyin group(P＜0.05),while there was no significant difference between the high-dose Roujishuncuiyin group and positive control group(P＞0.05).To conclude,by upregulating the protein levels of p-AKT and p-GSK3β in skeletal muscle tissue,the traditional Chinese medicine compound Roujishuncuiyin can improve structural disorders and mitochondrial morphology in skeletal muscle tissue,reduce insulin resistance in the skeletal muscle and regulate glucose homeostasis in the body.

BACKGROUND:Skeletal muscle insulin resistance is the key pathological link of type 2 diabetes.The traditional Chinese medicine compound Roujishuncuiyin can effectively improve skeletal muscle insulin resistance,but its mechanism has not been clarified.OBJECTIVE:To explore the mechanism of Roujishuncuiyin on skeletal muscle insulin resistance in type 2 diabetes mice.METHODS:Forty db/db mice with type 2 diabetes mellitus were randomized into a model group,a low-dose Roujishuncuiyin group,a high-dose Roujishuncuiyin group,and a positive drug group,with 10 mice in each group.The latter three administration groups were given 157.5 mg/g and 630 mg/g Roujishuncuiyin and 200 mg/g metformin hydrochloride aqueous solution by gavage once a day,respectively.In addition,10 db/dm mice were selected as the blank control group.Mice in the model and blank control groups were given the same dose of 0.9％NaCl solution by gavage.After 12 weeks of intervention,fasting blood glucose was measured in each group of mice,and oral glucose tolerance test was performed to calculate the area under the blood glucose curve.ELISA was used to detect serum insulin level and calculate the resistance index.Mitochondrial structure of skeletal muscle tissue was observed under transmission electron microscopy.Western blot was used to detect the expression levels and phosphorylation levels of protein kinase B(AKT)and glycogen synthase kinase 3β(GSK-3β)proteins in skeletal muscle.RESULTS AND CONCLUSION:(1)Compared with the blank control group,fasting blood glucose,fasting insulin and insulin resistance index were significantly higher in the model group(P＜0.05),the area under the curve of the oral glucose tolerance test was significantly increased(P＜0.05),the expression of p-AKT and p-GSK3β proteins in tibialis anterior muscle was significantly decreased(P＜0.05),and there was a large amount of mitochondrial damage in tibialis anterior muscle and a large number of lipid droplets in the interstitium.(2)Compared with the model group,fasting blood glucose,fasting insulin,and insulin resistance index were significantly reduced in the low-and high-dose Roujishuncuiyin groups and the positive control group(P＜0.05),the area under the curve of the oral glucose tolerance test was reduced(P＜0.05),the expression of p-AKT and p-GSK3β proteins in the tibialis anterior muscle was significantly elevated(P＜0.05),and mitochondrial damage in the tibialis anterior muscle was significantly ameliorated,with decreased lipid droplets in the interstitium.(3)The above indexes were better in the high-dose Roujishuncuiyin group than the low-dose Roujishuncuiyin group(P＜0.05),while there was no significant difference between the high-dose Roujishuncuiyin group and positive control group(P＞0.05).To conclude,by upregulating the protein levels of p-AKT and p-GSK3β in skeletal muscle tissue,the traditional Chinese medicine compound Roujishuncuiyin can improve structural disorders and mitochondrial morphology in skeletal muscle tissue,reduce insulin resistance in the skeletal muscle and regulate glucose homeostasis in the body.

Objective:To investigate and evaluate the clinical efficacy and safety of a modified anterior approach for transpupillary silicone oil removal combined with phacoemulsification and intraocular lens (IOL) implantation.Methods:A retrospective case-control study. A total of 148 patients (148 eyes) who underwent silicone oil removal combined with cataract surgery at the Department of Ophthalmology, Guangdong Provincial People's Hospital between January 2020 and November 2024 were included in the study. All affected eyes underwent preoperative examinations including best-corrected visual acuity (BCVA), intraocular pressure, corneal topography, and optical coherence tomography (OCT). Based on the method of silicone oil removal, the eyes were divided into two groups: group A (modified anterior approach transpupillary silicone oil removal combined with phacoemulsification and IOL implantation, 99 eyes) and group B (standard pars plana vitrectomy for silicone oil removal combined with phacoemulsification and IOL implantation, 49 eyes). The surgical duration, changes in BCVA and intraocular pressure at 1 day, 7 days, and 1 month postoperatively, as well as the incidence of complications such as corneal edema and its resolution, conjunctival congestion, iris prolapse, posterior capsule rupture, nucleus drop, IOL position, residual silicone oil in the vitreous cavity or anterior chamber, vitreous hemorrhage, recurrent retinal detachment (RD), and choroidal detachment or hemorrhage, were compared between the two groups. The independent sample t-test was used for the comparison of measurement data between the two groups, and the χ2 test was used for the comparison of count data. Results:The operation time of group A and group B was (17.01±1.28) min and (31.62±2.32) min, respectively. The operation time of group A was significantly shorter than that of group B, and the difference was statistically significant ( t=?41.002, P<0.001). The comparison of BCVA ( t =?0.561, ?0.833, ?1.386) and IOP ( t=?0.055, 1.375, ?0.507) between the two groups of affected eyes before surgery and at 1 day and 7 days after surgery showed no statistically significant differences ( P>0.05). There was no silicone oil residual in group A, while 3 eyes in group B were observed with silicone oil residual (6.1%, 3/49). Neovascular glaucoma was observed in one eye. Compared to group A, group B exhibited a statistically significant increase in the incidence of postoperative conjunctival congestion, silicone oil retention, and posterior capsular opacification ( χ2=10.600, 6.187, 92.617; P<0.05). In contrast, no statistically significant differences were observed between the groups in the incidence of corneal edema or recurrent retinal detachment (RD) ( χ2=0.272, 1.557; P>0.05). No intraoperative complications, such as iris prolapse, posterior capsular rupture, nucleus drop, zonular dehiscence, choroidal detachment, or hemorrhage, occurred in any of the operated eyes. Furthermore, no postoperative complications, including corneal endothelial decompensation, IOL displacement, or endophthalmitis, were observed during the follow-up period. Conclusion:Compared to the conventional pars plana approach for silicone oil removal combined with cataract surgery, the modified anterior perfusion transpupillary approach demonstrated significantly shorter surgical duration and a reduced incidence of postoperative complications.

Objective To evaluate the intraoperative identification of ectopic parathyroid tissue in the central neck region using autofluorescence point-spectral analysis(AFPSA)combined with immune colloidal gold technique(ICGT),for guiding total parathyroidectomy(TPTX)or clean parathyroidectomy(CPTX)in the management of secondary hyperparathyroidism(SHPT).Methods Retrospectively collected and compared the clinical data of 64 patients with SHPT from October 2019 to June 2023.In the observation group,TPTX was performed as the initial procedure in 36 cases,followed by sampling of suspicious targets using AFPSA in the central neck area and subsequent detection through ICGT.CPTX was then conducted if a positive result was obtained.On the other hand,the control group consisted of 28 cases where only TPTX was performed without any additional tests during surgery.The surgical data,parathyroid hormone(PTH)levels,blood calcium levels,blood phosphorus levels,alkaline phosphatase(ALP)levels,regression of clinical symptoms,changes in parathyroid function and occurrence of hypocalcemia were compared between these two groups.Results In the observation group,there were 9 cases of AFPSA-ICGT positivity,including 2 left-sided cases,4 right-sided cases,and 3 thymic cases;among these posi-tive cases,there were a total of 10 locations with mildly hyperplastic or nonhyperplastic microscopic parathyroid tissue.The difference in the number of total parathyroid glands removed(including ectopic)between the two groups was statistically significant(P<0.05).At both 3 and 6 months postoperatively,ALP levels in the observation group were significantly lower than those in the control group(P<0.01 and P<0.001 respectively);at 6 months postoperatively,differences in PTH and blood phosphorus levels between the two groups were also statistically significant(P<0.05 and P<0.001 respectively).Joint bone pain and skin itching recurred in some patients within the control group at six months after surgery(P<0.05),whereas recurrence of SHPT was less frequent within the observation group compared to controls(P<0.05);however,no statistically significant differences were observed regarding postoperative hypoparathyroidism or hyperparathyroidism as well as hypocalcemia between either groups.Conclusion The AFPSA-ICGT intraoperative test can be utilized to guide surgery for SHPT,enabling accurate and efficient identification as well as safe targeting of parathyroid tissues that may not exhibit obvious hyperplasia in the central cervical region.

With the advent of the era of 5G and big data, complex medical data with multiple dimensions and a large sample size bring both opportunities and challenges for clinical medicine in the new era. Compared with conventional methods, artificial intelligence can detect the hidden patterns within large datasets, and more and more scholars are applying such advanced technology in the diagnosis and treatment of diseases. After development and perfection for more than half a century, liver transplantation has become the most effective treatment method for end-stage liver diseases. Unlike the analysis of "single-patient" data in other fields, liver transplantation usually requires the consideration of the features of both the donor and the recipient and the variables during transplantation, thus generating a larger volume of medical data than other diseases, which is particularly in line with the advantages of artificial intelligence. Effective application of artificial intelligence and its combination with clinical research will usher in the new era of precision medicine. The advantages and limitations of artificial intelligence technology should be comprehensively discussed for the cross-application of artificial intelligence in liver transplantation, and the future directions of this field should also be proposed.

Objective:To improve the quality of 18F-fluorodeoxyglucose (FDG) PET images at different acquisition times through deep learning (DL) PET image reconstruction methods. Methods:A total of 45 patients (20 males, 25 females; age (52.0±13.6) years) with malignant tumors and PET/CT scans from September 2020 to October 2020 in the Department of Nuclear Medicine of the First Hospital of Shanxi Medical University were included in this retrospective study. The short acquisition time 30 s/bed PET images from the raw list mode were selected as the input of DL model. DL image reconstruction model, based on the Unet algorithm, was trained to output imitated PET images with full dose standard acquisition time (3 min). The image quality evaluation and quantitative analysis were carried out for four groups of images: DL images, 30 s, 90 s, and 120 s images, respectively. The quality of PET images in four groups was evaluated using the five-point method. Liver background activities, lesions quantification parameters (maximum standardized uptake value (SUV max), mean standardized uptake value (SUV mean), standard deviation (SD), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR)), and first-order texture features (skewness, kurtosis, uniformity, entropy) were measured. Kappa test, χ2 test and one-way analysis of variance (least significant difference t test) were used for data analysis. Results:The image quality scores between four groups were highly consistent ( Kappa=0.799, P<0.001). The number of patients with scores≥3 in DL, 30 s, 90 s and 120 s groups were 6, 4, 7 and 8, respectively ( χ2=125.47, P<0.001). The liver SD of DL group was significantly lower than that of 30 s group (0.26±0.07 vs 0.43±0.11; F=3.58, t=-7.91, P<0.05). The liver SNR of DL group was higher than that of 30 s group (11.04±4.36 vs 5.41±1.41; F=10.22, t=5.40, P<0.05). The liver SD and SNR of DL group were similar to those of 90 s group (0.39±0.16, 8.46±3.34; t values: -0.87 and 2.17, both P>0.05). In 18 tumor lesions with high uptake, SNR and CNR of DL group were significantly higher than those of 30 s group (60.21±29.26 vs 38.38±16.54, 22.26±15.85 vs 15.41±9.51; F values: 13.09 and 7.05; t values: 5.20 and 4.04, both P<0.001). There were statistically significant differences among four groups in the first-order texture features ( F values: 4.30-9.65, all P<0.05), but there was no significant difference between DL group and 120 s group ( t values: from -1.25 to 0.15, all P>0.05). Conclusion:DL reconstruction model can improve the quality of short-frame PET images, which meets the needs of clinical diagnosis, efficacy evaluation and radiomics research.

Objective:To compare four reconstruction algorithms of 18F-fluorodeoxyglucose (FDG) PET/CT on standardized uptake value (SUV) of pulmonary nodules. Methods:A total of 46 patients (27 males, 19 females; median age: 66 (range: 44-82) years) with solid pulmonary nodules from February 2018 to July 2019 in the First Hospital of Shanxi Medical University who performed 18F-FDG PET/CT imaging were enrolled. All PET/CT images were retrospectively reconstructed by using four algorithms reconstructions including ordered subset expectation maximization (OSEM), OSEM+ time of flight (TOF), OSEM+ TOF+ point spread function (PSF) and block sequential regularized expectation maximization (BSREM) (G1-G4). Nodule and background parameters were analyzed semi-quantitatively and visually. The maximum of SUV(SUV max), mean of SUV(SUV mean) and peak of SUV (SUV peak) were collected by the region of interest (ROI). Nodules were divided into small nodule group (diameter ≤10 mm) and large nodule group (10 mm < diameter ≤30 mm). Kruskal-Wallis rank sum test and Bonferroni method were performed to compare the differences of SUVs between G1-G4, and Spearman correlation analysis was used to analyze the correlation between the change rate of SUV (%ΔSUV) and the diameter of nodules. The receiver operating characteristic (ROC) curve analysis was used to analyze the diagnostic efficacy of SUV for the differential diagnosis of pulmonary nodules and to get the optimal threshold. Results:There were 114 pulmonary nodules (large nodules, n=55; small nodules, n=59). In visual analysis, the visual detection rates of small nodules in G4 were 55.93%(33/59), 44.07%(26/59), 20.34%(12/59) higher than those in G1-G3. Of 114 pulmonary nodules in 46 patients, there were differences in SUV max and SUV mean between G1-G4 (median SUV max : 2.65-5.29, median SUV mean: 2.05-2.99; H values: 20.628 and 17.749, respectively, both P<0.001), G4 had significant increases compared to G1 in SUV max (median 5.29 and 2.65, P<0.001) and SUV mean (median 2.99 and 2.05, P<0.001). The %ΔSUV max (median: 4.45%-52.96%) and %ΔSUV mean (median: 1.69%-47.56%) were negatively correlated with the diameter of nodules (9.75(6.20, 16.58) mm; r s values: -0.371 to -0.354, -0.371 to -0.320, all P<0.001). In 59 small nodules, G1 significantly increased the SUV max of G4 (median 4.05 and 2.14, H=18.327, P<0.001), while G4 significantly increased the SUV mean of G1 and G3 (median 2.31, 1.26 and 1.53, H=16.808, P<0.05). There was no significant difference in SUVs between G1-G4 in 55 large nodules ( H values: 0.812-7.290, all P>0.05). The optimal threshold values of SUV max in G1-G4 were 4.335, 5.185, 5.410, 5.745 and the area of under curves (AUCs) were 0.747, 0.699, 0.756, 0.778 respectively. The AUC of SUV mean and SUV peak also showed a similar trend. Conclusion:Among the four reconstruction algorithms, BRERM can not only enhance the image quality, but also significantly improve the SUV max and SUV mean of lung nodules diameter below 10 mm, and thus its diagnostic threshold of SUV should be appropriately increased.

Objective:To compare the incidence of coronary microvascular disease (CMVD) between patients with non-obstructive and obstructive coronary arteries.Methods:We retrospectively analyzed 97 patients with angina pectoris, who underwent the absolute quantitative PET examination of myocardial perfusion and coronary anatomy examination within 90 days. All patients were divided into two groups: non-obstructive group (72 cases, no stenosis ≥50% in all three coronary arteries) and obstructive group (25 cases, at least one coronary stenosis ≥50%; and at least one coronary stenosis<50%). Quantitative parameters derived from PET including rest myocardial blood flow (RMBF), stress myocardial blood flow (SMBF), coronary flow reserve (CFR) and cardiovascular risk factors were compared between the two groups. CMVD was defined as CFR<2.90 and SMBF <2.17 ml·min -1·g -1. Results:Incidence of CMVD was significant higher in the non-obstructive coronary arteries of the obstructive group than in the non-obstructive coronary arteries of non-obstructive group (47.1% (16/34) vs. 25.5% (55/216), χ 2=6.738, P=0.009) while incidence of CMVD was similar between non-obstructive and obstructive patients ((44% (11/25) vs. 33.3% (24/72), χ 2=0.915, P=0.339). RMBF ((0.83±0.14) ml·min -1·g -1 vs. (0.82±0.17) ml·min -1·g -1), SMBF ((2.13±0.60) ml·min -1·g -1 vs. (1.91±0.50) ml·min -1·g -1) and CFR (2.59±0.66 vs. 2.36±0.47) were similar between the two groups (all P>0.05). Conclusions:CMVD can occur in non-obstructive coronary arteries in both patients with non-occlusive coronary arteries and patients with obstructive coronary arteries. Prevalence of CMVD is significantly higher in patients with obstructive coronary arteries than in patients with non-obstructive coronary arteries. The CMVD severity is similar between the two groups.