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 the causal relationship between gut microbiota and polycystic ovary syndrome (PCOS) using a Mendelian randomization (MR) study, so as to provide insights into the pathogenesis of PCOS and the formulation of prevention and treatment strategies. Methods: The genetic data on gut microbiota was derived from a meta-analysis of genome-wide association studies (GWAS) involving 18 340 participants. The genetic data on PCOS was sourced from two GWAS meta-analyses in European populations, serving as the discovery set and the validation set, respectively. A two-sample MR analysis was conducted using the discovery set, with the inverse variance weighted (IVW) method as the primary approach. Sensitivity analyses employed the weighted median method, MR-Egger regression, and the MR-PRESSO test. The validation set was utilized for verification, and a meta-analysis was performed to combine the results from the two datasets. Results: Forward MR analysis results showed that nine types of gut microbiota were statistically associated with PCOS (all P<0.05). Specifically, the association of family Streptococcaceae (OR=1.442, 95%CI: 1.097-1.895), genus Actinomyces (OR=1.359, 95%CI: 1.036-1.784), genus Ruminococcaceae UCG 011 (OR=0.755, 95%CI: 0.619-0.921), genus Sellimonas (OR=0.766, 95%CI: 0.657-0.893) and genus Streptococcus with PCOS (OR=1.496, 95%CI: 1.136-1.972) remained consistent in the sensitivity analysis. Reverse MR analysis showed no evidence for the causal association between PCOS and the aforementioned five types of gut microbiota (all P>0.05). The MR analysis results of the validation set showed that there was no statistical association between the aforementioned five types of gut microbiota and PCOS (all P>0.05). However, the associations remained significant for genus Actinomyces (OR=1.226,95%CI：1.010-1.503) and genus Streptococcus (OR=1.266,95%CI：1.042-1.452) in the meta-analysis (both P<0.05). Conclusion This study provides the evidence that genus Actinomyces and genus Streptococcus are causally associated with PCOS.

Objective:To study the clinical manifestations, genetic profiles and treatment of Kagami-Ogata syndrome (KOS).Methods:A neonate admitted to our hospital was genetically diagnosed of KOS from amniocentesis sampling. The phenotype, genotype and treatment of the neonate were analyzed. Multiple databases were searched using key words including "Kagami-Ogata syndrome", "14q32 microdeletion syndrome", "coat-hanger ribs", "paternal uniparental disomy (pUPD)(14) " from the inception of the databases to Jan. 23th 2023. The clinical features, genotype and treatment of patients from the literature were summarized.Results:The neonate in our hospital was born at 30 weeks gestational age with a birth weight of 2 035 g. Prenatal ultrasound indicated overgrowth, bilateral fetal renal pelvis dilatation (FRPD), dilatation of intestines in lower abdomen, clenched hands with overlapping fingers and polyhydramnios. After birth, the neonate showed progressively worsening respiratory distress, distinct facial features (small jaw, short neck, flat nasal bridge, upward-facing nostrils, small and malformed ears with auricular deformity and narrow external auditory canals), bell-shaped thorax, diastasis recti and abnormal posture (overlapping fingers, clenched fists), as well as feeding difficulties, recurrent fever and dependence of respiratory support. Whole exome sequencing (WES) revealed a 268.2Kb deletion (101034306_101302541) in 14q32.2 region on both the neonate and the mother and the father was otherwise normal. The prognosis was poor and the parents refused further treatment. The neonate died at one month of age after two days of palliative care. A total of 36 articles were identified in the literature review, including 78 KOS cases with complete clinical data (a total of 79 cases adding our case).The primary clinical manifestations included distinctive facial and thoracic abnormalities (79/79, 100%), polyhydramnios (71/75, 94.7%), feeding difficulties (55/63, 87.3%), abdominal wall defects (57/72, 79.2%), joint contractures (39/70, 55.7%) and dependence of respiratory support (29/56, 51.8%). Long-term follow-up revealed 86.8% (59/68) experienced physical, movement and intellectual development delay, 39.7% (25/63) died or gave up treatments within five years. Genetic testing showed pUPD in 44 cases (55.7%), maternal deletions in 23 cases (29.1%), epimutations in 8 cases (10.1%) and unreported variations in 4 cases (5.1%).Conclusions:KOS is a genetic imprinting disorder affecting multiple organs. Prenatal screening can detect abnormalities such as polyhydramnios. Specific clinical signs, radiological findings and 14q32 gene analysis are helpful for the diagnosis of the disease.

MethodIn the experiment， 46% vol Red Star Erguotou （10 mL·kg·d^-1） was used to establish the AONFH rat model， and the intervention effect of JPHGP at different doses （2.5， 5.0， 10.0 g·kg^-1） was observed. Jiangusheng pill （JGS， 1.53 g·kg^-1） was selected as the positive control. After 8 weeks of administration， the bone histomorphometry of the femoral head was analyzed by Micro-CT imaging， and the area of medullary microvessels in the femoral head was detected by ink perfusion. The pathological change was observed by hematoxylin and eosin （HE） staining. The protein expressions of Platelet endothelial cell adhesion molecule-1 （CD31）， VEGF， VEGFR2， PI3K， phosphor-Akt （p-Akt） and phosphatase and Tensin homologue deleted on chromosome 10 （PTEN） in the femoral head were determined by immunohistochemistry and Western blot. ResultCompared with normal group， the model group presented the fracture and thinning of trabeculae in the femoral head， increased empty bone lacunae， and elevated number and diameter of adipocytes （P<0.01）. Micro-CT imaging revealed a decrease in bone mineral density （BMD）， bone volume fraction （BV/TV）， trabecular thickness （Tb.Th） and trabecular number （Tb.N） （P<0.05， P<0.01） while an increase in bone surface-to-volume ratio （BS/BV） and trabecular separation （Tb.Sp） （P<0.01）. The results of ink perfusion showed that the area of medullary microvessels in the femoral head was reduced （P<0.01）. Compared with model group， JPHGP lowered the empty bone lacunae rate as well as the number and diameter of adipocytes in the femoral head of AONFH rats. Micro-CT imaging indicated that JPHGP low-dose group had elevated BV/TV， Tb.Th and Tb.N （P<0.05， P<0.01） while decreased BS/BV （P<0.01）， and there was an upward trend in BMD while a downward trend in Tb.Sp， but without statistical difference. In addition， JPHGP medium- and high-dose groups had a rise in BMD， BV/TV， Tb.Th and Tb.N （P<0.05， P<0.01）， a decrease in BS/BV and Tb.Sp （P<0.05， P<0.01） and enlarged area of medullary microvessels in the femoral head （P<0.05， P<0.01）. The expressions of CD31， VEGF， VEGFR2， PI3K， p-Akt in the model group were lower than those in the normal group （P<0.01）， and after medium and high doses of JPHGP treatment， the expressions of CD31， PI3K and p-Akt in the femoral head of rats were up-regulated （P<0.01） while the protein expression of PTEN was down-regulated （P<0.01）. Moreover， JPHGP up-regulated the expressions of VEGF and VEGFR2 （P<0.05， P<0.01）. ConclusionJPHGP can repair the vascular injury in AONFH， and its mechanism may be related to the activation of VEGF/VEGFR2/PI3K/Akt signaling pathway. This study provides certain scientific basis and reference for the clinical application of JPHGP. ObjecctiveTo observe the repair effect of Jianpi Huogu prescription （JPHGP） on vascular injury in experimental alcohol-induced osteonecrosis of femoral head （AONFH）， and to explore its mechanism based on vascular endothelial growth factor （VEGF）/VEGFR2/phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway.

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 explore the strategy and experience for treating maxillofacial and cervical multi-space infection combined with descending necrotizing mediastinitis (DNM) via multidisciplinary team (MDT) collaboration.Methods:A total of 36 patients with maxillofacial and cervical multi-space infection complicated with DNM admitted to the First Affiliated Hospital of Zhengzhou University from July 2011 to July 2019 were included in the study. The clinical data of the patients were retrospectively analyzed, including gender, age, symptoms at admission, source of infection, preoperative and postoperative evaluation indicators, MDT strategy and prognosis.Results:There were 26 males and 10 females with an average age of (51.6±17.6) years (8-80 years). The course of disease before admission was (8.9±8.4) days (2-30 days). All patients were admitted with maxillofacial and neck swelling and pain as the main complaints. Odontogenic infection accounted for 39% (14/36), throat floor swelling and pain accounted for 25% (9/36) and unknown maxillofacial swelling accounted for 36% (13/36). There were 28 cases receiving surgical treatment, 26 cases were cured and discharged (72%), 10 cases died (28%). In the patients treated with multidisciplinary therapy (mainly by surgery), the white blood cell count, neutrophil percentage, C-reactive protein and procalcitonin levels were significantly improved compared with those at admission at each observation time point after operation ( P<0.05). The length of stay was positively correlated with the levels of C-reactive protein ( r=0.545, P<0.05) and procalcitonin ( r=0.504, P<0.05). The prognosis of patients treated with surgery (26/28) was better than that of patients without surgery (0/8) ( P<0.01). Conclusions:The patients with maxillofacial and cervical multi-space infection combined with DNM might be in critical condition. The surgical based MDT strategy has an important impact on the prognosis of patients. White blood cell count and other inflammatory indicators monitoring can effectively observe the changes of the patient′s condition.

Objective To investigate the effect of the multi?material artifact reduction (MMAR) algorithm of spectral CT in reducing the beam hardening artifacts in dental restoration material. Methods Three?unit fixed bridge restorations were fabricated on the first to third molars in pig jaw. Gold alloy, zirconia, cobalt chromium alloy, nickel chromium alloy and pure titanium were used as materials for these fixed bridges. After restoration delivery, the pig jaw was scaned using energy spectrum CT machines. Images in regular 120 kVp scan mode were used as conventional group, and reconstructed single?energy horizontal images of 80, 90, 100, 110, 120, 130 and 140 keV in energy spectrum scanning mode were used as energy spectrum group, and reconstructed images applied MMAR technology in energy spectrum scanning mode were used as energy spectrum MMAR group. Each group was scanned 10 times to measure CT value and noise of muscles around dental prosthetic materials and adjacent non?artifact layers. Artifact index was calculated. Two radiologists scored the image quality of each group subjectively. Kruskal Wallis rank sum test was used to compare the difference of image noise, artifact index and subjective score among the control group and the best keV condition in the energy spectrum group and the energy spectrum MMAR group. Results The image noise of energy spectrum group and energy spectrum MMAR group decreased gradually with the increase of single energy level. The artifact index of pure titanium restorations in conventional group, energy spectrum group and energy spectrum MMAR group were 71.0±8.0, 21.4±2.7 and 14.7±2.7 respectively, and these values were significantly lower than those of other materials in the same group (P<0.05). The subjective image quality scores in energy spectrum MMAR group were as follows: 3.0±0.2 for gold alloy, 4.3±0.5 for zirconia, 3.0±0.4 for cobalt chromium alloy, 3.1±0.4 for cobalt chromium alloy, and 4.6± 0.5 for pure titanium. These scores were significantly smaller than those in the conventional group (P<0.05). There was no significant difference in noise between energy spectrum group and energy spectrum MMAR group (P>0.05), and the noise values in energy spectrum group and energy spectrum MMAR group were significantly lower than that in the conventional group (P<0.05). Conclusions Artifacts of pure titanium is minimal. Energy spectrum CT combined with MMAR technology can effectively reduce the artifacts of gold, zirconia, cobalt?chromium alloy, nickel?titanium alloy and pure titanium. This technique can be used as an effective method to remove artifacts of dental prosthesis.

Objective: To investigate the effect of the multi-material artifact reduction (MMAR) algorithm of spectral CT in reducing the beam hardening artifacts in dental restoration material. Methods: Three-unit fixed bridge restorations were fabricated on the first to third molars in pig jaw. Gold alloy, zirconia, cobalt chromium alloy, nickel chromium alloy and pure titanium were used as materials for these fixed bridges. After restoration delivery, the pig jaw was scaned using energy spectrum CT machines. Images in regular 120 kVp scan mode were used as conventional group, and reconstructed single-energy horizontal images of 80, 90, 100, 110, 120, 130 and 140 keV in energy spectrum scanning mode were used as energy spectrum group, and reconstructed images applied MMAR technology in energy spectrum scanning mode were used as energy spectrum MMAR group. Each group was scanned 10 times to measure CT value and noise of muscles around dental prosthetic materials and adjacent non-artifact layers. Artifact index was calculated. Two radiologists scored the image quality of each group subjectively. Kruskal Wallis rank sum test was used to compare the difference of image noise, artifact index and subjective score among the control group and the best keV condition in the energy spectrum group and the energy spectrum MMAR group. Results: The image noise of energy spectrum group and energy spectrum MMAR group decreased gradually with the increase of single energy level. The artifact index of pure titanium restorations in conventional group, energy spectrum group and energy spectrum MMAR group were 71.0±8.0, 21.4±2.7 and 14.7±2.7 respectively, and these values were significantly lower than those of other materials in the same group (P<0.05). The subjective image quality scores in energy spectrum MMAR group were as follows: 3.0±0.2 for gold alloy, 4.3±0.5 for zirconia, 3.0±0.4 for cobalt chromium alloy, 3.1±0.4 for cobalt chromium alloy, and 4.6±0.5 for pure titanium. These scores were significantly smaller than those in the conventional group (P<0.05). There was no significant difference in noise between energy spectrum group and energy spectrum MMAR group (P>0.05), and the noise values in energy spectrum group and energy spectrum MMAR group were significantly lower than that in the conventional group (P<0.05). Conclusions Artifacts of pure titanium is minimal. Energy spectrum CT combined with MMAR technology can effectively reduce the artifacts of gold, zirconia, cobalt-chromium alloy, nickel-titanium alloy and pure titanium. This technique can be used as an effective method to remove artifacts of dental prosthesis.

Objective To investigate the analgesic efficacy and safety of decozine combined with sufentanil on patients after laparoscopic radical gastrectomy.Methods Sixty patients undergoing laparoscopic radical gastrectomy,American Society of Anesthesiologists (ASA) Ⅰ ～ Ⅱ,were selected,and were randomly divided into two groups.All of the patients were treated with intravenous-inhalation combined anesthesia,and was given patient controlled intraveous analgesia (PCIA) when the patient was awoken.PCIA was administered with subsequent bolus of 0.5 ml with lockout time 15 minutes and background infusion of 2 ml/h.A ratio (3 μg/kg) of sufentanil and 0.5 mg palonosetron were mixed in PCIA pump in sufentanil group (S group);and 1.5 μg/kg sufentanil,0.3 mg/kg dezocine,and 0.5 mg palonosetron in PCIA were mixed in dezocine combined with sufentainl group (DS group),they were diluted to 100 ml with saline.The visual analogue scale (VAS),Bruggrmann comfort scale (BCS),Ramsay and incidence of adverse reactions of two groups were observed in 2 h (T1),6 h (T2),12 h (T3),24 h (T4),48 h(T5) after operation.Results There was no significant difference of VAS and BCS between two groups at each time point after operation (P ＞ 0.05);The Ramsay score of S group was significantly higher than that of DS group at T1,T2,and T3 (P ＜ 0.05).The Ramsay scores of two groups at T4,T5 were lower than those of T1,T2,and T3.The incidence of nausea,vomiting of DS group was significantly lower than that of S group (P ＜0.05).Conclusions Dezocine combined with sufentainl used in PCIA on postoperative gastric cancer patients can obtain satisfactory analgesic effects,but has fewer side effects than single sufentainl.

BACKGROUND:At present, bone substitute filling is mainly used for bone defect repair. In order to understand the effect on bone defect repair, it is necessary to look into the microstructure changes of bone defects after bone substitute implantation. Synchrotron radiation-based micro-computed-tomography (SR-μCT) can be used to make high-resolution, high-resolution three-dimensional imaging without slicing and dyeing, and has high scientific and clinical value. OBJECTIVE:To explore the feasibility of SR-μCT in micron-level bone osseointegration examination in oral medicine. METHODS:This randomized controlled animal experiment was completed at the Fifth Central Hospital of Tianjin, Tianjin, China. A rabbit model of mandibular defect was made in 24 male New Zealand white rabbits. The model rats were randomly divided into four groups and received autologous bone, Bio-oss bone meal,β-tricalcium phosphate powder and no implantation (negative control group) in the defective area, respectively. Bone samples, including the defect area and the surrounding normal bone tissue, were taken at 2, 4, 8 weeks postoperatively for SR-μCT examination, fol owed by histopathological examination, in order to observe the repairing effects of different types of bone implant materials from different angles. The study protocol has been approved by the Ethics Committee of the Fifth Central Hespital of Tianjin in China. The study procedures were completed in accordance with the Guidance Suggestions for the Care and Use of Experimental Animals of China and the guidelines of the National Institutes of Health, USA. RESULTS AND CONCLUSION:In this study, SR-μCT could be used to observe the bone microstructure and osseointegration with no damage to samples to collect accurate quantitative data, including bone volume, number of bone trabeculae and bone mineral density. Therefore, SR-μCT can fully analyze the biocompatibility of bone implant material in vivo, give insight into the micron-level changes of different types of bone implant materials in the bone defect, thereby providing experimental evidence to improve bone defect healing.