ObjectiveTo explore the clinical safety of Feilike Mixture （FLK） in the real world. MethodsThe safety of all children who received FLK from 29 institutions in 12 provinces between January 21，2021 and December 25，2021 was evaluated through prospective centralized surveillance and a nested case control study. ResultsA total of 3 035 juveniles were included. There were 29 research centers involved，which are distributed across 12 provinces，including one traditional Chinese medicine （TCM） hospital and 28 general hospitals. The average age among the juveniles was （4.77±3.56） years old，and the average weight was （21.81±12.97） kg. Among them，119 cases （3.92%） of juveniles had a history of allergies. Acute bronchitis was the main diagnosis for juveniles，with 1 656 cases （54.46%）. FLK was first used in 2 016 cases （66.43%），and 142 juvenile patients had special dosages，accounting for 4.68%. Among them，92 adverse drug reactions （ADRs） occurred，including 73 cases of gastrointestinal system disorders，10 cases of metabolic and nutritional disorders，eight cases of skin and subcutaneous tissue diseases，two cases of vascular and lymphatic disorders，and one case of systemic diseases and various reactions at the administration site. The manifestations of ADRs were mainly diarrhea，stool discoloration，and vomiting，and no serious ADRs occurred. The results of multi-factor analysis indicated that special dosages （the use of FLK）［odds ratio （OR） of 2.642， 95% confidence interval （CI） of 1.105-6.323］，combined administration： spleen aminopeptide （OR of 4.978， 95%CI of 1.200-20.655），and reason for combined administration： anti-infection （OR of 1.814， 95%CI of 1.071-3.075） were the risk factors for ADRs caused by FLK. Conclusion92 ADRs occurred among 3 035 juveniles using FLK. The incidence of ADRs caused by FLK was 3.03%，and the severity was mainly mild or moderate. Generally，the prognosis was favorable after symptomatic treatment such as drug withdrawal or dosage reduction，suggesting that FLK has good clinical safety.

Qingfeitang， specialized in resolving phlegm to stop cough and producing fluid to moisten dryness， is a classic prescription inherited and developed by physicians of successive generations and has been included in the Catalogue of Ancient Classic Prescriptions （First Batch） published by the National Administration of Traditional Chinese Medicine （TCM） in 2018. Relevant ancient books data and modern literature were collected by bibliometrics to analyze the historic origin， formula composition， herb origin， preparation methods， processing methods， clinical effect， and indications of Qingfeitang. The key information of Qingfeitang was summarized to provide reference for the clinical application of the decoction. In this study， a total of 43 pieces of effective data on relevant ancient literature， including 35 ancient TCM books， were collected based on a systematic collation of relevant historic and modern literature. Results showed that "Qingfeitang" was originated from the "Renshen Qingfeitang" recorded in the Taiping Holy Prescriptions for Universal Relief from the Qing dynasty. The name of "Qinfeitang" was first recorded in the Yeshi Luyanfang written by YE Dalian in the Song dynasty. We suggested the modern dosage and usage of Qingfeitang as follows： "Scutellariae Radix of 5.60 g， Platycodon grandiflora， Poria， Tangerine， Fritillaria， and Cortex Mori of 3.73 g respectively， Angelicae Sinensis Radix， Asparagi Radix， Gardeniae Fructus， Armeniacae Semen Amarum， and Ophiopogonis Radix of 2.61 g respectively， Schisandra of 1 g， and Glycyrrhizae Radix et Rhizoma of 1.12 g， and they were taken 3 times daily. The above formula is recommended to be decocted with 400 mL of water， with 3.37 g ginger and 6 g jujubae fructus， to 320 mL， and taken after a meal， three times per day". Qingfeitang has the effect of resolving phlegm to stop cough and producing fluid to moisten dryness， specialized in treating cough， asthma， rash， and other symptoms in ancient times. Modern applications are mainly focused on the respiratory system， used for treating diseases such as bronchopneumonia and cough. The above research results provide a reference basis for the later development and research of Qingfeitang.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

AIM:To investigate the role of proviral integration site for Moloney murine leukemia virus 1(PIM1)in the phenotypic switching of vascular smooth muscle cells(VSMCs)induced by oxidized low-density lipoprotein(oxLDL),and to explore the underlying mechanisms.METHODS:Eighteen male ApoE-/-mice(8 weeks old)were ran-domly divided into general diet group and high-fat diet group,with 9 mice per group.After 16 weeks,aortic samples were analyzed using HE staining to observe plaque formation.In vitro,VSMCs were exposed to oxLDL to induce phenotypic transformation.Western blot and immunofluorescence were used to measure the protein expression levels of PIM1 and phe-notypic markers including α-smooth muscle actin(α-SMA),smooth muscle protein 22α(SM22α),osteopontin(OPN),and CD68.Glycolysis levels were assessed by detecting the expression of glycolytic enzymes 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase(PFKFB3)and hexokinase 2(HK2)by Western blot,and lactate secretion was measured using a lactate test kit.The effects of SMI-4a(a specific inhibitor of PIM1)and PIM1 small interfering RNA on oxLDL-in-duced phenotypic markers in VSMCs were evaluated.Moreover,the impact of 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one(3PO;a glycolysis inhibitor)on oxLDL-induced phenotypic switching and glycolysis in VSMCs was investigated.RESULTS:HE staining revealed atherosclerotic plaque formation in the aortas of ApoE-/-mice fed with high-fat diet.Im-munofluorescence showed high accumulation of PIM1 and OPN in the tunica intima of atherosclerotic plaques.Compared with control group,aortic plaques exhibited significantly elevated levels of PIM1,OPN and CD68 proteins(P<0.01),ac-companied by reduced expression of contractile phenotype markers α-SMA and SM22α(P<0.01).In vitro,oxLDL treat-ment led to gradual decrease in α-SMA and SM22α expression(P<0.05 or P<0.01),while OPN and CD68 expression in-creased(P<0.05 or P<0.01).Moreover,oxLDL significantly up-regulated the protein expression of PIM1,PFKFB3 and HK2,and increased lactate secretion in VSMCs(P<0.05 or P<0.01).Knockdown of PIM1 or treatment with SMI-4a markedly attenuated these oxLDL-induced effects on VSMCs(P<0.05 or P<0.01).Treatment with 3PO also abolished ox-LDL-induced phenotypic transformation and glycolysis in VSMCs(P<0.05 or P<0.01).CONCLUSION:PIM1 highly accumulates in the atherosclerotic plaques of ApoE-/-mice.The phenotypic transformation of VSMCs was correlated with the expression of PIM1.PIM1 can regulate the phenotypic transformation of oxLDL-treated VSMCs by inducing glycolysis.

BACKGROUND:Pulsed electromagnetic fields,as an important physical therapy,are exactly effective in the treatment of osteoarthritis,but the mechanism has not been fully clarified. OBJECTIVE:To observe the effect of pulsed electromagnetic field on the degeneration of knee joint cartilage in aged rats. METHODS:Eight 6-month-old Sprague-Dawley rats were selected as the young group and were subjected to normal diet with no treatment.Sixteen 22-month-old Sprague-Dawley rats were randomly divided into old group(n=8)and pulsed electromagnetic field group(n=8).The rats in the pulsed electromagnetic field group were subjected to a pulsed electromagnetic field intervention,once a day,5 days per week for continuous 8 weeks.The rats in the old group were given no treatment.All rats were anesthetized and executed after 8 weeks for the detection of relevant indexes. RESULTS AND CONCLUSION:Compared with the young group,serum type Ⅱ collagen C-terminal peptide level was increased in the old group(P<0.05);compared with the old group,serum type Ⅱ collagen C-terminal peptide level was decreased in the pulsed electromagnetic field group(P<0.05).Micro-CT showed that the bone volume fraction,bone mineral density,and number of bone trabeculae decreased(P<0.05)and the trabecular separation increased(P<0.05)in the tibia of rats in the aged group compared with the young group;and the bone volume fraction,bone density,and number of trabeculae increased(P<0.05)and the trabecular separation decreased(P<0.05)in the tibia of rats in the pulsed electromagnetic field group compared with the aged group.The tibial plateau Safranin O-fast green staining showed that the articular cartilage structure of rats in the aged group was disorganized,and the number of chondrocytes was obviously reduced,and the tidal line could not be distinguished.The above results were improved in the pulsed electromagnetic field group.RT-qPCR and western blot assay showed that the mRNA and protein expression levels of matrix metalloproteinase 1,matrix metalloproteinase 13,P53 and P21 in the articular cartilage and subchondral bone of rats were elevated in the aged group compared with the young group(P<0.05)and decreased in the pulsed electromagnetic field group compared with the old group(P<0.05).To conclude,pulsed electromagnetic fields may improve osteoarthritis in aged rats by inhibiting chondrocyte senescence,alleviating articular cartilage degradation and inhibiting subchondral bone osteoporosis through suppressing the expression of P53/P21.

Objective:To investigate the value of delta radiomics based on longitudinal changes of dynamic contrast enhanced MRI (DCE-MRI) in predicting pathological complete response (pCR) after neoadjuvant therapy (NAT) for breast cancer.Methods:The clinicopathological and imaging data of 117 patients with breast cancer confirmed by surgical pathology from April 2019 to November 2021 at Jiangxi Cancer Hospital were analyzed retrospectively. All patients were female with 23?74 (48±10) years old. The patients were randomly divided into training (81 cases) and test sets (36 cases) at the ratio of 7∶3 according to the number of random seeds in the software. All patients underwent DCE-MRI before and after early NAT (2 courses). The maximum diameter relative regression value of breast tumors before and after early NAT (D%) was calculated and used to construct a conventional imaging model. The delta radiomic features were extracted based on pre-NAT and early-NAT (2 courses) DCE-MRI and selected by redundancy analysis and least absolute shrinkage and selection operator algorithm. A ten-fold cross-validation method was used to construct the delta radiomic model and Radscore was calculated for each patient. All patients were classified into pCR group and non-pCR group according to the surgical pathology after NAT. Significant clinicopathological variables were selected by univariate analysis and stepwise regression method. They were integrated with D% and Radscore to build the combined model and nomogram. The model performance in predicting pCR after NAT in breast cancer was evaluated by the receiver operating characteristic curve and the area under the curve (AUC), and the clinical utility of the models was compared by using clinical decision curves.Results:The combined model had the best diagnostic performance among the three models, with an AUC of 0.90 in the training set and 0.87 in the test set. The Radscore had the highest weight in the nomogram. In the training set, the diagnostic performance of the combined model and delta radiomics model were better than that of the conventional imaging model ( Z=?3.48, P=0.001; Z=2.54, P=0.011). The clinical decision curves showed an overall greater clinical benefit of the combined model compared with the conventional imaging model and delta radiomic model. Conclusions:The addition of significant clinicopathological variables and Radscore of delta radiomic model which represents the longitudinal changes in tumor heterogeneity to the conventional imaging model may improve the predictive ability of pCR. The delta radiomic may serve as a noninvasive biomarker for early prediction of NAT response.

Objective:To study the clinical characteristics of neonatal gastric perforation (NGP) and risk factors of mortality.Methods:From January, 2015 to December, 2021, clinical manifestations of neonates diagnosed with NGP in the Department of Neonatology and Neonatal Surgical Intensive Care Unit of our hospital were retrospectively analyzed. Neonates were assigned into the survival group and the death group according to their prognosis. Risk factors of mortality were analyzed using multivariate logistic regression method.Results:A total of 50 cases were enrolled, including 41 in the survival group and 9 in the death group. 38 cases were males, 34 were premature infants, 30 were low birth weight infants and 5 had history of asphyxia. The clinical manifestations included abdominal distension, tachypnea, cyanosis, poor response, fever, diminished bowel sound and redness of the abdominal wall. Abdominal X-ray indicated pneumoperitoneum. Laboratory abnormalities included leukocytosis, thrombocytopenia, elevated C-reactive protein and procalcitonin, decreased blood pH and increased lactic acid. 30 cases had perforation at the greater curvature of stomach. Perforation was larger than 3 cm in 40 cases and intestinal necrosis was identified in 14 cases. Some patients suffered from sepsis, respiratory failure, pulmonary hemorrhage, shock, coagulopathy and other related complications. The death group had significantly higher incidences of dyspnea, fever, elevated procalcitonin, blood pH<7.3, intestinal necrosis, time from onset of clinical manifestations to operation (Tm-o) >24 h and complications than the survival group ( P<0.05). Multivariate logistic regression analysis showed that pH<7.3 ( OR=9.755, 95% CI 1.363-69.800), Tm-o>24 h (OR=11.831, 95%CI 1.305-107.301), septic shock and sepsis ( OR=29.622, 95% CI 3.728-235.369) were risk factors of mortality. Conclusions:The main manifestations of NGP are abdominal distension and pneumoperitoneum. The risk factors of mortality in NGP are sepsis, blood pH<7.3 and Tm-o>24 h.

Objective:To explore the mechanism of lysosomal membrane permeabilization(LMP)inuranyl acetate-induced death of human kidney proximal tubular epithelial HK-2 cells.Methods:HK-2 cells were exposed to uranyl acetate at concentrations of 100, 300 and 600 μmol/L for 24 h, then in tracellular reactive oxygen species (ROS)and mitochondrial superoxide were measured by DCFH-DA and MitoSOX probe, respectively. HK-2 cells were divided into four groups: blank control group, NAC or CA-074 Me group, uranyl acetate exposure group and uranyl acetate exposure plus NAC or CA-074 Me group. Two-color immune of luorescence staining was used to detect the co-localization of galectin-1 and lysosomal associated membrane protein-1 (LAMP-1) to measure the extent of LMP, and to detect the non- co-localization of cathepsin B and LAMP-1 to reflect the release of cathepsin B in lysosomes. Calcein-AM/PI double staining method was used to detect cell death. One-color immune of luorescence staining of cleaved-caspase-3 expression was used to detect apoptosis. Results:Intracellular ROS and mitochondrial superoxide levels were significantly increased in HK-2 cells after exposure with 100, 300 and 600 μmol/L uranyl acetate for 24 h, about 1.1-2.5 times or 4.0-28 times, respectively( tROS=17.98, 11.84, 11.75, P< 0.05; tmitochondrial superoxide=6.14, 16.02, 13.06, P< 0.05), and they also increased with uranyl acetate concentrations ( tROS=10.10, 10.37, 5.59, P< 0.05; tmitochondrial superoxide=21.50, 15.16, 5.93, P< 0.05). The percentage of co-localization of galectin-1 and LAMP-1 and the percentage of non- co-localization of cathepsin B and LAMP-1 were markedly increased in HK-2 cells after exposure with 600 μmol/L uranyl acetate for 24 h, 5.4-6.7 times or 1.5-2.1 times, respectively ( tGalectin-1=15.85, 12.70, P< 0.05; tCathepsin B=5.95, 6.69, P< 0.05), but these increases were inhibited by NAC ( tGalectin-1=4.74, P<0.05; tCathepsin B=4.51, P< 0.05). Moreover, the cell death rate and the cleaved-caspase-3 expression level were also significantly increased in HK-2 cells after exposure with 600 μmol/L uranyl acetate for 24 h, about 28-47 times or 2.4-6.0 times, respectively( tPI=30.40, 10.34, P<0.05; tCleaved-caspase-3=18.49, 9.52, P<0.05), and these increases were obviously diminished by CA-074 Me ( tPI= 6.76, P<0.05; tCleaved-caspase-3=13.47, P<0.05). Conclusions:Exposure to uranyl acetate induces a burst of intracellular ROSthat leads to LMP and consequently causes leakage of cathepsin B from lysosomes to cytoplasm, in turn triggering the lysosomal-dependent cell death and mitochondrial-regulated apoptosis of HK-2 cells.

Objective:Efficacy and safety analysis of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in promoting hematopoietic recovery after autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with lymphoma.Methods:A total of 149 patients after auto-HSCT in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were enrolled in this study from April 2016 to December 2021. There were 75 cases in the PEG-rhG-CSF group who were given a single subcutaneous dose of 100 μg/kg on the first day and +8 d, while 74 cases in the rhG-CSF group were given a dose of 5-10 μg·kg -1·d -1 by subcutaneous injection from +1d continuing to an absolute value of neutrophil (ANC) of more than 1.5×10 9/L. Results:①The time of grade 3/4 agranulocytosis and neutrophil implantation in the PEG-rhG-CSF group were significantly different from that in rhG-CSF group ( P=0.010, 0.030, 0.007) . There were no significant differences in the platelet implantation time, anemia incidence and duration, and platelet and red blood cell infusion within 1 month after transplantation between groups. ②The agranulocytosis with fever incidence in PEG-rhG-CSF group was similar to that in rhG-CSF group (84.0% vs 82.4% , P=0.798) , but the duration was shorter in the PEG-rhG-CSF group (4.0 d vs 5.5 d, P=0.005) . ③The incidence of infection in the PEG-rhG-CSF and the rhG-CSF groups were 22.7% (17/75) and 31.1% (23/74) , respectively ( P=0.247) , and the bloodstream infection incidence were 5.3% (4/75) and 9.5% (7/74) , respectively ( P=0.336) . ④The PEG-rhG-CSF group and rhG-CSF group’s mean length of hospital stay were 31.5 (23-43) days and 37 (25-75) days, respectively ( P<0.001) . ⑤The PEG-rhG-CSF group and rhG-CSF group’s disease-free survival rates were (96.4±2.5) % and (94.7±2.6) % ( P=0.638) , respectively, and the OS rates were 100.0% and (98.6±1.3) % ( P=0.312) , respectively. Conclusion:PEG-rhG-CSF application after auto-HSCT in patients with lymphoma can promote hematopoietic granulocyte reconstruction and shorten hospital stay, but has no significant effect on the incidence of infection, disease-free survival, and overall survival after transplantation.

Objective To evaluate the effects of surgery under ketamine anesthesia during mid-pregnancy on cognitive function of offspring rats.Methods Thirty healthy pregnant Sprague-Dawley rats at14 days of gestation,aged 9-10 weeks,weighing 270-310 g,were assigned to 3 groups (n=10 each)using a random number table method:exploratory laparotomy under ketamine anesthesia group (KSgroup),ketamine anesthesia group (K group) and control group (C group).In KS group,ketamine 20mg/kg was injected via the caudal vein,and then ketamine was continuously infused at a rate of 130mg · kg-1 · h-1 after loss of right reflex to maintain anesthesia for 2 h,and exploratory laparotomy was per-formed after anesthesia was stable.Group K received no exploratory laparotomy and the other treatmentswere similar to those previously described in group KS.The equal volume of normal saline was given insteadin group C.The cliff avoidance,passive avoidance,and Morris water maze tests were used to evaluate the spatial perception and learning and memory ability of the offspring rats on postnatal days 7,23 and 30.Hippocampal tissues of rat offsprings were obtained at 24 h after the end of Morris water maze test to determine neural precursor cell-expressed developmentally downregulated protein 9 (NEDD9) and postsynaptic density 95 (PSD-95) protein and mRNA expression by quantitative polymerase chain reaction or Western blot.Results Compared with group C,the score of cliff avoidance was significantly decreased,the results of Morris water maze test showed that the escape latency was significantly prolonged,the platform-crossing times were decreased,the time spent in the second quadrant was shortened,the expression of NEDD9 and PSD-95 was down-regulated (P ＜ 0.05),and no significant changes were found in the expression of NEDD9 and PSD-95 mRNA in KS group,and no significant changes were found in the indexes mentioned above in K group (P＞0.05).There was no significant difference in the numberof errors in passive avoidance test among the three groups (P＞0.05).Conclusion Ketamine anesthesia during mid-pregnancy exerts no effect on the cognitive function of offspring rats,abdominal surgery under ketamine anesthesia impairs the spatial perception and learning and memory ability of offspring rats,and the mechanism is related to down-regulating the expression of NEDD9 and PSD-95 in hippocampi of offspring rats.