The polymerase 1 and transcript release factor (PTRF)-cytoplasmic phospholipase A2 (cPLA2) phospholipid remodeling pathway facilitates tumor proliferation in glioma. Nevertheless, blockade of this pathway leads to the excessive activation of oncogenic receptors on the plasma membrane and subsequent drug resistance. Here, CD26/dipeptidyl peptidase 4 (DPP4) was identified through screening of CRISPR/Cas9 libraries. Suppressing PTRF-cPLA2 signaling resulted in the activation of the epidermal growth factor receptor (EGFR) pathway through phosphatidylcholine and lysophosphatidylcholine remodeling, which ultimately increased DPP4 transcription. In turn, DPP4 interacted with EGFR and prevented its ubiquitination. Linagliptin, a DPP4 inhibitor, facilitated the degradation of EGFR by blocking its interaction with DPP4. When combined with the cPLA2 inhibitor AACOCF3, it exhibited synergistic effects and led to a decrease in energy metabolism in glioblastoma cells. Subsequent in vivo investigations provided further evidence of a synergistic impact of linagliptin by augmenting the sensitivity of AACOCF3 and strengthening the efficacy of temozolomide. DPP4 serves as a novel target and establishes a constructive feedback loop with EGFR. Linagliptin is a potent inhibitor that promotes EGFR degradation by blocking the DPP4-EGFR interaction. This study presents innovative approaches for treating glioma by combining linagliptin with AACOCF3 and temozolomide.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective:To compare the efficacy of robot-assisted and conventional fluoroscopy-guided percutaneous vertebroplasty (PVP) combined with pediculoplasty in treating symptomatic chronic thoracolumbar osteoporotic vertebral fracture (SCOVF) without neurological symptoms.Methods:A retrospective cohort study was used to analyze the clinical data of 120 patients with thoracolumbar SCOVF without neurological symptoms, who were admitted to Honghui Hospital Affiliated to Xi′an Jiaotong University from January 2015 to January 2020. The patients included 34 males and 86 females, aged 63-85 years [(72.9±5.7)years]. All patients were treated with PVP combined with pediculoplasty. A total of 87 patients were treated with robot-assisted and C-arm X-ray machine guided puncture (robot group) and 33 patients with C-arm X-ray machine fluoroscopic-guided puncture (conventional group). The operation time, amount of bone cement injection and puncture accuracy were compared between the two groups. The results of vertebral body index, Cobb angle, visual analogue scale (VAS), and Oswestry disability index (ODI) were also compared before operation, at 1 day and 1 year after operation and at the final follow-up. Complications such as bone cement leakage and displacement were observed.Results:All patients were followed up for 24-36 months [(29.4±3.4)months]. The operation time was (85.2±10.5)minutes in the robot group, significantly longer than (37.2±3.7)minutes in the conventional group ( P<0.01). The amount of bone cement injection was (5.0±0.7)ml in the robot group, significantly less than (5.3±0.8)ml in the conventional group ( P<0.05). The puncture accuracy in the robot group was 95.4% (83/87), significantly higher than 81.8% (27/33) in the conventional group ( P<0.01). There were no significant differences in vertebral body index, Cobb angle, VAS or ODI between the two groups before operation (all P>0.05). The values of vertebral body index were 87.1±4.5, 86.9±4.3, 86.8±4.3 in the robot group at 1 day after operation, 1 year after operation and the final follow up, respectively, which were significantly higher than 83.6±4.4, 84.1±3.8, 84.4±3.9 in the conventional group (all P<0.01). There were no significant differences in Cobb angle or ODI between the two groups at 1 day after operation, 1 year after operation or the final follow-up (all P>0.05). The values of VAS were (2.9±1.0)points, (1.8±0.7)points, (1.8±0.7)points in the robot group at 1 day after operation, 1 year after operation and the final follow-up, respectively, which were significantly lower than (4.4±1.1)points, (3.1±0.8)points, (3.0±0.9)points in the conventional group (all P<0.01). The bone cement leakage occurred in 7 patients in the robot group [8.0%(7/87)] and in 10 in the conventional group [30.3%(10/33)] ( P<0.01). No delayed bone cement displacement [0.0%(0/87)] occurred in the robot group from 1 day after operation to the final follow-up, but 3 patients [9.1%(3/33)] were noted in the conventional group ( P<0.05). Conclusion:Both robot-assisted and conventional fluoroscopy-guided PVP combined with pediculoplasty have satisfactory effect for SCOVF patients without neurological impairment, but the robot-assisted one has the advantages of higher puncture accuracy, more satisfactory vertebral height recovery, more rapid pain relief, lower incidence of bone cement leakage and effective avoidance of cement displacement.

Cytisine derivatives are a group of alkaloids containing the structural core of cytisine, which are mainly distributed in Fabaceae plants with a wide range of pharmacological activities, such as resisting inflammation, tumors, and viruses, and affecting the central nervous system. At present, a total of 193 natural cytisine and its derivatives have been reported, all of which are derived from L-lysine. In this study, natural cytisine derivatives were classified into eight types, namely cytisine type, sparteine type, albine type, angustifoline type, camoensidine type, cytisine-like type, tsukushinamine type, and lupanacosmine type. This study reviewed the research progress on the structures, plant sources, biosynthesis, and pharmacological activities of alkaloids of various types.
Alkaloids/chemistry* ; Quinolizines/pharmacology* ; Azocines/chemistry* ; Fabaceae

Objective:To investigate the clinical features of adenoviral encephalitis (AE), and to provide reference for clinical diagnosis and treatment of adenoviral encephalitis.Methods:From January 2012 to December 2020, 1 185 cerebrospinal fluid (CSF) samples of hospitalized children with suspected central nervous system infection in the Second Affiliated Hospital of Shantou University Medical College were collected for the detection of 22 common respiratory pathogens and common pathogens for encephalitis by polymerase chain reaction. Records of patients with adenovirus positive in CSF were reviewed and relevant clinical manifestations, laboratory tests and imaging examination results were collected for analysis.Results:Among 1 185 CSF samples, 242 samples were positive for viral nucleic acid, with detection rate of 20.4%, including 1.9%(23/1 185) of adenovirus. As for 23 children diagnosed with AE, 18 were male, five were female, with the age of (44.8±35.9) months, ranging from two months and 19 days to 10 years. Of 23 children, 21(91.3%) presented with fever, followed by convulsions (16 cases, 69.6%), headache (four cases, 17.4%), vomiting (11 cases, 47.8%), consciousness change (11 cases, 47.8%) and emotion disturbance (three cases, 13.0%). Among 23 children, eight cases had white blood cell counts (WBC) of (6 to <10)×10 9/L, 10 cases had WBC of (10 to 20)×10 9/L and the white blood cell classification was mainly neutrophils (21 cases, 91.3%), and C reactive protein of 20 cases (87.0%) was in the normal range. Cerebrospinal fluid examination showed that WBC were less than 15×10 6/L in 20 cases (87.0%), and WBC ≥15×10 6/L in three cases, which were up to 500×10 6/L; the protein of 19 cases was in the normal range, the glucose of 15 cases was in the normal range, and the chloride of 19 cases was in the normal range. Among 16 cases with brain magnetic resonance imaging examination, eight cases did not show abnormality, six cases with local meningeal linear enhancement, one case with small intracranial malacia, and one case with extensive intracranial lesions. For 13 cases who received electroencephalogram (EEG) test, seven cases showed normal EEG or marginal state, four cases showed extensive medium and high amplitude slow wave, one case showed spike wave or spike slow wave and one case had both of the above two changes. Among 23 children, 22 cases recovered including one case had secondary epilepsy, and the remaining one case had severe brain dysfunction and was unable to suck when discharged, with an indwelling gastric tube and accompanied by secondary epilepsy. Conclusions:The clinical manifestations and auxiliary examinations of children with AE have no obvious specificity. Most children with AE have a good prognosis, but a small number of them may have serious sequelae.

Objective:To investigate the efficacy of the novel bone cement bridging screw system combined with percutaneous vertebroplasty (PVP) in the treatment of symptomatic chronic osteoporotic vertebral fractures (SCOVF) with intravertebral vacuum cleft (IVC).Methods:A retrospective case series study was used to analyze the clinical data of 27 patients with SCOVF admitted to Honghui Hospital affiliated to Xi′an Jiaotong University from August 2016 to August 2018, including 6 males and 21 females; age 69-88 years [(75.2±4.9)years]. All patients were treated by the novel bone cement bridging screw combined with PVP. The operation time, amount of bone cement injected and occurrence of bone cement leakage or displacement were recorded. The vertebral body index (VBI), vertebral body angle (VBA), two-segment Cobb angle (BCA), visual analogue score (VAS) and Oswestry disability index (ODI) were compared preoperatively, at day 1 after operation and at the last follow-up. The results of the MOS 36-item short form health survey (SF-36) and Odom′s criteria were compared preoperatively and at the last follow-up to evaluate pain relief and neurological recovery.Results:All patients were followed up for 36-48 months [(40.2±3.7)months]. The operation time was 37-70 minutes [(49.6±10.8)minutes], with the amount of bone cement injected for 3-6 ml [(34.7±0.9)ml]. Intraoperative bone cement leakage occurred in 4 patients (15%), among which 3 had lateral vertebral leakage and 1 superior intervertebral disc leakage. There was no bone cement displacement during the postoperative period to the last follow-up. The VBI, VBA, BCA, VAS and ODI were (43.1±5.9)%, (21.0±2.6)°, (45.0±6.3)°, 7.6 (7.0, 8.0)points, (79.9±7.6)% preoperatively, were (78.7±2.6)%, (12.7±2.1)°, (26.1±4.7)°, 3.2 (3.0, 4.0)points, (50.0±9.3)% at day 1 after operation, and were (78.0±2.3)%, (13.2±2.4)°, (27.1±4.9)°, 2.0 (2.0, 2.0)points, (22.9±5.1)% at the last follow-up. There were significant differences in above five measures at day 1 after operation and at the final follow-up in comparison with the preoperative values (all P<0.05), and their values measured at day 1 after operation and at the final follow-up were also significantly different (all P<0.05). The SF-36 score in physical function, role physical, body pain, vitality and social function was 45.2 (40.0, 50.0)points, 28.7 (25.0, 50.0)points, 15.9 (10.0, 22.0)points, 48.3 (40.0, 60.0)points, 29.2 (25.0, 37.5)points preoperatively, significantly different from 78.0 (75.0, 85.0)points, 75.0 (75.0, 75.0)points, 68.1 (64.0, 74.0)points, 62.0 (55.0, 70.0)points, 34.7 (25.0, 37.5)points at the last follow-up (all P<0.05). However, there were no significant differences in SF-36 before operation and at the last follow-up in dimensions of general health, emotional function and mental health (all P>0.05). According to Odom′s criteria, 19 patients were graded as excellent, 7 good, 1 fair and 0 poor, with an excellent and good rate of 96%. Conclusion:For SCOVF patients with IVC, the novel bone cement bridging screw system combined with PVP has advantages of no displacement of bone cement, satisfactory fixation, significant pain relief and satisfactory functional recovery.

Objective:To compare the clinical efficacy of two-dimensional (2D) fluoroscopic guided robot-assisted and conventional TESSYS surgery in the treatment of lumbar disc herniation, the feasibility and precautions of 2D fluoroscopic guided robot-assisted TESSYS surgery were discussed.Methods:A retrospective analysis was performed on 34 male and 36 female patients aged 44.57±6.10 years (range 27 to 60 years) who received 2D guided robot-assisted TESSYS surgery and conventional TESSYS surgery from July 2019 to April 2020. 2D guided robot assisted TESSYS surgery group (the robot group) 32 cases, conventional TESSYS surgery (the conventional group) 38 cases. The number of puncture, number of fluoroscopy, puncture-channel time, operation time, visual analogue scale (VAS) and Oswestry disability index (ODI) before and after surgery and at the last follow-up were compared between the two groups to verify the clinical efficacy, and the complications were analyzed.Results:There were no significant differences in age, gender, body mass index, surgical level, Michigan State University (MSU) grading and average follow-up time between the robot group and the conventional group (all P>0.05). All patients completed surgery. The number of puncture times was 1.22±0.79 in the robot group and 4.66±1.86 in the conventional group, and the difference was statistically significant ( t=10.320, P<0.001). The number of fluoroscopy in the robot group was 10.97±1.96 times, and that in the conventional group was 17.45±4.30 times, the difference was statistically significant ( t=8.313, P<0.001). The puncture-channel time of the robot group was 10.66±3.62 min and that of the conventional group was 20.21±5.47 min, and the difference was statistically significant ( t=8.446, P<0.001). The operation time of the robot group was 62.25±6.68 min, and that of the conventional group was 72.89±10.48 min, the difference was statistically significant ( t=4.956, P<0.001). VAS scores of the robot group were 6.91±0.93 points before surgery, 2.97±0.65 points 1 d after surgery, and 1.53±0.51 points at the last follow-up, while those of the conventional group were 7.29±1.14 points before surgery, 2.89±0.56 points 1 d after surgery, and 1.42±0.50 points at the last follow-up. The ODI index of the robot group was 40.13%±1.54% before surgery, 17.28%±1.69% 1 day after surgery, and 10.84%±1.25% at the last follow-up, while that of the conventional group was 40.03%±1.46% before surgery, 17.42%±2.45% 1 day after surgery, and 10.92%±1.17% at the last follow-up. There were no statistically significant differences (all P>0.05). Two patients (6.3%) in the robot group and four (10.5%) in the conventional group had residual disc, there was no significant difference ( P>0.05). Conclusion:2D guided robot assisted TESSYS surgical treatment of lumbar disc herniation, which can plan puncture path in the stage of percutaneous target puncture, rigid guidance and accurate puncture target, and has obvious advantages in reducing puncture times and fluoroscopy times.

Qualitative and quantitative methods were used to establish the quality of different medicinal parts of Poria cocos (Poriae Cutis, rubra Poria, white Poria, Poria cum Radix Pini) by using ultra-performance convergence chromatography coupled with photo-diode array and quadrupole time-of-flight mass spectrometry (UPC²-PDA-Q-TOF/MS^E). A total of 18 chromatographic peaks were detected from Poria cocos by UPC²-PDA. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were used to compare the four medicinal parts. The results showed that there were significant differences in the components of different medicinal parts, and the main triterpenoic acids were poricoic acid A, poricoic acid B, dehydroeburicoic acid, and dehydrotrametenolic acid. When combined with the common active component polyporenic acid C, a method for determination of five triterpenoic acids in different parts of Poria cocos was established. These components could be separated within 15 min, and the amount of methanol was 3.63% of that of HPLC method. Taking the five triterpenoid acids as an index, the content of triterpenoid acids in different parts of Poria cocos from high to low were Poriae Cutis, rubra Poria, white Poria and Poria cum Radix Pini. The method is simple, rapid, and uses minimal solvent. The mobile phase of environment-friendly gas carbon dioxide has unique advantages in reducing environmental pollution, which can provide a basis for the development and standard formulation of Poria cocos and its related products.

Coinfection/drug therapy* ; HIV ; HIV Infections/drug therapy* ; Hepacivirus ; Hepatitis B/drug therapy* ; Hepatitis C/drug therapy* ; Humans ; Prevalence

OBJECTIVES: To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients. METHODS: A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed. RESULTS: An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048). CONCLUSIONS Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).
Administration, Inhalation ; Adult ; China ; Coronavirus Infections ; diagnosis ; drug therapy ; mortality ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Integrative Medicine ; Interferon-alpha ; administration & dosage ; Lopinavir ; administration & dosage ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnosis ; drug therapy ; mortality ; Risk Assessment ; Severe Acute Respiratory Syndrome ; diagnosis ; drug therapy ; mortality ; Severity of Illness Index ; Survival Rate