Detection of 14 sulfonate esters impurities of active pharmaceutical ingredients based on GC-MS/MS and LC-MS/MS / 药学学报

Two methods including gas chromatography tandem mass spectrometry (GC-MS/MS) and high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) were established to detect common alkyl sulfonates and aryl sulfonates genotoxic impurities. Four alkyl sulfonates and methyl benzenesulfonate were determined by GC-MS/MS using butyl methanesulfonate as the internal standard, the chromatographic column was HP-5MS UI (30 mm × 0.25 mm, 0.25 µm), the carrier gas was helium, the flow rate was 1.0 mL·min-1 in a constant flow mode, the sample inlet temperature was set to 250 ℃, the split ratio was 10∶1, and the initial temperature of the heating program was 80 ℃, maintained for 1 minute, and then increased to 240 ℃ at a heating rate of 30 ℃·min-1 for 2 minutes. The mass spectrometry detector was an electron bombardment ion source (EI source), the data collection condition was multi reaction monitoring mode (MRM), and method validation using the raw material of clinical drug citalopram hydrobromide as a sample. The results showed that the linear range of four alkyl sulfonates and methyl benzenesulfonate were good at 3-50 ng·mL-1 and 9-150 ng·mL-1, with a correlation coefficient of r > 0.999, The spiked recovery was 80%-120%. The detection limits were 1 and 3 ng·mL-1; Ten aryl sulfonates determined by LC-MS/MS, the chromatographic column was CSH Fluoro phenyl (100 mm × 2.1 mm, 1.7 µm), the mobile phase was methanol (B)-5 mmol·L-1 ammonium formate (D), with a flow rate of 0.2 mL·min-1, and gradient elution was performed. The gradient program (T/% B) was set as 0/20, 25/90, 35/90, 42/20. The mass spectrometer detector was electro spray ionization with positive ionization mode (ESI+), the data collection was in dynamic multi reaction monitoring mode (dMRM), and the method was validated using the raw material of the clinical drug citalopram hydrobromide as a sample. The results showed that the linear range of aryl sulfonates were good at 9-2 000 ng·mL-1, 3-100 ng·mL-1 and 0.9-30 ng·mL-1, respectively. The correlation coefficient r > 0.999, the spiked recovery was 80%-120%. The detection limits were 30, 1 and 0.3 ng·mL-1. Two detection methods did not detect potential sulfonate genotoxicity impurities in the above APIs. The established analytical methods are reliable and effective, which can provide reference for drug quality control and detection.

Structure and Function of Rhizomicrobes Recruited by Acteoside in Root Exudates of Rehmannia glutinosa / 中国实验方剂学杂志

ObjectiveTo reveal the correlation of Rehmannia glutinosa-soil feedback process with the formation of its continuous cropping obstacles through the identification of the root exudates of R. glutinosa and analysis of the specific rhizomicrobes recruited by the root exudate. MethodThe root exudates of R. glutinosa seedlings germinated under sterilized condition and those enriched in the rhizosphere of R. glutinosa cultivated in the field were collected and analyzed using the ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry（UPLC-Q-TOF-MS）. The highly abundant compounds identified in the root exudates were added into blank soil， and the soil microbial community was profiled using Illumina Miseq sequencing. The bacterial and fungal functions were predicted by PICRUSt and FUNGuild， respectively. ResultThe identification results showed that seven phenylethanoid glycosides were found in R. glutinosa root exudates， and acteoside possessed the highest abundance. In the soil enriched with acteoside， the bacterial genera such as Agromyces， Pseudomonas， Lysobacter， Sphingobium， Pseudoxanthomonas and Sphingomonas were enriched. For the fungi， the genera Neocosmospora， Plectosphaerella and Dactylonectria， and the species such as Neocosmospora rubicola， Plectosphaerella cucumerina， Dactylonectria alcacerensis and Fusarium solani showed higher abundance. The functional analysis indicated the above-mentioned bacterial genera may realize rapid proliferation by utilizing， biodegrading and transforming phenylethanoid glycosides， and some potential fungal pathogens were colonized. ConclusionThe R. glutinsoa-soil feedbacks were likely generated by the phenylethanoid glycosides in the root exudates together with the specific rhizomicrobes. The investigations of R. glutinsoa-soil feedbacks under continuous cropping system are critical to the further understanding of the underlying mechanisms related to its continuous cropping obstacles.

A novel TNKS/USP25 inhibitor blocks the Wnt pathway to overcome multi-drug resistance in TNKS-overexpressing colorectal cancer

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APCmin/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

The Role of SDF-1α-CXCR4/CXCR7 in Migration of Human Periodontal Ligament Stem Cells

Background and Objectives@#Regenerative endodontic procedures (REPs) are a research hotspot in the endodontic field. One of the biggest problems of REPs is that it is difficult to realize regeneration of pulp-dentin complex and functional reconstruction. The reason is still not clear. We hypothesize that the migration may be different in different dental stem cells. Periodontal ligament stem cells (PDLSCs) may migrate faster than stem cells of apical papilla (SCAPs), differentiating into cementum-like tissue, bone-like tissue and periodontal ligament-like tissue and, finally affecting the outcomes of REPs. Hence, this study aimed to explore the mechanism that regulates the migration of PDLSCs. @*Methods@#and Results: After isolating and culturing PDLSCs and SCAPs from human third molars, we compared the migration of PDLSCs and SCAPs. Then we investigated the role of SDF-1α-CXCR4/CXCR7 axis in PDLSC migration. We further investigated the impact of Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS) on PDLSC migration and the potential mechanism. PDLSCs showed better migration under both noninflammatory and inflammatory conditions than SCAPs. SDF-1α can promote the migration of PDLSCs by elevating the expression of CXCR4 and CXCR7, increasing the interaction between them, promoting expression of β-arrestin1 and activating the ERK signaling pathway. P. gingivalis LPS can promote the migration of PDLSCs toward SDF-1α through increasing the expression of CXCR4 via the NF-κB signaling pathway, promoting the expression of β-arrestin1, and activating the ERK signaling pathway. @*Conclusions@#This study helped elucidate the potential reason for the difficulty in forming pulp-dentin complex.

Observation of vortex venous anastomosis in central serous chorioretinopathy / 中华眼底病杂志

Objective:To observe the anastomotic status of the vortex veins in patients with central serous chorioretinopathy (CSC).Methods:A cross-sectional study of clinical practice. From July 2021 to July 2022, 50 cases (50 eyes) of monocular CSC patients diagnosed through ophthalmic examination at the First Affiliated Hospital of Zhengzhou University were included in the study. Among them, there were 37 males (74.0%, 37/50) and 13 females (26.0%, 13/50), with the mean age of (44.30±9.59) years old. The course of disease from the onset of symptoms to the time of treatment was less than 3 months. The affected eye and contralateral eye of CSC patients were divided into the affected eye group and contralateral eye group, respectively. Fifty healthy volunteers of the same age and gender were selected as the normal control group with 50 eyes. The macular area scanning source optical coherence tomography (OCT) vascular imaging examination was performed with Visual Microimaging (Henan) Technology Co., Ltd. VG200D. Horizontal watershed vortex veins anastomosis rate and asymmetric vortex-venous dilation rate were observed by en face OCT. The device comes with software to calculate the central foveal choroidal thickness (SFCT), mean choroidal thickness (MCT), and choroidal vascular index (CVI). One-way analysis of variance and χ2 test were used to compare the three groups. When variances were unequal between groups, nonparametric tests were performed. Results:The SFCT values of the affected eye group, contralateral eye group, and normal control group were (567.12±129.02), (513.26±133.17), (327.64±97.40) μm, respectively; MCT were (407.38±97.54), (388.24±94.13), (275.46±60.55) μm, respectively; CVI were 0.34±0.05, 0.32±0.04, and 0.27±0.04, respectively; anastomosis rates of vortex veins were 98% (49/50), 78% (39/50), and 40% (20/50), respectively; asymmetric dilation rates of vortex veins were 96% (48/50), 88% (44/50), and 48% (24/50), respectively. The differences of SFCT ( F=53.974), MCT ( Z=51.415), CVI ( F=28.082), vortex vein anastomosis rate ( χ2=43.056), asymmetric dilation rate of vortex veins ( χ2=37.728) among three groups were statistically significant ( P<0.001). Compared with the contralateral eye group, the SFCT, MCT, CVI, vortex vein anastomosis rate, and vortex vein asymmetric dilation rate in the affected eye group were significantly higher than those in the contralateral eye group. Among them, the differences of SFCT ( t=2.054), CVI ( t=2.211), and vortex vein anastomosis rate ( χ2=9.470) were statistically significant ( P<0.05); the differences of MCT ( Z=7.490), asymmetric dilation rate of vortex veins ( χ2=2.714) were not statistically significant ( P=1.000, 0.140). Conclusions:SFCT, MCT, and CVI in the affected and contralateral eyes of monocular CSC patients significantly increase. The anastomotic rate and asymmetric dilation rate of the vortex vein in the opposite eye were lower than those in the affected eye.

Effect of surgical resection after preoperative immunotherapy combined chemotherapy on unresectable stage Ⅲ non-small cell lung cancer / 中华胸心血管外科杂志

Objective:Immune checkpoint inhibitors have a high remission rate in the preoperative application of resectable and potentially resectable non-small cell lung cancer when combined with chemotherapy. For the unresectable stage Ⅲ non-small cell lung cancer, whether the transformation can be achieved through this regimen to provide opportunities for surgical resection is controversial. In this study, we evaluated the pattern of transformation therapy by reviewing the efficacy and safety of preoperative therapy and surgery of this group.Methods:A review of 23 patients undergoing surgical resection after transformation therapy by preoperative immunotherapy combined chemotherapy between November 2019 and November 2021 was performed. All patients must clarify the pathological diagnosis of non-small cell lung cancer by biopsy. After the multi-disciplinary treatment team and preoperative imaging assessment, the diagnosis should be consistent with unresectable stage III as described in the Expert Consensus on Multidisciplinary Management of Stage Ⅲ Non-Small Cell Lung Cancer, 2019 Edition. After 2 to 4 cycles of preoperative anti-PD-1 monoclonal antibody combined with chemotherapy, the surgical team assessed the chance of resection and performed surgery. Important indicators such as surgical resection rate, R0 resection rate, MPR, pCR, incidence of grade 3-5 adverse reactions and various other perioperative data were counted.Results:In the whole group, initial imaging evaluation was 10 of stage cⅢA and 13 of stage cⅢB.15 cases had multiple stations N2 lymph nodes metastasis, 9 had enlarged fused N2 lymph nodes metastasis, 6 had large vessel invasion(T4), and 1 had contralateral mediastinal lymph node metastasis(N3). After preoperative neoadjuvant therapy, 17 cases achieved PR, 3 achieved SD and 3 achieved PD. The surgical resection rate of the whole group was 91.3%(21/23, 1 lobectomy combined with superior vena cava reconstruction, 2 sleeve lobectomy, 5 pneumonectomy, 12 lobectomy/combined lobectomy, 1 wedge resection and 2 unresectable cases), R0 resection rate was 95.2%(20/21). MPR was achieved in 13 cases, 8 of them reached pCR. There were no perioperative deaths, median surgical time was 260(190-460) min, median bleeding volume was 100(50-750) ml, median drainage time was 5(3-9) days, and median hospitalization was 7(5-11) days. Two cases got immunotherapy-related grade 3 adverse reactions, one was interstitial pneumonia and the other was immune-related injury involving the eye, oral and genital mucosa. Two cases got surgical complications and one was persistent lung leakage, which stopped after 46 days of conservative treatment; The other was pleural effusion, which was relieved after drainage.Conclusion:For the unresectable stage Ⅲ NSCLC, immunotherapy combined chemotherapy is an effective preoperative downstage method. It can convert 91.3% cases to resectable ones while achieving a good degree of pathological remission. Its side reactions are generally controllable and safety.

Minimally invasive percutaneous anterior column screwing assisted by blocking screws for pelvic and acetabular fractures / 中华创伤骨科杂志

Objective:To investigate the feasibility and clinical efficacy of percutaneous anterior column screwing assisted by blocking screws for pelvic and acetabular fractures.Methods:A retrospective analysis was conducted of the 13 patients who had been admitted from July 2019 to April 2022 for pelvic and acetabular fractures. There were 8 males and 5 females with an age of (49.1±13.3) years, 7 acetabular fractures (6 on one side and 1 on both sides; by the Letournel-Judet classification: 5 anterior column fractures on 6 sides, and 2 transverse and posterior wall fractures on 2 sides), and 6 pelvic fractures (5 complicated with pelvic posterior ring fracture; by the Tile classification: 1 case of type B2, 3 cases of type C1, and 2 cases of type C2). According to the anatomic zones of the anterior column, 5 fractures were at zone Ⅲ, 3 ones at zone Ⅳ, and 6 ones at zone Ⅴ. The time from injury to surgery ranged from 3 to 14 days, averaging (8.2±2.9) days. Anterograde anterior column screwing assisted by blocking screws was performed for all the 13 patients; the posterior ring was fixated with percutaneous sacroiliac joint screws for the 5 patients complicated with pelvic posterior ring fracture. The surgical time, intraoperative fluoroscopy frequency, and intraoperative bleeding volume for insertion of anterior column screws, fracture reduction quality, and hip joint function at the last follow-up were recorded.Results:A total of 14 anterior column screws were inserted percutaneously in the 13 patients. For insertion of anterior column screws, the surgical time was (65.0±10.2) min, the intraoperative fluoroscopy frequency (63.5±14.5) times, and the intraoperative bleeding volume for each screw less than 30 mL. All the incisions healed primarily after surgery, without such complications as iatrogenic neurovascular injury or poor wound healing. All the 13 patients were followed up for (11.1±2.2) months after surgery. In the patient with bilateral acetabular anterior column fractures for which 2 anterior column screws had been inserted, one screw had to be removed due to its displacement at 1 month after surgery; no such complications as loosening of internal fixation or fracture re-displacement was found in the other patients. All fractures healed after (10.2±2.1) months. According to the Matta scoring for quality of fracture reduction, 7 sides were excellent, 5 sides good, and 2 sides poor; according to the Majeed scoring for the 6 patients with pelvic fracture at the last follow-up, the efficacy was rated as excellent in 4 cases and as good in 2 ones; according to the modified Merle d'Aubigné & Postel scoring for the 7 patients with 8 acetabular fractures at the last follow-up, the efficacy was rated as excellent in 4 hips, as good in 3 hips, and as fair in 1 hip.Conclusion:For pelvic and acetabular fractures, minimally invasive percutaneous anterior column screwing assisted by blocking screws can result in fine clinical efficacy, in addition to its easy procedures, safety and reliability.

A wound diagnosis and treatment mode with integrated medical care for repair of chronic infectious wounds plus bone exposure at lower extremities / 中华创伤骨科杂志

Objective:To evaluate a wound diagnosis and treatment mode with integrated medical care in the repair of chronic infectious wounds plus bone exposure at lower extremities.Methods:A retrospective analysis was conducted of the 64 patients with chronic infectious wound plus bone exposure at the lower 1/3 of the leg who had been admitted to Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University from January 2019 to December 2021. The patients were divided into 2 groups according to the wound diagnosis and treatment mode. In the observation group of 31 patients subjected to the wound diagnosis and treatment mode with integrated medical care led by specialist nurses, there were 24 males and 7 females with an age of (53.6±12.4) years, the wound was located at the tibial side in 15 cases and at the fibular side in 16 cases, the wound areas averaged [28.27 (23.56, 37.70) cm 2], and the time from injury to treatment was (27.3±4.1) d. Evaluation of the patient's condition, wound diagnosis and formulation of treatment protocols were performed jointly by a doctor-nurse team after the patients were admitted, and continuous diagnosis and treatment of the wounds were carried out mainly by specialist nurses during the doctors' follow-up. In the control group of 33 patients subjected to the conventional wound diagnosis and treatment mode led by doctors, there were 25 males and 8 females with an age of (51.3±14.3) years, the wound was located at the tibial side in 17 cases and at the fibular side in 16 cases, the wound areas averaged [27.49 (17.84, 40.45) cm 2], and the time from injury to treatment was (27.6±4.0) d. The 2 groups were compared in the wound healing rate, wound recurrence rate, hospitalization time and patients' satisfaction. Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). The observation group achieved a significantly higher wound healing rate within 1 month after treatment [83.87% (26/31)] than the control group [60.61% (20/33)], a significantly lower wound recurrence rate within 6 months after treatment [0% (0/31)] than the control group [18.18% (6/33)], significantly shorter hospitalization time [18.0 (15.1, 20.9) d] than the control group [26.8 (18.4, 40.1) d], and significantly higher patients' satisfaction [50 (50, 50) points] than the control group [50 (42, 50) points] (all P<0.05). Conclusion:In the repair of chronic infectious wounds plus bone exposure at lower extremities, the wound diagnosis and treatment mode with integrated medical care led by specialist nurses may result in a higher wound healing rate, a lower wound recurrence rate, a shorter hospital stay and higher patients' satisfaction than the conventional wound diagnosis and treatment mode led by doctors.

Efficacy comparison of different machine learning models to predict adverse inhospital outcome in patients with severe trauma / 中华创伤杂志

Objective:To compare the predictive performance of different machine learning models using pre-hospital data to predict adverse inhospital outcome in patients with severe trauma.Methods:A retrospective cohort study was conducted to analyze the clinical data of 100 135 patients with severe trauma from the National Trauma Data Bank (NTDB) from January 2017 to December 2018. There were 69 644 males and 30 480 females apart from 11 patients with missing gender information, with the range age of 16-89 years [(50.1±21.1)years]. Clinical characteristics included demographic information (sex and age), trauma type (blunt or penetrating trauma), pre-hospital time [emergency medical services (EMS) response time, EMS scene time, and EMS transport time], pre-hospital vital signs (systolic blood pressure, pulse rate, respiratory rate, and oxygen saturation), trauma score [Glasgow coma score (GCS) and injury severity score (ISS)]. The original data were divided into the training set (in the year 2017) and the testing set (in the year 2018) according to the year of admission, including 50 429 patients in the training set and 49 706 patients in the testing set. The patients were classified into non-adverse outcome group ( n=94 526) and adverse outcome group ( n=5 609), according to whether they had an adverse outcome or not. There were 2 808 patients with adverse outcome in the training set and 2 801 patients with adverse outcome in the testing set. All models were built based on the training set. Eight machine learning algorithms consisting of neural network (NNET), naive Bayes (NB), gradient boosting machine (GBM), adaptive boosting (Ada), random forest (RF), bagging tree (BT), categorical boosting (CatBoost) and extreme gradient boosting (XGB) were used to construct prediction models for clinical outcomes among patients with severe trauma based on their clinical features. Models were evaluated according to the sensitivity, specificity, area under the receiver operating characteristic (ROC) curve (AUC) and Hosmer-Lemeshow goodness-of-fit test. Results:Of the NNET, NB, GBM, Ada, RF, BT, CatBoost and XGB models in the testing set, the sensitivity was 0.84, 0.83, 0.27, 0.79, 0.83, 0.81, 0.62 and 0.78, respectively; the specificity was 0.79, 0.76, 0.81, 0.79, 0.79, 0.74, 0.83 and 0.79, respectively; the AUC was 0.89 (95% CI 0.88, 0.90), 0.86 (95% CI 0.85, 0.87), 0.54 (95% CI 0.53, 0.55), 0.86 (95% CI 0.85, 0.87), 0.88 (95% CI 0.88, 0.90), 0.83 (95% CI 0.82, 0.85), 0.77 (95% CI 0.76, 0.79) and 0.86 (95% CI 0.85, 0.87), respectively. The NNET model had the best differentiation. In terms of calibration degree, both NNET and NB showed good performance ( P>0.05 for Hosmer-Lemeshow goodness-of-fit test). Conclusion:The NNET model has a favorable predictive performance for adverse inhospital outcome in patients with severe trauma, which may provide a reference for the rapid prediction of prognosis in patients with severe trauma.

Chinese expert consensus on emergency surgery for severe trauma and infection prevention during corona virus disease 2019 epidemic (version 2023) / 中华创伤杂志

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

Analysis of the change trend of etiological burden of disease of liver cancer in the Chinese population from 1990 to 2019 / 中华消化外科杂志

Objective:To investigate the change trend of etiological burden of disease of liver cancer in the Chinese population from 1990 to 2019.Methods:The descriptive epidemiologic method was conducted. Based on the Global Burden of Disease data from the Institute for Health Metrics and Evaluation at the University of Washington, the data related to liver cancer burden caused by hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, alcohol, nonalcoholic steatohepatitis (NASH) and other factors, including number of new cases, the crude incidence rate, age-specific incidence rate, number of deaths, crude mortality rate and age-specific mortality rate, in the Chinese population from 1990 to 2019 were collected. The age-standardized rate was calculated based on the world standardized population structure in 2019 from the Global Burden of Disease data. Observation indicators: (1) the incidence of liver cancer caused by different etiologies in the Chinese population from 1990 to 2019; (2) the mortality of liver cancer caused by different etiologies in the Chinese population from 1990 to 2019; (3) the change trend of age-specific incidence rate of liver cancer caused by different etiologies in the Chinese population from 1990 to 2019; (4) the age-specific mortality rate of liver cancer caused by different etiologies in the Chinese population from 1990 to 2019. Count data were expressed as absolute numbers, percentages and ratio. Based on the junction point regression model, the Joinpoint software (V.4.9.1.0) was used to calculate the annual percentage change, average annual percentage change (AAPC) and 95% confidence intervals ( CI) of age-specific incidence rate and age-specific mortality rate of liver cancer caused by different etiologies. Results:(1) The incidence of liver cancer caused by different etiologies in the Chinese population from 1990 to 2019. From 1990 to 2019, the number of new cases of liver cancer in Chinese population decreased from 236 825 to 210 462, and the crude incidence rate decreased from 20.01/100,000 to 14.80/100,000. The new cases of liver cancer caused by HBV infection, HCV infection and other factors showed a downward trend, and the absolute change rates were ?14.76%, ?3.98% and ?26.67%, respectively. The new cases of liver cancer caused by alcohol and NASH showed a increase trend, and the absolute change rates were 9.31% and 13.91%, respectively. (2) The mortality of liver cancer caused by different etiologies in the Chinese population from 1990 to 2019. From 1990 to 2019, the number of deaths of liver cancer in Chinese population decreased from 232 449 to 187 700, and the crude mortality rate decreased from 19.64/100,000 to 13.20/100,000. The number of deaths of liver cancer caused by HBV infection, HCV infection and other factors showed a down-ward trend, and the absolute change rates were ?23.34%, ?10.99% and ?33.75%, respectively. The number of deaths of liver cancer caused by alcohol showed a slow downward trend, and the absolute change rate was ?0.51%. The number of deaths of liver cancer caused by NASH showed a increase trend, and the absolute change rate was 6.03%. (3) The change trend of age-specific incidence rate of liver cancer caused by different etiologies in the Chinese population from 1990 to 2019. From 1990 to 2019, the AAPC of age-specific incidence rate of liver cancer caused by HBV infection, HCV infection, alcohol, NASH and other factors was ?3.61%(95% CI as ?4.10% to ?3.11%), ?3.57%(95% CI as ?3.99% to ?3.14%), ?2.79%(95% CI as ?3.24% to ?2.33%), ?2.65%(95% CI as ?3.09% to ?2.21%) and ?3.62%(95% CI as ?4.05% to ?3.19%), respectively. (4) The age-specific mortality rate of liver cancer caused by different etiologies in the Chinese population from 1990 to 2019. From 1990 to 2019, the AAPC of age-specific mortality rate of liver cancer caused by HBV infection, HCV infection, alcohol, NASH and other factors was ?3.92%(95% CI as ?4.42% to ?3.41%), ?3.90%(95% CI as ?4.45% to ?3.35%), ?3.15%(95% CI as ?3.71% to ?2.58%), ?2.86%(95% CI as ?3.34% to ?2.38%) and ?4.09%(95% CI as ?4.64% to ?3.55%), respectively. Conclusions:From 1990 to 2019, the liver cancer burden of the Chinese population shows an overall downward trend, in which the liver cancer burden caused by HBV and HCV infection decreases the most, but HBV and HCV infection is still the main reason for the heavy burden of liver cancer. The age-specific incidence rate and age-specific mortality rate of liver cancer caused by alcohol and NASH show a downward trend, but the number of new cases of liver cancer caused by alcohol and NASH shows significant growth. The liver cancer burden caused by other factors shows a downward trend.

Influence factors of delayed recovery after right ventricular-extrapulmonary arterial conduit reconstruction / 中国小儿急救医学

Objective:To explore the risk factors of early delayed recovery after right ventricular-extrapulmonary arterial(RV-PA)conduit reconstruction.Methods:From 2017 to 2021, the children with RV-PA conduit reconstruction, who were treated in our hospital were retrospectively analyzed.The demographic data and peri-operative clinical data of the patients were collected for statistical analysis.Results:Fifty-five patients were included in the study.The patients were sequenced by the length of ICU stay.The time at the 75th percentile was defined as the critical value for grouping.According to the ICU stay time of the children, they were divided into normal recovery group(ICU stay ≤7 days, n=40)and delayed recovery group(ICU stay>7 days, n=15).The mechanical ventilator time in the whole group was 24(0, 1 408)h, and the ICU stay time was 4(1, 67)d.Six cases required extracorporeal membrane oxygenation (ECMO) support, and two cases died.In the multivariate Logistic regression analysis of two groups, long cardiopulmonary bypass(CPB) time( OR=1.034, 95% CI 1.009-1.061, P=0.009)and poor right ventricular function( OR=9.536, 95% CI 1.010-90.037, P=0.049)were independent risk factors for early delayed recovery. Conclusion:The risk of RV-PA conduit reconstruction is high.The proportion of ECMO support is increased.The mortality rate is higher.Right heart dysfunction and prolonged CPB time are risk factors for delayed postoperative recovery.

Clinical study of cytokine models to predict organ functional impairment after treatment with chimeric antigen receptor T cells in children with B-lineage lymphocytic leukemia / 中国小儿急救医学

Objective:To explore the predictive value of peripheral blood cytokine models on organ functional impairment after chimeric antigen receptor T(CAR-T) cell therapy in children with B-lineage lymphocytic leukemia.Methods:The clinical data of 44 children with acute B-lineage lymphoblastic leukemia who received CAR-T cell therapy at Children′s Hospital of Soochow University from September 2018 to October 2020 were retrospectively analyzed.Peripheral blood cytokines, including interleukin(IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-α, interferon(IFN)-γ and IL-17A, were measured daily for 14 days after receiving CAR-T cell therapy.The trend of peripheral blood cytokine levels was analyzed at the endpoint of organ function recovery or death within 14 days after CAR-T cell treatment.Receiver operating characteristic curve was used to establish a mathematical prediction model to predict the occurrence of organ damage in the children.Results:Of the 44 children, 31 cases were boys and 13 cases were girls, with a median age of 7.96 (5.19, 11.48)years.Cytokine release syndrome(CRS) response occurred in 95.5% (42/44) children, with 88.1% (37/42) had a grade 1-3 CRS response, and 16.7% (7/42) had a severe grade 4-5 CRS response.Using IL-6>3 892.95 pg/mL as cut-off value, the area under the curve(AUC) for predicting acute respiratory failure was 0.818, with a sensitivity of 0.8 and a specificity of 0.735, while combining IFN-γ>414.4 pg/mL, IL-6>3 892.95 pg/mL and IL-2>27.05 pg/mL were the three cut-off values, with an AUC of 0.741, sensitivity of 0.6 and specificity of 0.912 for predicting acute respiratory failure. Using IFN-γ>1 699.5 pg/mL as cut-off value, the AUC for predicting shock was 0.908, with a sensitivity of 0.722 and a specificity of 1.With IL-6>4 607.3 pg/mL as cut-off value, the AUC for predicting liver injury was 0.964, with a sensitivity of 1 and a specificity of 0.906, while combining both IL-6>4 607.3 pg/mL and IFN-γ>1 446.2 pg/mL as cut-off values, the AUC for predicting liver injury was 0.977, with a sensitivity of 1 and a specificity of 0.906.Combining both IL-6>6 972.2 pg/mL and IFN-γ>3 981.5 pg/mL predicted a positive predictive value of 62.5% and a negative predictive value of 94.4% for grade 4-5 CRS response, with an AUC of 0.846, a predictive sensitivity of 0.714 and a specificity of 0.838, and all children had a combination of two or more organ function injuries.Conclusion:The combination of IL-6 and IFN-γ can effectively predict the incidence of liver injury and cytokine release syndrome.The combination of peripheral blood cytokines IFN-γ, IL-6 and IL-2 can be used to predict the incidence of acute respiratory failure after the treatment of CAR-T cells in children with acute B-lineage lymphoblastic leukaemia.IFN-γ single index can be used to predict the incidence of shock.The combination of IL-6 and IFN-γ can be used to predict the incidence of liver injury and the severity of CRS.

Reflections on development status of Traditional Chinese Medicine in Central Asian countries / 国际中医中药杂志

Central Asia is an important hub connecting the Asian continent and European continent, and one of the key regions for China's foreign exchange and cooperation in Traditional Chinese Medicine (TCM). Central Asian countries have relatively backward medical conditions, and TCM has become an important part of local healthcare. Regulations on traditional/complementary and alternative medicine have been issued in Kyrgyzstan, Kazakhstan and Tajikistan; acupuncture and moxibustion has been covered by medical insurance in Kyrgyzstan; TCM has existed in other Central Asian countries in form of folk medicine. Central Asian countries are extremely rich in medicinal plant resources, but weak in foundation of pharmaceutical industry. Chinese government has signed cooperation agreements on TCM with many Central Asian countries, and the practical cooperation in the field of traditional medicine have continued to expand. At present, the development of TCM in Central Asian countries still faces problems such as weak foundation for the development and utilization of medicinal materials, shortage of professionals talents in TCM education and small scale of TCM clinics. In view of the above, in order to promote the dissemination and development of TCM in Central Asian countries, it is recommended that relevant units promote the establishment of joint laboratories or research centers of Chinese materia medica; give full play to local resource advantages and promote the development of medicinal plant industry; to strengthen the construction of overseas centers of TCM; actively carry out joint education or further education projects, and cultivate localized senior talents.

Progress of ketogenic diet on treatment of infantile spasms / 国际儿科学杂志

Infantile spasms(IS)is an age-dependent severe epilepsy syndrome, mainly treated with hormones and anti-seizure medications.However, due to poor efficacy and even serious side effects among some pediatric patients, searching for better alternative treatment options has become a research hotspot.In recent years, as a special diet treatment, ketogenic diet(KD)has been widely studied and gradually applied to the clinical treatment of IS, which has achieved satisfactory results.This article briefly reviews the KD regimen and mechanism of action, and focuses on the research progress in efficacy, safety and short-term prognosis of KD in the treatment of IS, whose purpose is to provide effective reference for clinical application.

Rapid prediction of G protein-coupled receptor structures using nanoluciferase assay / 药学学报

Using beta-2 adrenergic receptor, 5-hydroxytryptamine and angiotensin II type 1 receptor as control, we here established a method for rapid prediction of the initial position amino acids of N-terminal, C-terminal, intracellular loops, extracellular loops and transmembrane (TM) regions in G protein-coupled receptors (GPCRs), and successfully predicted the structure of Mas-related G protein-coupled receptors X3 (MRGPRX3). To achieve this purpose, nanoluciferase (Nluc) was inserted into the different sites of these GPCRs′ sequence by sequence and ligation-independent cloning (SLIC) method, and the luminescence value were measured to distinguish the different parts of GPCRs. The results showed that luminescence values of NLuc luciferase at TM region were less than 100 000, and the values were higher than 1 000 000 at N terminal, C terminal, or extracellular loops and intracellular loops, and the values were between 100 000 and 500 000 at junction. The predicted MRGPRX3 structure was analyzed in detail and was compared with AlphaFold predicted structure. In conclusion, this method could provide useful information of GPCR structure model for the ligand virtual screening, and could provide certain experimental basis for structural pharmacology.

Correlation between axial lengths and anterior segment parameters evaluated by swept-source optical coherence tomography / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To evaluate the correlation between axial lengths and anterior segment parameters using swept-source optical coherence tomography(SS-OCT).METHODS:For the cross-sectional clinical study, a total of 109 adult volunteers with different degrees of myopia recruited from January 1, 2022, to March 31, 2022, at the ophthalmology clinic of the First Affiliated Hospital of Zhengzhou University were included. Participants were divided into 4 groups based on axial length(AL): group A(AL≤24.0mm), group B(24.0mm&#x003C;AL≤25.0mm), group C(25.0mm&#x003C;AL≤26.0mm)and group D(AL&#x003E;26.0mm). Anterior segment examinations were performed using SS-OCT, including: central corneal thickness(CCT), lens thickness(LT), anterior chamber depth(ACD), anterior chamber width(ACW), angle opening distance(AOD500), angle recess area(ARA500), trabecular iris space area(TISA500), trabecular iris angle(TIA500), crystalline lens rise(CLR). The relationships between these data and AL, spherical equivalent(SE)were analyzed.RESULTS:There was no difference in the comparison of CCT among the four groups(P&#x003E;0.05). There were differences in SE, LT, ACD, ACW, AOD500, ARA500, TISA500, TIA500 and CLR among the four groups(all P&#x003C;0.01). SE and LT were negatively correlated with AL(r=-0.75, -0.41, all P&#x003C;0.01); ACD, ACW and CLR were positively correlated with AL(r=0.58, 0.45, 0.54, all P&#x003C;0.01); AOD500, ARA500, TISA500 and TIA500(temporal and nasal side)were positively correlated with AL(all P&#x003C;0.01). ACD and CLR were negatively correlated with SE(r=-0.21,-0.25, all P&#x003C;0.01), and LT was positively correlated with SE(r=0.21, P&#x003C;0.05).CONCLUSION:As AL increases, CCT remains unchanged while the ACD and ACW increase. The position of the crystalline lens moves backward and LT decreases.

Progress of schistosomiasis control in People’s Republic of China in 2022 / 中国血吸虫病防治杂志

This report presented the endemic status of schistosomiasis and analyzed the data collected from the national schistosomiasis prevention and control system and national schistosomiasis surveillance program in the People’s Republic of China in 2022. Among the 12 provinces (municipality and autonomous region) endemic for schistosomiasis, Shanghai Municipality, Zhejiang Province, Fujian Province, Guangdong Province and Guangxi Zhuang Autonomous Region continued to maintain the achievements of schistosomiasis elimination, and Sichuan and Jiangsu provinces maintained the criteria of transmission interruption, while Yunnan, Hubei, Anhui, Jiangxi and Hunan provinces maintained the criteria of transmission control by the end of 2022. A total of 452 counties (cites, districts) were found to be endemic for schistosomiasis in China in 2022, with 27 434 endemic villages covering 73 424 400 people at risk of infections. Among the 452 endemic counties (cities, districts), 75.89% (343/452), 23.45% (106/452) and 0.66% (3/452) achieved the criteria of elimination, transmission interruption and transmission control of schistosomiasis, respectively. In 2022, 4 317 356 individuals received serological tests for schistosomiasis, and 62 228 were sero-positive. A total of 208 646 individuals received stool examinations for schistosomiasis, with one positive and another two cases positive for urine microscopy, and these three 3 cases were imported schistosomiasis patients from Africa. There were 28 565 cases with advanced schistosomiasis documented in China by the end of 2022. Oncomelania hupensis snail survey was performed in 18 891 endemic villages in China in 2022 and O. hupensis snails were found in 6 917 villages (36.62% of all surveyed villages), with 8 villages identified with emerging snail habitats. Snail survey was performed at an area of 655 703.01 hm2 and 183 888.60 hm2 snail habitats were found, including 110.58 hm2 emerging snail habitats and 844.35 hm2 re-emerging snail habitats. There were 477 200 bovines raised in the schistosomiasis endemic areas of China in 2022, and 113 946 bovines received serological examinations for schistosomiasis, with 204 sero-positives detected. Among the 131 715 bovines received stool examinations, no positives were identified. In 2022, there were 19 726 schistosomiasis patients receiving praziquantel chemotherapy, and expanded chemotherapy was performed in 714 465 person-time for humans and 234 737 herd-time for bovines in China. In 2022, snail control with chemical treatment was performed at an area of 119 134.07 hm2, and the actual area of chemical treatment was 65 825.27 hm2, while environmental improvements were performed at an area of 1 163.96 hm2. Data from the national schistosomiasis surveillance program of China showed that the mean prevalence of Schistosoma japonicum infections was both zero in humans and bovines in 2022, and no S. japonicum infection was detected in O. hupensis snails. These data demonstrated that the endemic status of schistosomiasis continued to decline in China in 2022, with 3 confirmed schistosomiasis patients that had a foreign nationality and all imported from Africa, and the areas of snail habitats remained high. Further improvements in the construction of the schistosomaisis surveillance and forecast system, and reinforcement of O. hupensis survey and control are required to prevent the re-emerging schistosomiasis.

Single-center experience with vascularized adrenal displacement for the treatment of primary bilateral macronodular adrenal hyperplasia / 现代泌尿外科杂志

【Objective】 To explore a new treatment of primary bilateral macronodular adrenal hyperplasia (PBMAH) and its efficacy. 【Methods】 Clinical data of 20 PBMAH patients treated in our hospital during Mar.2010 and Apr.2021 were retrospectively analyzed. All patients underwent laparoscopic subcutaneous displacement of vascularized adrenal. The clinical symptoms, plasma free cortisol, adrenocorticotrophic hormone (ACTH), and 24 h urinary free cortisol were regularly monitored after surgery. 【Results】 Of all 20 patients, 19 were followed up for 18 to 120 months (median 60 months). Three months after surgery, reexamination showed 1 patient had decreased plasma free cortisol and increased ACTH, but had no symptoms of low corticosteroids. After another 3 months, the plasma free cortisol and ACTH returned to normal. After 4 to 48 months, the parameters recovered in all patients and the clinical symptoms disappeared. 【Conclusion】 Laparoscopic vascularized adrenal displacement is a new and effective method for the treatment of PBMAH. It can alleviate the Cushing syndrome with no obvious adverse reactions.

Application of "Internet +" hospital-community-family trinity linkage management model in maternal perinatal depression / 四川精神卫生

BackgroundPerinatal depression seriously affects the physical and mental health of pregnant women， such as affecting their role transition， identity， and family relationships， etc. In severe case， it can even lead to suicidal behavior， causing a heavy burden on pregnant women and their families. A hierarchical management model centered on pregnant women， involving collaboration of families， communities， and hospitals， facilitates comprehensive and dynamic management of perinatal depression. ObjectiveTo evaluate the application effect of "Internet +" hospital-community-family trinity linkage management model on perinatal depression in pregnant women， in order to provide a reference for the clinical intervention. Methods80 pregnant women who established medical records from the Department of Obstetrics and Gynecology of Mianyang Third People's Hospital from January to December 2022， with Edinburgh Postnatal Depression Scale （EPDS） score>9， were selected as the research objects. According to the random number table method， they were divided into a study group and a control group， each group consisting of 40 cases. Both groups received routine nursing intervention in the pregnant women's school of obstetrics and gynecology outpatient department before delivery， and in the study room of the department of obstetrics and gynecology after being admitted to the hospital for delivery. After discharge， they received routine follow-up until 42 days postpartum. The study group received the "Internet +" hospital-community-family ternary linkage management on the basis. EPDS， Pittsburgh Sleep Quality Index （PSQI）， Generic Quality of Life Inventory （GQOLI-74） and Nursing Satisfaction questionnaire were assessed before intervention and 42 days postpartum. ResultsAfter intervention， the EPDS score and PSQI score of the study group were lower than those of the control group （F=42.823， 60.453， P<0.05）， GQOLI-74 score and nursing satisfaction were higher than those of the control group （F=198.902， χ2=5.165， P<0.05） . Conclusion"Internet +" hospital-community-family trinity linkage management model may help to improve the severity of perinatal depression symptoms， improve the quality of sleep and life， and increase the satisfaction of pregnant women.［Funded by Mianyang Health Scientific Research Commission Project （number， 202134）］