Melatonin inhibits arrhythmias induced by increased late sodium currents in ventricular myocytes / 药学学报

Melatonin (Mel) has been shown to have cardioprotective effects, but its action on ion channels is unclear. In this experiment, we investigated the inhibitory effect of Mel on late sodium currents (INa.L) in mouse ventricular myocytes and the anti-arrhythmic effect at the organ level as well as its mechanism. The whole-cell patch clamp technique was applied to record the ionic currents and action potential (AP) in mouse ventricular myocytes while the electrocardiogram (ECG) and monophasic action potential (MAP) were recorded simultaneously in mouse hearts using a multichannel acquisition and analysis system. The results demonstrated that the half maximal inhibitory concentration (IC50) values of Mel on transient sodium current (INa.T) and specific INa.L opener 2 nmol·L-1 sea anemone toxins II (ATX II) increased INa.L were 686.615 and 7.37 μmol·L-1, respectively. Mel did not affect L-type calcium current (ICa.L), transient outward current (Ito), and AP. In addition, 16 μmol·L-1 Mel shortened ATX II-prolonged action potential duration (APD), suppressed ATX II-induced early afterdepolarizations (EADs), and significantly reduced the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) in Langendorff-perfused mouse hearts. In conclusion, Mel exerted its antiarrhythmic effects principally by blocking INa.L, thus providing a significant theoretical basis for new clinical applications of Mel. Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of Wuhan University of Science and Technology (2023130).

Development and prospects of predicting drug polymorphs technology / 药学学报

Most chemical medicines have polymorphs. The difference of medicine polymorphs in physicochemical properties directly affects the stability, efficacy, and safety of solid medicine products. Polymorphs is incomparably important to pharmaceutical chemistry, manufacturing, and control. Meantime polymorphs is a key factor for the quality of high-end drug and formulations. Polymorph prediction technology can effectively guide screening of trial experiments, and reduce the risk of missing stable crystal form in the traditional experiment. Polymorph prediction technology was firstly based on theoretical calculations such as quantum mechanics and computational chemistry, and then was developed by the key technology of machine learning using the artificial intelligence. Nowadays, the popular trend is to combine the advantages of theoretical calculation and machine learning to jointly predict crystal structure. Recently, predicting medicine polymorphs has still been a challenging problem. It is expected to learn from and integrate existing technologies to predict medicine polymorphs more accurately and efficiently.

Recent advances in small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase / 药学学报

Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.

Recent advances in drug screening methods of SARS-CoV-2 spike protein / 药学学报

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a serious impact on global public health and the economy. SARS-CoV-2 infiltrates host cells via its surface spike protein, which binds to angiotensin-converting enzyme 2 on the host cell membrane. As a result, small molecules targeting spike protein have emerged as a hotspot in anti-SARS-CoV-2 drug research. Activity screening is an important step in seeking small molecule drugs. Therefore, this article aims to review the biological activity evaluation methods of small molecule inhibitors targeting SARS-CoV-2 spike protein, with the goal of laying the foundation for the discovery of new anti-SARS-CoV-2 drugs.

Calcitonin gene-related peptide inhibits neuronal apoptosis in heatstroke rats via PKA/p-CREB pathway / 中华创伤杂志(英文版)

PURPOSE@#The incidence of heatstroke (HS) is not particularly high; however, once it occurs, the consequences are serious. It is reported that calcitonin gene-related peptide (CGRP) is protective against brain injury in HS rats, but detailed molecular mechanisms need to be further investigated. In this study, we further explored whether CGRP inhibited neuronal apoptosis in HS rats via protein kinase A (PKA)/p-cAMP response element-binding protein (p-CREB) pathway.@*METHODS@#We established a HS rat model in a pre-warmed artificial climate chamber with a temperature of (35.5 ± 0.5) °C and a relative humidity of 60% ± 5%. Heatstress was stopped once core body temperature reaches above 41 °C. A total of 25 rats were randomly divided into 5 groups with 5 animals each: control group, HS group, HS+CGRP group, HS+CGRP antagonist (CGRP8-37) group, and HS+CGRP+PKA/p-CREB pathway blocker (H89) group. A bolus injection of CGRP was administered to each rat in HS+CGRP group, CGRP8-37 (antagonist of CGRP) in HS+CGRP8-37 group, and CGRP with H89 in HS+CGRP+H89 group. Electroencephalograms were recorded and the serum concentration of S100B, neuron-specific enolase (NSE), neuron apoptosis, activated caspase-3 and CGRP expression, as well as pathological morphology of brain tissue were detected at 2 h, 6 h, and 24 h after HS in vivo. The expression of PKA, p-CREB, and Bcl-2 in rat neurons were also detected at 2 h after HS in vitro. Exogenous CGRP, CGRP8-37, or H89 were used to determine whether CGRP plays a protective role in brain injury via PKA/p-CREB pathway. The unpaired t-test was used between the 2 samples, and the mean ± SD was used for multiple samples. Double-tailed p < 0.05 was considered statistically significant.@*RESULTS@#Electroencephalogram showed significant alteration of θ (54.50 ± 11.51 vs. 31.30 ± 8.71, F = 6.790, p = 0.005) and α wave (16.60 ± 3.21 vs. 35.40 ± 11.28, F = 4.549, p = 0.020) in HS group compared to the control group 2 h after HS. The results of triphosphate gap terminal labeling (TUNEL) showed that the neuronal apoptosis of HS rats was increased in the cortex (9.67 ± 3.16 vs. 1.80 ± 1.10, F = 11.002, p = 0.001) and hippocampus (15.73 ± 8.92 vs. 2.00 ± 1.00, F = 4.089, p = 0.028), the expression of activated caspase-3 was increased in the cortex (61.76 ± 25.13 vs. 19.57 ± 17.88, F = 5.695, p = 0.009) and hippocampus (58.60 ± 23.30 vs. 17.80 ± 17.62, F = 4.628, p = 0.019); meanwhile the expression of serum NSE (5.77 ± 1.78 vs. 2.35 ± 0.56, F = 5.174, p = 0.013) and S100B (2.86 ± 0.69 vs. 1.35 ± 0.34, F = 10.982, p = 0.001) were increased significantly under HS. Exogenous CGRP decreased the concentrations of NSE and S100B, and activated the expression of caspase-3 (0.41 ± 0.09 vs. 0.23 ± 0.04, F = 32.387, p < 0.001) under HS; while CGRP8-37 increased NSE (3.99 ± 0.47 vs. 2.40 ± 0.50, F = 11.991, p = 0.000) and S100B (2.19 ± 0.43 vs. 1.42 ± 0.30, F = 4.078, p = 0.025), and activated the expression caspase-3 (0.79 ± 0.10 vs. 0.23 ± 0.04, F = 32.387, p < 0.001). For the cell experiment, CGRP increased Bcl-2 (2.01 ± 0.73 vs. 2.15 ± 0.74, F = 8.993, p < 0.001), PKA (0.88 ± 0.08 vs. 0.37 ± 0.14, F = 20.370, p < 0.001), and p-CREB (0.87 ± 0.13 vs. 0.29 ± 0.10, F = 16.759, p < 0.001) levels; while H89, a blocker of the PKA/p-CREB pathway reversed the expression.@*CONCLUSIONS@#CGRP can protect against HS-induced neuron apoptosis via PKA/p-CREB pathway and reduce activation of caspase-3 by regulating Bcl-2. Thus CGRP may be a new target for the treatment of brain injury in HS.

Research progress on brain functional near-infrared spectroscopy technology in the field of neonates / 中国当代儿科杂志

Functional near infrared spectroscopy (fNIRS) is an emerging neuroimaging tool that reflects the activity and function of brain neurons by monitoring changes in brain oxygen metabolism based on the neurovascular coupling mechanism. It is non-invasive and convenient, especially suitable for monitoring neonatal brain function. This article provides a comprehensive review of research related to the developmental patterns of brain networks concerning language, music, and emotions in neonates using fNIRS. It also covers brain network imaging in neonatal care, resting-state brain network connectivity patterns, and characteristics of brain functional imaging in disease states of neonates using fNIRS.

High-value utilization technology and approach of Chinese medicinal residues under background of "Dual Carbon" / 中国中药杂志

In recent years, the traditional Chinese medicine(TCM)industry has experienced rapid development, resulting in a significant amount of Chinese medicinal residues generated during the industrial manufacturing process. Currently, the main methods of handling Chinese medicinal residues include stacking, landfilling, and incineration, which lead to substantial resource waste and potential environmental pollution. With "carbon peak" and "carbon neutrality"( "Dual Carbon")becoming national strategic goals, the TCM industry is ushering in a new wave of "low-carbon" trends, and the high-value utilization of Chinese medicinal residues has become a breakthrough for implementing a low-carbon economy in the TCM sector. From the perspective of a low-carbon economy, this article reviewed literature in China and abroad to summarize the microbial transformation technology, enzymatic conversion technology, biomass pyrolysis, gasification, hydrothermal liquefaction, and other high-value utilization technologies for Chinese medicinal residues. It also overviewed the applications of Chinese medicinal residue in feed additives, organic fertilizers, edible mushroom cultivation substrates, preparation of activated carbon for wastewater treatment, and new energy batteries. Considering the current status of resource utilization of Chinese medicinal residues, feasible strategies and suggestions for resource development and utilization were proposed to improve the quality and efficiency of the Chinese medicinal resource industry chain and promote green development, thereby providing research ideas and theoretical basis for achieving carbon peak and carbon neutrality goals.

Current status, trends, and challenges of continuous manufacturing technology for oral traditional Chinese medicine solid preparations / 中国中药杂志

In recent years, continuous manufacturing technology has attracted considerable attention in the pharmaceutical industry. This technology is highly sought after for its significant advantages in cost reduction, increased efficiency, and improved productivity, making it a growing trend in the future of the pharmaceutical industry. Compared to traditional batch production methods, continuous manufacturing technology features real-time control and environmentally friendly intelligence, enabling pharmaceutical companies to produce drugs more efficiently. However, the adoption of continuous manufacturing technology has been slow in the field of traditional Chinese medicine(TCM) pharmaceuticals. On the one hand, there is insufficient research on continuous manufacturing equipment and technology that align with the characteristics of TCM preparations. On the other hand, the scarcity of talent with diverse expertise hampers its development. Therefore, in order to promote the modernization and upgrading of the TCM pharmaceutical industry, this article combined the current development status of the TCM industry to outline the development status and regulatory requirements of continuous manufacturing technology. At the same time, it analyzed the problems with existing TCM manufacturing models and explored the prospects and challenges of applying continuous manufacturing technology in the field of TCM pharmaceuticals. The analysis focused on continuous manufacturing control strategies, technical tools, and pharmaceutical equipment, aiming to provide targeted recommendations to drive the development of the TCM pharmaceutical industry.

Application of artificial intelligence based on neural network radiation field in repair of soft tissue defects at lower limbs / 中华创伤骨科杂志

Objective:To investigate the application of artificial intelligence based on the neural network radiation field in repair of soft tissue defects at lower limbs.Methods:A retrospective analysis was performed of the 23 patients who had been admitted to Department of Orthopedic Surgery, Renmin Hospital of Wuhan University from June 2020 to May 2022 for soft tissue defects at lower limbs. There were 14 males and 9 females, aged (38.6±6.7) years. Causes for soft tissue defects: traffic injury in 9 cases, benign or malignant primary soft tissue tumor in 6 cases, mechanical injury in 4 cases, crush injury in 2 cases, and chronic ulcer in 2 cases. Defect locations: the thigh in 3 cases, the lower leg in 7 cases, and the ankle and distal foot in 13 cases. The areas of soft tissue defect ranged from 6.0 cm×3.8 cm to 14.7 cm×12.8 cm. The defects were repaired and reconstructed by transplantation of an anterolateral femoral free flap in 7 cases and a pedicled flap in 16 cases with the assistance of artificial intelligence based on the neural network radiation field, a cutting-edge artificial intelligence algorithm that can quickly construct and process three-dimensional model images through volume rendering under the radiation field. The flap survival rate, aesthetic satisfaction before and after treatment, time for skin flap harvesting and transplantation, functional recovery of lower limbs and incidence of complications were recorded.Results:All the 23 patients were followed up for 32(28, 36) weeks. All the flaps were harvested smoothly and survived. The time for flap harvesting and transplantation was 65.8(50.0, 76.0) min. The aesthetic satisfaction scored (2.3±0.7) points before treatment and (8.4±1.6) points 4 weeks after treatment, showing a statistically significant difference ( P<0.05). The skin flaps healed well with no complications such as hematoma or infection in all but one patient who suffered from superficial necrosis at the distal skin flap due to venous crisis but healed with a scar. On average, the functional recovery of lower limbs scored 23.7(22.0, 25.0) points at 12 weeks after operation according to the Enneking evaluation system, and the functional recovery of lower limbs was 79% (23.7/30.0). Conclusion:Application of artificial intelligence based on the neural network radiation field can achieve ideal results in repair of soft tissue defects at lower limbs, due to its advantages of rapid and accurate surgical procedures, limited damage to the donor site, and a short learning curve.

Arthroscopic minimally invasive reduction for talus posterior process fractures / 中华创伤骨科杂志

Objective:To evaluate the efficacy of arthroscopic minimally invasive reduction in the treatment of talus posterior process fractures.Methods:The clinical data were retrospectively studied of the 42 patients with talus posterior process fracture who had been admitted to Department of Orthopedics, The Fourth Hospital of Wuhan from January 2010 to June 2021. There were 25 males and 17 females, aged from 21 to 60 years (average, 40.5 years). They were assigned into 2 groups according to their different treatments. In the arthroscopic group of 15 cases, arthroscopic reduction and internal fixation (ARIF) were conducted via the posteromedial and posterolateral approaches; in the open reduction group of 27 cases, open reduction and internal fixation (ORIF) were conducted via the posteromedial para-Achilles approach. The 2 groups were compared in terms of operation time, blood loss, hospital stay, fracture clinical healing time, postoperative complications, and the American Society for Foot and Ankle Surgery (AOFAS) ankle-hindfoot score at one year postoperation.Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P> 0.05). The arthroscopic group incurred significantly less blood loss [(32.0±11.5) mL], hospital stay [(5.3±1.8) d], and fracture clinical healing time [(4.6±1.0) months], and a significantly lower incidence of postoperative complications [20.0% (3/15)] than the open reduction group did [(80.0±15.2) mL, (8.4±2.4) d, (6.3±2.2) months, and 29.6% (8/27)], but significantly longer operation time [(74.0±8.9) min] than the open reduction group [(62.9±5.1) min] ( P<0.05). The AOFAS ankle-hindfoot scores at one year postoperation in both groups were higher than those before operation. The AOFAS ankle-hindfoot scores in the arthroscopic group [(83.0±13.0) points] were significantly higher than those in the open reduction group [(72.3±16.0) points] ( P<0.05). Conclusion:ARIF is a preferred minimally invasive treatment for talus posterior process fractures, because it leads to a smaller incision, less blood loss, shorter hospital stay, quicker clinical healing, a lower incidence of postoperative complications, and better functional improvement of the ankle and hindfoot than ORIF.

Facilitation of behavioral and cortical emergence from isoflurane anesthesia by GABAergic neurons in basal forebrain / 中国药理学与毒理学杂志

OBJECTIVE To reveal the role of the basal forebrain(BF)GABAergic neurons in the regulation of isoflurane anesthesia and to elucidate the underlying neural pathways.METHODS The activity of BF GABAer-gic neurons was monitored during isoflurane anesthesia using a genetically encoded calcium indicator in Vgat-Cre mice of both sexes.The activity of BF GABAer-gic neurons was manipulated by chemogenetic and opto-genetic approaches.Sensitivity,induction time and emer-gence time of isoflurane anesthesia were estimated by righting reflex.The electroencephalogram(EEG)power and burst-suppression were monitored by EEG recording.The effects of activation of GABAergic BF-thalamic reticu-lar nucleus(TRN)pathway on isoflurane anesthesia were investigated with optogenetics.RESULTS The activity of BF GABAergic neurons was generally inhibited during isoflurane anesthesia,obviously decreased during the induction of anesthesia and gradually restored during the emergence from anesthesia.Activation of BF GABAergic neurons with chemogenetics and optogenetics promoted behavioral emergence from isoflurane anesthesia,with decreased sensitivity to isoflurane,delayed induction and accelerated emergence from isoflurane anesthesia.Optogenetic activation of BF GABAergic neurons prom-oted cortical activity during isoflurane anesthesia,with decreased EEG delta power and burst suppression ratio during 0.8%and 1.4%isoflurane anesthesia,respectively.Similar to the effects of activating BF GABAergic cell bod-ies,photostimulation of BF GABAergic terminals in the TRN also strongly promoted cortical activation and behav-ioral emergence from isoflurane anesthesia.CONCLU-SION The GABAergic neurons in the BF is a key neural substrate for general anesthesia regulation that facilitates behavioral and cortical emergence from general anesthe-sia via the BF-TRN pathway.

Disposable disinfection cap for preventing catheter-related blood stream infections: a Meta-analysis / 中国实用护理杂志

Objective:To evaluate the efficacy of disposable disinfection cap in preventing catheter-related blood stream infections (CRBSIs).Methods:Literature on the prevention of CRBSIs by disposable disinfection caps were retrieved from CNKI, Wanfang Database, VIP database, Chinese Biomedical Literature Database, PubMed, Cochrane Library, Embase and Web of Science databases. The retrieval period was from the database construction to June 30, 2022. After literature screening, data extraction and quality evaluation were independently carried out by 2 researchers, RevMan5.4 software was used for analysis.Results:A total of 12 articles were included, including 9 832 patients. Meta-analysis results showed that compared with conventional manual disinfection, disposable disinfection cap could reduce the incidence of CRBSIs, and the difference was statistically significant ( RR = 0.58, 95% CI 0.43-0.79, P<0.01). Disposable disinfection cap could reduce the incidence of CRBSIs in adults, but there was no significant difference in the incidence of CRBSIs in children ( P>0.05). It could reduce the incidence of CRBSIs in patients with indwelling vascular catheters in ICU ( RR = 0.58, 95% CI 0.38-0.89, P<0.05), but there was no statistical difference in the incidence of CRBSIs in patients without indwelling vascular catheters in ICU ( P>0.05). In addition, the compliance of the use of disinfection caps by nursing staff was improved by 80% - 90% and the treatment cost was saved by about 282 - 464 dollars. Conclusions:Disposable disinfection caps can reduce the occurrence of CRBSIs, improve the disinfection compliance of nursing staff, and save the hospitalization cost of patients. It is suggested to be popularized in clinical practice.

Current status and influencing factors of anticipatory grief among family caregivers of first stroke patients / 中国实用护理杂志

Objective:To investigate the current situation of expected sadness of family caregivers of first stroke patients and analyze its influencing factors, so as to provide reference for the formulation of psychological decompression intervention program for family caregivers of stroke patients.Methods:Convenience sampling method was used to conduct cross-sectional survey of 212 family caregivers of first stroke patients who were hospitalized in the First Affiliated Hospital of Shandong First Medical University from March 2020 to May 2021, using general information questionnaires and Anticipatory Grief Scale and Connor-Davidson Resilience Scale to investigate and anlalyzed its influencing factors.Results:The scare of anticipatory grief of the caregivers of first stroke patients was 87.93 ± 17.36. The results of multiple stepwise regression analysis showed that the age of family caregivers, psychological elasticity, the degree of relationship with patients, patients′ cognitive ability and self-care ability were the influencing factors of anticipatory grief of family caregivers of first stroke patients ( t values were -6.73 -11.77, P <0.05). Conclusions:The caregivers of first stroke patients have serious anticipatory grief. Staff should pay attention to the psychological conditions of the family caregivers and take effective measures to promote their physical and mental health.

Analysis of Predictive Factors for Efficacy of Yiqi Yangxue Prescription Combined with Western Medicine in Treatment of Aplastic Anemia in Non-elderly Adults / 中国实验方剂学杂志

ObjectiveTo explore the predictive factors for the efficacy of Yiqi Yangxue prescription combined with western medicine in treating aplastic anemia （AA） in non-elderly adults， so as to provide a reference for predicting the prognosis of this therapy. MethodA retrospective study was conducted with the clinical data of non-elderly adult AA patients who visited 19 hospitals including Xiyuan Hospital of the China Academy of Chinese Medical Sciences from September 2018 to March 2021 and were treated with Yiqi Yangxue Prescription combined with western medicine. According to the efficacy evaluation results at the 6th month of treatment， the patients were assigned into effective and ineffective groups. The two groups were compared in terms of the gender， age， disease classification ［non-severe aplastic anemia （NSAA）/severe aplastic anemia （SAA）］， course of disease， family history， complications， history of drug allergy， baseline blood routine examination ［hemoglobin （HGB）， white blood cell （WBC）， neutrophil （ANC）， platelet （PLT）， and reticulocyte （Ret）］， T lymphocyte subsets， degree of proliferation of nucleated cells in bone marrow， and expression of T-bet and GATA-3. ResultA total of 101 non-elderly adult AA patients were enrolled in this study， including 81 in the effective group and 20 in the ineffective group. The effective group had a higher proportion of the patients without a history of drug allergy than the ineffective group （P<0.05）. The body height， body weight， gender， age， disease classification， course of disease， family history， and complications showed no significant differences between two groups. The effective group had higher levels of ANC and PLT before treatment （P<0.05） and higher proportion of patients with ANC≥1.6×109/L and PLT≥25×109/L （P<0.05， P<0.01） than the ineffective group. The baseline levels of WBC， HGB， and Ret showed no significant statistical differences between two groups. The levels of CD3+HLA-DR+T cells in the effective group before treatment was higher than that in the ineffective group （P<0.05）. The levels of CD3+CD19-T cells， CD4+T cells， CD8+T cells， Th1 cells， Th2 cells， and CD3+CD25+T cells showed no significant statistical differences between two groups before treatment. The proportion of patients with active bone marrow nucleated cells proliferation in the effective group before treatment were significantly higher than that in the ineffective group, while the proportion of patients with reduced or extremely reduced proliferation were significantly lower than that in the ineffective group （P<0.05）. The expression levels of T-bet and GATA-3 genes had no significant differences between two groups before treatment. The multivariate binary logistic regression analysis showed that the ANC level before treatment and history of drug allergy were independent influencing factors for efficacy （P<0.05， P<0.01）， while other indicators were not influencing factors for efficacy. The receiver operating characteristic （ROC） curve was applied to analyze the predictive value of the ANC level before treatment in the treatment of AA in non-elderly adults with Yiqi Yangxue prescription combined with western medicine. The area under the curve was 0.679 （P<0.05）， with the critical value of 1.595×109/L， the sensitivity of 0.42， and the specificity of 0.95. ConclusionThe history of drug allergy， pre-treatment ANC， PLT， CD3+HLA-DR+ T cell levels， and proliferation of nucleated cells in bone marrow before treatment are predictive factors for the efficacy of Yiqi Yangxue prescription combined with western medicine in treating AA in non-elderly adults. This therapy tends to be more effective for the patients with no history of drug allergy， higher ANC and PLT levels before treatment， especially those with ANC≥1.6×109/L， PLT≥25×109/L， and higher CD3+ HLA-DR+T cell levels and the more active proliferation of nucleated cells in bone marrow before treatment.

Impact of body mass index on perioperative efficacy and complications of robot-assisted radical cystectomy with intracorporeal urinary diversion / 中华泌尿外科杂志

Objective:To determine the impact of body mass index (BMI) on perioperative and oncological outcomes after robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion.Methods:Clinical data of bladder cancer patients undergoing robot-assisted radical cystectomy with intracorporeal urinary diversion in Zhejiang Provincial People's Hospital from January 2017 to January 2020 were retrospectively analyzed. Patients were divided into three groups according to BMI, including 61 cases in normal group (<25.0 kg/m2), 52 cases in overweight group (25.0-29.9 kg/m2) and 33 cases in obese group (≥30.0 kg/m2). In the normal group, the median age was 73.6(59, 79), including 45 male(73.8%), with 51 cases(83.6%) of ASA score 0-2, 10 cases (16.4%)of 3 or higher, and 10 cases (16.4%) undergoing neoadjuvant chemotherapy. Past medical history included smoking in 34 cases (55.7%), hypertension in 19 cases (31.1%), diabetes in 10 cases (16.4%), heart disease in 12 cases (19.7%), and abdominal surgery in 6 cases (9.8%). In the overweight group, the median age was 69.7(60, 78), including 38 male (73.1%), with 25 cases (48.1%)of ASA score 0-2, 27 cases (51.9%) of 3 or higher, and 9 cases (17.3%) undergoing received neoadjuvant chemotherapy. Past medical history included smoking in 30 cases (57.7%), hypertension in 20 cases (38.5%), diabetes in 10 cases (19.2%), heart disease in 9 cases (17.3%), and abdominal surgery in 5 cases (9.6%). In the obses group, the median age was 69.9(61, 78), including 21 male(63.7%), with 20 cases (60.6%)of ASA score 0-2, 13 cases(39.4%) of 3 or higher, 9 cases (27.3%) undergoing neoadjuvant chemotherapy. Past medical history included smoking in 18 cases (54.5%), hypertension in 17 cases (51.5%), diabetes in 19 cases (57.6%), heart disease in 7 cases (21.2%), and abdominal surgery in 4 cases (12.1%). After statistical comparison among the three groups, it was found that the proportion of patients with hypertension and diabetes in the obesity group and overweight group was higher than that in the normal group (all P<0.05), but there was no significant difference in other factors (all P>0.05). During the surgical process, robot-assisted radical cystectomy and bilateral pelvic lymph node dissection were performed firstly. The scope of lymph node dissection was divided into standard range and expanded range, and the diversion was divided into orthotopic neobladder and ileal bladder. During the orthotopic neobladder process, 40-50 cm ileum at the distance of 15 cm away from ileocecum was obtained by stapler, and then the U-shaped neobladder was made, and the new bladder was anastomosed with urethra and bilateral ureter. For ileal bladder, the ileum was cut off 15cm away from the ileocecum with stapler to obtain the 15 cm ileum to prepare the ileal conduit and restore the continuity of the ileum. The bilateral ureteral spacing 3cm was implanted on the ileal conduit. In the normal group, standard range lymphatic dissection was performed in 20 cases (32.8%), enlarged dissection in 41 cases (67.2%), orthotopic neobladder in 22 cases(36.1%), and ileal conduit in 39 cases (63.9%). In the overweight group, standard range lymphatic dissection was performed in 12 cases (23.1%), enlarged dissection in 40 cases (76.9%), orthotopic neobladder in 26 cases (49.1%), and ileal conduit in 26 cases (50.9%). In the obesity group, the standard range of lymphatic dissection was performed in 7 cases (21.2%), enlarged dissection in 26 cases (78.7%), orthotopic neobladder in 7 cases (21.2%), and ileal conduit in 26 cases (78.8%). There was no significant difference among the three groups (all P>0.05). Compared the operation time, intraoperative blood loss, postoperative exhaust time, postoperative time of taking solid food, postoperative hospital stay, postoperative complications (according to the Clavien-Dindo grading system, postoperative complications are reported inⅠ-Ⅱ grade as mild complications and above Ⅲ grade as serious complications) and pathology results in three groups. Results:All cases successfully underwent robotically without conversion or major intraoperative complications. The operation time in overweight and obsess group were longer than that of normal group with RARC or orthotopic neobladder [310(250, 350) min, 370(310, 420) min, 250(230, 310) min, ( P<0.05)], but there was no significant difference in RARC and ileal conduit[270(220, 300) min, 280(230, 300) min, 240(220, 290)min, P>0.05]. The estimated blood loss in overweight and obsess group was more than that in normal group [230(150, 450)ml, 310(250, 600)ml, 190(100, 350)ml, P<0.05], but there was no difference in blood transfusion rate [4(7.7%), 2(6.1%), 5(8.2%), P>0.05]. The exhaust time [2(1, 3) days, 2(1, 4)days, 2(1, 4)days], postoperative solid food intake time [4(3, 5)days, 4(3, 6)days, 4(3, 6)days] and the hospital stay[10(5, 16)days, 10(6, 17)days, 12(6, 20)days] were not different in three groups(all P>0.05). The mild complication rates in 90 days were significant higher in overweight and obsess groups[28 (53.8%), 16(48.5%), 20(32.8%), P<0.05], but the total and severe complication rates were not significantly different. The incidences of urinary system complications and incision complications in obese and overweight patients were significantly higher than those in normal group ( P<0.05). There was no significant difference in the incidence of gastrointestinal complications and ureteral anastomosis-related complications (stricture or urinary leakage)( P>0.05). There was no significant difference in the number of dissected lymph node, positive lymph node, positive rate of incisional margin and postoperative pathological stage among three different BMI groups(all P>0.05). Conclusion:Robot-assisted radical cystectomy combined with intracorporeal urinary diversion is a safe and effective method for the treatment of overweight, obese and even morbidly obese patients with bladder cancer. The recovery of intestinal function and the oncological results are not affected by body mass index. However, laparoscopic radical cystectomy for overweight and obese patients, especially for orthotopic neobladder, has the risk of long operation time, large amount of intraoperative bleeding and increased risk of minor postoperative complications.

Exosomes secreted by hypoxia-preconditioned BMSCs promote cartilage regeneration / 中华骨科杂志

Objective:Observing the effect of exosomes derived from hypoxic Bone marrow mesenchymal stem cells (BMSCs) on the function of chondrocytes, and exploring the role and mechanism of exosomal miR-196b-5p. Evaluating the application prospects of hypoxic BMSCs exosomes and miR-196b-5p for cartilage regeneration.Methods:Chondrocytes were cultured in the supernatant of BMSCs cultured under normoxia or hypoxia, respectively. The proliferation of chondrocytes was detected by CCK-8 assay and the expressions of Collagen type 2 (Col2), Col1, Aggrecan and SOX9 were detected by qPCR to evaluate the effect of hypoxic BMSCs paracrine on chondrocyte functions. Obtaining normoxic and hypoxic exosomes through ultracentrifugation, and testing their effects on the proliferation and anabolic-related genes of chondrocytes through CCK-8 assay and qPCR. Verifying the expression of miR-196b-5p in hypoxic exosomes based on exosomal miRNA array. Knocking out miR-196b-5p in hypoxic BMSCs, and detecting the effect of hypoxic exosomal miR-196b-5p on the functions of chondrocytes by loss-of-function assay. Predicting the downstream of miR-196b-5p through bioinformatics tools, and exploring the mechanism of hypoxic exosomal miR-196b-5p by gain-of-function assays. Hypoxic exosomes and miR-196b-5p-knockout hypoxic exosomes were loaded on silk fibroin hydrogel and subcutaneously into nude mice. After 4 weeks of culture, histological staining of saffron O, Masson and biochemical content of sGAG and collagen were performed to assess the application prospect of hypoxic exosomes and hypoxic exosomal miR-196b-5p on cartilage regeneration. Results:The results of CCK-8 assay and qPCR indicated that the supernatant of hypoxic BMSCs significantly promoted the proliferation of chondrocytes 1.20±0.07 and the expression of cartilage-related markers (Col2 2.95±0.17, Aggrecan 2.45±0.27, SOX9 2.92±0.29) compared to normoxic BMSCs (0.94±0.04, 1.89±0.09, 1.67±0.21, 1.76±0.16), the differences were statistically significant ( P<0.05). The result of CCK-8 assay showed that hypoxic exosomes (1.28±0.04) promoted the proliferation of chondrocytes compared to normoxic exosomes 1.05±0.06, the differences were statistically significant ( P<0.05). CCK-8 assay revealed that the down-regulation of miR-196b-5p in hypoxic exosomes 0.99±0.06 attenuated the proliferation of chondrocytes compared to control group 1.20±0.07, the differences were statistically significant ( P<0.05); the expression of Col2 0.56±0.04, Aggrecan 0.74±0.09, and SOX9 0.45±0.05 in chondrocytes was reduced in the miR-196b-5p knockdown group compared to the control group (1.00±0.09, 1.00±0.12, 1.00±0.07), the differences were statistically significant ( P<0.05). Co-transfection of pmirGLO-BACH1-WT reporter vector with miR-196b-5p mimics decreased the luciferase activity 0.73±0.06, the differences were statistically significant ( P<0.05). Co-transfection of pmirGLO-BACH1-MUT reporter vector with miR-196b-5p mimics showed no change in luciferase activity. BACH1 is the target of miR-196b-5p. Subcutaneous culture in nude mice showed that hypoxic exosomes significantly promoted the deposition of sGAG 383.2±21.54 and collagen 67.40±3.45, while reducing the expression of miR-196b-5p in hypoxic exosomes weakened the deposition of sGAG 258.4±19.50 and collagen 57.15±4.95, the differences were statistically significant ( P<0.05). Conclusion:Hypoxic exosomes promoted the functions of chondrocytes by inhibiting the expression of BACH1 through miR-196b-5p. Hypoxic exosomes can be applied in cartilage regeneration.

Effect of patellar tilt angle after total knee arthroplasty without patellar resurfacing / 中华骨科杂志

Objective:To analyze the effect of patellar tilt angle on postoperative outcomes after total knee arthroplasty (TKA) without patella resurfacing.Methods:A total of 143 patients with end-stage knee osteoarthritis who underwent TKA without patellar replacement in the First Affiliated Hospital of Nanjing Medical University from October 2020 to October 2021 were retrospectively analyzed. There were 32 males and 111 females, aged 68.44±6.79 years (range, 52-86 years). Patients were divided into three groups according to the postoperative patellar tilt angle: tilt angle<5° was the mild tilt group (97 cases), 5°≤tilt angle<10° was the moderate tilt group (31 cases), and tilt angle≥10° was the severe tilt group (15 cases). All patients were followed up in the outpatient clinic at 3, 6 and 12 months after surgery, and knee visual analogue score (VAS), Hospital for Special Surgery (HSS) score and patella Feller score were observed and recorded to compare the postoperative knee pain and function of patients in different patella tilt groups.Results:All patients were followed up for 1.16±0.23 years (range, 1.0-2.0 years). There was no significant difference in baseline data between the groups. There were significant differences in the intra-group comparison of the VAS score before and after surgery among the three groups ( F=51.12, P<0.001; F=36.90, P<0.001; F=15.76, P<0.001). The VAS scores at 3, 6 and 12 months after operation were significantly lower than those before operation ( P<0.05). The knee VAS of the severe group was higher than that of the mild and moderate groups at 3, 6 and 12 months after surgery, and the difference was statistically significant ( P<0.05). There were statistically significant differences in knee HSS scores before and after surgery among the three groups ( F=81.12, P<0.001; F=36.05, P<0.001; F=32.93, P<0.001). The knee HSS scores at 3, 6 and 12 months after surgery were higher than those before surgery, and the difference was statistically significant ( P<0.05). The knee HSS scores of the severe tilt group at 3, 6 and 12 months after surgery were lower than those of the mild and moderate groups, and the difference was statistically significant ( P<0.05). There were statistically significant differences in the intra-group comparison of the patella Feller score before and after surgery among the three groups ( F=88.81, P<0.001; F=49.59, P<0.001; F=37.40, P<0.001). The patellar Feller score at 3, 6 and 12 months after surgery was higher than that before surgery, and the difference was statistically significant ( P<0.05). The patellar Feller score of the severe group at 3, 6 and 12 months after surgery was lower than that of the mild and moderate groups, and the difference was statistically significant ( P<0.05). Conclusion:Patellar tilt angle after TKA without patellar resurfacing will increase knee pain and limit joint function.

Current research status and application prospect of numerical simulation in traditional Chinese medicine drying / 中国中药杂志

With the rapid development of computer technology, numerical simulation has gradually become an important method to study drying process and improve drying equipment. Using computer to simulate the drying process of traditional Chinese medicine(TCM) is characterized by intuitiveness, scientificity, and low cost, which serves as an auxiliary means for technical innovation in TCM drying. This paper summarizes the theories of different drying methods and the research status of numerical simulation in drying, introduces the modeling methods and software of numerical simulation, and expounds the significance of numerical simulation modeling in shortening the research and development cycle, improving drying equipment, and optimizing drying parameters. However, the current numerical simulation method for drying process has problems, such as low accuracy, lack of quantitative indicators for the control of simulation results on the process, and insufficient in-depth research on the mechanism of drug quality changes. Furthermore, this paper put forward the application prospect of numerical simulation in TCM drying, providing reference for the further study of numerical simulation in this field.

Epidemiological characteristics of norovirus acute gastroenteritis outbreaks and influencing factors in China, 2007-2021 / 中华流行病学杂志

Objective: To analyze the epidemiological characteristics of norovirus-caused acute gastroenteritis outbreaks in China, identify the factors influencing the scale of outbreaks, and provide scientific evidences for early control of norovirus infection outbreaks. Methods: The descriptive epidemiological analysis approach was applied to analyze the incidence of national norovirus infection outbreaks by using the data from the Public Health Emergency Event Surveillance System in China from January 1, 2007 to December 31, 2021. The unconditional logistic regression model was applied to analyze the risk factors that affected the outbreaks' scale. Results: A total of 1 725 norovirus infection outbreaks were recorded in China from 2007 to 2021, with an upward trend in the number of the reported outbreaks. The southern provinces had their annual outbreak peaks from October to March; the northern provinces had two outbreak peaks from October to December and from March to June annually. The outbreaks occurred mainly in southeastern coastal provinces with a trend of gradual spread to central, northeastern and western provinces. The outbreaks mainly occurred in schools and childcare setting (1 539 cases, 89.22%), followed by enterprises and institutions (67 cases, 3.88%) and community households (55 cases, 3.19%). Human to human transmission was the main infection route (73.16%), and norovirus GⅡ genotype was the predominate pathogen causing the outbreaks (899 cases, 81.58%). The time interval between the onset of the primary case and the outbreak reporting M (Q1, Q3) was 3 (2, 6) days and the case number of the outbreak M (Q1, Q3) was 38 (28, 62). The timeliness of outbreak reporting was improved in recent years and the scale of the outbreaks showed a decreasing trend over the years, the differences in reporting timeliness and outbreak scale among different settings were significant (P<0.001). The factors that affected outbreaks' scale included the outbreak setting, transmission route, outbreak reporting timeliness and type of living areas (P<0.05). Conclusions: From 2007 to 2021, the number of the norovirus-caused acute gastroenteritis outbreaks increased in China and the more areas were affected. However, the outbreak scale showed a decreasing trend and the outbreak reporting timeliness was improved. It is important to further improve the surveillance sensitivity and reporting timeliness for the effective control of the outbreak scale.

Epidemiological characteristics of typhoid fever and paratyphoid fever in China, 2004-2020 / 中华流行病学杂志

Objective: To analyze the incidence trend and epidemiological characteristics of typhoid fever and paratyphoid fever in China from 2004 to 2020, understand the high-incidence population and hotspot areas, and provide evidences to develop more targeted prevention and control measures. Methods: The descriptive epidemiological method and spatial analysis method were applied to analyze the epidemiological characteristics of typhoid fever and paratyphoid fever in China during this period by using the surveillance data collected from the National Notifiable Infectious Disease Reporting System of Chinese Center for Disease Control and Prevention. Results: A total of 202 991 cases of typhoid fever were reported in China from 2004 to 2020. More cases occurred in men than in women (sex ratio: 1.18∶1). Most cases were reported in adults aged 20-59 years (53.60%). The incidence rate of typhoid fever decreased from 2.54/100 000 in 2004 to 0.38/100 000 in 2020. The highest incidence rate was reported in young children aged <3 years after 2011, ranging from 1.13/100 000 to 2.78/100 000, and during this period the proportion of cases in this age group increased from 3.48% to 15.59%. The proportion of the cases in the elderly aged ≥60 years increased from 6.46% in 2004 to 19.34% in 2020. The hotspot areas existed in Yunnan, Guizhou, Guangxi and Sichuan Provinces and expanded to Guangdong, Hunan, Jiangxi, and Fujian Provinces. A total of 86 226 paratyphoid fever cases were reported from 2004 to 2020, the male to female ratio of the cases was 1.21∶1. Most cases were reported in adults aged 20-59 years (59.80%). The incidence rate of paratyphoid fever decreased from 1.26/100 000 in 2004 to 0.12/100 000 in 2020. The highest incidence rate of paratyphoid fever was in young children aged <3 years after 2007, ranging from 0.57/100 000 to 1.19/100 000, and during this period the proportion of the cases in this age group increased from 1.48% to 30.92%. The proportion of the cases in the elderly aged ≥60 years increased from 4.52% in 2004 to 22.28% in 2020. The hotspot areas expanded to the east, including Guangdong, Hunan and Jiangxi Provinces, from Yunnan, Guizhou, Sichuan, and Guangxi Provinces. Conclusions: The results showed a low level of incidence of typhoid fever and paratyphoid fever in China with a trend of decreasing per year. The hotspots were mainly in the of Yunnan, Guizhou, Guangxi and Sichuan Provinces, with an expanding trend to eastern China. It is necessary to strengthen the typhoid fever and paratyphoid fever prevention and control in southwestern China, among young children aged <3 years and the elderly aged ≥60 years.