First-in-class small molecule drugs in 2023 / 药学学报

In 2023, drug discovery develops steadily, with improvement of small molecule drugs discovery keeps pace with biological drugs in this year. The Center for Drug Evaluation and Research of U.S. Food and Drug Administration has totally approved 55 kinds of new drugs which have significantly promotion compared to 37 new drugs approval in 2022, including 38 kinds of new molecular entities, 17 kinds of biological drugs, 5 kinds of gene therapeutics and 2 cell therapeutics. The proportion of first-in-class drugs increased steadily, with 13 small molecule first-in-class drugs and 7 biological first-in-class drugs approved this year, mostly in the fields of cancer and rare diseases. Among them, a plurality of first-initiated small molecule drugs exhibits breakthrough significance, such as the first neurokinin 3 (NK3) receptor antagonist fezolinetant, the first retinoic acid receptor (RIG-I) agonist palovarotene, the first protein kinase B (AKT) inhibitor capivasertib, the first complement factor B inhibitor iptacopan, etc. The pioneering drug has huge academic and commercial value, and has become the target of the academic and industrial circles. However, first-in-class drugs not only need new targets, new mechanisms and new molecules, but also need to comprehensively verify the causality between new targets and diseases, study the correlation between new mechanisms and drug efficacy, and explore the balance between new molecules and drug-manufacturing properties. This article analyzed the research background, development process and therapeutic application of three first-initiated small molecule drugs in this year, expecting to provide more research ideas and methods for more first-in-class drugs.

Comparison of safety and effectiveness of active migration technique and in situ lithotripsy technique in the treatment of 1-2 cm upper ureteral calculi by flexible ure-teroscopy / 北京大学学报(医学版)

OBJECTIVE@#To compare the safety and effectiveness of active migration technique and in situ lithotripsy technique in the treatment of 1-2 cm upper ureteral calculi by retrograde flexible ureteroscopy.@*METHODS@#A total of 90 patients with 1-2 cm upper ureteral calculi treated in the urology department of Beijing Friendship Hospital from August 2018 to August 2020 were selected as the subjects. The patients were divided into two groups using random number table: 45 patients in group A were treated with in situ lithotripsy and 45 patients in group B were treated with active migration technique. The active migration technique was to reposition the stones in the renal calyces convenient for lithotripsy with the help of body position change, water flow scouring, laser impact or basket displacement, and then conduct laser lithotripsy and stone extraction. The data of the patients before and after operation were collected and statistically analyzed.@*RESULTS@#The age of the patients in group A was (51.6±14.1) years, including 34 males and 11 females. The stone diameter was (1.48±0.24) cm, and the stone density was (897.8±175.9) Hu. The stones were located on the left in 26 cases and on the right in 19 cases. There were 8 cases with no hydronephrosis, 20 cases with grade Ⅰ hydronephrosis, 11 cases with grade Ⅱ hydronephrosis, and 6 cases with grade Ⅲ hydronephrosis. The age of the patients in group B was (51.8±13.7) years, including 30 males and 15 females. The stone diameter was (1.52±0.22) cm, and the stone density was (964.6±214.2) Hu. The stones were located on the left in 22 cases and on the right in 23 cases. There were 10 cases with no hydronephrosis, 23 cases with grade Ⅰ hydronephrosis, 8 cases with grade Ⅱ hydronephrosis, and 4 cases with grade Ⅲ hydronephrosis. There was no significant diffe-rence in general parameters and stone indexes between the two groups. The operation time of group A was (67.1±16.9) min and the lithotripsy time was (38.0±13.2) min. The operation time of group B was (72.2±14.8) min and the lithotripsy time was (40.6±12.6) min. There was no significant difference between the two groups. Four weeks after operation, the stone-free rate in group A was 86.7%, and in group B was 97.8%. There was no significant difference between the two groups. In terms of complications, 25 cases of hematuria, 16 cases of pain, 10 cases of bladder spasm and 4 cases of mild fever occurred in group A. There were 22 cases of hematuria, 13 cases of pain, 12 cases of bladder spasm and 2 cases of mild fever in group B. There was no significant difference between the two groups.@*CONCLUSION@#Active migration technique is safe and effective in the treatment of 1-2 cm upper ureteral calculi.

Short-course radiotherapy combined with CAPOX and PD-1 inhibitor for the total neoadjuvant therapy of locally advanced rectal cancer: the preliminary single-center findings of a prospective, multicentre, randomized phase II trial (TORCH) / 中华胃肠外科杂志

Objective: Total neoadjuvant therapy has been used to improve tumor responses and prevent distant metastases in patients with locally advanced rectal cancer (LARC). Patients with complete clinical responses (cCR) then have the option of choosing a watch and wait (W&W) strategy and organ preservation. It has recently been shown that hypofractionated radiotherapy has better synergistic effects with PD-1/PD-L1 inhibitors than does conventionally fractionated radiotherapy, increasing the sensitivity of microsatellite stable (MSS) colorectal cancer to immunotherapy. Thus, in this trial we aimed to determine whether total neoadjuvant therapy comprising short-course radiotherapy (SCRT) combined with a PD-1 inhibitor improves the degree of tumor regression in patients with LARC. Methods: TORCH is a prospective, multicenter, randomized, phase II trial (TORCH Registration No. NCT04518280). Patients with LARC (T3-4/N+M0, distance from anus ≤10 cm) are eligible and are randomly assigned to consolidation or induction arms. Those in the consolidation arm receive SCRT (25Gy/5 Fx), followed by six cycles of toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Those in the induction arm receive two cycles of ToriCAPOX, then undergo SCRT, followed by four cycles of ToriCAPOX. Patients in both groups undergo total mesorectal excision (TME) or can choose a W&W strategy if cCR has been achieved. The primary endpoint is the complete response rate (CR, pathological complete response [pCR] plus continuous cCR for more than 1 year). The secondary endpoints include rates of Grade 3-4 acute adverse effects (AEs) etc. Results: Up to 30 September 2022, 62 patients attending our center were enrolled (Consolidation arm: 34, Induction arm:28). Their median age was 53 (27-69) years. Fifty-nine of them had MSS/pMMR type cancer (95.2%), and only three MSI-H/dMMR. Additionally, 55 patients (88.7%) had Stage III disease. The following important characteristics were distributed as follows: lower location (≤5 cm from anus, 48/62, 77.4%), deeper invasion by primary lesion (cT4 7/62, 11.3%; mesorectal fascia involved 17/62, 27.4%), and high risk of distant metastasis (cN2 26/62, 41.9%; EMVI+ 11/62, 17.7%). All 62 patients completed the SCRT and at least five cycles of ToriCAPOX, 52/62 (83.9%) completing six cycles of ToriCAPOX. Finally, 29 patients achieved cCR (46.8%, 29/62), 18 of whom decided to adopt a W&W strategy. TME was performed on 32 patients. Pathological examination showed 18 had achieved pCR, four TRG 1, and 10 TRG 2-3. The three patients with MSI-H disease all achieved cCR. One of these patients was found to have pCR after surgery whereas the other two adopted a W&W strategy. Thus, the pCR and CR rates were 56.2% (18/32) and 58.1% (36/62), respectively. The TRG 0-1 rate was 68.8% (22/32). The most common non-hematologic AEs were poor appetite (49/60, 81.7%), numbness (49/60, 81.7%), nausea (47/60, 78.3%) and asthenia (43/60, 71.7%); two patients did not complete this survey. The most common hematologic AEs were thrombocytopenia (48/62, 77.4%), anemia (47/62, 75.8%), leukopenia/neutropenia (44/62, 71.0%) and high transaminase (39/62, 62.9%). The main Grade III-IV AE was thrombocytopenia (22/62, 35.5%), with three patients (3/62, 4.8%) having Grade IV thrombocytopenia. No Grade V AEs were noted. Conclusions: SCRT-based total neoadjuvant therapy combined with toripalimab can achieve a surprisingly good CR rate in patients with LARC and thus has the potential to offer new treatment options for organ preservation in patients with MSS and lower-location rectal cancer. Meanwhile, the preliminary findings of a single center show good tolerability, the main Grade III-IV AE being thrombocytopenia. The significant efficacy and long-term prognostic benefit need to be determined by further follow-up.

Nomogram for Predicting Early Death in Patients with Metastatic Colon Cancer Based on SEER Database / 肿瘤防治研究

Objective To construct a Nomogram model that can accurately predict early death of metastatic colon cancer (mCC). Methods A total of 6 669 patients from the SEER database were identified using inclusion and exclusion criteria. Multivariate logistic regression was used to identify risk factors for early mortality and to construct a Nomogram. The predictive performance of the Nomogram was evaluated by C-index, calibration curve, and decision curve analysis (DCA). Results Primary tumor location, differentiation grade, T stage, M stage, bone metastases, brain metastases, CEA, tumor size, age and marital status were independent factors for early death in patients with mCC. A Nomogram was constructed based on these variables. The C-index and the calibration curve of the Nomogram showed the good predictive ability of the nomogram. DCA showed that the Nomogram had a superior clinical net benefit in predicting early death compared with TNM stage. Conclusion The developed Nomogram has good predictive ability and can help guide clinicians to identify patients with high-risk mCC for individualized diagnosis and treatment.

Research Progress of Deep Learning in Bladder Cancer Pathology / 肿瘤防治研究

The incidence of bladder cancer is increasing annually, and the gold standard for its diagnosis relies on histopathological biopsy. Whole-slide digitization technology can produce thousands of high-resolution captured pathological images and has greatly promoted the development of digital pathology. Deep learning, as a new method of artificial intelligence, has achieved remarkable results in the analysis of pathological images for tumor diagnosis, molecular typing, and prediction of prognosis and recurrence of bladder cancer. Traditional pathology relies heavily on the professional level and experience of pathologists; as such, it is highly subjective and has poor reproducibility. Deep learning can automatically extract image features. It can also improve diagnostic efficiency and repeatability and reduce missed and misdiagnosed rates when used to assist pathologists in making decisions. This technology cannot only alleviate the pressure of the current shortage of skilled workforce and uneven medical resources but also promote the development of precision medicine. This article reviews the latest research progress and prospects of deep learning in pathological image analysis of bladder cancer.

Effects of screen exposure on language skills in children / 中华儿科杂志

Objective: To investigate the association between screen exposure and language skills in children aged 2-5 years. Methods: There were 299 children aged 2-5 years, recruited by convenience sampling from those who visited the Center of Children's Healthcare, Children's Hospital, Capital Institute of Pediatrics for routine physical examination from November 2020 to November 2021. Their development status were evaluated by the children neuropsychological and behavioral scale (revision 2016). A self-designed questionnaire for parents was conducted to collect demographic and socioeconomic information and screen exposure characteristics (time and quality). One-way ANOVA and independent sample t test were applied to compare the differences in language development quotient of children with different screen exposure time and quality. Multiple linear regression was used to analyze the correlation between screen exposure time and quality with language developmental quotient. Multivariate Logistic regression was used to analyze the risk of language underdevelopment in children with different screen exposure time and quality. Results: Among 299 children, 184 (61.5%) were boys and 115 (38.5%) were girls, with the age of (3.9±1.1) years. The number of children with daily screen time <60, 60-120 and>120 min was 163 children (54.5%), 86 children (28.8%) and 50 children (16.7%), respectively, with the language development quotients of 94±13, 90±13, 84±14, respectively, demonstrating a statistically significant difference (F=8.92, P<0.001). Logistic regression analysis revealed that screen exposure time of 60-120 and >120 min per day were both risk factors for children's language developmental quotients (OR=2.28, 95%CI 1.00-5.17, P=0.043; OR=3.96, 95%CI 1.86-9.17, P<0.001), and co-viewing and exposure to educational programs were both protective factors for children's language developmental quotients (OR=0.48, 95%CI 0.25-0.91, P=0.024, OR=0.36, 95%CI 0.19-0.70, P=0.003). Conclusions: Excessive exposure screen time and inappropriate screen exposure habits are associated with children's poorer language development. Screen exposure time should be limited and screen use should be rational to promote children's language skills.

Long-term outcome of transcatheter repair of paravalvular leak post surgical mitral valve replacement / 中华心血管病杂志

Objective: To explore the long-term clinical efficacy of transcatheter repair of mitral paravalvular leak (PVL) post surgical mitral valve replacement. Methods: This study is a retrospective study. Patients who completed transcatheter repair of paravalvular leak after surgical mitral valve replacement at Shanghai Chest Hospital, Shanghai Jiaotong University School of Medicine from March 2010 to December 2018 were included. Technical success was defined as the occluder being stably implanted in the paravalvular leak site without affecting the function of the mitral valve and surrounding tissues; and there were no intervention-related complications, such as new hemolysis or aggravated hemolysis, and echocardiography confirmed mitral paravalvular regurgitation reduced by more than 1 grade. Patients were followed up at 30 days, 1, and 3 years after the intervention. The main endpoints were all-cause death and re-surgery due to interventional failure or serious complications. The occurrence of occluder-mediated hemolysis and chronic renal insufficiency was recorded, and patients were monitored with echocardiography during follow up. Results: A total of 75 patients were included, aged (54.3±22.9) years old, and 38 patients were males. All patients had decreased cardiac function and/or hemolysis before intervention. Procedural success was achieved in 54 patients (72.0%). Incidence of device-mediated hemolysis was 18.7% (14/75). During the follow-up period, all-cause death occurred in 7 patients (9.3%), and 3 were cardiac deaths.The 3-year event-free survival rate was 81.3% (61/75). The need for cardiac surgery was 9.3% (7/75): 3 cases due to severe device-mediated hemolysis, 2 cases due to prosthetic valve failure and 2 cases due to moderate to severe residual regurgitation. The echocardiography follow-up results showed that the position of the occluder was stable, there was no impact on the artificial valve function and surrounding structures, and the residual regurgitation was stable without progressive increase in event-free patients. Compared with pre-intervention, the left ventricular end systolic diameter ((33.9±7.4)mm vs. (38.3±8.9) mm, P=0.036), end diastolic diameter ((53.7±8.3) mm vs. (58.4±9.1) mm, P=0.045) and left atrial diameter (59.3 (44.5, 90.7) mm vs. 64.3 (44.8, 96.6) mm, P=0.049) were significantly reduced, pulmonary artery systolic pressure was also significantly decreased ((36.5±15.8) mmHg vs. (46.3±14.9) mmHg, P=0.022, 1 mmHg=0.133 kPa). There was no significant difference between 3 years and 1 year after transcatheter repair of mitral paravalvular leak post surgical mitral valve replacement (all P>0.05). Conclusion: Transcatheter repair of mitral paravalvular leak post surgical mitral valve replacement is an effective treatment option in selective patients.

Muscone inhibits opening of mPTP to alleviate OGD/R-induced injury of HT22 cells / 中国中药杂志

This study aims to investigate the mechanism of muscone in inhibiting the opening of mitochondrial permeability transition pore(mPTP) to alleviate the oxygen and glucose deprivation/reoxygenation(OGD/R)-induced injury of mouse hippocampal neurons(HT22). An in vitro model of HT22 cells injured by OGD/R was established. CCK-8 assay was employed to examine the viability of HT22 cells, fluorescence microscopy to measure the mitochondrial membrane potential, the content of reactive oxygen species(ROS), and the opening of mPTP in HT22 cells. Enzyme-linked immunosorbent assay was employed to determine the level of ATP and the content of cytochrome C(Cyt C) in mitochondria of HT22 cells. Flow cytometry was employed to determine the Ca~(2+) content and apoptosis of HT22 cells. The expression of Bcl-2(B-cell lymphoma-2) and Bcl-2-associated X protein(Bax) was measured by Western blot. Molecular docking and Western blot were employed to examine the binding between muscone and methyl ethyl ketone(MEK) after pronase hydrolysis of HT22 cell proteins. After the HT22 cells were treated with U0126, an inhibitor of MEK, the expression levels of MEK, p-ERK, and CypD were measured by Western blot. The results showed that compared with the OGD/R model group, muscone significantly increased the viability, mitochondrial ATP activity, and mitochondrial membrane potential, lowered the levels of ROS, Cyt C, and Ca~(2+), and reduced mPTP opening to inhibit the apoptosis of HT22 cells. In addition, muscone up-regulated the expression of MEK, p-ERK, and down-regulated that of CypD. Molecular docking showed strong binding activity between muscone and MEK. In conclusion, muscone inhibits the opening of mPTP to inhibit apoptosis, thus exerting a protective effect on OGD/R-injured HT22 cells, which is associated with the activation of MEK/ERK/CypD signaling pathway.

Preparation of vitexin albumin nanoparticles and its pharmacokinetic study / 中国中药杂志

This study aims to prepare vitexin albumin nanoparticles(VT-BSA-NPs) to alleviate the low bioavailability of vitexin(VT) in vivo due to its poor water solubility. VT micro powders were prepared by the antisolvent crystallization method, and the morphology, size, and physicochemical properties of VT micro powders were studied. The results showed that the VT micro powder had a particle size of(187.13±7.15) nm, an approximate spherical morphology, and a uniform size distribution. Compared with VT, the chemical structure of VT micro powders has not changed. VT-BSA-NPs were prepared from VT micro powders by desolvation-crosslinking curing method. The preparation process was screened by single factor test and orthogonal test, and the quality evaluation of the optimal prescription particle size, PDI, Zeta potential, EE, and morphology was performed. The results showed that the average particle size of VT-BSA-NPs was(124.33±0.47) nm; the PDI was 0.184±0.012; the Zeta potential was(-48.83±2.20) mV, and the encapsulation rate was 83.43%±0.39%, all of which met the formulation-related requirements. The morphological results showed that the VT-BSA-NPs were approximately spherical in appearance, regular in shape, and without adhesion on the surface. In vitro release results showed a significantly reduced release rate of VT-BSA-NPs compared with VT, indicating a good sustained release effect. LC-MS/MS was used to establish an analytical method for in vivo analysis of VT and study the plasma pharmacokinetics of VT-BSA-NPs in rats. The results showed that the specificity of the analytical method was good, and the extraction recovery was more than 90%. Compared with VT and VT micro powders, VT-BSA-NPs could significantly increase AUC, MRT, and t_(1/2), which was beneficial to improve the bioavailability of VT.

Developing a development index system of Shanghai district-level disease prevention and control institutions using the Delphi method / 上海预防医学

ObjectiveTo construct an evaluation index system for the development of district-level disease prevention and control centers according to the requirements of the modernization of Shanghai’s disease control system and public health work practices， and to comprehensively assess the construction and development of district-level disease prevention and control institutions. MethodsAccording to the national and municipal requirements for the development of disease prevention and control institutions， an index framework was proposed through literature search and expert interviews. 39 representative experts in the field of public health at the national， provincial， and municipal （district） levels were selected to participate in the consultation and construction of the index system. The authority coefficient， the coefficient of variation， etc. were used to carry out quality control and determination of each index on the Delphi method. ResultsThe questionnaire response rate was 100%， the expert authority coefficient was 0.86，the degree of familiarity was 0.79， and the judgment basis was 0.92. The coefficients of variation of the necessary indicators in the index system were all <0.25 in the dimension of importance， and there were statistical differences in the statistical test of Kendall’s W coordination coefficients at all levels and dimensions （all P<0.001）. After multiple rounds of consultation， experts reached a consensus， forming a development evaluation index system of district-level CDCs with 6 first-level indicators， 24 second-level indicators， and 105 third-level indicators （including 63 necessary indicators and 42 recommended indicators）. ConclusionThe evaluation index system of Shanghai district-level CDCs based on the Delphi method has good authority， reliability， sensitivity and operability. This indicator system can effectively support the development of Shanghai district-level CDCs， and can be used for evaluation at multiple levels and in an all-round way in the future. The evaluation results can provide an evidence-based basis for the modernization of the disease prevention and control system and the continuous and dynamic updating of the development goals in the future.

Patent analysis of new target oral drugs for type 2 diabetes mellitus / 中国药房

OBJECTIVE To analyze the patents of new target oral drugs for type 2 diabetes mellitus （T2DM）， and to provide references for the research and development direction and patent layout of new domestic diabetes drugs. METHODS Based on global patent data in the HimmPat database， from multiple perspectives such as the number of patent applications and authorization， development trend， regional distribution and main applicants， statistics and analysis were performed for the patents related to 3 types of new target oral drugs for T2DM， such as glucokinase activator （GKA）， protein tyrosine phosphatase 1B inhibitor （PTP-1B-IN）， and 11β-hydroxysteroid dehydrogenase 1 inhibitor （11β-HSD1-IN）. RESULTS & CONCLUSIONS A total of 1 649 patents of GKA， 709 patents of PTP-1B-IN， 592 patents of 11β-HSD1-IN were obtained， the main applicants were well-known pharmaceutical companies， which possessed the core patents of pharmaceutical compounds. The research on GKA drugs was more mature， with a larger number of patent applications and a more comprehensive enterprise layout. Domestic enterprises， universities and research institutions had advantages in the field of PTP-1B-IN. Domestic enterprises and research institutions can leverage the advantages of traditional Chinese medicine and resources to enhance their research capabilities and improve technological competitiveness through core technology exploration， the exploration of process route， patent layout， industry- university-research cooperation and the establishment of patent pool.

Imbalance between myopic shift and the minimum amplitude of accommodation: a hypothesis for the pathogenesis of ocular hypertension secondary to drug-induced bilateral acute ciliochoroidal effusion / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To report 5 cases with drug-induced bilateral acute ciliochoroidal effusion(DBACE)and myopic shift, with or without ocular hypertension(OHT), summarize patients' clinical characteristics and recovery process of DBACE, and investigate the possible pathophysiological mechanism.METHODS:A retrospective observational case study conducted from June 2017 to February 2021. The included patients were subjected to a series of ocular examinations listed as follows: 1)best corrected visual acuity; 2)intraocular pressure(IOP); 3)slit-lamp microscopy; 4)fundus photography; 5)ultrasound biomicroscopy(UBM); 6)subjective optometry; 7)axial length and anterior chamber depth. All patients were followed up every 2d until the diopters were completely restored to the state before the disease onset.RESULTS:In total, 5 patients aged 10-45 years old, including 3 female and 2 male patients, were enrolled in this study. All patients were bilaterally involved(5/5), and had myopic shift(5/5), of whom 3 patients had OHT(3/5). With the increase of age, myopic shift decreased, while OHT increased. Based on OHT, the dynamic aggravation process of DBACE was subdivided into 2 stages, stage 1(myopic shift without OHT)and stage 2(myopic shift with OHT). With the deterioration of DBACE, when myopic shift approached or exceeded the minimum amplitude of accommodation(MAA), IOP gradually rose, and DBACE progressed from stage 1 to stage 2. With the recovery of DBACE after discontinuing the suspicious drugs, DBACE in stage 2 first returned to stage 1, and then returned to normal.CONCLUSION:Pathophysiological mechanism of DBACE was subdivided into 2 stages, including stage 1(myopic shift without OHT)and stage 2(myopic shift with OHT). The transition between the two stages depends on the imbalance between myopic shift and MAA.

Development of traditional Chinese medicine rehabilitation curriculum based on World Health Organization rehabilitation competency framework / 中国康复理论与实践

ObjectiveTo develop a high-quality rehabilitation major curriculum using the World Health Organization rehabilitation competency framework (RCF), to improve the level of traditional Chinese medicine (TCM) rehabilitation major, to meet the requirements of competency-based education development. MethodsThe competence requirements of rehabilitation professionals of higher traditional TCM colleges and universities were analyzed using the theory and method of RCF. ResultsThe competency structure of TCM rehabilitation talents based on RCF was built, and the curriculum setting of TCM rehabilitation based on RCF was proposed. According to the characteristics of the educational environment of colleges and universities, a competency model suitable for undergraduate-level TCM rehabilitation major was established. ConclusionThe theory and methods of RCF are of great significance for the construction of competency-based education system of TCM rehabilitation major. Based on RCF, this study constructs the basic and practical curriculum system of TCM rehabilitation at the undergraduate level to promote the training of applied talents in TCM rehabilitation.

Dendrobium Polysaccharides Mitigate CSE-induced Inflammatory Damage of Human Bronchial Epithelial Cells via TLR4/NF-κB Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effects of Dendrobium polysaccharides on the secretion of inflammatory cytokines and Toll-like receptor 4 （TLR4）/nuclear factor （NF）-κB pathway in 16HBE cells exposed to cigarette smoke extract （CSE）. MethodThe 16HBE cells were classified into the control， CSE， and CSE+ Dendrobium polysaccharides （100， 200， 400 mg·L-1） groups. The cell-counting kit-8 （CCK-8） assay was employed to measure the cell viability， and a microscope was used to observe the cell morphology. The enzyme-linked immunosorbent assay was employed to measure the levels of interleukin （IL）-8， IL-1β， IL-4， IL-13， and transforming growth factor （TGF）-β in cell culture supernatants. Real-time PCR was carried out to determine the mRNA levels of Toll-like receptor 4 （TLR4）， nuclear factor-κB （NF-κB）， and IL-4. Western blot was employed to determine the protein levels of interleukin-4 receptor （IL-4R）， TLR4， myeloid differentiation primary response protein 88 （MyD88）， NF-κB， phosphorylated nuclear factor-κB （p-NF-κB）， and nucleoproteins nuclear factor-κB （NEs-NF-κB）. The immunofluorescence assay was employed to measure the nuclear translocation of NF-κB. ResultCompared with the control group， the CSE group showed elevated levels of IL-8， IL-1β， IL-4， IL-13， and TGF-β in the cell culture supernatants （P<0.05， P<0.01）， up-regulated expression levels of TLR4， MyD88， NF-κB， p-NF-κB， NEs-NF-κB， and IL-4 （P<0.01）， and significant nuclear translocation of NF-κB. Compared with the CSE group， Dendrobium polysaccharides increased the cell survival rate， recovered the cell activity， lowered the levels of IL-8， IL-1β， IL-4， IL-13， and TGF-β， down-regulated the expression of TLR4， MyD88， NF-κB， p-NF-κB， NEs-NF-κB， and IL-4 （P<0.05， P<0.01）， and reduced the nuclear translocation of NF-κB. ConclusionDendrobium polysaccharides showed significant protective effects on the 16HBE cells exposed to CSE by inhibiting the TLR4/NF-κB signaling pathway.

Clinical application of Ivor-Lewis procedure under uniportal video-assisted thoracoscopy for esophageal cancer / 中华胸心血管外科杂志

Objective:To investigate the safety and feasibility of Ivor-Lewis procedure under uniportal video-assisted thoracoscopy(VATS) for esophageal cancer and Siewert type I esophago-gastric junction carcinoma.Methods:The patients with middle-lower segment esophageal cancer or Siewert type I esophago-gastric junction carcinoma received minimally invasive esophagectomy between October 2020 and June 2021, and the clinical data was collected and analyzed.Results:26 patients received Ivor-Lewis procedure underwent uniportal VATS, while 45 patients underwent McKeown surgery under multiport VATS. The average operation time of patients in the two groups were(265±110)min and (235±94)min, and the average intraoperative blood loss were(80±57)ml and(105±60)ml. The mean number of lymph nodes removed in the surgery were (19.3±2.9) and 18.6±2.7 respectively in two groups, and the mean length of hospital stay was(7.5±3.5)days and(8.3±2.7)days. The incidence of perioperative complications were not significantly different in two groups. The VAS score of patients received Ivor-Lewis procedure underwent uniportal VATS was lower than that of patients received McKeown surgery in ostoperative day 1, day 3, day 7 and 1 month. The difference was statistically significant in two groups( P<0.05). Conclusion:The Ivor-Lewis procedure under uniportal VATS for esophageal cancer and Siewert type I esophago-gastric junction carcinoma has the advantage of less postoperative pain, and the procedure is feasible in clinical practice.

Comparison between endoscopic submucosal dissection and gastrectomy in clinical benefit for metachronous early gastric cancer in the remnant stomach / 中华消化内镜杂志

Objective:To compare the histopathological features and treatment efficacy of different methods for metachronous early gastric cancer (MEGC) in the remnant stomach.Methods:A total of 66 patients [38 endoscopic submucosal dissection (ESD) and 28 gastrectomy] with MEGC in the remnant stomach from January 2014 to December 2020 in Drum Tower Hospital were divided into the ESD group and the gastrectomy group. The baseline characteristics, histopathological features, treatment efficacy, and cost differences of the two groups were analyzed.Results:The MEGC in the remnant stomach mostly occurred in elderly male patients, with the mean age of 69.7±8.5 years. The mean interval of the occurrence of MEGC in the remnant stomach was 6 years. As for the tumor location, the gastric body (31.6%) was the main location in the ESD group and gastric cardia (53.6%) in the gastrectomy group with significant difference ( χ2=11.07, P=0.026). The mean operation time, hospital stay, postoperative fasting time, and total treatment cost were 80.0 min, 6.0 d, 1.5 d, ￥19 436 in the ESD group and 215.0 min, 19.0 d, 6.5 d, and ￥68 665 in the gastrectomy group, respectively, with significant differences between the two groups ( P<0.05). The overall survival rate during follow-up was 76.3% in the ESD group and 71.4% in the gastrectomy group with no significant difference between the two groups ( χ2=0.736, P=0.778). In terms of postoperative complications, the incidences of bleeding and infection were 7.9% and 5.3% in the ESD group, and those of obstruction and infection were both 14.3% in the gastrectomy group. There was significant difference in the incidences of postoperative obstruction between the two groups ( P<0.05). Conclusion:ESD is safe and effective for MEGC in the remnant stomach and is better than gastrectomy in terms of the treatment cost and operation time, but the long-term efficacy still needs to be validated by large-scale prospective studies.

Safety and efficacy of endoscopic ultrasound-guided hepaticogastrostomy for the treatment of hilar and distal biliary obstruction: a retrospective cohort study / 中华消化内镜杂志

Objective:To compare the safety and efficacy of endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) for the treatment of biliary obstruction at different locations.Methods:From January 2016 to June 2021 data of 82 patients with obstructive jaundice treated with EUS-HGS in Nanjing Drum Tower Hospital were reviewed in this retrospective cohort study. According to the location of biliary obstruction,patients were divided into hilar biliary obstruction group ( n=30) and distal biliary obstruction group ( n=52). Univariate and multivariate logistic regression analyses were conducted adjusting covariates to compare the technical success rate, the clinical success rate, the adverse reaction incidence, hospital stay and cost of the two groups. Results:The technical success rates were 93.3% (28/30) and 94.2% (49/52) in the hilar biliary obstruction group and the distal biliary obstruction group with no significant difference between the two groups ( P=0.870, OR=1.17, 95% CI: 0.18-7.41). The clinical success rates were 83.3% (25/30) and 88.5% (46/52) in the hilar biliary obstruction group and the distal biliary obstruction group with no significant difference between the two groups ( P=0.514, OR=1.53, 95% CI: 0.43-5.53). The incidence of adverse events in hilar biliary obstruction group was 10.0% (3/30), including cholangitis 3.3% (1/30), biliary fistula 6.7% (2/30), biliary peritonitis 6.7% (2/30). The incidence of adverse events in patients with distal biliary obstruction was 17.3% (9/52), including cholangitis 9.6% (5/52), biliary fistula 7.7% (4/52) and biliary peritonitis 5.8% (3/52). There was no significant difference in the incidence of adverse events between the two groups ( P>0.05). Conclusion:There is no significant difference in safety or efficacy of EUS-HGS for hilar biliary obstruction and distal biliary obstruction.

Prevalence of Mycoplasma pneumoniae among children undergoing physical examination / 中华微生物学和免疫学杂志

Objective:To investigate the prevalence of Mycoplasma pneumoniae ( Mp) in children undergoing physical examination. Methods:This study randomly enrolled 1 303 children at the age of 6-12 years who underwent physical examination in 2023. Their oral and pharyngeal swabs as well as venous blood samples were collected. The prevalence of Mp in these subjects was detected using isolation and culturing, nucleic acid detection and serological test. Chi-square test was used for statistical analysis. Results:Among the 1 303 children, the detection rate of Mp was 4.1% (53/1 303) by culturing, 7.3% (95/1 303) by nucleic acid detection and 13.6% (177/1 303) by serological test. Statistical analysis showed that there were significant differences in the the detection rates of Mp among children undergoing physical examination between the three methods ( P<0.05). Conclusions:The detection rate of Mp in children undergoing physical examination in 2023 was about 4.1%. Isolation and culturing was more accurate than nucleic acid detection and serological test in the detection of Mp in healthy population as the latter two methods would overestimate the rate.

The effects on the language ability and life quality of aphasic stroke survivors of synchronous, long-distance speech rehabilitation training based on Oral Reading for Language with Aphasia / 中华物理医学与康复杂志

Objective:To observe any effect of long-distance application of Oral Reading for Language with Aphasia (ORLA) training on patients with post-stroke aphasia.Methods:A total of 42 stroke survivors with aphasia were randomly divided into an inpatient group, and two online groups, each of 14. All three groups had their routine rehabilitation treatment supplemented with ordinary multimodal language therapy and ORLA. The inpatient group completed the routine in the rehabilitation treatment room, while the online groups completed it at home using Tencent video conferencing software. The conventional multimodal language therapy was conducted once daily, 5 days a week for 4 weeks. For the inpatient group and online group 2 the daily session lasted 30 minutes, while for the online 1 groups the daily length was doubled. The ORLA therapy was also conducted once daily, 5 days a week for 4 weeks, for the inpatient group and online group 2 the daily session lasted 1h, while for the online 1 groups the daily length was 30min.The speech function, reading ability and life quality of the three groups were evaluated before and after the intervention using the Western Aphasia Battery, the Chinese Standard Aphasia Examination Scale and the Chinese version of the Stroke Aphasia Quality of Life Scale.Results:After treatment, the average aphasia quotient (AQ), reading, naming and quality of life scores in all three groups had improved significantly compared with those before treatment. And related language ability scores (such as retelling, fluency, information volume, listening comprehension, etc.) had also improved significantly in all three groups. However, the average AQ, reading, and oral fluency scores of the inpatient group and online group 2 were significantly higher than those of online group 1. Significant improvement was also observed in the reading aloud and life quality of all three groups, but the average improvement in reading aloud was significantly greater in the inpatient group and in online group 2 compared to online group 1. The average life quality of the online groups was significantly superior to that of the inpatient group.Conclusion:Medium- and high-intensity ORLA synchronous remote speech rehabilitation can significantly improve the speech ability, reading ability and life quality of aphasic stroke survivors.

Efficacy analysis of anti-platelet in the treatment of high-risk non-disabling ischemic cerebrovascular events guided by point-of-care testing of CYP2C19 gene / 中华神经科杂志

Objective:To explore the efficacy and safety of different anti-platelet regimens in the treatment of high-risk non-disabling ischemic cerebrovascular events (HR-NICE) guided by point-of-care testing of CYP2C19 gene. Methods:A single-centre, prospective, randomised, open-label, and blinded endpoint design was uesd in the study. From July 2020 to January 2022, HR-NICE patients were enrolled in the Stroke Green Channel and Department of Neurology of Xuzhou Central Hospital, and all patients were scraped the buccal mucosa for screening for CYP2C19 loss-of-function allele carriers by point-of-care testing . Patients with intermediate metabolism were defined as those who carried 1 loss-of-function allele and patients with poor metabolism were those who carried 2 loss-of-function alleles. This study reduced the test turnaround time to 1 hour by using a fully automated medical polymerase chain reaction analyzer for a point-of-care test of CYP2C19 genotype. CYP2C19 loss-of-function allele carriers were divided according to the random number table method into the conventional treatment group (clopidogrel 75 mg, once a day), the ticagrelor group (ticagrelor 90 mg, twice a day) and the intensive dose group (clopidogrel 150 mg, once a day) separately combined with aspirin (100 mg, once a day) dual antiplatelet for 21 days. Baseline information, Acute Stroke Org 10172 Treatment Trial staging, 90-day modified Rankin Scale score, occurrence of adverse events and severe adverse events were collected for all the 3 groups. The primary efficacy outcome was new stroke within 90 days, and the primary safety outcome was severe or moderate bleeding within 90 days. Results:A total of 716 patients were included: 240 in the conventional treatment group, 240 in the ticagrelor group and 236 in the intensive dose group. There was no statistically significant difference between the 3 groups at baseline (all P>0.05). There were 26 cases (10.8%) with new stroke events in the conventional treatment group, 11 cases (4.6%) in the ticagrelor group and 4 cases (1.7%) in the intensive dose group, with statistically significant differences among the 3 groups (χ 2=19.28, P<0.05), and the differences between the conventional treatment group and the ticagrelor group (χ 2=6.59, P=0.010) and between the conventional treatment group and the intensive dose group (χ 2=16.83, P<0.001) were statistically significant, whereas the difference between the ticagrelor group and the intensive dose group was not statistically significant ( P>0.05). In the 3 groups, there was 1 case (0.4%) of severe bleeding in the conventional treatment group, 6 cases (2.5%) in the ticagrelor group and none in the intensive dose group, which showed statistically significant differences (χ 2=7.23, P<0.05), and there was statistically significant difference between the ticagrelor group and the intensive dose group ( P=0.030). Among the patients with intermediate CYP2C19 metabolism, there were 13 cases (13/158, 8.2%) with 90-day recurrent stroke in the conventional treatment group, 4 cases (4/153, 2.6%) in the ticagrelor group, and 0 case (0/159) in the intensive dose group, with statistically significant difference (χ 2=16.04, P<0.001), and the differences between the intensive dose group and the conventional treatment group were statistically significant (χ 2=13.64, P<0.001), whereas there was no statistically significant difference between the intensive dose group and the ticagrelor group ( P>0.05). In the patients with 90-day recurrent stroke in the intensive dose group, there was 0 case (0/159) with intermediate metabolism and 4 cases (4/77,5.2%) with poor metabolism, with statistically significant differences ( P=0.011), whereas there were no statistically significant differences in the conventional treatment group and the ticagrelor group ( P>0.05). Conclusions:Screening carriers of CYP2C19 loss-of-function alleles by point-of-care testing can quickly and precisely guide the treatment of patients with non-cardiogenic HR-NICE. An intensive clopidogrel dose of 150 mg, once a day combined with aspirin was effective in reducing stroke recurrence with less occurrence of any bleeding and adverse events, and patients with intermediate CYP2C19 metabolism may be the best population to benefit.