Effects of Bisphenol A and Its Substitute, Bisphenol F, on the Gut Microbiota in Mice / 生物医学与环境科学（英文）

OBJECTIVE@#The aim of this study was to assess the impact of bisphenol A (BPA) and its substitute, bisphenol F (BPF), on the colonic fecal community structure and function of mice.@*METHODS@#We exposed 6-8-week-old male C57BL/6 mice to 5 mg/(kg∙day) and 50 μg/(kg∙day) of BPA or BPF for 14 days. Fecal samples from the colon were analyzed using 16S rRNA sequencing.@*RESULTS@#Gut microbiome community richness and diversity, species composition, and function were significantly altered in mice exposed to BPA or BPF. This change was characterized by elevated levels of Ruminococcaceae UCG-010 and Oscillibacter and decreased levels of Prevotella 9 and Streptococcus. Additionally, pathways related to carbohydrate and amino acid metabolism showed substantial enrichment.@*CONCLUSION@#Mice exposed to different BP analogs exhibited distinct gut bacterial community richness, composition, and related metabolic pathways. Considering the essential role of gut bacteria in maintaining intestinal homeostasis, our study highlights the intestinal toxicity of BPs in vertebrates.

Factors associated with loss to follow-up before and after treatment initiation among patients with tuberculosis: A 5-year observation in China.

Background: Loss to follow-up (LTFU) is a significant barrier to the completion of anti-tuberculosis (TB) treatment and a major predictor of TB-associated deaths. Currently, research on LTFU-related factors in China is both scarce and inconsistent. Methods: We collected information from the TB observation database of the National Clinical Research Center for Infectious Diseases. The data of all patients who were documented as LTFU were assessed retrospectively and compared with those of patients who were not LTFU. Descriptive epidemiology and multivariable logistic regression analyses were conducted to identify the factors associated with LTFU. Results: A total of 24,265 TB patients were included in the analysis. Of them, 3,046 were categorized as LTFU, including 678 who were lost before treatment initiation and 2,368 who were lost afterwards. The previous history of TB was independently associated with LTFU before treatment initiation. Having medical insurance, chronic hepatitis or cirrhosis, and providing an alternative contact were independent predictive factors for LTFU after treatment initiation. Conclusion: Loss to follow-up is frequent in the management of patients with TB and can be predicted using patients' treatment history, clinical characteristics, and socioeconomic factors. Our research illustrates the importance of early assessment and intervention after diagnosis. Targeted measures can improve patient engagement and ultimately treatment adherence, leading to better health outcomes and disease control.

Advancements in virtual screening techniques for study of enzyme inhibitor compounds / 中国中药杂志

Enzymes are closely associated with the onset and progression of numerous diseases, making enzymes a primary target in innovative drug development. However, the challenge remains in identifying compounds that exhibit potent inhibitory effects on the target enzymes. With the continuous expansion of the total number of natural products and increasing difficulty in isolating and enriching new compounds, traditional high-throughput screening methods are finding it increasingly challenging to meet the demands of new drug development. Virtual screening, characterized by its high efficiency and low cost, has gradually become an indispensable technology in drug development. It represents a prominent example of the integration of artificial intelligence with biopharmaceuticals and is an inevitable trend in the rapid development of innovative drug screening in the future. Therefore, this article primarily focused on systematically reviewing the recent applications of virtual screening technology in the development of enzyme inhibitors and explored the prospects and advantages of using this technology in developing new drugs, aiming to provide essential theoretical insights and references for the application of related technologies in the field of new drug development.

Association between periconceptional supplementation of folic acid or multiple-micronutrients containing folic acid and preterm delivery in women / 北京大学学报(医学版)

OBJECTIVE@#To explore the association between periconceptional supplementation of folic acid or multiple-micronutrients containing folic acid(MMFA) and risk of preterm delivery in women with natural conception, singleton pregnancy and vaginal delivery.@*METHODS@#A retrospective cohort study was performed based on the prenatal health care system and hospital information system of Tongzhou Maternal and Child Health Hospital of Beijing and the women who had their prenatal care in the hospital from January 2015 to December 2018 were included. The information of 16 332 women who conceived naturally, had a singleton pregnancy, and delivered vaginally was collected. Compliance scores were constructed based on the time of initiation and the frequency of taking nutritional supplements. The association between maternal periconceptional micronutrient supplementation, including pure folic acid (FA) pills or MMFA and the rate of preterm delivery was evaluated using Logistic regression models.@*RESULTS@#The preterm delivery rate (gestational week < 37 weeks) of the study population was 3.8%, and the mean (standard deviation) of gestational age was (38.98±1.37) weeks. A total of 6 174 (37.8%) women took FA during the periconceptional period, 8 646 (52.9%) women took MMFA, and 1 512 (9.3%) women did not take any nutritional supplements. The association between periconceptional supplementation of FA or MMFA and risk of preterm delivery in women was not statistically significant [adjusted odds ratio (aOR)=1.01, 95%CI: 0.74-1.37]. The associations with preterm birth were not statistically significant in further analysis by the type of nutritional supplements, time of initiation, and the frequency of supplementation. In addition, the association between the compliance score of taking supplements and the rate of preterm delivery was not statistically significant, either.@*CONCLUSION@#This study did not find an association between the risk of preterm delivery and the use of FA or MMFA during the periconcep-tional period in women with natural conception, singleton pregnancy, and vaginal delivery. In the future, multicenter studies with large-scale prospective cohort or population-based randomized controlled trials are warranted to confirm the association between taking FA or MMFA during the periconceptional period and preterm delivery among women.

Pharmacokinetics effect of 8 components of Baizhu Shaoyao San with processing method based on UPLC-MS/MS / 国际中医中药杂志

Objective:To explore the pharmacokinetics effect of 8 components of processed Baizhu Shaoyao San on rats.Methods:The rats were divided into processing group and unprocessing group, administered with decoction of Baizhu Shaoyao San by gavage respectively. Then, blood was collected from fundus vein at certain time to obtain the plasma. Finally, the contents of 8 components in plasma were detected and compared by UPLC-MS/MS method, and the methodology of the experiment was tested. The drug concentration in blood and the collection time of blood were analyzed by DAS software, and the time curves of different groups were obtained, the pharmacokinetic parameters were calculated.Results:The blood peak concentration, peak time, area under the drug time curve, and average residence time of 8 components in the serum of rats in the raw product group and the fried product group were different to varying degrees.Conclusion:Processed Baizhu Shaoyao San could influence the behavior of the components measured in rats, which may affect the clinical therapeutic effect of Baizhu Shaoyao San.

Correlation and consistency of three methods for tear evaluation in the diagnosis of dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To explore the correlation and consistency of three tear assessment methods in the diagnosis of dry eye, which include the Schirmer Ⅰ test(SⅠt), tear meniscus height(TMH)measurement and a new generation of tear detection technology-Strip meniscometry tube(SMTube).METHODS: A diagnostic test study. A total of 183 dry eye outpatients(183 right eyes)in the Dry Eye Center of Henan Eye Hospital were enrolled from May to June 2021. The SⅠt, TMH and SMTube were performed on all patients, and the correlation and consistency of the measurement results were analyzed.RESULTS:The ocular surface disease index(OSDI)of all included patients was 43.75(31.25, 58.33), noninvasive breakup time(NIBUT)was 7.26(4.97, 9.37)s, and the results of SⅠt, TMH and SMTube were 6(2, 12)mm/5min, 0.18(0.14, 0.22)mm and 5(3,8)mm/5s, respectively; The results of correlation analysis: TMH was positively correlated with SMTube(rs=0.751, P<0.001), however, SⅠt had no correlation with TMH(rs=0.139, P=0.060)and SMTube(rs=0.019, P=0.799). The results of consistency analysis: TMH showed good consistency with SMTube(Kappa=0.794, P=0.044), however, SⅠt showed poor consistency with TMH(Kappa=0.271, P=0.074)and SMTube(Kappa=0.193, P=0.070)respectively.CONCLUSION:SMTube is a new, simple and convenient tool for evaluating tear volume. It has a good correlation and consistency with TMH measurement results. Therefore, it can replace TMH measurement, but cannot replace SⅠt in clinical application.

Comparative analysis of immunosuppressive therapies for myelin oligodendrocyte glycoprotein antibody-associated optic neuritis: a cohort study.

AIMS: The optimal immunosuppressive therapy (IST) in patients with myelin oligodendrocyte glycoprotein antibody-associated optic neuritis (MOG-ON) remains uncertain. This study aimed to observe the disease course of MOG-ON and evaluate the therapeutic efficacy and tolerability of conventional immunosuppressants through Chinese cohort analysis. METHODS: This bidirectional cohort study included 121 patients with MOG-ON between January 2015 and December 2018. The clinical features and annualised relapse rate (ARR) of patients with and without IST were analysed. RESULTS: The median age at onset was 17.5 years, and the sex ratio (F:M) was 1.24. Of 121 patients, 77 patients relapsed and 61 patients were younger than 18 years at disease onset. The overall median ARR of 63 patients in the non-IST group was 0.5, with 46.0% patients showing relapse at a median follow-up of 33.5 months. In the IST group, the ARR decreased from 1.75 pre-IST to 0.00 post-IST in 53 patients who received IST exceeding 6 months, with 20.8% patients showing relapse at a median follow-up of 23.8 months. The relapse rates of patients treated with rituximab (RTX) and mycophenolate mofetil (MMF) were not statistically different, but the rate of discontinuation was significantly lower in the RTX-treated group (18.2% vs 57.7%, p=0.0017). CONCLUSION: This study provides Class III evidence that both MMF and RTX may lower disease activity in patients with MOG-ON, and RTX showed better tolerability than MMF. However, observation after a single attack remains a good option because less than half of patients not on treatment suffered a relapse.

Effects of feeding patterns on sleep of infants aged 0-5 months / 中华围产医学杂志

Objective:To investigate the sleep of infants aged 0 to 5 months and explore its association with feeding patterns.Methods:A cross-sectional survey on infant sleep was conducted from February to August 2019 using "Brief Infant Sleep Questionnaire" posted on a WeChat public account, which mainly included two dimensions of sleep duration and habits. In addition, information on maternal and infant characteristics as well as feeding patterns was also collected. Multiple linear regression and multinomial logistic regression were used to analyze the association between sleep and feeding patterns.Results:This study included 28 444 singleton infants aged 0 to 5 months and their mothers from 31 provincial-level administrative regions in mainland China. The median sleep duration of infants at night and during the day was 9 h and 6 h, respectively. These infants sharing the bed with their parents accounted for 53.5% (15 221/28 444). Of all infants, 46.0% (13 092/28 444) slept on their backs; 84.7% (24 078/28 444) woke up two times or more at night; 58.3% (16 597/28 444) stayed awake 2 h or more at night; 89.7% (25 523/28 444) had a sleep latency of 1 h or more. Falling asleep while being fed was the most common way to fall asleep (40.2%, 11 426/28 444). The numbers of infants who were exclusively breastfed, exclusively formula-fed and mixed-fed were 7 164 (25.2%), 4 097 (14.4%) and 17 183 (60.4%), respectively. Compared with exclusively breastfed infants, exclusively formula-fed infants slept for shorter periods at night (a β=－0.14, 95% CI:－0.22 to－0.06, P<0.05), while mixed-fed infants slept longer (a β=0.08, 95% CI: 0.02-0.13, P<0.05). Exclusively formula-fed infants had less overall sleep time than recommended ( aOR=1.10, 95% CI: 1.00-1.21, P<0.05). Exclusively formula-fed and mixed-fed infants were less likely to sleep in cribs in separate rooms ( aOR=0.50, 95% CI: 0.44-0.56; aOR=0.35, 95% CI: 0.32-0.38; both P<0.05). Exclusively formula-fed infants were less likely to share the bed with their parents ( aOR=0.91, 95% CI: 0.83-0.99, P<0.05), but the likelihood in mixed-fed infants was high ( aOR=1.19, 95% CI: 1.11-1.27, P<0.05). Mixed-fed infants were more likely to sleep on their backs ( aOR=1.12, 95% CI: 1.06-1.18, P<0.05). Exclusively formula-fed infants were more likely to stay awake for four hours or more at night ( aOR=1.12, 95% CI: 1.01-1.25, P<0.05). Conclusions:Exclusively breastfeeding was the best feeding pattern for infant sleep quantity. But much attention should be paid to sleeping habits including sleeping place and sleeping position associated with exclusively breastfeeding to improve infant sleep and feeding.

Analysis of clinical efficacy of radiotherapy alone and concurrent chemoradiotherapy in cervical cancer patients with intermediate risk factors after surgery / 中华放射肿瘤学杂志

Objective:To retrospectively analyze the differences of survival, recurrence, acute side effects and prognostic factors between early stage (stage ⅠB-ⅡA) cervical cancer patients with intermediate risk factors receiving postoperative concurrent chemoradiotherapy (CCRT) or radiotherapy (RT) alone.Methods:Clinical data of 211 patients with intermediate risk factors after early stage cervical cancer surgery admitted to Department of Radiation Oncology of General Hospital of Ningxia Medical University from January 2016 to December 2018, were retrospectively analyzed. Among them, 91 cases were assigned in the RT group and 120 cases in CCRT group. The 3- and 5-year overall survival (OS), progression-free survival (PFS), recurrence and acute side effects were compared between two groups by Chi-square test. Univariate analysis of OS and PFS was performed by Kaplan-Meier method and log-rank test was performed. Multivariate prognostic analysis was conducted by using Cox model. Results:The 3- and 5-year OS of 211 patients were 95.0% and 93.8%, respectively. The 3- and 5-year PFS were 86.8% and 83.2%, respectively. The OS of CCRT and RT group were 93.9%, 96.5% (3-year), 91.8%, 96.5% (5-year) respectively ( χ2=1.763, P=0.184), and the PFS were 84.4%, 89.9% (3-year), 79.3%, 88.3% (5-year) ( χ2=2.619 ,P=0.106), with no difference between the two groups. The total recurrence rate was 15.64%, and there was no significant difference in the recurrence rate and recurrence area between two groups ( χ2=2.623 ,P=0.105; χ2=6.745 ,P=0.080). Locoregional recurrence and lung metastasis were the main patterns of failure. Multivariate prognostic analysis showed that pathological type might significantly affect the OS ( χ2=3.849, P=0.05), and depth of invasion significantly affected the PFS ( χ2=4.095, P=0.043). The incidence of acute gastrointestinal side effect and bone marrow suppression in the CCRT group was significantly higher than that in the RT group ( χ2=56.425, 27.833; both P<0.001). Conclusions:Patients with intermediate risk factors after early cervical cancer surgery obtain high efficacy after radiotherapy. The main patterns of failure are locoregional recurrence and lung metastasis. The pathological type may be an independent prognostic factor of OS and the depth of invasion is an independent prognostic factor of PFS. Compared with RT, CCRT increases the risk of acute gastrointestinal side effects and myelosuppression, which can be tolerated. There is no significant difference in the clinical efficacy between RT and CCRT, which remains to be validated by large sample size studies.

Clinical effects and prognosis of radiotherapy for early cervical cancer patients with postoperative lymph node metastasis / 中华放射医学与防护杂志

Objective:To retrospectively analyze the prognosis and related risk factors of lymph node metastasis in early-stage (Ⅰ B-Ⅱ A) cervical cancer patients with postoperative positive lymph nodes who were treated with intensity modulated radiotherapy (IMRT). Methods:A retrospective analysis was conducted for 292 early-stage cervical cancer patients with postoperative high and/or moderate risk factors who were treated with pelvic-abdominal IMRT with/without concurrent chemotherapy in Ningxia Medical University General Hospital from January 2016 to December 2018. These patients included 239 with negative pelvic lymph nodes and 53 with positive lymph nodes, who were incorporated into the negative group and the positive group, respectively. Multivariate and univariate analyses of the risk factors of lymph node metastasis and prognosis were performed for both groups.Results:The univariate and multivariate analyses showed that the lesion ≥4 cm, deep interstitial invasion, and the number of risk factors were independent factors influencing pelvic lymph node metastasis ( χ2 = 7.11, 9.05, 90.08, P < 0.05). There was no statistically significant difference in the 3- and 5-year OS ( P>0.05) between both groups. The 3-year disease-free survival (DFS) and 5-year DFS of the negative group were 87.6% and 84.5%, respectively, and those of the positive group were 72.5% and 69.3%, respectively ( χ2=8.59, P=0.003). Regarding failure modes, distant metastasis mainly occurred in the positive group, while local recurrence was dominant in the negative group ( χ2=9.40, P<0.05). The univariate analysis of the DFS in 53 patients with postoperative positive lymph nodes showed that deep interstitial invasion affected DFS, with statistically significant differences ( χ2 = 7.25, P < 0.05). The result of the multivariate analysis showed that the lesion size >4 cm, positive residual, and deep interstitial invasion significantly influenced the DFS ( χ2 = 4.37, 4.69, 4.39, P < 0.05). Conclusions:The lesion size, deep interstitial invasion, and risk factor number were independent factors influencing lymph node metastasis, and the DFS after radiotherapy of patients with pelvic lymph node metastasis was significantly lower than the patients with negative lymph nodes. The main recurrence type of patients with lymph node metastasis was distant metastasis. Moreover, the deep interstitial invasion was independent factor affecting the DFS of early-stage cervical cancer patients with postoperative positive lymph nodes.

Relationship between micronutrients supplementation during periconceptional period and serum concentration of vitamin E in the 1st trimester of gestational period / 北京大学学报(医学版)

OBJECTIVE@#To explore the association of maternal periconceptional folic acid or multiple micronutrients supplementation during periconceptional period and the serum vitamin E (Vit.E) concentration in the 1st trimester of gestational period.@*METHODS@#A retrospective cohort study was conducted based on the prenatal health care system and clinical laboratory information system. Totally, 22 171 pregnant women who had their prenatal health care and gave birth in Tongzhou Maternal & Child Health Hospital of Beijing from Jan. 2016 to Dec. 2018 were recruited. The usage patterns of nutritional supplements [folic acid (FA) or multiple micronutrients (MM)] during periconceptional period were independent variables, and serum Vit.E concentration and serum Vit.E concentration≥11.2 mg/L in the 1st trimester of gestational period were outcome variables for generalized linear regression model and Logistic regression model, respectively, to analyze the relationships between the independent and outcome variables.@*RESULTS@#The range of the serum Vit.E concentration in the 1st trimester of gestational period was 5.2-24.0 mg/L, and the median concentration was 10.1 (8.8-11.6) mg/L; the excess rate of the serum Vit.E of those who took MM supplementation was 0.3%, and the rates for the groups of FA only or no nutritional supplements used were both 0.1%. Compared with women without nutritional supplement or the women taking FA, the women who took MM had higher serum Vit.E levels in the 1st trimester of gestational period (both P < 0.05). The women taking FA or MM initiated before the conception showed that the serum Vit.E concentration in the 1st trimester of gestational period was higher than that after the conception (P < 0.05), and the serum Vit.E concentration of women who took regularly was higher than that of irregular taking (P < 0.05); with taking compliance elevated, the serum Vit.E concentration of the two groups of women taking FA or MM increased (P < 0.05). The risk of serum Vit.E concentration≥11.2 mg/L among the women taking MM was higher than that of the women without nutritional supplements or taking FA only [odds ratio (OR)=1.36, 95% confidence interval (95%CI): 1.21-1.53; OR=1.39, 95%CI: 1.31-1.48)]; women who took FA or MM showed a lower risk for serum Vit.E concentration≥11.2 mg/L of taking it after the conception than before, the ORs (95%CI) were 0.86 (95%CI: 0.77-0.96) and 0.88 (95%CI: 0.81-0.95), respectively; the women taking the two supplements regularly had higher risk for serum Vit.E concentration≥11.2 mg/L than irregular taking, the ORs (95%CI) were 1.16 (95%CI: 1.05-1.29) and 1.13 (95%CI: 1.04-1.22) for FA and MM users, respectively; with the compliance increasing, the women taking MM had a higher risk of serum Vit.E levels≥11.2 mg/L in the 1st trimester [OR (95%CI) was 1.10 (1.07-1.14)], but for FA users, the OR (95%CI) was 1.04(1.00-1.08).@*CONCLUSION@#Vit.E nutritional status in women in early gestational period in Beijing was generally good, and the excess rate of serum Vit.E was higher in women who took MM during periconceptional period than those without nutritional supplement or taking FA only, suggesting that women need to consider their own Vit.E nutritional status to choose the type of nutritional supplements during periconceptional period, so as to avoid related health hazards.

Force balance reconstruction of orbicularis oris in correction of unilateral cleft lip deformity.

OBJECTIVES: Short-term outcome evaluation for the correction of unilateral cleft lip deformity with a new technique. METHODS: Forty-four patients with unilateral cleft lip deformity were included in the study and in which the orbicularis oris muscle was reconstructed to achieve the optimal force balance of reconstructed orbicularis oris. The photometric two-dimensional indexes, including the philtrum oblique angle and asymmetry ratios (lip height, lip width, vertical distance from the white roll to the vermilion bottom at the Cupid's bow point, and vertical distance from the Cupid 's bow points to facial midline), were employed to measure and evaluate the outcome. RESULTS: Several indexes showed statistically significant difference, and they included the philtrum oblique angle, asymmetry ratio of the lip height, and asymmetry ratio of the vertical distance from the white roll to the vermilion bottom at Cupid ' s bow points (P<0.05). CONCLUSIONS: The results suggested that the new muscle reconstruction technique can significantly improve the short-term outcome of the correction of unilateral cleft lip deformity.

Short-term nasal symmetry repaired by force-balanced muscular reconstruction technique.

OBJECTIVES: This study aimed to compare the postoperative outcome of the new and classical muscular reconstruction technique combined with nasal internal-fixation method for secondary deformity post unilateral cleft lip repair. A rationale is provided for the further surgical improvement of secondary deformities. METHODS: Sixty patients aged 4-18 years with secondary unilateral cleft lip-nose deformity were involved in this research. The deformities of 28 patients were repaired using the muscular force balance technique through nasal internal fixation method, and 32 were repaired using classical muscular reconstruction technique. Two-dimensional analysis was used to evaluate the nose-lip morphology of pre- and post-operative patients through standardized photographs seven days after surgery. RESULTS: Compared with preoperative nasal morphology in the muscular force balance technique group, the 7-days postoperative results of this group showed the significantly improved short-term outcomes in the correction of columellar deflection, alar rim angle, nasal shape, and the symmetry of alar base width, nostril width, nostril height, alar rim angle (P<0.05). CONCLUSIONS: The new muscular reconstruction technique with nasal internal-fixation method has a significant effect on nasal repair.

Wnt7a promotes muscle regeneration in branchiomeric orbicularis oris muscle.

BACKGROUND: The orbicularis oris muscle exhibits a deficiency in cleft lip patients. Compared with the somite-derived limb muscles, the regeneration performance of the branchiomeric orofacial muscle has seldom been investigated. OBJECTIVE: This study aims to explore the possibility of augmenting the orbicularis oris muscle through the stimulus of Wnt7a. METHODS: Adult rat orbicularis oris muscle and tibialis anterior muscle were injected with recombinant human Wnt7a protein. The muscles were harvested at different time points after Wnt7a delivery. Muscle regeneration-related activity, including cell proliferation, stem cell proportion, myofiber plasticity, and total fiber number, was examined. RESULTS: Adult rat orbicularis oris muscle and tibialis anterior muscle exhibit similar regeneration-related activities after Wnt7a administration. Recombinant human Wnt7a administration resulted in enhanced cell proliferation, stem cell expansion, and fiber type remodelling in rat orbicularis oris muscle. In addition, newly formed myofibers were detected, contributing to an increased total fiber number. CONCLUSION: Wnt7a induces vigorous regeneration in rat orbicularis oris muscle. This study helps lay a foundation for developing biotherapies to combat orofacial muscle deficiency.

Maintenance Long-Term Multiple Cycles Treatment with Docetaxel in Metastatic Castration-Resistant Prostate Cancer: A Report of Three Cases.

Prostate cancer (PCa) is one of the most common types of malignancy, most patients with PCa will eventually progress to metastatic castration-resistant prostate cancer (mCRPC), which has a poor prognosis. Since 2004, chemotherapy has been approved by the FDA as the first-line treatment for mCRPC, and docetaxel-based regimens have been shown to improve both the patients' symptoms and overall survival (OS). 10 cycles of docetaxel therapy are usually given to patients with mCPRC, but there is still no consensus on the optimal number of treatment cycles. Here, we present three cases of mCRPC patients that received maintenance long-term multiple-cycles docetaxel treatment. We believe that this new treatment strategy may benefit carefully selected mCRPC patients and provide several key advantages such as maximum exposure to drugs, improvements in drug efficacy, and reduce the risk of developing drug resistance.

Pathologic complete response after neoadjuvant tislelizumab and chemotherapy for Pancoast tumor: A case report.

A 60-year-old man was hospitalized because of numbness and weakness in the right upper limb. Magnetic resonance imaging revealed a large mass in the right upper lobe invading the right eighth cervical and first thoracic nerve root. Biopsy pathology confirmed primary lung adenocarcinoma with a clinical stage of cT4N0M0 IIIA, negative for anaplastic lymphoma kinase fusion gene and epidermal growth factor receptor mutations but positive for programmed death ligand 1 (3%). Neoadjuvant tislelizumab and chemotherapy were offered to this patient with Pancoast tumor, and tumor shrinkage of 71% was achieved. After the operation, surgical pathology indicated pathologic complete response (pCR). Circulating tumor cells testing was negative after the first adjuvant treatment. In this case, we provide real-world evidence of encouraging pCR with neoadjuvant tislelizumab and chemotherapy for a patient with Pancoast tumor.

An "Umpolung Relay" Strategy: One-Pot, Twice Polarity Inversion Cascade Synthesis of Diversified [60]Fulleroindoles.

An "umpolung relay" strategy, which includes an one-pot, twice polarity inversion cascade of C60 via carbanion and carbocation polarity reversed relay pathway, has been developed for the synthesis of a diverse range of novel [60]fulleroindole derivatives.

Macrophage exosomes transfer angiotensin II type 1 receptor to lung fibroblasts mediating bleomycin-induced pulmonary fibrosis / 中华医学杂志(英文版)

BACKGROUND@#Macrophages are involved in the pathogenesis of idiopathic pulmonary fibrosis, partially by activating lung fibroblasts. However, how macrophages communicate with lung fibroblasts is largely unexplored. Exosomes can mediate intercellular communication, whereas its role in lung fibrogenesis is unclear. Here we aim to investigate whether exosomes can mediate the crosstalk between macrophages and lung fibroblasts and subsequently induce fibrosis.@*METHODS@#In vivo, bleomycin (BLM)-induced lung fibrosis model was established and macrophages infiltration was examined. The effects of GW4869, an exosomes inhibitor, on lung fibrosis were assessed. Moreover, macrophage exosomes were injected into mice to observe its pro-fibrotic effects. In vitro, exosomes derived from angiotensin II (Ang II)-stimulated macrophages were collected. Then, lung fibroblasts were treated with the exosomes. Twenty-four hours later, protein levels of α-collagen I, angiotensin II type 1 receptor (AT1R), transforming growth factor-β (TGF-β), and phospho-Smad2/3 (p-Smad2/3) in lung fibroblasts were examined. The Student's t test or analysis of variance were used for statistical analysis.@*RESULTS@#In vivo, BLM-treated mice showed enhanced infiltration of macrophages, increased fibrotic alterations, and higher levels of Ang II and AT1R. GW4869 attenuated BLM-induced pulmonary fibrosis. Mice with exosomes injection showed fibrotic features with higher levels of Ang II and AT1R, which was reversed by irbesartan. In vitro, we found that macrophages secreted a great number of exosomes. The exosomes were taken by fibroblasts and resulted in higher levels of AT1R (0.22 ± 0.02 vs. 0.07 ± 0.02, t = 8.66, P = 0.001), TGF-β (0.54 ± 0.05 vs. 0.09 ± 0.06, t = 10.00, P < 0.001), p-Smad2/3 (0.58 ± 0.06 vs. 0.07 ± 0.03, t = 12.86, P < 0.001) and α-collagen I (0.27 ± 0.02 vs. 0.16 ± 0.01, t = 7.01, P = 0.002), and increased Ang II secretion (62.27 ± 7.32 vs. 9.56 ± 1.68, t = 12.16, P < 0.001). Interestingly, Ang II increased the number of macrophage exosomes, and the protein levels of Alix (1.45 ± 0.15 vs. 1.00 ± 0.10, t = 4.32, P = 0.012), AT1R (4.05 ± 0.64 vs. 1.00 ± 0.09, t = 8.17, P = 0.001), and glyceraldehyde-3-phosphate dehydrogenase (2.13 ± 0.36 vs. 1.00 ± 0.10, t = 5.28, P = 0.006) were increased in exosomes secreted by the same number of macrophages, indicating a positive loop between Ang II and exosomes production.@*CONCLUSIONS@#Exosomes mediate intercellular communication between macrophages and fibroblasts plays an important role in BLM-induced pulmonary fibrosis.

Effect of modified vaginal cervical cerclage in the treatment of cervical insufficiency during pregnancy / 中国基层医药

Objective:To investigate the efficacy of modified vaginal cervical cerclage in the treatment of cervical insufficiency during pregnancy.Methods:The clinical data of 18 women with cervical insufficiency during pregnancy who received treatment in Changzhi Maternal and Child Health Hospital from January 2018 to January 2020 (including nine cases receiving modified Shirodkar operation and nine cases receiving modified McDonald operation) were retrospectively analyzed.Results:The operation process was successful in all 18 women, and there were no postoperative complications. After modified Shirodkar operation, the average gestational weeks were prolonged by 14.7 weeks. Six cases had a smooth vaginal delivery [full-term delivery in five cases and preterm premature rupture of membranes (35 weeks + 1 day) in one case]. Three women had a cesarean delivery [cesarean delivery at full-term in two cases, including twin pregnancy in one case and previous cesarean delivery in one case; preterm premature rupture of membranes because of chorioamnionitis (32 weeks + 1 day) with poor prognosis in one case]. The rate of holding babies home was 88.9%. After modified McDonald operation, the average gestational weeks were prolonged by 11.5 weeks. Five cases had a smooth vaginal delivery [full-term delivery in three cases, preterm premature rupture of membranes in one case (35 weeks + 3 days) and in one case (31 weeks)]. Three women had a cesarean delivery at full-term [secondary cesarean delivery in one case, twin pregnancy in one case, and preterm premature rupture of membrane because of preeclampsia in one case]. One case had infectious abortion, and the rate of holding the baby home was 88.9%.Conclusion:Selection of different modified operations according to the length of cervical canal can prolong gestational weeks and increase the survival rate of newborns. The modified vaginal cervical cerclage is simple and easy to operate with minimal damage to pregnant women, which is suitable for clinical promotion.

Cholesterol metabolism and tumor / 浙江大学学报·医学版

Cholesterol is an important lipid in the body of mammals and an essential component of membrane structures. Cholesterol homeostasis is critical for the maintenance of cellular and body activities, and is mainly regulated by the balance of cholesterol biosynthesis and the exogenous cholesterol uptake. Aberrantly regulated cholesterol metabolism promotes tumor cell proliferation，survival，invasion and metastasis，and their adaptability into the tumor microenvironment. Therefore，targeting cholesterol biosynthesis and reduction of plasma cholesterol levels and cholesterol esterification will provide new strategies for cancer treatment. This review summarizes the current understanding in cholesterol homeostasis regulation and its function in the occurence and development of cancer，as well as current metabolism-targeted cancer treatments.