Immune cell-related prognostic risk model and tumor immune environment modulation in esophageal carcinoma based on single-cell and bulk RNA sequencing.

BACKGROUND: Immune cells play a pivotal role in the tumor microenvironment, exerting significant influence on tumor progression and patient outcomes, but the current biomarkers are insufficient to fully capture the complex and diverse tumor immune microenvironment and the impact of immunotherapy. METHODS: The advent of single-cell sequencing allows us to explore the tumor microenvironment at an unprecedented resolution, enabling the identification and characterization of distinct subsets of immune cells, thereby paving the way for the development of prognostic models using immune cells. Leveraging single-cell data, our study deeply investigated the intricacies of immune microenvironment heterogeneity in esophageal carcinoma. RESULTS: We elucidated the composition, functionality, evolution, and intercellular communication patterns of immune cells, culminating in the construction of an independent prognostic model at the single-cell level. Furthermore, we conducted a comprehensive analysis of disparities in immune infiltration and immune checkpoint expression between patients categorized into high- and low-risk groups, which may impact patient prognosis. CONCLUSION: In summary, our study harnessed multiomics data to delineate the immune profile of esophageal carcinoma patients, provide a method for leveraging molecular signatures of immune cells to identify potential biomarkers, while concurrently providing evidence for the potential benefits of immunotherapy.

A Probiotic Targets Bile Acids Metabolism to Alleviate Ulcerative Colitis by Reducing Conjugated Bile Acids.

SCOPE: Gut microbiota (GM) dysbiosis and dysregulated bile acids (BAs) metabolism have been linked to ulcerative colitis (UC) pathogenesis. The possibility of utilizing live probiotics with a defined BAs-metabolizing capability to modify the composition BAs for UC treatment remains unexplored. METHODS AND RESULTS: In this study, Strain GR-4 is sourced from traditional Chinese fermented food, "Jiangshui," and demonstrated the ability to deconjugate two common conjugated BAs by over 69% and 98.47%, respectively. It administers strain GR-4 to dextran sulfate sodium (DSS)-induced UC mice, and observes an overall alleviation of UC symptoms, as evidence by improved colon morphology, reduces inflammation and oxidative stress, and restores intestinal barrier function. Importantly, these effects are reliant on an intact commensal microbiota, as depletion of GM mitigated GR-4s efficacy. Metabolomics analysis unveils a decline in conjugated BAs and an increase in secondary BAs following GR-4 administration. GM analysis indicates that GR-4 selectively enriches bacterial taxa linked to BAs metabolism, enhancing GM's capacity to modify BAs. CONCLUSION: This research demonstrates the potential for natural fermented foods and probiotics to effectively manipulate BAs composition, including conjugated and secondary BAs, to alleviate UC symptoms, underscoring the benefits of these approaches for gut health.

Design, synthesis and evaluation of a myricetin and nobiletin hybrid compound for alleviating hyperuricemia based on metabolomics and gut microbiota.

Hyperuricemia (HUA) is the fourth most common basic metabolic disease that can cause damage to multiple organs throughout the body. In this study, a hybrid compound consisting of myricetin and nobiletin was synthesized and its biological activity was evaluated. We named the hybrid compound MNH, and its structure was confirmed by spectroscopy. This study used serum metabolomics profiling with LC/MS and 16S rRNA gene sequencing analysis to explore the anti-HUA efficacy of MNH on a yeast paste-induced mouse model. The results showed that serum uric acid (UA), creatinine (CRE) and urea nitrogen (BUN) levels were significantly decreased after the intervention of MNH. The efficacy of MNH in lowering UA was somewhat greater than that of myricetin and nobiletin. In addition, MNH could repair the renal histopathological damage. Moreover, serum metabolomics demonstrated that MNH regulated the metabolic pathways involved in glycerophospholipid metabolism, arachidonic acid metabolism and alanine etc. Furthermore, MNH supplementation restored the composition of gut microbiota with remarkable reductions in Lactobacillus and Limosilactobacillus and significant elevations in norank_f_Muribaculaceae and Bacteroides at the genus level. Taken together, these results indicated that MNH might represent a protective effect against HUA via modulating gut microbiota and metabolomics.

Correction: Formal synthesis of cyclotheonellazole A.

Correction for 'Formal synthesis of cyclotheonellazole A' by Bohua Long et al., Org. Biomol. Chem., 2023, https://doi.org/10.1039/d3ob00038a.

Concise Enantioselective Total Synthesis of Isopavine Alkaloids.

Herein, we report a concise asymmetric total synthesis of isopavine alkaloids, which feature a special azabicyclo[3.2.2]nonane tetracyclic skeleton. The key steps include iridium-catalyzed asymmetric hydrogenation of unsaturated carboxylic acids, Curtius rearrangement, and Eschweiler-Clarke methylation, which enable an enantioselective approach to isopavine alkaloids in 6-7 linear steps. Furthermore, for the first time, isopavine alkaloids, especially (-)-reframidine (3), are found to display effective antiproliferative effects on various cancer cell lines.

Influence of axial rotation on measurement of medial proximal tibial angle / 中国骨伤

OBJECTIVE@#To measure and compare medial proximal tibial angle (MPTA) of lower limbs under different axial rotation angles(neutral position, 30° internal rotation, 30° external rotation) on the load position radiographs, and explore changes and significance of MPTA measured within and between groups of tibia at different axial rotation positions.@*METHODS@#From January 2018 to December 2018, 40 patients with knee osteoarthritis (KOA) were selected, with a total of 80 limbs, including 12 males and 28 females, aged from 29 to 73 years old with an average of (59.6±12.7) years old. Full length radiographs of the lower limbs were taken on neutral tibia position, 30° internal rotation and 30° external rotation, respectively. MPTA was measured and the results were compared between groups and within groups.@*RESULTS@#MPTA measured on the left lower extremity of neutral tibia, 30° internal rotation and 30° external rotation were (86.08±2.48) °, (88.62±2.94) ° and (83.47±3.10) °, respectively. MPTA measured on the right lower limb were (86.87±1.97) °, (89.02±2.39) ° and (83.80±2.77) °, respectively, and there were no significant difference in MPTA measured between rotation angle group (P>0.05). While there were statistical difference in MPTA on the same limb between groups (P<0.05). On 30° internal rotation, MPTA of left and right lower limbs increased by (2.54±1.74) ° and (2.15±1.78) ° compared with tibia neutral position. On 30° external rotation, MPTA of left and right lower limbs decreased (2.61±2.03) ° and (3.07±1.75) ° compared with tibial neutral position.@*CONCLUSION@#When a full-length X-ray film is taken on the weight-bearing position of both lower limbs, if there is axial rotation or external rotation of tibia, MPTA will increase or decrease compared with neutral position, which may cause a certain degree of deviation in clinical operation based on the accurate measurement of MPTA. However, the extent to which this bias affects the clinical operation effect remains to be verified. In addition, limited by the total number of samples and the number of measurement groups, whether there is a linear relationship between MPTA deviation and tibial axial rotation needs to be further studied.

Influence of interaction between hypertension and abdominal obesity on the prevalence of diabetes / 上海预防医学

ObjectiveTo explore the effect of interaction of hypertension and abdominal obesity on morbidity of diabetes and to provide the scientific bases for preventing diabetes. MethodsA total of 11 914 people who took the physical examination in 2019 were examined with cluster sampling method for the interaction analysis. The data was collected by physical measurements and laboratory tests. SPSS 16.0 and interaction models were used for data analysis. ResultsIn the subjects there were 75.19% with abdominal obesity， 47.99% with hypertension， 16.26% with diabetes， and 39.42% had abdominal obesity plus hypertension. Multivariate logistic regression analysis showed， after adjusting gender and age， the abdominal obesity（OR=1.29， 95%CI：1.14‒1.46） and hypertension （OR=2.93， 95%CI： 2.63‒3.26） were related to high risk of diabetes. There was no multiplicative interaction effect between abdominal obesity and hypertension （OR=0.98，95%CI： 0.76‒1.27）. The additive interaction was significant between abdominal obesity and hypertension with RERI=0.53（95%CI：0.09‒0.98）， AP=0.14（95%CI：0.02‒0.26）， and SI=1.24（95%CI：1.01‒1.52）. ConclusionThere is a synergistic effect on morbidity of diabetes between abdominal obesity and hypertension. The improvement of weight and control of blood pressure could prevent significantly the diabetes.

Evaluation of knee cartilage based on MRI artificial intelligence reconstruction model of knee joint / 中华骨科杂志

Objective:To explore the feasibility of the AI intelligent reconstruction model based on knee joint magnetic resonance data developed by Nuctech Company Limited for evaluating knee cartilage injury.Methods:Thirty-three patients (a total of forty-one knees) who were hospitalized with severe knee osteoarthritis in Beijing Tsinghua Changgung Hospital from May 2021 to April 2022 were selected. All of them were planned to be performed total knee arthroplasty (TKA) for the treatment of knee osteoarthritis. Fifteen males with an average age of 71±5 years old and twenty six females with an average age of 71±9 years old were included in this study. There were 19 cases of left knee and 22 cases of right knee. Thin layer MRI examination on the patients' knee joints was performed before the surgery, and artificial intelligence model based on the thin layer MRI data of the knee joint was reconstructed. The cartilage part of the model was selected and corrected by Principal Component Analysis (PCA) in order to realize model straightening. The tibial plateau cartilage of knee joint which intercepted during operation was classified according to the International Cartilage Repair Society (ICRS). Finally the results were compared with the ICRS classification results of knee artificial intelligence reconstruction model and artificial recognition of knee joint MRI images.Results:Compared with the grade of cartilage injury intercepted during our operation which was according to the ICRS classification, the sensitivity of artificial intelligence reconstruction model for the diagnosis of cartilage injury with ICRS classification grade four was 93.1%. The specificity of artificial intelligence reconstruction model was 91.4%. The positive predictive value (PPV) of artificial intelligence reconstruction model was 92.2%. And the negative predictive value (NPV) of artificial intelligence reconstruction model was 80.3%. The area under ROC curve (AUC) was 0.92. The ICRS classification consistency between artificial intelligence model and physical inspection results was good with kappa value 0.81 ( P<0.001) . In the aspect of artificial recognition of cartilage injury grading in MRI images, the sensitivity of artificial recognition was 92.10% compared with the manual identification of cartilage injury classification in MRI images. The specificity of artificial recognition was 91.60%. The positive predictive value (PPV) of artificial recognition was 97.20% and the negative predictive value (NPV) of artificial recognition was 78.8%. The kappa value of the cartilage injury classification in MRI images consistency between artificial recognition and manual identification was 0.79 ( P<0.001). Conclusion:Based on the evaluation of cartilage injury by AI reconstruction model of knee joint, the sensitivity and specificity of the diagnosis of ICRS grade IV cartilage injury can be acceptable, but still needs to be improved.

Design, synthesis and biological evaluation of a novel colchicine-magnolol hybrid for inhibiting the growth of Lewis lung carcinoma in Vitro and in Vivo.

Colchicine is a bioactive alkaloid originally from Colchicum autumnale and possesses excellent antiproliferative activity. However, colchicine-associated severe toxicity, gastrointestinal side effects in particular, limits its further therapeutic use. In the current study, we thus designed and synthesized a novel hybrid (CMH) by splicing colchicine and magnolol, a multifunctional polyphenol showing favorable gastrointestinal protection. The antitumor activity of CMH in Lewis lung carcinoma (LLC) was then evaluated in vitro and in vivo. Biologically, CMH inhibited the growth of LLC cells with an IC50 of 0.26 µM, 100 times more potently than cisplatin (26.05 µM) did. Meanwhile, the cytotoxicity of CMH was 10-fold lower than that of colchicine in normal human lung cells (BEAS-2B). In C57BL/6 mice xenograft model, CMH (0.5 mg/kg) worked as efficacious as colchicine (0.5 mg/kg) to inhibit tumor growth and 2 times more potently than cisplatin (1 mg/kg). In terms of mortality, 7 out of 10 mice died in colchicine group (0.75 mg/kg), while no death was observed in groups receiving CMH or cisplatin at 0.75 mg/kg. Mechanistic studies using Western blot revealed that CMH dose-dependently suppressed the protein expression of phosphorylated ERK. Molecular docking analysis further indicated that CMH was well fitted in the colchicine binding site of tubulin and formed several hydrogen bonds with tubulin protein. These results enable our novel hybrid CMH as a potential antineoplastic agent with lower toxicity, and provide perquisites for further investigation to confirm the therapeutic potentiality of this novel hybrid.

Efficient synthesis of novel colchicine-magnolol hybrids and evaluation of their inhibitory activity on key proteases of 2019-nCoV replication and acute lung injury.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV), is a life-threatening infectious condition. Acute lung injury is a common complication in patients with COVID-19. 3-chymotrypsin-like protease (3CLpro) of 2019-nCoV and neutrophil elastase are critical targets of COVID-19 and acute lung injury, respectively. Colchicine and magnolol are reported to exert inhibitory effects on inflammatory response, the severe comorbidity in both COVID-19 and acute lung injury. We thus designed and synthesized a series of novel colchicine-magnolol hybrids based on a two-step synthetic sequence. It was found that these novel hybrids provided unexpected inhibition on 3CLpro and neutrophil elastase, a bioactivity that colchicine and magnolol did not possess. These findings not only provide perquisites for further in vitro and in vivo investigation to confirm the therapeutic potentiality of novel colchicine-magnolol hybrids, but also suggest that the concurrent inhibition of 3CLpro and neutrophil elastase may enable novel colchicine-magnolol hybrids as effective multi-target drug compounds.

Sleep quality and sleep disturbances in Chinese pregnant women: a multicenter cross-sectional study / 中华耳鼻咽喉头颈外科杂志

Objective: This study aims to investigate the sleep quality of pregnant women in Xuhui District, Shanghai, and the related factors of sleep disturbances during pregnancy. Methods: From February 2019 to February 2021, we used online integrated sleep questionnaire (including PSQI, BQ, ESS, AIS) in Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital, The International Peace Maternity and Child Health Hospitals of China Welfare Institution, and Shanghai Eighth People's Hospital, to investigate the sleep quality across pregnancy. We also collected maternal physical examination results, childbearing history, sociodemographic, and other clinical data. The prevalences and related factors of various sleep disturbances in pregnant women were analyzed, including insufficient/excessive nighttime sleep, low sleep efficiency, difficulty falling asleep, poor sleep quality, insomnia, daytime sleepiness, and high risk of sleep-disordered breathing (SDB). Results: This study includes 1 898 cases in the first trimester (T1), 3 099 cases in the second trimester (T2), and 1 539 cases in the third trimester (T3). Poor sleep quality (38.6%), daytime sleepiness (mild 41.9%, moderate 17.7%, severe 2.1%), and suspicious insomnia (32.3%) are most prevalent among women in T1 (P<0.01). In comparison, short sleep time (2.7%), long sleep time (8.6%), difficulty falling asleep (12.2%), poor sleep efficiency (35.4%), very poor sleep quality (6.7%), clinical insomnia (21.8%), and high-risk SDB (6.4%) are most prevalent among women in T3 (P<0.05). During pregnancy, late gestation (OR=1.016, 95%CI: 1.006-1.025) and multiple induced/drug abortions (OR=1.329, 95%CI: 1.043-1.692) are risk factors for poor sleep quality (PSQI>5), while multiple full-term deliveries (OR=0.800, 95%CI: 0.675-0.949) is its protective factor. Advanced maternal age (OR=0.976, 95%CI: 0.956-0.997), multiple full-term deliveries (OR=0.808, 95%CI: 0.680-0.959), late gestation (OR=0.983, 95%CI: 0.974-0.992) and hypertension (OR=0.572, 95%CI: 0.401-0.814) are protective factors for daytime sleepiness (ESS>6). The high-risk pregnancy category (OR=9.312, 95%CI: 1.156-74.978) is a risk factor for insomnia (AIS≥4), while multiple full-term deliveries (OR=0.815, 95%CI: 0.691-0.961) is its protective factor. High BMI (OR=1.334, 95%CI: 1.270-1.402) and hypertension (OR=4.427, 95%CI: 2.539-7.719) are risk factors for high-risk SDB in pregnant women. Conclusions: The prevalences of various sleep disturbances are high throughout pregnancy. Noticeably, symptoms of maternal SDB develop along with pregnancy. Different types of sleep disturbances are associated with different factors. Women of high-risk pregnancy category, in late gestation, with high BMI, hypertension, a history of induced/drug abortion, or without a history of full-term delivery can be at high risk of sleep disturbances during pregnancy.

The prevalence of myopic refractive error and its associated risk factors among primary school students in a community in Shanghai / 上海预防医学

Objective To analyze the prevalence of myopic refractive error and its associated risk factors among primary school students in Shanghai Minhang Distict. Methods A total of 11 356 primary school students who participated in the children's refraction screening project in Meilong Community， Minhang District， Shanghai from January 1 to December 31， 2019 were selected for visual inspection and computer optometry Results The detection rate of myopic refractive error among 6-10 year-old students was 45.59%， with a higher rate in girls and older age group. The detection rates of 6-10 year-old students were 22.88% （6 year-old）， 31.77% （7 year-old）， 47.62% （8 year-old）， 60.53% （9 year-old） and 69.84% （10 year-old）， respectively， showing a linear trend（χ 2=1.31， P<0.001）. Multivariate logistic regression revealed that myopic refractive error was statistically significantly associated with gender， age and parents' myopic. Birth weight， preterm birth and body mass index （BMI） had no influence on refractive myopic in primary school students. Conclusion Myopic refractive error is still a major public health problem in primary school students. A combined strategies for myopic refractive error reduction should be called to focus on high risk persons and behaviors.

Evaluation of acetabular anteversion after total hip arthroplasty / 中国骨伤

OBJECTIVE@#To investigate whether the anteversion angle of acetabular prosthesis can be evaluated on the anteroposterior X-ray film of common double hip joint.@*METHODS@#Total 32 patients(41 hips) after total hip arthroplasty were selected, including 18 males and 14 females, aged(66.2±4.1) years. All patients completed the positive X-ray film of both hips and plain CT scan of pelvis after operation. Acetabular anteversion was measured by plain CT scan of pelvis, and measured by Saka and other measurement formulas on X-ray film.@*RESULTS@#The acetabular anteversion measured by X-ray film was(16.2±5.0)° and that measured by CT was (31.8±9.7)°(P=0.00). In addition, there was a significant linear correlation between X-ray film and CT(Pearson correlation coefficient (r=0.84, P=0.00).@*CONCLUSION@#CT can accurately measure the acetabular anteversion, but it has obvious disadvantages, such as large radiation, high cost, phantom CT artifact and so on. Although Saka measurement formula can not directly obtain the accurate acetabular anteversion as CT measurement, it has a high correlation with the acetabular anteversion measured by CT. Therefore, the method proposed in this study can also preliminarily evaluate the acetabular anteversion.

Clinical study on lymph node dissection of gastrocolic ligament in colon cancer at hepatic flexure / 中华普通外科杂志

Objective:To investigate the regularity of lymph node metastasis of gastrocolic ligament in colon cancer at hepatic flexure,and to explore the feasibility and necessity of the dissection.Methods:The dissection number and the metastasis number of gastrocolic lymph nodes in 96 patients with colon cancer on the hepatic flexure were analyzed retrospectively.The related factors affecting the lymph node metastasis of gastrocolonic ligament were analyzed.Results:Lymph node metastasis of gastrocolic ligament was found in 7 of 96 patients, and the metastasis rate was 7%. Metastasis was found in all three parts of gastrocolic lymph node. Gastrocolic lymph nodes metastasis were related to perineural invasion,tumor budding, N stage and intestinal obstruction (all P<0.05). Conclusion:The dissection of gastrocolic lymph node of hepatic flexure colon cancer is safe and feasible, and can provide more accurate pathological staging, which provides a basis for follow-up adjuvant therapy.

Obstructive sleep apnea and metabolic syndrome: an association study based on a large sample clinical database / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the prevalence and associated risk factors of metabolic syndrome (MS) in patients with obstructive sleep apnea (OSA). Methods: From July 2007 to June 2017, a total of 8 155 adult subjects, including 6 484 males and 1 671 females, aged 18-90 (43.13±12.28), body mass index 14.61~59.56 (25.59±3.98) kg/m2,who were admitted to the Department of Otorhinolaryngology head and Neck surgery of The Sixth People's Hospital affiliated to Shanghai Jiao Tong University, were retrospectively analyzed. All patients underwent polysomnography and biochemical tests. Subjects were divided into four groups (non-OSA, mild OSA, moderate OSA, and severe OSA) according to OSA severity. The prevalence of MS was expressed as percentage, and the correlation between OSA and MS and its characteristic pathophysiological indicators was evaluated by logistic regression model after adjusting for factors such as gender, age, BMI, neck circumference, hip circumference, smoking and alcohol consumption, and was expressed by odds ratio (OR). SPSS 25.0 software was used for statistical analysis. Results: The overall prevalence of MS was 43.6%, and that of non-/mild/moderate/severe OSA group was 18.6%, 30.4%, 43.8%, 57.1%.Logistic regression showed that patients with mild/moderate/severe OSA had an increased risk of MS compared with non-OSA patients, with adjusted OR values and confidence intervals of 1.27 (1.05-1.54), 1.84 (1.53-2.22), and 2.08 (1.76-2.46), respectively (P<0.01).In addition, indicators of OSA anoxic burden [oxygen drop index(Toxygen=7.1), minimum blood oxygen(Tminimum=56.3), blood oxygen saturation below 90% cumulative time ratio (TCT90=10.6) ]were closely associated with MS disease(P<0.01), but sleep fragmentation index (arousals index) was not significantly associated with MS disease. Conclusion: The risk of MS gradually increases with the severity of OSA, and the indicators reflecting OSA hypoxia burden are closely related to MS disease.

Efficacy of Han-uvulopalatopharyngoplasty (HUPPP) combined with radiofrequency ablation of tongue base or HUPPP with traction of tongue base on moderate to severe patients with obstructive sleep apnea hypopnea syndrome (OSAHS):a multicenter randomized controlled trial / 中华耳鼻咽喉头颈外科杂志

Objective: To compare the therapeutic efficacy of Han-uvulopalatopharyngoplasty (HUPPP) combined with radiofrequency ablation of tongue base or HUPPP with traction of tongue base on moderate to severe patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: This is a multicenter randomized controlled trial. From March 2017 to July 2019, moderate to severe OSAHS patients from three clinical center in Shanghai who were intolerant to continuous positive airway pressure (CPAP) and with velopharyngeal and glossopharyngeal plane obstruction were enrolled in this study. According to the surgical type, they were 1∶1 randomized to HUPPP plus radiofrequency ablation of tongue base group (Ablation group) or HUPPP plus traction of tongue base group (Traction group). All patients completed over-night standard Polysomnography (PSG), upper-airway assessment (Friedman classification, Müller test, CT and cephalometric examination), preoperative routine examination, Epworth Sleepiness Scale (ESS) and Quebec sleep questionnaire (QSQ). Six to 12 months after operation, all the above-mentioned examinations were repeatedly performed. Changes of aforementioned variables before and after operation were assessed. Results: A total of 43 patients with moderate to severe OSAHS were enrolled in this study. One patient lost to follow-up, the remaining 21 were allocated to Ablation group and 21 were allocated to Traction group. The total therapeutic efficacy of all patients was 69.05% (61.90% in Ablation group and 76.19% in Traction group), but there was no statistical significance between the two groups (P= 0.317). The value of sleep scale score (ESS and QSQ), objective sleep variables (apnea-hypopnea index, oxygen saturation, percentage of time with blood oxygen less than 90% in total sleep time, oxygen desaturation index and micro-arousals) and upper airway cross-sectional area (palatopharyngeal and retrolingual area) of the two groups were improved (P<0.05), but the differences between the two groups were not statistically significant (P>0.05). Conclusion: For moderate to severe OSAHS who had glossopharyngeal plane obstruction, both HUPPP plus radiofrequency ablation of tongue base or HUPPP plus traction of tongue base are effective treatment for OSAHS, and the curative effect is similar. The choice of surgical type could be selected according to patient's or surgical conditions.

Enantioselective Total Syntheses of Pentacyclic Homoproaporphine Alkaloids.

Herein we report the first enantioselective total syntheses of pentacyclic homoproaporphine alkaloids by means of a route, which includes a tandem retro-oxa-Michael addition and nucleophilic substitution to generate the oxa-benzobicyclco[3.3.1]nonane core structure, a Pictet-Spengler cyclization to construct the fused B and C rings, and sequential Baeyer-Villiger oxidation and pinacol-type cyclization to install the hydroxyl-lactol moiety of D ring. With this unified route, six pentacyclic homoproaporphine alkaloids have been synthesized enantioselectively.

"Acupuncture stimulation of Yamen (GV 15), Fengfu (GV 16), Baihui (GV 20), Shuigou (GV 26) and Hegu (LI 4) reduces brain microglia activation in a traumatic brain injury rat model".

OBJECTIVE: To evaluate the effect of acupuncture on neuroinflammation in traumatic brain injury (TBI) rats by stimulating Yamen (GV 15), Fengfu (GV 16), Baihui (GV 20), Shuigou (GV 26) and Hegu (LI 4) acupoints and to investigate the mechanism underpinning this effect. METHODS: A TBI model was induced in Sprague- Dawley rats using Feeney's freefall impact method. Acupuncture to stimulate the Yamen (GV 15), Fengfu (GV 16), Baihui (GV 20), Shuigou (GV 26) and Hegu (LI 4) acupoints was performed on the TBI rats. After 3 consecutive days of acupuncture treatment, we investigated signal molecules, receptors and microglia related to neuroinflammation in brain tissue of the TBI rats and analyzed the possible mechanism underlying the effect of acupuncture on neuroinflammation. RESULTS: After the acupuncture treatment, ionized calcium binding adaptor molecule 1(Iba1), a protein specific to microglia, was investigated. In the cortical layer of damaged brain tissue in TBI rats, the Iba1-positive area was 3.3% ± 0.9% in the rats that received acupuncture compared with 5.2% ± 1.4% in the TBI rats that did not receive acupuncture, and the microglia were smaller with more slender protrusions in the acupuncture-treated rats. This result indicates that acupuncture can significantly reduce microglia activation in TBI rats. A possible mechanism for this effect is that acupuncture reduces the expression of autotaxin and lysophosphatidic acid. Together, these constitute the autotaxin-lysophosphatidic acid axis, which induces microglial activation in the brains of TBI rats. Acupuncture treatment may downregulate the expression of Lysophosphatidic acid (LPA) receptor (LPAR) 1 and LPAR2 on the microglial cytomembrane, which affects the microglia activation process. CONCLUSION: Acupuncture stimulating the Yamen (GV 15), Fengfu (GV 16), Baihui (GV 20), Shuigou (GV 26) and Hegu (LI 4) acupoints can effectively inhibit the development of neuroinflammation after TBI. One possible mechanism for this effect is that acupuncture downregulates LPA synthesis and affects the LPA-LPAR pathway by inhibiting LPAR1 and LPAR2, thereby inhibiting microglial activation and reducing neuroinflammation.

Manual acupuncture relieves microglia-mediated neuroinflammation in a rat model of traumatic brain injury by inhibiting the RhoA/ROCK2 pathway.

OBJECTIVE: To investigate the regulatory mechanism of manual acupuncture (MA) on microglial polarization-mediated neuroinflammation after traumatic brain injury (TBI), focusing on the RhoA/Rho-associated coiled coil-forming protein kinase (ROCK2) pathway. METHODS: Sprague Dawley (SD) rats were used to generate a TBI model using Feeney's freefall epidural impact method. MA was performed on half of the TBI model rats, while the others remained untreated. Acupuncture was administered at GV15, GV16, GV20, GV26, and LI4. At the end of the intervention, rat brain tissue samples were collected, and the microglial M1 polarization status was observed by immunofluorescence labeling of CD86, an M1 microglia-specific protein. RhoA/ROCK2 signaling components were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. An enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of inflammatory factors. RESULTS: Compared with normal rats, the CD86 expression density in the untreated TBI model rats was high and showed an aggregated expression pattern. The genes and proteins of the RhoA/ROCK2 signaling pathway were highly expressed, and inflammatory factors were significantly increased. The CD86 expression density in TBI rats after MA was reduced compared to that in untreated TBI rats and showed a scattered distribution. The expression of RhoA/ROCK2 signaling pathway genes and proteins was also significantly reduced, and inflammatory factors were decreased. CONCLUSION: These results show that MA may inhibit M1 polarization of microglia by regulating the RhoA/ROCK2 signaling pathway, thereby reducing neuroinflammation in TBI.

Methylenetrahydrofolate Reductase Gene C677T Polymorphism and Diabetic Retinopathy: a Meta-Analysis / 中国医学科学杂志(英文版)

Objective To investigate the association between the methylenetetrahydrofolate reductase gene C677T (MTHFR C677T) polymorphism and diabetic retinopathy (DR). Methods A total of 6971 subjects including 2707 DR patients and 4264 controls from 23 studies were enrolled in the study. A random-effects model was applied to estimate the overall effects and the stratified effects of the MTHFR C677T polymorphism on the risk of DR, and study quality was also assessed. Results Strong associations were observed between the MTHFR C677T polymorphism and DR. The carries of MTHFR C677T were more likely to be found in the DR group in relative to the healthy control group with odds ratio 1.68, 2.55, and 2.31 respectively in allele contrast model (T vs. C, 95%CI: 1.29-2.18, P<0.001, I 2=78.4%), homozygous model (TT vs. CC, 95%CI: 1.70-3.83, P=0.008, I 2=54.4%) and dominant model (TT+CT vs. CC, 95%CI: 1.62-3.29, P<0.001, I 2=74.7%). This association can also be found in contrast to the Ncd (non-complicated diabetic mellitus) group (allele contrast, OR=1.50, 95%CI: 1.07-2.11, P=0.032, I 2=62.1%; homozygous, OR=2.39, 95%CI: 1.06-5.38, P=0.017, I 2=66.7%; dominant, OR=1.59, 95%CI: 0.97-2.62, P=0.056, I 2=56.5%). For the heterozygous model (CT vs. CC), the association was significant in contrast to the healthy control group (OR=1.46, 95%CI: 1.64-3.69, P=0, I 2=77.3%), while in contrast to the Ncd control group the association was not statistically meaningful (OR=1.38, 95%CI: 0.87-2.18, P=0.131, I 2=43.7%). For the recessive model, 1.92-fold increased risk was found only in contrast to the Ncd control group (95%CI: 1.07-3.43, P=0.064, I 2=55.0%). There was no significant association found in the models in contrast to the DM control group. Conclusion In this meta-analysis, we found an association between the MTHFR C677T polymorphism and DR, especially in contrast to the Ncd control group. Further studies are required to establish more definite relationship.