Regio- and stereoselective access to highly substituted vinylphosphine oxides via metal-free electrophilic phosphonoiodination of alkynes.

In general, the P-centered ring-opening of quaternary phosphirenium salts (QPrS) predominantly leads to hydrophosphorylated products, while the C-centered ring-opening is primarily confined to intramolecular nucleophilic reactions, resulting in the formation of phosphorus-containing cyclization products instead of difunctionalized products generated through intermolecular nucleophilic processes. Here, through the promotion of ring-opening of three-member rings by iodine anions and the quenching of electronegative carbon atoms by iodine cations, we successfully synthesize ß-functionalized vinylphosphine oxides by the P-addition of QPrS intermediates generated in situ. Multiple ß-iodo-substituted vinylphosphine oxides can be obtained with exceptional regio- and stereo-selectivity by reacting secondary phosphine oxides with unactivated alkynes. In addition, a variety of ß-functionalized vinylphosphine oxides converted from C-I bonds, especially the rapid construction of benzo[b]phospholes oxides, demonstrates the significance of this strategy.

Combining pathological risk factors and T, N staging to optimize the assessment for risk stratification and prognostication in low-risk stage III colon cancer.

BACKGROUND: This study aimed to investigate the combined pathological risk factors (PRFs) to stratify low-risk (pT1-3N1) stage III colon cancer (CC), providing a basis for individualized treatment in the future. PATIENTS AND METHODS: PRFs for low-risk stage III CC were identified using COX model. Low-risk stage III CC was risk-grouped combining with PRFs, and survival analysis were performed using Kaplan-Meier. The Surveillance, Epidemiology, and End Results (SEER) databases was used for external validation. RESULTS: Nine hundred sixty-two stage III CC patients were included with 634 (65.9%) as low risk and 328 (34.1%) as high risk. Poor differentiation (OS: P = 0.048; DFS: P = 0.011), perineural invasion (OS: P = 0.003; DFS: P < 0.001) and tumor deposits (OS: P = 0.012; DFS: P = 0.003) were identified as PRFs. The prognosis of low-risk CC combined with 2 PRFs (OS: HR = 3.871, 95%CI, 2.004-7.479, P < 0.001; DFS: HR = 3.479, 95%CI, 2.158-5.610, P < 0.001) or 3 PRFs (OS: HR = 5.915, 95%CI, 1.953-17.420, P = 0.002; DFS: HR = 5.915, 95%CI, 2.623-13.335, P < 0.001) was similar to that of high-risk CC (OS: HR = 3.927, 95%CI, 2.317-6.656, P < 0.001; DFS: HR = 4.132, 95%CI, 2.858-5.974, P < 0.001). In the SEER database, 18,547 CC patients were enrolled with 10,023 (54.0%) as low risk and 8524 (46.0%) as high risk. Low-risk CC combined with 2 PRFs (OS: HR = 1.857, 95%CI, 1.613-2.139, P < 0.001) was similar to that of high-risk CC without PRFs (HR = 1.876, 95%CI, 1.731-2.033, P < 0.001). CONCLUSION: Combined PRFs improved the risk stratification of low-risk stage III CC, which could reduce the incidence of undertreatment and guide adjuvant chemotherapy.

ErZhiTianGui Decoction alleviates age-related ovarian aging by regulating mitochondrial homeostasis and inhibiting ferroptosis.

AIM: This study was designed to investigate the pharmacological effects and mechanisms of ErZhiTianGui Decoction (EZTG) for age-related ovarian aging in mice. METHODS: This study used naturally aging mice as a model, and EZTG was used for intragastric administration. Ovarian pathological changes, as well as follicular reserve were assessed by hematoxylin and eosin staining, and serum hormone levels (anti-mullerian hormone, follicle-stimulating hormone), mitochondrial reactive oxygen species (ROS) and mitochondrial DNA (mtDNA) damage marker 8-hydroxy-2'-deoxyguanosine(8-OHdG), and lipid peroxidation markers glutathione(GSH) and malondialdehyde(MDA) were determined by enzyme-linked immunosorbent assay. Mitochondrial membrane potential (MMP) levels in ovaries were determined using flow cytometry. The levels of PINK1 and Parkin were observed using immunofluorescence staining. Mitochondrial-derived vesicles (MDVs) and mitochondrial morphology were observed using electron microscopy. Prussian blue staining was used to observe iron ion aggregation in ovarian tissue. The Iron assay kits detected total iron levels. Western blot was used to detect the expression of proteins related to mitochondrial and ferroptosis related genes. RESULTS: After EZTG treatment, aged mice showed increased ovarian reserve, improved serum hormone levels, increased MMP, GSH levels, and decreased mitochondrial ROS, 8-OHdG, and MDA levels. Immunofluorescence staining showed decreased levels of PINK1 and Parkin, and the same trend was observed for the Western blot. Meanwhile, electron microscopy showed that EZTG improved the mitochondrial morphology in the ovaries of aged mice. EZTG also decreased the total iron and protein levels of Acyl-CoA synthetase long-chain family4 (ACSL4) and increased the protein level of glutathione peroxidase 4 (GPX4) in the ovaries of aged mice. CONCLUSIONS: EZTG can maintain PINK1/Parkin-mediated mitochondrial homeostasis, reduce the lipid peroxidation caused by the accumulation of ROS, and inhibit the occurrence of ferroptosis and delaying ovarian aging. These findings suggest that EZTG may be a promising drug for treating age-related ovarian aging in females.

Which patients with coronary artery disease should include oral nitrates on their discharge medication list?

BACKGROUND: Which patients with coronary artery disease (CAD) should have oral nitrates on their discharge medication list after coronary angiography (CAG)? To assess the relationship between oral nitrates included in the discharge medication list and major adverse cardiovascular events (MACEs) among CAD patients, we designed this retrospective cohort study. METHODS: A total of 2979 CAD patients hospitalised in the Department of Cardiology, Affiliated Hospital of Jining Medical University from May 2013 to October 2015 were enrolled, grouped according to whether oral nitrates were included at discharge after CAG, and followed up for MACEs for a mean of 4.42 years after discharge. The primary endpoint was MACEs. Multivariate Cox proportional hazards models were used to analyses potential confounding factors. Stratified analysis was used to observe the relationship between oral nitrates and MACEs by different covariates. RESULTS: The median follow-up time was 4.61 years, and 296 (9.94%) patients experienced MACEs. Multivariate Cox proportional hazards model analysis showed no association between oral nitrates on the discharge medication list and the occurrence of MACEs among patients with CAD (p > 0.05) after adjusting for some covariates, such as SYNTAX score (hazard ratio (HR): 1.18, 95% confidence interval (CI): 0.90-1.55, p = 0.2420). Stratified analysis revealed a higher incidence of MACEs among hypertensive patients prescribed oral nitrates at discharge (HR: 1.67, 95% confidence CI: 1.13-2.46, p = 0.0046). However, prescribing nitrates at discharge for patients with low uric acid levels increased the incidence of MACEs, which showed a possible trend towards significance (HR: 1.44, 95% CI: 0.99-2.09, p = 0.0525). CONCLUSION: There was no association between oral nitrates included in the discharge medication list and the development of MACEs among patients with CAD after adjusting for some covariates, such as SYNTAX score. Oral nitrates after discharge for CAD patients combined with hypertension increased the occurrence of MACEs. Oral nitrates after discharge for CAD patients combined with low uric acid levels may increase theoccurrence of MACEs, and close monitoring for any adverse events is recommended.

Quantitative analysis of macular capillaries in diabetic patients using optical coherence tomography angiography / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To quantify early changes of macular capillary parameters in type 2 diabetic patients using optical coherence tomography angiography(OCTA).METHODS: Retrospective case study. A total of 49 healthy subjects, 52 diabetic patients without retinopathy(noDR)patients, and 43 mild nonproliferative diabetic retinopathy(mNPDR)patients were recruited. Capillary perfusion density, vessel length density(VLD), and average vessel diameter(AVD)were calculated from macular OCTA images(3 mm×3 mm)of the superficial capillary plexus after segmenting large vessels and the deep capillary plexus. Parameters were compared among control subjects, noDR, and mNPDR patients. The area under the receiver operating characteristic curve estimated the abilities of these parameters to detect early changes of retinal microvascular networks.RESULTS: Significant differences were found in the VLD and AVD among the three groups(P&#x0026;#x003C;0.001). Compared with the control group, the noDR group had significantly higher AVD(P&#x0026;#x003C;0.05). VLD of both layers in patients of mNPDR group was significant decreased compared with that of noDR group(all P&#x0026;#x003C;0.01). Deep AVD had a higher area under the curve(AUC)of 0.796 than other parameters to discriminate the noDR group from the healthy group. Deep AVD had the highest AUC of 0.920, followed by that of the deep VLD(AUC=0.899)to discriminate the mNPDR group from the healthy group.CONCLUSIONS: NoDR patients had wider AVD than healthy individuals and longer VLD than mNPDR patients in both layers. When compared with healthy individuals, deep AVD had a stronger ability than other parameters to detect early retinal capillary impairments in noDR patients.

Association of age-related hearing loss with cognitive impairment and dementia: an umbrella review.

Background: Hearing loss, cognitive impairment and dementia have become common problems for older adults. Currently, systematic reviews and meta-analyses of the association between age-related hearing loss (ARHL) with cognitive impairment and dementia may have inconsistent results. To explore and validate the association between ARHL with cognitive impairment and dementia through summarizing and evaluating existing evidence. Methods: From inception to February 01, 2023, PubMed, Web of Science, Embase, and Cochrane Library databases were systematically searched. AMSTAR 2 was used to evaluate methodological quality and GRADE system was used to evaluate evidence quality. We summarized the basic characteristics of the included studies and extracted effect data for ARHL with cognitive impairment and dementia. Forest plots were used to describe the relative risk associated with ARHL and cognitive impairment, and the relative risk associated with ARHL and dementia, respectively. Results: A total of 11 systematic reviews and meta-analyses met the inclusion criteria. Overall, the methodological quality of the included SRs/MAs was moderate and the quality of the evidence was low. The combined results found that the pooled risk ratio of ARHL and cognitive impairment was 1.30 (random-effects; 95% CI 1.16 to 1.45), and the pooled risk ratio of ARHL and dementia was 1.59 (random-effects; 95% CI 1.34 to 1.90). Conclusion: Based on the evidence reported in this umbrella review, age-related hearing loss is significantly associated with cognitive impairment and dementia. Hearing loss may be a high risk factor for cognitive impairment and dementia in older adults.

Effects of Friction Stir Welding on the Mechanical Behaviors of Extrusion-Based Additive Manufactured Polymer Parts.

The friction stir welding (FSW) of thermoplastic polymers is gradually receiving attention because of its advantages including high efficiency and pollution-free manufacturing. The extrusion-based additive manufacturing (EAM) of polymers has also become one of the main processing methods for thermoplastic parts. In this paper, a hybrid manufacturing method for the FSW process and EAM technology is proposed and explored. The effects of the FSW process using two different welding tools on the mechanical behaviors of 3D printing polymer parts were compared and investigated and the corresponding mechanism was analyzed. The results show that the appropriate welding tool is beneficial for eliminating the anisotropy and decreasing the porosity of 3D-printed parts. Therefore, the improving effects of the FSW process on the mechanical behaviors of the EAM parts are verified. The mechanism was attributed to the high-speed rotation of the welding tool with the appropriate shape, which can promote the flow of polymer melt in the welding region, leading to the formation of dense structures caused by the entanglement of the molecular chains. This study may provide some assistance in modern industrial manufacturing for the processing of large custom components.

De novo mutation of NAXE (APOAIBP)-related early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-1: A case report.

BACKGROUND: Early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-1 (PEBEL1) is a rare autosomal recessive severe neurometabolic disease. The aim of this study was to investigate the clinical characteristics and genetic pathogenicity of PEBEL1 caused by rare NAXE (or APOA1BP)-related defects. CASE SUMMARY: The patient was a girl aged 2 years and 10 mo. She was hospitalized due to walking disorder for > 40 d. The clinical manifestations were ataxia, motor function regression, hypotonia, and eyelid ptosis. Within 1 mo of hospitalization, she developed sigh breathing, respiratory failure, cerebellar edema and brain hernia, and finally she died. Changes were found in cranial imaging, including cerebellar edema accompanied by symmetrical myelopathy. Through whole exome sequencing, we detected NAXE compound heterozygous variation (NM 144772.3) c.733A>C (p. Lys245Gln, dbSNP: rs770023429) and novel variation c.370G>T (p.Gly124Cys) in the germline gene. The clinical features and core phenotypes of this case were consistent with 18 previously reported cases of PEBEL1. CONCLUSION: This is the first case of NAXE-related PEBEL1 with severe clinical phenotype in Mainland China. The p.Gly124Cys mutation discovered in this case has enriched the pathogenic variation spectrum of NAXE.

Novel Sulfonamide Derivatives Containing a Piperidine Moiety as New Bactericide Leads for Managing Plant Bacterial Diseases.

Plant bacterial diseases are an intractable problem due to the fact that phytopathogens have acquired strong resistances for traditional pesticides, resulting in restricting the quality and yield of agricultural products around the world. To develop new agrochemical alternatives, we prepared a novel series of sulfanilamide derivatives containing piperidine fragments and assessed their antibacterial potency. The bioassay results revealed that most molecules displayed excellent in vitro antibacterial potency towards Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas axonopodis pv. citri (Xac). In particular, molecule C4 exhibited outstanding inhibitory activity toward Xoo with EC50 value of 2.02 µg mL-1, which was significantly better than those of the commercial agents bismerthiazol (EC50 = 42.38 µg mL-1) and thiodiazole copper (EC50 = 64.50 µg mL-1). A series of biochemical assays confirmed that compound C4 interacted with dihydropteroate synthase, and irreversibly damaged the cell membrane. In vivo assays showed that the molecule C4 presented acceptable curative and protection activities of 34.78% and 39.83%, respectively, at 200 µg mL-1, which were greater than those of thiodiazole and bismerthiazol. This study highlights the valuable insights for the excavation and development of new bactericides that can concurrently target dihydropteroate synthase and bacterial cell membranes.

Construction of a predictive model for cognitive impairment risk in patients with advanced cancer.

AIMS: The purpose of this study was to identify risk factors for cognitive impairment in advanced cancer patients and to develop predictive models based on these risk factors. BACKGROUND: Cancer-related cognitive impairment seriously affects the quality of life of advanced cancer patients. However, neural network models of cognitive impairment in patients with advanced cancer have not yet been identified. DESIGN: A cross-sectional design was used. METHODS: This study collected 494 questionnaires between January and June 2022. Statistically significant clinical indicators were selected by univariate analysis, and the artificial neural network model and logistic regression model were used for multivariate analysis. The predicted value of the model was estimated using the area under the subject's working characteristic curve. RESULT: The artificial neural network and the logistic regression models suggested that cancer course, anxiety and age were the major risk factors for cognitive impairment in advanced cancer patients. All the indexes of artificial neural network model constructed in this study are better than those of the logistic model. CONCLUSION: The artificial neural network model can better predict the risk factors of cognitive impairment in patients with advanced cancer. Better prediction will enable nurses and other healthcare professionals to provide better targeted and timely support.

Anticancer Effect of Chlorambucil Enhanced by Chiral Phthalidyl Promoiety.

Phthalidyl promoiety has been used in several drugs, but they were all marketed in racemic form. The pharmaceutical effects of each enantiomer have not been clearly demonstrated. In this project, an anticancer chemotherapy drug, chlorambucil, was modified as enantiopure phthalidyl prodrugs. The enantiomers, together with phthalidyl unit and their racemic mixture, were then subject to the in vivo bioactivity tests against B16F10 melanoma cells. It was found that proper chirality within the promoiety had noticeably better in vivo pharmacological effects than the parent drug, the enantiomer and racemic mixture. This merit perhaps could be extended from the phthalidyl prodrugs to other chirality containing prodrugs.

In vitro bacteriostatic and serum pharmacological tests of Qiguiyin decoction combined with levofloxacin against pseudomonas aeruginosa / 中国药理学通报

Aim To investigate the antibacterial activity and anti-resistant mutation ability of Qiguiyin decoction (a traditional Chinese herbal formula) combined with levofloxacin against pseudomonas aeruginosa byantibacterial experiment in vitro and serum pharmacology. Methods The minimal inhibitory concentrations (MICs) of levofloxacin and Qiguiyin decoction were detected respectively by the broth dilution technique.The MIC of the combination of two drugs was determined by the micro chessboard dilution method. The effects of combined drugs on enhancing the antibacterial activity of different strains were evaluated respectively by calculating the fractional inhibitory concentration index (FICI). The drug-containing serum of levofloxa-cin group, Qiguiyin decoction group, Qiguiyin decoction combined with levofloxacin group and control group was prepared. The antibacterial rate, MIC and MBC of 10% ~ 90% serum against the two strains were determined. Results Combined with Qiguiyin decoction, MIC of levofloxacin against pseudomonas aeruginosa (standard/resistant) decreased significantly, 0. 5 < FICI

Dapagliflozin regulates myocardial SK2 protein expression in diabetic rats / 中国药理学通报

Aim To investigate the effect of dapagliflozin on the small conductance calcium-activated potassium channel 2 (SK2 channel) protein in the myocardium of diabetic rats and its possible mechanism of action. Methods In vivo: type 2 diabetes model was established by high-glucose and high-fat diet combined with intraperitoneal injection of low-dose streptozotocin (35 mg

Study on the strategy of medical security for rare diseases in China from the perspective of public concern and emotion：taking nosinasine as an example / 中国药房

OBJECTIVE To mine the focus and emotional attitude of the public on rare diseases， and to provide decision- making reference for relevant departments to formulate and implement relevant policies， systems and strategies for medical security of rare diseases. METHODS Latent Dirichlet allocation （LDA） topic model and sentiment analysis method were used to analyze the comment text of short videos related to the “nosinasine” medical insurance admission event on the Bilibili video website， mine the theme and sentiment tendency of the text， and put forward relevant strategy suggestions. RESULTS A total of 8 videos with tens of thousands of playback and 7 109 text data were obtained. According to the LDA analysis， online public paid attention to 9 topics related to rare diseases （the price of rare disease drugs， the inclusion of rare disease drugs in medical insurance， the status quo of research and development of rare disease drugs， the scope of medical insurance and the medical security system， the plight of rare disease patients， the prevention and screening of rare diseases， the value of rare disease drugs in medical insurance， the Chinese and western medical methods of rare diseases， and the supply and demand status of rare disease drugs）， which could be summarized into 4 categories according to the objects of concern （rare disease drugs， rare disease medical insurance， rare disease medical and health services and rare disease patient groups）. On the whole， the emotional tendency of the Internet public towards each topic showed a low positive and high negative tendency. CONCLUSIONS The public paid more attention to the price， research and development， supply and demand of rare disease drugs， and was deeply worried about the current medical status of rare diseases in China. To strengthen and improve the medical security for patients with rare diseases， such as actively carrying out public health services for rare diseases， strengthening cooperation in the diagnosis and treatment of rare diseases， and researching rare disease drugs， etc. Chinese medical and health departments can make concerted efforts in medical and health services， drug supply security， medical security and other social security.

Clinical analysis of 11 patients with neuroendocrine carcinoma in maxillofacial region / 中华口腔医学杂志

Objective: To investigate the clinicopathological features, treatment and prognosis of maxillofacial neuroendocrine carcinoma. Methods: A total of 11 patients with maxillofacial neuroendocrine carcinoma diagnosed in the Department of Pathology of The First Affiliated Hospital of Zhengzhou University from December 2010 to July 2022 were retrospectively enrolled, including 8 males and 3 females, aged (65.2±9.5) years (ranged from 49 to 87 years), with a disease course of 0.5 to 6.0 months. The clinicopathological data including head and neck CT, MRI and treatment methods were analyzed. Results: Submandibular gland and maxilla were involved in 3 cases, parapharynx in 2 cases, and face, tongue root and soft palate in 1 case respectively. Clinically, the initial symptom is a rapidly growing painless or tender mass, which may be accompanied by restricted mouth opening, dysphagia, and local numbness after invasion of masticatory muscles and nerves. The tumors were all invasive and low-density, with unclear boundaries from the surrounding tissues. Among the patients, 9 received surgical treatment, and 5 received adjuvant treatment after surgery (2 received chemotherapy, 3 received radiotherapy+chemotherapy). According to the 5th edition of the World Health Organization classification of head and neck tumors in 2022, there were 1 case (1/11) with poorly differentiated large cells and 10 cases (10/11) with poorly differentiated small cells. Histologically, the macrocell type is composed of large cells with rough chromatin, obvious vacuolar nucleolus, protruding nucleolus, and necrosis. The small cell type is dominated by small blue round cells with neuroendocrine characteristics, with active growth and multifocal necrosis. Immunohistochemical staining showed that cytokeratin (CK), epithelial membrane antigen (EMA) and synaptophysin (Syn) were diffusively expressed, 10 cases expressed CD56, 8 cases expressed p63, 6 cases expressed weakly punctated chromograin-A (CgA), and S-100 was not expressed. The Ki-67 index ranges from 20 to 90 percent. By the end of follow-up (0.5 to 127.0 months), 3 patients were alive, and the mean progression-free survival (21.0 months) of postoperative chemoradiotherapy patients was significantly longer than that of surgery and/or chemotherapy alone (3.3 months). Conclusions: Maxillofacial neuroendocrine carcinoma is characterized by low differentiation of small cells, high degree of malignancy and poor prognosis. Radical surgery combined with chemoradiotherapy has better local control effect.

Correlation analysis and benchmark dose study on bone metabolic biochemical index of low doses of exposed hydrogen fluoride workers / 中华劳动卫生职业病杂志

Objective: To analyze correlation of occupational hydrogen fluoride exposure to low doses of bone metabolism index through occupational epidemiological investigation and benchmark dose calculation. Methods: In May 2021, using cluster sampling method, 237 workers exposed to hydrogen fluoride in a company were selected as the contact group, and 83 workers not exposed to hydrogen fluoride in an electronics production company were selected as the control group. The external exposure dose and urinary fluoride concentration, blood and urine biochemical indicators of the workers was measured.The relationship between external dose and internal dose of hydrogen fluoride was analyzed. The external dose, urinary fluoride was used as exposure biomarkers, while serum osteocalcin (BGP), serum alkaline phosphatase (AKP) and urinary hydroxyproline (HYP) were used as effect biomarkers for bone metabolism of hydrogen fluoride exposure. The benchmark dose calculation software (BMDS1.3.2) was used to calculate benchmark dose (BMD) . Results: Urine fluoride concentration in the contact group was correlated with creatinine-adjusted urine fluoride concentration (r=0.69, P=0.001). There was no significant correlation between the external dose of hydrogen fluoride and urine fluoride in the contact group (r=0.03, P=0.132). The concentrations of urine fluoride in the contact group and the control group were (0.81±0.61) and (0.45±0.14) mg/L, respectively, and the difference between the two groups was statistically significant (t=5.01, P=0.025). Using BGP, AKP and HYP as effect indexes, the urinary BMDL-05 values were 1.28, 1.47 and 1.08 mg/L, respectively. Conclusion: Urinary fluoride can sensitively reflect the changes in the effect indexes of biochemical indexes of bone metabolism. BGP and HYP can be used as early sensitive effect indexes of occupational hydrogen fluoride exposure.

Gene mutation profiles and clinicopathological features of patients with non-small cell lung cancer harboring KRAS G12C mutation: a single-center retrospective study / 中华病理学杂志

Objective: To accurately screen non-small cell lung cancer (NSCLC) patients with KRAS G12C mutation and to evaluate their clinicopathological features, prognostic factors and current treatment status. Methods: A total of 19 410 NSCLC cases diagnosed at the Department of Pathology of Shanghai Chest Hospital, Shanghai, China from January 2018 to September 2021 were retrospectively reviewed, and the cases with KRAS gene mutation detected by next-generation sequencing were included. The clinicopathological and genetic mutation data of these cases were collected and analyzed. Results: A total of 1 633 (8.4%) NSCLC patients carried a KRAS gene mutation, among whom G12C was the most frequent (468 cases, 28.7%) mutant subtype. The mutation was more commonly found in males (414/468, 88.5%), patients with a history of smoking (308/468, 65.8%), and patients with a pathological type of invasive adenocarcinoma (231/468, 49.4%). The most common co-mutated genes in KRAS G12C mutant NSCLC were TP53 (52.4%, 245/468), STK11 (18.6%, 87/468) and ATM (13.2%, 62/468). The proportion of PD-L1 expression (≥1%) in KRAS G12C mutant NSCLC was significantly higher than that in patients without G12C mutation [64.3% (90/140) vs. 56.1% (193/344), P=0.014]. Immune checkpoint inhibitors (ICIs) treatment significantly prolonged progression-free survival (PFS) in NSCLC patients (10.0 months vs. 5.0 months, P=0.011). However, combination of chemotherapy and ICIs with anti-angiogenesis inhibitors or multi-target inhibitors did not significantly improve PFS in patients with KRAS G12C mutant NSCLC (P>0.05). Patients with KRAS G12C mutation NSCLC treated with ICIs and KRAS G12C patients with TP53 mutation had significantly longer median PFS than those with STK11 mutation (9.0 months vs. 4.3 months, P=0.012). Conclusions: Patients with KRAS G12C mutant NSCLC have relatively higher levels of PD-L1 expression and can benefit from ICIs treatment. The feasibility of chemotherapy, ICIs therapy and their combination needs further investigation.

Mitochondrial Function Reveals Connotation of "Seven-Seven" Theory of Huangdi's Internal Classic and Mechanism of Herbal Intervention for Elderly Women Undergoing IVF-ET / 中国实验方剂学杂志

ObjectiveTo study the changes of mitochondrial function of ovarian granulosa cells in women of different ages and the effect of Erzhi-Tiangui prescription on in vitro fertilization-embryo transfer （IVF-ET） outcomes for elderly women， so as to verify the connotation of the "Seven-Seven" theory in the Huangdi's Internal Classic （《黄帝内经》）. MethodA total of 150 infertility patients undergoing IVF-ET at the Reproductive and Genetic Center of Integrative Medicine， Affiliated Hospital of Shandong University of Traditional Chinese Medicine were recruited and assigned into "hree-Seven/Four-Seven （30 cases）， Five-Seven （60 cases）， and Six-Seven （60 cases） groups according to the "Seven-Seven" theory. The Five-Seven and Six-Seven groups were further assigned into control and Chinese medicine subgroups using the random number plus envelope method， and the Chinese medicine group was administrated with Erzhi Tiangui prescription from the start day of controlled ovulation stimulation cycle to the trigger day. The IVF outcome was observed， and Western blot was employed to determine the levels of mitofusin 1 （MFN1）， mitofusin 2 （MFN2）， and dynamin-related protein 1 （Drp1） in the ovarian granulosa cells. ResultCompared with the Three-Seven/Four-Seven group， the control subgroups of the Five-Seven and Six-Seven groups showed decreased retrieved oocytes， two pronuclear （2PN） embryos， available embryos， high-quality embryos， clinical pregnancy rate， and live birth rate （P<0.05）. Moreover， the control subgroup of the Six-Seven group showed decreased fresh embryo transfer rate（P<0.05）. Compared with the control subgroup of the Five-Seven group， that of the Six-Seven group showed reduced retrieved oocytes， 2PN embryos， available embryos， high-quality embryos， and clinical pregnancy rate （P<0.05）. The Chinese medicine subgroup had more retrieved oocytes， 2PN oocytes， and available embryos than the control subgroup in the Five-Seven groups （P<0.05）. The Chinese medicine subgroup had more retrieved oocytes， than the control subgroup in the Six-Seven groups （P<0.05）. The control subgroup of the Six-Seven group showed lower expression levels of Mfn1 and Mfn2 and higher level of Drp1 than the control subgroup of the Five-Seven group （P<0.05）， which indicated that the levels of Mfn1 and Mfn2 in ovarian granulosa cells were down-regulated while the expression of Drp1 was up-regulated with aging （P<0.05）. The Chinese medicine subgroup had higher Mfn2 level and lower Drp1 level than the control subgroup in the Five-Seven group （P<0.05）， and the Chinese medicine subgroup had higher Mfn1 and Mfn2 levels and lower Drp1 level than then control subgroup in the Six-Seven group （P<0.05）. ConclusionsThe prognosis of IVF in women after "Five-Seven" became worse with aging， and the mitochondria in ovarian granulosa cells showed decreased fusion ability and increased fission， which verified the connotation of the "Seven-Seven" theory from the mitochondrial function. Erzhi Tiangui prescription can regulate the mitochondrial function of ovarian granulosa cells in elderly women， up-regulate the expression levels of Mfn1 and Mfn2 to promote mitochondrial fusion， and down-regulate the expression of Drp1 to reduce mitochondrial fission， thus alleviating the ovarian hypofunction caused by aging， improve the development potential of oocytes， and improve the IVF outcomes of elderly women. However， this prescription has limited efficacy for the elderly women in the age range of "Six-Seven".

Exploration of hapten-induced atopic dermatitis murine models for non-clinical pharmacodynamics study of drugs / 药学学报

Atopic dermatitis (AD) is a chronic, relapsing, inflammatory dermatosis with a variety of clinical manifestations and difficult to cure. Currently, many AD drug candidates have entered the research and development pipeline. In order to provide technical specifications for the clinical development of AD drugs, the Center for Drug Evaluation of National Medical Products Administration released the "Technical Guidelines for Clinical Trials of Drugs for AD Treatment" (Draft for Comments) in November 2022. Non-clinical pharmacodynamics evaluation is an important research before the drug enters clinical trials. Oxazolone (OXA)- and 2,4-dinitro-fluorobenzene (DNFB)-induced models are the most popular classical hapten-induced AD murine models, but variations of modeling are existing in the methods from different studies, including sensitization sites, haptens' dosages, the period of challenges, and the skin lesions severity evaluation as well. In this study, the investigation of OXA- and DNFB-induced AD murine models with various conditions of modeling was performed to compare the characteristics of hapten-induced AD murine models in the pathological process and severity according to the appearance of AD patients, and the guidance of pharmacodynamics evaluation of AD-therapeutic drugs in clinical trials as well, which may provide a proposal for AD treatment drug candidates in the non-clinical pharmacodynamics evaluation. All animal experiments were approved by the Animal Care & Welfare Committee of Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (approval No.: 00007782 and 00007784).

HPV vaccination in China based on website platform information / 上海预防医学

ObjectiveTo analyze the online public Q&A texts on HPV vaccine， focus on the important issues related to HPV vaccination and cervical cancer prevention in China， and propose strategies and suggestions. MethodsThe latent Dirichlet allocation （LDA） topic model was employed to extract key topics of 15 565 Q&A texts related to HPV vaccines from the social Q&A platform "Zhihu". The Baidu AI sentiment analysis tool was used to analyze the emotional tendencies of the texts corresponding to each topic， and the topics were classified based on the strategic coordinate method. ResultsOnline users focused on eight topics about HPV vaccine information. Among them， vaccination knowledge， HPV vaccination hesitation， and HPV vaccine development and marketing belonged to the low positivity-high negativity emotional topics， HPV infection and high-risk factors belonged to the low positivity-low negativity emotional topics， and HPV vaccine appointment channels， comparison between domestic and imported vaccines， HPV vaccines and cervical cancer prevention， and HPV vaccine types and selection were grouped under high positivity-low negativity emotional topics. ConclusionPublic concerns regarding HPV vaccines can be classified into three major dimensions： health knowledge， health beliefs， and health behaviors. Overall， the public's views and attitudes towards vaccine-related issues are not optimistic. Strengthening science publicity and education， enhancing vaccine supervision， and encouraging enterprises’ innovative research and development capability are effective strategies to improve public awareness of cervical cancer prevention and accelerate the full HPV vaccination coverage.