Objective To assess causal associations between specific gut microbiota and different types of cancer by using the two-sample Mendelian randomization(MR)analysis method.Methods On the basis of summary statistics of gut microbiota from a genome-wide association study(GWAS)conducted in German population(n=8956),single nucleotide polymorphisms(SNPs)that were significantly associated with 430 gut microbiota features were extracted as instrumental variables(Ⅳs).Summary statistics from the GWAS of 17 types of cancer were used as outcomes.Two-sample MR analysis was used to explore the causal relationship between gut microbiota and pan-cancer,where the analysis results were dominated by inverse variance weighting.Meanwhile,sensitivity analyse of heterogeneity and horizontal pleiotropy test were done to keep the stability of results.Results The genetic susceptibility of 17 gut microbiota features was causally associated with the occurrence and development of 11 different types of cancer,respectively.Conclusion By exploring the causal relationship between different gut microbiota features and pan-cancer,this study has found a potential causal relationship between specific gut microbiota features and cancer,and these gut microbiota may become new biomarkers to provide new ideas for cancer prevention,early screening,and treatment.

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.

Closed-loop hospital management can effectivly cope with the COVID-19 pandemic. In order to ensure the continuity of treatments for hemodialysis patients under closed-loop management and minimize possible medical and infection risks, Huashan Hospital affiliated to Fudan University and 9 hospitals in Shanghai established a hemodialysis alliance in January 2021.The alliance optimized hemodialysis resources within the region through overall planning by preparing sites, materials and personnel shifts in advance, and establishing management systems and work processes to ensure that patients could be quickly and orderly diverted to other blood dialysis centers for uninterrupted high-quality hemodialysis services, in case that some hemodialysis centers in the alliance under closed-loop management.From November 2021 to April 2022, 317 of 1 459 hemodialysis patients in the alliance were diverted to other centers for treatment, accumulating 1 215 times/cases of treatments without obvious adverse reactions. The practice could provide a reference for medical institutions to quickly establish mutual support mode under major public health events.

Objective:To investigate the clinical and pathological features and immunophenotyping of keloidal cutaneous fibrous histiocytoma (FH) and dermatofibrosarcoma protuberans (DFSP) to provide evidence for clinical diagnosis and treatment.Methods:The clinical data were colleceted from March 2015 to March 2019 and retrospectively analyzed, including 12 cases of FH, 5 males and 7 females, aged 14-76 years, with average age (37.67±17.71) years and 9 cases of DFSP, 5 males and 4 females, aged 19-64 years, with average age (42.56±13.82) years. The clinical manifestations, histopathological features and immunophenotyping of FH and DFSP were compared.Results:The clinical manifestations of all cases were keloid-like lesions. All patients underwent surgical treatment. 12 cases of FH were diagnosed in the postoperation routine pathological examination and immunohistochemical staining, CD68 was positive in 10 cases, 9 cases of SMA were positive and all of S-100 were negative. 9 cases of DFSP were diagnosed and 2 cases were fibrosarcomatous DFSP among them. For the 7 cases of DFSP, CD34 were all positive, 5 cases of CD68 were negative, 6 cases of SMA were negative. For 2 cases of fibrosarcomatous DFSP, CD34, CD68 and SMA were all negative. During the follow-up period from 6 months to 4 years, there was no recurrence of FH cases, and 3 cases of DFSP recurred, 2 cases were fibrosarcomatous DFSP among them, and 1 case of fibrosarcomatous DFSP presented distant metastasis.Conclusions:The clinical manifestations and pathological features of some FH and DFSP are similar to keloids in a certain extent, and there is a little difficulty for clinical differential diagnosis. Early diagnosis and standardized treatment are crucial for prognosis.

Objective:To understand the status quo and impact of Beijing Standardized Residency Training program following three years of the medical education synergy policy from the perspective of residents.Methods:Online questionnaire was used from April to May 2018 to investigate two types of residents who had completed the program in Beijing in 2018, and a comparison was made with the 2014 training program, activities, evaluation, and support conditions. Statistical descriptions and Wilcoxon signed-rank test were used for analysis.Results:A total of 3 293 residents completed the Beijing Standardized Residency Training, of which 54.75% were resident physicians, and 45.25% were graduate students in clinical medicine. Compared with 2014, the completion rate of the disease types and quantity, clinical operation types and quantity required by the training plan has been significantly improved, with the proportions being 93.77% and 92.80%, respectively. The implementation rate of examinations in 7 departments including Internal Medicine was greater than 90%, which is significantly higher than that in 2014; The conditions for training support had improved significantly.Conclusions:The impact of Beijing Standardized Residency Training Program was already emerging since the medical education synergy policy in place. It was recommended that various measures be taken to steadily improve the quality of the " dual-track system" .

OBJECTIVE： To investigate the effects of different polar parts of 5 kinds of Alpinia on the function of sympathetic-adrenal system in gastric ulcer model rats with cold syndrome， such as the root of Alpinia officinarum， the rhizome and fruit of Alpinia galangal， the seed of Alpinia katsumadai， and the fruit of Alpinia oxyphylla. METHODS： SD rats were given Anemarrhena asphodeloides decoction at 4 ℃ and Glacial acetic acid solution intragastrically to induce gastric ulcer model with cold syndrome； the model rats were randomly divided into model group， Fuzi lizhong pills group （positive control， 9.0 g/kg）， cimetidine group （positive control， 0.003 3 g/kg）， low-dose and high-dose groups of petroleum ether， ethyl acetate， n-butanol and water extraction parts from 5 medicinal materials （hereinafter referred to as “gaoshidi” “gaoshigao” “dashidi” “dashigao” “hongshidi” “hongshigao” “caoshidi” “caoshigao” “yishidi” “yishigao” “gaoyidi” “gaoyigao” “dayidi” “dayigao” “hongyidi” “hongyigao” “caoyidi” “caoyigao” “yiyidi” “yiyigao” “gaozhengdi” “gaozhenggao” “dazhengdi” “dazhenggao” “hongzhengdi” “hongzhenggao” “caozhengdi” “caozhenggao” “yizhengdi” “yizhenggao” “gaoshuidi” “gaoshuigao” “dashuidi” “dashuigao” “hongshuidi” “hongshuigao” “caoshuidi” “caoshuigao” “yishuidi” “yishuigao”， 0.064/0.256， 0.032/ 0.128， 0.008/0.032， 0.075/0.3， 0.1/0.4， 0.064/0.256， 0.108/0.432， 0.16/0.64， 0.064/0.25， 0.125/0.5， 0.056/0.224， 0.108/0.432， 0.08/0.32， 0.2/0.8， 0.3/1.2， 0.14/0.56， 0.032/0.128， 0.028/0.112， 0.05/0.2， 0.087/0.348 g/kg， by mass of extraction parts）， with 10 rats in each group； and the blank group （normal temperature water） was set up. Next day after modeling， blank group and model group were given constant volume of normal temperature water intragastrically； administration group was given relevant solution 2 mL/100 g intragastrically， q12 h， 4 times in total. After last medication， urine contents of 17-OHCS， CAs substances （A， NE， DA） and serum contents of ACTH and D-β-H were determined by ELISA. RESULTS： Compared with blank group， the contents of 17-OHCS， A， NE and DA in urine， the contents of ACTH and D-β-H in serum were decreased significantly in model group （P＜0.01）. Compared with model group， the contents of 17-OHCS （Fuzi lizhong pills group， cimetidine group， gaoshidi， gaoshigao， dashigao， hongshigao， caoshigao and yishigao groups， ethyl acetate part groups of 5 medicinal materials， dazhenggao， hongzhenggao， caozhenggao and yizhenggao groups， gaoshuigao， dashuigao and hongshuigao groups）， A （Fuzi lizhong pills group， cimetidine group， gaoshigao， dashigao， hongshidi， hongshigao， caoshidi， caoshigao and yishigao groups， ethyl acetate part groups of 5 medicinal materials， gaozhenggao， dazhenggao， hongzhengdi， hongzhenggao， caozhenggao and yizhenggao groups， hongshuigao group）， NE （Fuzi lizhong pills group， cimetidine group， petroleum ether part， ethyl acetate part and n-butanol part groups of 5 medicinal materials， gaoshuigao， dashuigao and hongshuigao groups）， DA [Fuzi lizhong pills group， cimetidine group， petroleum ether part （except for gaoshidi group） and ethyl acetate part groups of 5 medicinal materials， gaozhenggao， dazhenggao， hongzhenggao， caozhenggao and yizhenggao groups， hongshuigao group] in urine， serum contents of ACTH [Fuzi lizhong pills group， petroleum ether part （except for gaoshidi， dashidi and caoshidi groups） and ethyl acetate part （except for dayidi and hongyidi groups） groups of 5 medicinal materials， hongzhenggao group， dashuigao group]， and D-β-H [Fuzi lizhong pills group， gaoshigao， dashigao， hongshidi， hongshigao and yishigao groups， ethyl acetate part groups of 5 medicinal materials （except for dayidi， hongyidi and yiyidi groups）， dazhenggao and hongzhenggao groups， hongshuigao group] were increased significantly （P＜0.05 or P＜0.01）. The contents of 17-OHCS and D-β-H in dashigao group， the contents of ACTH and D-β-H in caoshigao group and the contents of D-β-H in gaoshigao and yishigao groups were significantly lower than hongshigao group. The contents of DA in gaoyigao， caoyigao and yiyigao groups as well as the contents of D-β-H in gaoyigao， hongyigao， caoyigao and yiyigao groups were significantly lower than dayigao group； the contents of DA in gaoyigao and caoyigao groups were significantly lower than hongyigao group， the contents of ACTH in gaoyigao， dayigao， caoyigao and yiyigao groups were significantly higher than hongyigao group. The contents of 17-OHCS， DA and ACTH in gaozhenggao， dazhenggao， caozhenggao and yizhenggao groups， the contents of A in dazhenggao， caozhenggao and yizhenggao groups as well as the contents of D-β-H in gaozhenggao， caozhenggao and yizhenggao groups were significantly lower than hongzhenggao group. The contents of 17-OHCS and D-β-H in caoshuigao and yishuigao groups were significantly lower than dashuigao group. The contents of 17-OHCS， DA and D-β-H in caoshuigao and yishuigao groups as well as the contents of DA and D-β-H in gaoshuigao groups were significantly lower than hongshuigao group （P＜0.05 or P＜0.01）. CONCLUSIONS： Different polar parts of 5 kinds of Alpinia can improve gastric ulcer model rats with cold syndrome to different extents； among them， the fruit of A. galangal is the best， followed by the root of A. officinarum. Above medicinal materials can regulate the function of sympathetic-adrenal system by increasing the contents of 17-OHCS， CAs and D-β-H.

Mitophagy is an essential intracellular process that eliminates dysfunctional mitochondria and maintains cellular homeostasis. Mitophagy is regulated by the post-translational modification of mitophagy receptors. Fun14 domain-containing protein 1 (FUNDC1) was reported to be a new receptor for hypoxia-induced mitophagy in mammalian cells and interact with microtubule-associated protein light chain 3 beta (LC3B) through its LC3 interaction region (LIR). Moreover, the phosphorylation modification of FUNDC1 affects its binding affinity for LC3B and regulates selective mitophagy. However, the structural basis of this regulation mechanism remains unclear. Here, we present the crystal structure of LC3B in complex with a FUNDC1 LIR peptide phosphorylated at Ser17 (pS), demonstrating the key residues of LC3B for the specific recognition of the phosphorylated or dephosphorylated FUNDC1. Intriguingly, the side chain of LC3B Lys49 shifts remarkably and forms a hydrogen bond and electrostatic interaction with the phosphate group of FUNDC1 pS. Alternatively, phosphorylated Tyr18 (pY) and Ser13 (pS) in FUNDC1 significantly obstruct their interaction with the hydrophobic pocket and Arg10 of LC3B, respectively. Structural observations are further validated by mutation and isothermal titration calorimetry (ITC) assays. Therefore, our structural and biochemical results reveal a working model for the specific recognition of FUNDC1 by LC3B and imply that the reversible phosphorylation modification of mitophagy receptors may be a switch for selective mitophagy.
Crystallography, X-Ray ; Membrane Proteins ; chemistry ; metabolism ; Microtubule-Associated Proteins ; chemistry ; metabolism ; Mitochondrial Degradation ; Mitochondrial Proteins ; chemistry ; metabolism ; Peptides ; chemistry ; metabolism ; Phosphorylation ; Protein Structure, Quaternary

Algorithms ; Carrier Proteins ; chemistry ; Crystallography, X-Ray ; Humans ; Magnetic Resonance Spectroscopy ; Molecular Dynamics Simulation ; Nuclear Proteins ; chemistry ; Principal Component Analysis ; Protein Structure, Tertiary ; Proteins ; chemistry ; Scattering, Small Angle ; X-Ray Diffraction ; methods

BACKGROUNDLaparoendoscopic single-site (LESS) surgery through the retroperitoneal approach has been seldom reported. We aimed to evaluate the outcomes of LESS and conventional laparoscopic surgery via the retroperitoneal approach in the management of large, impacted ureteral calculi.

METHODSBetween November 2011 and July 2013, retroperitoneal LESS ureterolithotomy was performed in 12 patients using a homemade single-port device comprising a surgical glove and several strips of tape. Another 16 patients underwent conventional retroperitoneal laparoscopic ureterolithotomy. We compared the operative time, complications, and surgical outcomes, retrospectively.

RESULTSAll patients were completed without conversion to conventional laparoscopic or open surgery. The operative time of the LESS group and of the conventional laparoscopic group were (125.3 ± 12.8) minutes and (116.9 ± 14.4) minutes, respectively (P = 0.119). The intraoperative blood loss was (42.9 ± 8.9) and (43.4 ± 14.7) ml, respectively (P = 0.914). Postoperative radiologic evaluation revealed that the stones had been removed completely. Cosmetic results were superior in the LESS group (P = 0.001).

CONCLUSIONRetroperitoneal LESS ureterolithotomy using a homemade single-port device can be considered a feasible and safe alternative to conventional laparoscopic ureterolithotomy.

Adult ; Female ; Humans ; Laparoscopy ; methods ; Male ; Middle Aged ; Retroperitoneal Space ; surgery ; Ureteral Calculi ; surgery ; Urologic Surgical Procedures ; methods

Humans ; Neoplastic Stem Cells ; Stem Cell Research ; Stomach ; Stomach Neoplasms