Allergic rhinitis (AR), a globally prevalent immune-mediated inflammatory condition, is still an incurable disease. In the present study, we have validated the impact of the Kelch-like ECH associated protein 1 (Keap1)-related oxidative stress and inflammatory response in clinical AR patient peripheral blood and nasal swab samples, emphasizing the biological relevance of Keap1 and AR. Targeting Keap1 -nuclear factor erythroid 2-related factor 2 (Nrf2) related anti-oxidative stress may be effective for AR intervention. Drawing inspiration from the Keap1 homodimerization and the E3 ligase characteristics, we herein present a design of novel bivalent molecules for chemical knockdown of Keap1. For the first time, we characterized ternary complexes of Keap1 dimer and one molecule of bivalent compounds. The best bivalent molecule 8 encompasses robust capacity to degrade Keap1 as a homoPROTAC^KEAP1. It efficaciously suppresses inflammatory cytokines in extensively different cells, including human nasal epithelial cells. Moreover, in an AR mouse model, we confirmed that the chemical degradation induced by homoPROTAC^KEAP1 led to therapeutic benefits in managing AR symptoms, oxidative stress and inflammation. In summary, our findings underscore the efficacy of targeting the Keap1 system through the homoPROTAC-ing technology as an innovative and promising treatment strategy for the incurable allergic disorders.

The biological samples of oral genetic diseases and rare diseases are extremely precious. Collecting and preserving these biological samples are helpful to elucidate the mechanisms and improve the level of diagnose and treatment of oral genetic diseases and rare diseases. The standardized construction of biobanks for oral genetic diseases and rare diseases is important for achieving these goals. At present, there is very little information on the construction of these biobanks, and the standards or suggestions for the classification and coding of biological samples from oral and maxillofacial sources, and this is not conducive to the standardization and information construction of biobanks for special oral diseases. This consensus summarizes the background, necessity, principles, and key points of constructing the biobank for oral genetic diseases and rare diseases. On the base of the group standard "Classification and Coding for Human Biomaterial" (GB/T 39768-2021) issued by the National Technical Committee for Standardization of Biological Samples, we suggest 76 new coding numbers for different of biological samples from oral and maxillofacial sources. We hope the consensus may promote the standardization, and smartization on the biobank construction as well as the overall research level of oral genetic diseases and rare diseases in China.

Acute gastrointestinal dysfunction is a common and important complication of sepsis. As no exiting formal definition and classification of gastrointestinal dysfunction, most of the treatment strategies for gastrointestinal dysfunction are not based on clinical evidence, but on their own clinical experience. Experts of traditional Chinese medicine, integrated traditional Chinese and Western medicine and Western medicine from various disciplines in Shanghai are organized by the Shanghai Society of Integrated Traditional Chinese and Western Medicine and the Emergency Department Branch of Shanghai Physicians Association. After repeated discussion, literature search and formulation of the outline, we developed consensus on gastrointestinal dysfunction secondary to sepsis with integrating Traditional Chinese Medicine and Western medicine by consulting extensively on clinical experts in the fields of emergency medicine, gastroenterology, general surgery, infectious medicine and traditional Chinese medicine, and holding several expert forums and consultation meetings. This clinical expert consensus focused on acute gastrointestinal injury (AGI) classification and inducer of sepsis. In this consensus, the common symptoms, diagnosis, classifications, treatment strategies and suggestions of acute gastrointestinal injury or dysfunction secondary to sepsis were explored from the aspect of both Traditional Chinese Medicine and Western medicine.

Objective:To investigate the mid-term clinical outcomes of selective column arthrodesis based on the three-column theory in the treatment of malunion of Lisfranc injury.Methods:The 28 patients with malunion of Lisfranc injury were analyzed retrospectively who had been treated by selective column arthrodesis at Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine from January 2011 to January 2020.They were 18 males and 10 females, with an average age of 37.2 years(from 18 to 65 years). Twelve left and 16 right sides were affected. According to Myerson's three-column classification, one case was medial column injury (type A), 4 ones middle column injury (type B), 7 ones medial plus middle columns injury and 16 ones three-column injury. Medial column arthrodesis was conducted in 7, middle column arthrodesis in 4 and medial plus middle columns arthrodesis in 17. The American Orthopaedic Foot and Ankle Society (AOFAS) midfoot score and visual analogue scale (VAS) were compared between preoperation and the last follow-up to evaluate the improvements in foot function and pain. The operation-related complications were recorded.Results:All patients were followed up for an average of 35.6 months (from 18 to 60 months). The AOFAS midfoot score increased from 43.1±4.1 at pre-operation to 84.1± 7.4 at the last follow-up and the VAS score decreased from 5.7±1.3 at pre-operation to 2.0±0.9 at the last follow-up (both P<0.001). The wounds healed in 28 patients, 3 of whom had postoperative wound exudation but responded to dressing change. There were no such complications as injury to the deep peroneal nerve or deep venous thrombosis. The internal fixation was removed in 5 patients at about one year after arthrodesis. Conclusion:Selective column arthrodesis based on the three-column theory can result in satisfactory med-term clinical outcomes in the treatment of malunion of Lisfranc injury.

Objective:To investigate the curative effect of suture anchor in the treatment of ankle joint fracture complicated with distal tibiofibular syndesmosis injury.Methods:From January 2017 to August 2019, data of 65 patients with Weber C type ankle fracture combined with posterior malleolus fracture in our hospital who underwent surgical treatment were retrospectively analyzed and were divided into two groups according to the treatment method of injury: suture-anchor repair group (suture-anchor was used to repair the anterior inferior tibiofibular ligament) and screw fixation group (cortical bone screw was used to fix the tibiofibular syndesmosis). Among them, 17 cases were treated with suture-anchors to repair the anterior inferior tibiafibular ligament, including 7 males, 10 females, 11 left and 6 right. In the Lauge-Hanson subgroup, there were 10 cases of pronation external rotation (PER), and 7 cases of pronation abduction (PA). The mean age was 43.76±15.83 years old. Forty-eight patients were treated with cortical screw fixation, including 33 males, 15 females, 34 left and 14 right. In the Lauge-Hanson subgroup, there were 30 cases of PER, and 18 cases of PA. The mean age was 39.90±13.57 years old. The differences in operation time, number of fluoroscopy, quality of reduction and postoperative complications were compared between the two groups. The ankle joint function was compared at 16 weeks postoperatively and at the last follow-up. The ankle joint function score was based on the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score.Results:All the 65 patients were followed up and the average follow-up time of 65 cases was 16.88±4.46 months. All the fractures were clinically healed 12-16 weeks after operation. The operative time of screw fixation group was 123.71±41.36 min, and the number of fluoroscopy was 25.17±16.29 times, while the operative time of suture-anchor repair group was 99.94±24.16 min and the number of fluoroscopy was 16.26±10.58 times. The difference between the two groups was statistically significant ( t=2.048, 2.175; P=0.045, 0.033). In the screw fixation group, the mean anterior and posterior distance of the tibiofibular syndesmosis was 3.15±1.35 mm, and 6.48±1.43 mm, respectively. In the suture-anchor repair group, the mean anterior distance of the syndesmosis was 2.06±1.47 mm, and the mean posterior distance of the syndesmosis was 6.76±1.78 mm. There was statistically significant difference in the distance of anterior distance of the syndesmosis ( t=3.328, P=0.002), while there was no statistically significant difference in the posterior distance of the syndesmosis ( t=0.701, P=0.486). The incidence of postoperative complications was 16.67% (8/48) in the screw fixation group and 5.88% (1/17) in the suture-anchor repair group, which was no statistically different ( χ2=1.282, P=0.258). The excellent and good rates of AOFAS ankle-hindfoot scores were 91.67% (44/48) in the screw fixation group and 88.24% (15/17) in the suture-anchor repair group at 16 weeks; 95.83% (46/48) in the screw fixation group and 94.12% (16/17) in the suture-anchor repair group at the last follow-up. There was no significant difference ( P >0.05). Conclusion:Compare with screw fixation in the treatment of acute distal tibiofibular syndesmosis injury, suture-anchor repair of anterior inferior tibiofibular ligament is a safe and effective method. It can increase the anatomical reduction rate of anterior distance of the syndesmosis, and reduce the operation time without increasing the incidence of complications.

Deciphering the metabolites of multiple components in herbal medicine has far-reaching significance for revealing pharmacodynamic ingredients.However,most chemical components of herbal medicine are secondary metabolites with low content whose in vivo metabolites are close to trace amounts,making it difficult to achieve comprehensive detection and identification.In this paper,an efficient strategy was proposed:herb-derived metabolites were predicted according to the structural characteristics and metabolic reactions of chemical constituents in Corydalis Rhizoma and chemical structure screening tables for metabolites were conducted.The fragmentation patterns were summarized from represen-tative standards combining with specific cleavage behaviors to deduce structures of metabolites.Ion abundance plays an important role in compound identification,and high ion abundance can improve identification accuracy.The types of metabolites in different biological samples were very similar,but their ion abundance might be different.Therefore,for trace metabolites in biological samples,we used the following two methods to process:metabolites of high dose herbal extract were analyzed to char-acterize those of clinical dose herbal extracts in the same biological samples;cross-mapping of different biological samples was applied to identify trace metabolites based on the fact that a metabolite has different ion abundance in different biological samples.Compared with not using this strategy,44 more metabolites of clinical dose herbal extract were detected.This study improved the depth,breadth,and accuracy of current methods for herb-derived metabolites characterization.

OBJECTIVE: To analyze the current status of diagnosis and management of acute appendicitis (AA) in China. METHODS: Questionnaire survey was used to retrospectively collect data of hospitalized patients with AA from 43 medical centers nationwide in 2017 (Sort by number of cases provided: Jinling Hospital of Medical School of Nanjing University, The First Affiliated Hospital of Xinjiang Medical University, Lu'an People's Hospital, Tengzhou Central People's Hospital, Dalian Central Hospital, The Affiliated Hospital of Xuzhou Medical University, Dongying People's Hospital, Jinjiang Hospital of Traditional Chinese Medicine, Huangshan Shoukang Hospital, Xuyi People's Hospital, Nanjing Jiangbei People's Hospital, Lanzhou 940th Hospital of PLA, Heze Municipal Hospital, The First College of Clinical Medical Science of China Three Gorges University, Affiliated Jiujiang Hospital of Nanchang University, The Second People's Hospital of Hefei, Affiliated Central Hospital of Shandong Zaozhuang Mining Group, The Third People's Hospital of Kunshan City, Xuzhou First People's Hospital, The 81st Group Army Hospital of PLA, Linyi Central Hospital, The General Hospital of Huainan Eastern Hospital Group, The 908th Hospital of PLA, Liyang People's Hospital, The 901th Hospital of Joint Logistic Support Force, The Third Affiliated Hospital of Chongqing Medical University, The Fourth Hospital of Jilin University, Harbin Acheng District People's Hospital, The First Affiliated Hospital of Zhengzhou University, Nanjing Luhe People's Hospital, Taixing Municipal People's Hospital, Baotou Central Hospital, The Affiliated Hospital of Nantong University, Linyi People's Hospital, The 72st Group Army Hospital of PLA, Zaozhuang Municipal Hospital, People's Hospital of Dayu County, Taixing City Hospital of Traditional Chinese Medicine, Suzhou Municipal Hospital, Beijing Guang'anmen Hospital, Langxi County Hospital of Traditional Chinese Medicine, Nanyang Central Hospital, The Affiliated People's Hospital of Inner Mongolia Medical University).The diagnosis and management of AA were analyzed through unified summary. Different centers collected and summarized their data in 2017 and sent back the questionnaires for summary. RESULTS: A total of 8 766 AA patients were enrolled from 43 medical centers, including 4 711 males (53.7%) with median age of 39 years and 958 (10.9%) patients over 65 years old. Of 8 776 patients, 5 677 cases (64.6%) received one or more imaging examinations, and the other 3 099 (35.4%) did not receive any imaging examination. A total of 1 858 (21.2%) cases received medical treatment, mainly a combination of nitroimidazoles (1 107 cases, 59.8%) doublet regimen, followed by a single-agent regimen of non-nitroimidazoles (451 cases, 24.4%), a nitroimidazole-free doublet regimen (134 cases, 7.2%), a triple regimen of combined nitroimidazoles (116 cases, 6.3%), nitroimidazole alone (39 cases, 2.1%) and nitroimidazole-free triple regimen (3 cases, 0.2%). Of the 6 908 patients (78.8%) who underwent surgery, 4 319 (62.5%) underwent laparoscopic appendectomy and 2589 (37.5%) underwent open surgery. Ratio of laparotomy was higher in those patients under 16 years old (392 cases) or over 65 years old (258 cases) [15.1%(392/2 589) and 10.0%(258/2 589), respectively, compared with 8.5%(367/4 316) and 8.0%(347/4 316) in the same age group for laparoscopic surgery, χ²=91.415, P<0.001; χ²=15.915,P<0.001]. Patients with complicated appendicitis had higher ratio of undergoing open surgery as compared to those undergoing laparoscopic surgery [26.7%(692/2 589) vs. 15.6%(672/4 316), χ²=125.726, P<0.001].The cure rates of laparoscopic and open surgery were 100.0% and 99.8%(2 585/2 589) respectively without significant difference (P=0.206). Postoperative complication rates were 4.5%(121/2 589) and 4.7%(196/4 316) respectively, and the difference was not statistically significant (χ²=0.065, P=0.799). The incidence of surgical site infection was lower (0.6% vs. 1.7%, χ²=17.315, P<0.001), and hospital stay was shorter [6(4-7) days vs. 6(5-8) days, U=4 384 348.0, P<0.001] in the laparoscopic surgery group, while hospitalization cost was higher (median 12 527 yuan vs. 9 342 yuan, U=2 586 809.0, P<0.001). CONCLUSIONS The diagnosis of acute appendicitis is still clinically based, supplemented by imaging examination. Appendectomy is still the most effective treatment at present. Laparoscopic appendectomy has become the main treatment strategy, but anti-infective drugs are also very effective.
Acute Disease ; Adolescent ; Adult ; Aged ; Anti-Bacterial Agents ; therapeutic use ; Appendectomy ; Appendicitis ; diagnosis ; therapy ; China ; Female ; Health Care Surveys ; Humans ; Laparoscopy ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult

Objective To compare the effect and prognosis outcome of open reduction internal fixation and primary arthrodesis in treatment of Lisfranc injuries combined with the first tarsal jointdislocation.Methods A retrospective case control study was conducted on the clinical data with complete follow up data of 126 patients with Lisfranc injuries combined with the first tarsal joint dislocation in nine ankle surgery centers of China from January 2009 to June 2015.There were 76 males (60.3％) and 50 females (39.7％) with an average age of 45.5 years (range,20-87 years).Among the 126 cases,simple dislocation occurred in 41 cases (32.5％),and fracture dislocation in 85 cases (67.5％).The duration from injury to surgery was 11.7 days (range,4-26 days).According to surgery method,the patients were divided into open reduction internal fixation group (n =92) and primary arthrodesis group (n =34).The outcomes were evaluated by American Orthopedic Foot and Ankle Society(AOFAS) score,36-items short form health survey (SF-36),and visual analogue score (VAS).Complications were also followed up.Results All patients were followed up for 18-80 months,with an average of 29.5 months.Primary union was seen in all the patients.At the last follow up,the mean AOFAS midfoot score was (79.4 ± 6.7) points in open reduction and internal fixation group and (85.1 ±8.3) points in primary arthrodesis group (P ＜ 0.05).The mean VAS was (3.1 ± 0.6) points in open reduction and internal fixation group and (2.2± 0.3)points in primary arthrodesis group(P ＜ 0.05).The physiological function of SF-36 was (80.3 ± 5.3) points in open reduction and internal fixation group and (83.5 ± 6.9) points in primary arthrodesis group(P ＞ 0.05).The body pain score of SF-36 was (76.1 ±4.6) points in open reduction and internal fixation group and (84.6 ± 8.7) points in primary arthrodesis group (P ＜ 0.05).In open reduction and internal fixation group,there were five cases (5％) with internal fixator loosening or fracture,16 cases (17％) with redislocation,36 cases (39％) with obvious pain of the middle foot during walking,and eight cases (6％) with tarsal joint traumatic arthritis which was given phase Ⅱ arthrodesis.In primary arthrodesis group,two patients (6％) reported pain due to internal fixation,and the pain was relieved after fixator removal.No re-dislocation,loosening of internal fixation,or traumatic arthritis were found (P ＜ 0.05).Conclusion For Lisfranc injuries combined with first tarsal joint dislocation,primary arthrodesis can stabilize the first tarsal joint and avoid complications or adverse consequences such as redislocation,pain,internal fixation failure,or reoperation.

Dementia is a comprehensive category of brain diseases that is great enough to affect a person's daily functioning. The most common type of dementia is Alzheimer's disease, which makes most of cases. New researches indicate that gastrointestinal tract microbiota are directly linked to dementia pathogenesis through triggering metabolic diseases and low-grade inflammation progress. A novel strategy is proposed for the management of these disorders and as an adjuvant for psychiatric treatment of dementia and other related diseases through modulation of the microbiota (e.g. with the use of probiotics).
Alzheimer Disease ; metabolism ; microbiology ; physiopathology ; therapy ; Gastrointestinal Microbiome ; Humans

Objective To report the clinical outcomes of the patients with open comminuted intra-articular calcaneal fracture who were treated with our self-designed bilateral triangle external fixators which are extensible and gimbaled.Methods Between January 2011 and June 2014,12 patients with open comminuted intra-articular calcaneal fracture were treated and followed up.They were 8 men and 4 women,aged from 23 to 58 years (average,36.8 years).According to the Sanders classification,the fractures were type Ⅱ in 4 cases,type Ⅲ in 7,and type Ⅳ in one.According to the Gustilo classification,the soft tissue injury was type Ⅱ in 2 cases,type ⅢA in 7,and type Ⅲ B in 3.All the patients were treated with immediate debridement and preventive intravenous antibiotics.First stage wound closure or temporary coverage with vacuum sealed drainage was chosen according to the condition of soft tissue injury.Our self-designed bilateral triangle external fixators were applied together with cannulated screws or Kirschner wire in all the patients after Kirschner wire poking.Of them,7 received emergency treatment and 5 were treated 3 to 5 days after injury.After no wound infection was observed for sure,6 cases received selective open reduction and internal fixation via a lateral incision while 6 continued external fixation with Kirschner wire for 8 to 10 weeks (average,9.1 weeks).Results The 12 patients were followed up for 6 to 36 months (average,18.5 months).Their AOFAS scores averaged 84.6 points (range,from 74 to 94 points).One case required tissue transfer for wound coverage.Wound shallow infection developed in 3 cases.No deep infection or amputation happened.No wound infection or necrosis occurred in the 6 cases that had undergone open reduction and internal fixation at the second stage.Conclusion Application of our self-designed extensible gimbaled bilateral triangle external fixators in the treatment of open comminuted intra-articular calcaneal fractures may help effectively reduce the deep infection or incidence of osteomyelitis after operation as long as early debridement is thorough,internal fixation is timely applied,and indications for internal fixation are properly followed.