Objective: To explore the mechanism of moxibustion for rheumatoid arthritis (RA) by observing the metabolite changes in urine using liquid chromatography-mass spectrometry (LC-MS)-based metabolomic analysis. Methods: Twenty-four rats were randomly divided into a control group, a model group, and a moxibustion group. Rats in the model and moxibustion groups were established as collagen-induced arthritis (CIA) models. The control and model groups did not receive any intervention; rats in the moxibustion group received moxibustion at Shenshu (BL23) and Zusanli (ST36). After three weeks of intervention, ankle joint, serum, and urine samples were collected for pathological examinations and metabolomic tests. Results: After moxibustion treatment, the CIA rats showed increased body mass, reduced swelling of the hind paws and arthritis score, decreased serum cytokine levels, and improved histopathological evaluation of the ankle joint. Twenty-four significantly altered metabolites were found, mainly involved in alanine metabolism, taurine and hypotaurine metabolism, tricarboxylic acid cycle, phenylalanine metabolism, tyrosine metabolism, and primary bile acid biosynthesis. These metabolites may serve as potential biomarkers for RA. Conclusion: Moxibustion can effectively resist inflammation in CIA rats. The potential biomarkers and the abnormal metabolic pathways of RA can be identified by LC-MS-based metabolomics. Metabolomics may be an effective way to explain the mechanism of moxibustion in treating RA.

Aged ; Drug-Related Side Effects and Adverse Reactions ; blood ; therapy ; Emergency Treatment ; Female ; Hemoperfusion ; Humans ; Hypnotics and Sedatives ; poisoning ; Male ; Middle Aged ; Serum ; chemistry

Objective The purpose of this paper is to study the problems and challenges faced by the university in the management of science funds,in order to provide evidence for improving the management level of science funds at university,at the same time to provide possible reference for other universities.Methods Through retrospective analysis of the application and funding of the National Natural Science Foundation of China of Chongqing Medical University during the period of 2013 to 2018.Results In recent years,the funding level of science funds in our university has entered the bottleneck period,main influencing factors include policy,talents,management and so on.Conclusions It is suggested to strengthen the top-level design of scientific research management,strengthen the training of scientific research personnel,and ensure the capability of scientific research management.

Objective To investigate the distribution and expression changes of voltage-gated chloride channel CLC-2 and CLC-3 in rat models with lithium-pilocarpine-induced chronic epileptic,and discuss the significance of these changes in epileptic pathogenesis.Methods Eighty Wistar rats were randomly divided into status epilepticus(SE,n=60)and control(n=20)groups and rats in the SE group were assigned to 3 subgroups according to the different sacrificed times(24 h,14 d and 30 d).Rat models with chronic epileptic in the SE group were induced by lithium-pilocarpine.Immunohistochemistry was employed to observe the changes of voltage-gated chloride channel CLC-2 and CLC-3 in rat's hlppocampal formation different time points after seizure.The mRNA changes of chloride channel CLC-2 and CLC-3 at different time points after seizure were observed by RT-PCR.Results Compared with those in the control group,the quantity of CLC-2 immune positive neurons and the average optical density in the SE group decreased obviously 14 and 30 d after seizure;so was the mRNA expression of CLC-2(P<0.05).Compared with the control group,the SE group showed obviously increased quantity of CLC-3 immune positive neurons and optical density at each area of the hippocampus 24 h after seizure;so was the mRNA expression of CLC-3(P<0.05).Conclusion Seizures at chronic phase have relation with the decreased expressions of CLC-2.

Purpose To study the clinicopathologic features of ganglioglioma. Methods The clinicopathologic data of the cases pathologically diagnosed as ganglioglioma that underwent resection of epileptic focus were retrospectively analyzed. Results In the 19 cases studied, the mean onset age was 9.1 years, and the duration of disease was 9.3 years. MRI images showed abnormal signals. The majority of the site was temporal lobe (14/19, 73.7％). The tumors showed heterogeneity and often accompanied by focal cortical dysplasias (13/19, 68.4％). Immunohistochemical staining showed CD34 positive in 18 cases, Nestin positive in 16 cases, and BRAF-V600E positive in 6 case. The positive expression rate of CD34 and Nestin did not have significant differences. Conclusion The diagnosis of ganglioglioma relies on pathological observations combined with clinical features and neuroradiological examinations. Differential diagnosis should be done from other tumors or cortical dysplasia. Immunohistochemical staining of CD34 and Nestin can help diagnosis.

Objective: To understand the perceptions, attitudes and treatment selection of Chinese surgeons on the "watch and wait" strategy for rectal cancer patients after achieving a clinical complete response (cCR) following neoadjuvant chemoradiotherapy (nCRT). Methods: A cross-sectional survey was used in this study. Selection of subjects: (1) Domestic public grade III A (provincial and prefecture-level) oncology hospitals or general hospitals possessing the radiotherapy department and the diagnosis and treatment qualifications for colorectal cancer. (2) Surgeons of deputy chief physician or above. Using the "Questionnaire Star" online survey platform to create a questionnaire about cognition, attitude and treatment choice of the "watch and wait" strategy after cCR following nCRT for rectal cancer. The questionnaire contained 32 questions, such as the basic information of doctor, the current status of rectal cancer surgery, the management of pathological complete remission (ypCR) after nCRT for rectal cancer, the selection of examination items for diagnosis of cCR, the selection of suitable people undergoing "watch and wait" approach, the nCRT mode for promotion of cCR, the choice of evaluation time point, the willingness to perform "watch and wait" approach and the treatment choice, and the risk and monitoring of "watch and wait" approach. A total of 116 questionnaires were sent to the respondents via WeChat between January 31 and February 19, 2019. Statistical analysis was performed using Fisher′s exact test for categorical variables. Results: Forty-eight hospitals including 116 surgeons meeting criteria were enrolled, of whom 77 surgeons filled the questionnaire with a response rate of 66.4%. "Watch and wait" strategy was carried out in 76.6% (59/77) of surgeons. Seventy surgeons (90.9%) were aware of the ypCR rate of rectal cancer after preoperative nCRT and 49 surgeons (63.6%) knew the 3-year disease-free survival of patients with ypCR in their own hospitals. Fifty-five surgeons (71.4%) believed that patients with ypCR undergoing radical surgery met the treatment criteria and were not over-treated. Three most necessary examinations in diagnosing cCR were colonoscopy (96.1%, 74/77), digital rectal examination (DRE) (90.9%,70/77) and DWI-MRI (83.1%, 64/77). Responders preferred to consider a "watch and wait" strategy for patients with baseline characteristics as mrN0 (77.9%, 60/77), mrT2 (68.8%, 53/77) and well-differentiated adenocarcinoma (68.8%, 53/77). Sixty-six surgeons (85.7%) believed that long-term chemoradiotherapy (LCRT) with combination or without combination of induction and/or consolidation of the CapeOX regimen (capecitabine + oxaliplatin) should be the first choice as a neoadjuvant therapy to achieve cCR. Forty-one surgeons (53.2%) believed that a reasonable interval of judging cCR after nCRT should be ≥ 8 weeks. Forty-four surgeons (57.1%) routinely, or in most cases, informed patient the possibility of cCR and proposed to "watch and wait" strategy in the initial diagnosis of patients with non-metastatic rectal cancer. Thirteen surgeons (16.9%) would take the "watch and wait" strategy as the first choice after the patient having cCR. Fifty-two surgeons (67.5%) would be affected by the surgical method, that was to say, "watch and wait" approach would only be recommended to those patients who would achieve cCR and could not preserve the anus or underwent difficult anus-preservation surgery. Sixteen surgeons (20.8%) demonstrated that "watch and wait" strategy would not be recommended to patients with cCR regardless of whether the surgical procedure involved anal sphincter. Eleven surgeons (14.3%) believed that the main risk of "watch and wait" approach came from distant metastasis rather than local recurrence or regrowth. Twenty-nine of surgeons (37.7%) did not understand the difference between "local recurrence" and "local regrowth" during the period of "watch and wait". Twenty-six surgeons (33.8%) thought that the monitoring interval for the first 3 years of "watch and wait" strategy was 3 months, and the follow-up monitoring interval could be 6 months to 5 years. Surgeons from cancer specialist hospitals had higher approval rate, notification rate, and referral rate of "watch and wait" strategy than those from general hospitals. Thirty-one surgeons (42.5%) considered that the difficulty and concern of carrying out "watch and wait" approach in the future was the disease progress leading to medical disputes. Twenty-six surgeons (35.6%) demonstrated that their concern was lack of uniform evaluation standard for cCR. Conclusions Chinese surgeons seem to have inadequate knowledge of non-operative management for rectal cancer patients achieving cCR after nCRT and show relatively conservative attitudes toward the strategy. Chinese consensus needs to be formed to guide the non-operative management in selected patients. Chinese Watch & Wait Database (CWWD) is also needed to establish and provide more evidence for the use of alternative procedure after a cCR following nCRT.

β/γ-Crystallins are predominant structural proteins in the cytoplasm of lens fiber cells and share a similar fold composing of four Greek-key motifs divided into two domains. Numerous cataract-causing mutations have been identified in various β/γ-crystallins, but the mechanisms underlying cataract caused by most mutations remains uncharacterized. The S228P mutation in βB1-crystallin has been linked to autosomal dominant congenital nuclear cataract. Here we found that the S228P mutant was prone to aggregate and degrade in both of the human and E. coli cells. The intracellular S228P aggregates could be redissolved by lanosterol. The S228P mutation modified the refolding pathway of βB1-crystallin by affecting the formation of the dimeric intermediate but not the monomeric intermediate. Compared with native βB1-crystallin, the refolded S228P protein had less packed structures, unquenched Trp fluorophores and increased hydrophobic exposure. The refolded S228P protein was prone to aggregate at the physiological temperature and decreased the protective effect of βB1-crystallin on βA3-crystallin. Molecular dynamic simulation studies indicated that the mutation decreased the subunit binding energy and modified the distribution of surface electrostatic potentials. More importantly, the mutation separated two interacting loops in the C-terminal domain, which shielded the hydrophobic core from solvent in native βB1-crystallin. These two interacting loops are highly conserved in both of the N- and C-terminal domains of all β/γ-crystallins. We propose that these two interacting loops play an important role in the folding and structural stability of β/γ-crystallin domains by protecting the hydrophobic core from solvent access.
Amino Acid Substitution ; Cataract ; genetics ; metabolism ; HeLa Cells ; Humans ; Molecular Dynamics Simulation ; Mutation, Missense ; Protein Aggregation, Pathological ; genetics ; metabolism ; Protein Domains ; Protein Structure, Secondary ; Proteolysis ; beta-Crystallin B Chain ; chemistry ; genetics ; metabolism

In this paper， through the collection and collation of ancient materia medica， medical books and medical formulary， combining with modern literature， the historical changes of the name， origin， position， harvesting time， medicinal parts， toxicity， functions and indications， processing methods of Rhododendri Mollis Flos （RMF） were systematically combed and verified， so as to provide reference for clinical application， processing standard and basic research of RMF. According to textual research， RMF is the dried flower of Rhododendron molle. In each historical period， there are many aliases and local names， being with phenomenon of homonyms and synonyms. RMF is mostly wild and planted in a small amount， harvesting time is mostly in March to April. However， the harvesting flowering period is differently described as initial bloom， full bloom and extensive bloom. RMF was first recorded in Shennong Bencaojing (《神农本草经》)， but it did not mention its medicinal parts. Then the flowers， fruits， roots are be used as medicine， but flowers are still the main medicinal parts. RMF had a long processing history， included fried， vinegar-fried， wine-fried， steamed， wine-steamed， vinegar-steamed， and many other processing methods in ancient times. However， at present， only raw products are used in clinical practice， and only a few modern books retain the methods of stir-fried and wine-steamed， believing that the processing can reduce toxicity of RMF.

Aim To explore the effeets of Salvianolie aeirl A (SAA) on platelet recruitment, activation and neutrophils in heart of myocardial infarction ( Ml ) mice.Methods C57BL/6 mice were randomly divid¬ed into: Sham operation group.Ml model group, SAA (5, 10 mg • kg 1 ) group, tirofiban (Tirofiban, 0.87 mg • kg ' ) group, using tail vein injection for 3 d.Echocardiography and HE staining were used to detect mouse heart function and infarct area; 1HC, FCS, ELISA, Western blot and other methods were used to explore the inhibitory effect of SAA on platelet and neutrophil activation.Results Compared with Ml group, SAA could improve the cardiac function and cardiac physiology changes of Ml mice, reduce the ex¬pression of CD42c in myocardial tissue and CD62p in peripheral blood without affecting tail bleeding time, reduce ADP-induced platelet activation and increase p- VASP/VASP ratio, reduce the ratio of p-PI3K/PI3K and p-AKT/AKT, reduce the expression of CD45, Ly6G, CXCL1 and CXCL2 in myocardial tissue, re¬duce the expression of complement component C3aR in myocardial tissue, and reduce C3a-induced NE and MPO, MMP9, LF level.Conclusions SAA has an anti-platelet activation effect by inhibiting the PI3K/ AKT and VASP pathways and an anti-neutrophil acti¬vation effect by inhibiting the expression of C3aR and C3a.

OBJECTIVETo explore the applicable value of transanal total mesorectal excision (taTME) in male low rectal cancer patients with narrow pelvis-"difficult pelvis", which remains difficult for both open and laparoscopic sphincter-saving operations.

METHODSClinical data of male low rectal cancer patients diagnosed by pathology undergoing taTME between June 2016 and January 2018 at Peking University Cancer Hospital were collected. A retrospective cohort study was performed. Patients were selected according to the following criteria: (1) low rectal cancer, the distance between inferior margin of tumor and anal verge ≤5 cm; (2) the distance between two sciatic tubercles <5 cm; (3) body mass index (BMI) >25 kg/m; (4) tumor horizontal diameter ≤4 cm. Operation time, intraoperative blood loss, postoperative hospital stay, postoperative complications and anal function were analyzed.

RESULTSA total of 20 patients were included in this study. All the patients received preoperative neoadjuvant chemoradiation and hybrid transabdominal and transanal surgery. The median BMI was 27.7(26.2-36.4) kg/m; the median distance between two sciatic tubercles was 92.5 (78-100) mm; the median distance between the inferior margin of tumor to the anal verge was 4 (2-5) cm; the median operation time was 302 (215-402) min; the median intraoperative blood loss was 100 (50-200) ml; the median postoperative hospital stay was 9 (5-15) d. Postoperative complications occurred in 5 patients (25%), including 3 pelvic infection, 1 intestinal obstruction, 1 anastomotic leakage receiving sigmoid colostomy. There was no perioperative death. Sphincter-preservation rate was 100%. Nineteen patients received anal manometry 1 month after operation with normal resting pressure (41.5±8.6) mmHg and squeeze pressure (121.0±11.6) mmHg. All the patients were followed up to March 2018, and the median follow-up time was 4.5 months. Only 1 patient had supraclavicular lymph node metastasis and no local recurrence was found.

CONCLUSIONSThe safety of transanal total mesorectal excision for male patients with low rectal cancer and difficult pelvis is acceptable. TaTME is helpful to preserve the anal sphincter.

Adult ; Anal Canal ; surgery ; Humans ; Laparoscopy ; Male ; Neoplasm Recurrence, Local ; Pelvis ; surgery ; Postoperative Complications ; Rectal Neoplasms ; surgery ; Retrospective Studies ; Treatment Outcome ; Universities