OBJECTIVETo compare the differences of the efficacy and adverse reaction of Oxaliplatin (L-OHP) treatment to oral squamous cell carcinoma (OSCC) at four different daily time points, and to analyze the characteristics of circadian rhythms.

METHODSSeventy-five nude mice were placed under 12h light and 12h dark cycles. Human OSCC cell line BcaCD885 was inoculated on the cheek of nude mice to establish a nude mice model of OSCC. After 3 weeks, mice were divided into 5 groups (4 experimental groups and 1 control group), with 15 in each group. L-OHP (17 mg x kg(-1)) was injected intravenously at 4 different time points during a period of 24 h, including 4 hours after lights on JHALO), 10 HALO, 16 HALO and 22 HALO for 4 experimental groups. The control group received normal saline of the same volume as that of L-OHP. The efficacy (tumor inhibition rate and survival time) and adverse reaction (body weight, white blood cell and perianal swelling) were observed after administration. The circadian rhythms of the efficacy and adverse reaction were examined by cosine analysis.

RESULTSL-OHP injected at 4, 16 and 22 HALO had great tumor inhibition rates, however, only 16 and 22 HALO groups significantly prolonged survival time of mice. The adverse reactions at 4 and 10 HALO were significantly severer than that of 16 and 22 HALO. Cosine analysis showed survival time, body weight and white blood cell counts had significant circadian rhythms. Mice received L-OHP at 14.88 HALO had the longest survival time.

CONCLUSIONThe time factor should be considered in L-OHP chronchemotherapy of patients with OSCC in order to increase the efficacy, decrease the adverse reaction of the drug and to improve the life quality of patients with OSCC.

Objective: To analyse the genomic characteristics of Novirus(NoV) GII.4 genotype JN010 strain isolated form Jinan in 2017. Methods: Seven pairs of primers were designed and used to amplify the JN010 genome. Sequence analyses, alignment and phylogenetic trees of ORF1 and ORF2 genes were performed using the software Lasergene7.1 and MEGA5.2. At the same time the major protein VP1 amino acid mutations were analyzed. Results: The 7 516 bp complete genome sequence of JN010 strain was obtained, the most mutation sites were located in P2 subdomain of VP1. Two substitutions I293N and H373N of VP1 were locate neighboring epitope A, and R297H mutation happened within epitope A and the site A that binding with histo-blood group antigens(HBGAs). The JN010 strain was GII.Pe/GII.4 genotype and genetically closest to the strains found in Osaka of Japan(GenBank accession number LC066046) and the strains in Zhongshan city of Guangdong (GenBank accession number KY407064) respectively according to ORF1 and ORF2 gene homologous and phylogenetic analysis. Conclusions The NoV GII.4 variant strain JN010 has occurred mutations in the key site of the epitope A and site A that bind with HBGAs, and maybe affect its antigenicity and interaction with HBGAs.

Objective:To explore the precision treatment effect of multidrug-resistant pulmonary tuberculosis (MDR-PTB) based on the proportion method for drug susceptibility test, and to provide a scientific basis for formulating MDR-PTB treatment plan.Methods:One hundred and eighty patients with MDR-PTB treated in Shenzhen Center for Chronic Disease Control from January 5, 2016 to April 30, 2018 were enrolled. The initial treatment plan after diagnosis was six months of amikacin (AM), pyrazinamide (Z), levofloxacin (LFX), ethambutol (E), prothionamide (PTO) and 18 months of Z, LFX, E, PTO. According to whether proportion method for drug susceptibility test for 10 commonly used drugs was implemented, patients were divided into precision treatment group and empirical treatment group. In the precision treatment group, the treatment plans were adjusted according to the results of the drug susceptibility test. The treatment plans and disease outcomes of the two groups of patients were retrospectively analyzed. Chi-square test was used for statistical analysis.Results:Among the 180 patients, there were 113 patients in the precision treatment group and 67 patients in the empirical treatment group. The drug resistance rates of the precision treatment group from low to high were: capromycin (CM) (0, 0/113), AM (2.65%, 3/113) and kanamycin (KM) (2.65%, 3/113), para-aminosalicylic acid (PAS) (7.96%, 9/113), PTO (11.50%, 13/113), ofloxacin (OFX)(38.05%, 43/113), E (39.82%, 45/113), and streptomycin(S) (76.99%, 87/113). In the precision treatment group, the drugs were adjusted for 104 person-times according to the proportion method for drug susceptibility test during the treatment, from low to high: AM (3 person-times), PTO (13 person-times), LFX (43 person-times) and E (45 person-times). The treatment success rate of the precision treatment group was 78.8%(89/113), which was higher than that of the experience treatment group (52.2%(35/67)), the difference was statistically significant ( χ2=13.805, P=0.000 2). In the precision treatment group and empirical treatment group, there were no statistically significant differences of alanine aminotransferase elevated (32.3%(31/96) vs 34.0%(18/53)), serum creatinine elevated (4.2%(4/96) vs 5.7%(3/53)), and white blood cell count decreased (24.0%(23/96) vs 22.6%(12/53)) (all P>0.05). Conclusion:The traditional treatment plan based on the proportion method for drug susceptibility test has a high success rate in the treatment of MDR-PTB, which is still a worthy choice.

Based on the suMmary of the implementation of two-way referral system in Changning district,the article describes the system construction,path design,information platform support and achievements,taking into account of general practitioners,specialist and patients.Through a series of reforms,a two-way referral service and its operation mechanism with the local characteristics has been established in Changning district,which guides the first contact care at community and two-way referral as a rational medical service system.

The clinical characteristics, mutation analysis results, and family tree of a patient with autosomal dominant Alport syndrome (ADAS), who had nephrotic syndrome as the first manifestation were examined.The proband was a 11-month-old girl who presented with nephrotic syndromes and gross hematuria.During the treatment course, the patient had steroid resistance and a poor response to Cyclosporine and Cyclophosphamide pulse therapy.Renal biopsy was performed 2 years after disease onset.Under the light microscopy, glomerular segmental mesangio-proliferative lesions were observed.The staining of type Ⅳ collagen showed the loss of the α3 chain in the glomerular basement membrane (GBM) and tubular basement membrane, and α5 chain loss in GBM.Electron microscopy showed uneven thickness of GBM, with obviously delaminated and tearing dense basement membrane (BM) layer, showing a typical lace-like change.The segmental BM was loosened and widened.Her father did not develop microscopic hematuria until 10 years later, while her grandmother had asymptomatic hematuria and proteinuria when the proband was diagnosed.A new mutation in the COL4A4 gene was found in the proband, namely c. 1715delG (p.G572Vfs * 81). Her father and grandmother carried the same mutation, but her mother and sister did not have.The clinical manifestation of ADAS is clinically heterogeneous and its incidence may be higher than what we have expected.

OBJECTIVE: To explore the clinical characteristics and genetic etiology for a child with atypical Hemolytic uremic syndrome (aHUS) in conjunct with nephrotic level proteinuria. METHODS: A child patient who had visited the Affiliated Hospital of Qingdao University on June 25, 2020 was selected as the study subject. Clinical data of the patient was collected. Whole exome sequencing (WES) was carried out for the child, and candidate variant was verified by Sanger sequencing of the child and his parents. RESULTS: The child, an 8-month-old male, had presented mainly with edema, oliguria, hematuria, nephrotic level proteinuria, anemia, thrombocytopenia, increased creatinine and urea, hypercholesterolemia but normal complement levels. Genetic testing revealed that he has harbored compound heterozygous variants of the DGKE gene, namely c.12_18dupGAGGCGG (p.P7fs*37) and c.1042G>T (p.D348Y), which were respectively inherited from his father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variants were classified as likely pathogenic and variant of uncertain significance, respectively. By combining his clinical manifestations and results of genetic testing, the child was diagnosed with aHUS with nephrotic level proteinuria. CONCLUSION For infants and young children with aHUS in conjunct with nephrotic level proteinuria, variants of the DGKE gene should be screened. Above finding has expanded the mutational spectrum of the DGKE gene.
Infant ; Female ; Humans ; Child ; Male ; Child, Preschool ; Atypical Hemolytic Uremic Syndrome/diagnosis* ; Mutation ; Genetic Testing ; Thrombocytopenia/genetics* ; Proteinuria/genetics*

Objective:In general, patients with seropositive rheumatoid arthritis (RA) are considered to show an aggressive disease course. However, the relationship between the two subgroups in disease severity is controversial. Our study is aimed to compare the clinical characteristics and prognosis of double-seropositive and seronegative RA in China through a real-world large scale study.Methods:RA patients who met the 1987 American College of Rheumatology (ACR) classification criteria or the 2010 ACR/European Anti-Rheumatism Alliance RA classification criteria, and who attended the 10 hospitals across the country from September 2015 to January 2020, were enrolled. According to the serological status, patients were divided into 4 subgroups [rheumatoid factor (RF)(-) anti-cyclic citrullinated peptide (CCP) antibody (-), RF(+), RF(+) anti-CCP antibody(+), anti-CCP antibody(+)] and compared the disease characteristics and treatment response. One-way analysis of variance was used for measurement data that conformed to normal distribution, Kruskal-Wallis H test was used for measurement data that did not conform to normal distribution; paired t test was used for comparison before and after treatment within the group if the data was normally distributed else paired rank sum test was used; χ2 test was used for count data. Results:① A total of 2 461 patients were included, including 1 813 RF(+) anti-CCP antibody(+) patients (73.67%), 129 RF(+) patients (5.24%), 245 RF(-) anti-CCP antibody(-) patients (9.96%), 74 anti-CCP antibody(+) patients (11.13%). ② Regardless of the CCP status, RF(+) patients had an early age of onset [RF(-) anti-CCP antibody(-) (51±14) years old, anti-CCP antibody(+) (50±15) years old, RF(+) anti-CCP antibody(+) (48±14) years old, RF(+)(48±13) years old, F=3.003, P=0.029], longer disease duration [RF(-) anti-CCP antibody(-) 50 (20, 126) months, anti-CCP antibody(+) 60(24, 150) months, RF(+) anti-CCP antibody(+) 89(35, 179) months, RF(+) 83(25, 160) months, H=22.001, P<0.01], more joint swelling counts (SJC) [RF(-) anti-CCP antibody(-) 2(0, 6), Anti-CCP antibody(+) 2(0, 5), RF(+) anti-CCP antibody(+) 2(0, 7), RF(+) 2(0, 6), H=8.939, P=0.03] and tender joint counts (TJC) [RF(-) anti-CCP antibody(-) 3(0, 8), anti-CCP antibody(+) 2(0, 6), RF(+) anti-CCP antibody(+) 3(1, 9), RF(+) 2(0, 8), H=11.341, P=0.01] and the morning stiff time was longer [RF(-) anti-CCP antibody(-) 30(0, 60) min, anti-CCP antibody(+) 20(0, 60) min, RF(+) anti-CCP antibody(+) 30(10, 60) min, RF(+) 30(10, 60) min, H=13.32, P<0.01]; ESR [RF(-) anti-CCP antibody(-) 17(9, 38) mm/1 h, anti-CCP antibody(+) 20(10, 35) mm/1 h, RF(+) anti-CCP antibody(+) 26(14, 45) mm/1 h, RF(+) 28(14, 50) mm/1 h, H=37.084, P<0.01] and CRP [RF(-) anti-CCP antibody(-) 2.3 (0.8, 15.9) mm/L, Anti-CCP antibody(+) 2.7(0.7, 12.1) mm/L, RF(+) anti-CCP antibody(+) 5.2(1.3, 17.2) mm/L, RF (+) 5.2(0.9, 16.2) mm/L, H=22.141, P<0.01] of the RF(+)patients were significantly higher than RF(-) patients, and RF(+) patients had higher disease severity(DAS28-ESR) [RF(-) anti-CCP antibody(-) (4.0±1.8), anti-CCP antibody(+) (3.8±1.6), RF(+) anti-CCP antibody(+) (4.3±1.8), RF(+) (4.1±1.7), F=7.269, P<0.01]. ③ The RF(+) anti-CCP antibody(+) patients were divided into 4 subgroups, and it was found that RF-H anti-CCP antibody-L patients had higher disease severity [RF-H anti-CCP antibody-H 4.3(2.9, 5.6), RF-L anti-CCP antibody-L 4.5(3.0, 5.7), RF-H anti-CCP antibody-L 4.9(3.1, 6.2), RF-L anti-CCP antibody-H 2.8(1.8, 3.9), H=20.374, P<0.01]. ④ After 3-month follow up, the clinical characteristics of the four groups were improved, but there was no significant difference in the improvement of the four groups, indicating that the RF and anti-CCP antibody status did not affect the remission within 3 months. Conclusion:Among RA patients, the disease activity of RA patients is closely related to RF and the RF(+) patients have more severe disease than RF(-) patients. Patients with higher RF titer also have more severe disease than that of patients with low RF titer. After 3 months of medication treatment, the antibody status does not affect the disease remission rate.

Objective:To investigate the safety and efficacy of self-made multifunctional endoscopic instrument accessory stent in endoscopic mucosal dissection (ESD).Methods:A total of 80 patients who received ESD in 924th Hospital of Joint Logistic Support Force of Chinese People′s Liberation Army from May 2019 to February 2021 were selected as research object. Random number table method was used to divide patients into control group and experimental group, 40 cases in each group. The experimental group used self-made endoscopic instrument accessory stent, and the control group did not use self-made endoscopic instrument accessory stent. The length of operation, the number of instruments taken by mistake, the number of instruments polluted during operation and the infection of postoperative 3-7 days under the same operation position, operating doctors and nurses were analyzed and compared between the two groups.Results:The incidence of instruments taken by mistake, the incidence of instruments polluted during operation and the infection rate of postoperative 3-7 days were 0.9% (8/856), 1.4% (12/856) and 2.5% (1/40) in the experimental group, which in the control group were 10.8% (96/887), 11.8% (105/887) and 15.0% (6/40) respectively, there were significant differences between the two groups ( χ2=75.92, 75.76, 3.91, all P<0.05). The length of operation in the experimental group was (51.56 ± 2.32) min, and that in the control group was (79.02 ± 2.83) min, the difference was statistically significant ( t=-8.72, P<0.05). Conclusions:When the patients underwent ESD surgery, the self-made multifunctional accessory stent was used to place the required instrument accessory. The length of operation was shorter, the incidence of instruments taken by mistake, the incidence of instruments polluted during operation and the infection rate of postoperative 3-7 days were reduced, the quality of minimally invasive endoscopic surgery was improved.

OBJECTIVE: To investigate short-term effectiveness of arthroscopic repair via modified subacromial viewing portal (hereinafter referred to as modified viewing portal) in treatment of LafosseⅠsubscapularis tendon tears. METHODS: A clinical data of 52 patients with LafosseⅠsubscapularis tendon tears, who underwent the arthroscopic repair via modified viewing portal between October 2020 and November 2022 and met the selective criteria, was retrospectively analyzed. There were 15 males and 37 females with an average age of 63.4 years (range, 41-76 years). Twelve patients had trauma history and the other 40 patients had no obvious inducement. The main clinical symptom was shoulder pain and the hug resistance tests were positive in all patients. The interval between symptom onset and admission ranged from 3 to 26 months (mean, 7.2 months). The shoulder pain and function were evaluated by visual analogue scale (VAS) score, American Shoulder and Elbow Surgeons (ASES) score, and University of California Los Angeles (UCLA) score before operation and at 12 months after operation. The shoulder range of motion (ROM) of forward flexion, abduction, and external rotation and the internal rotation strength were measured before operation and at 3 and 12 months after operation. MRI was performed at 3-6 months after operation to assess the tendon healing and the structural integrity and tension of reattached tendon. Patient's satisfactions were calculated at last follow-up. RESULTS: All incisions healed by first intention, no complication such as incision infection or nerve injury occurred. All patients were followed up 12-37 months (mean, 18.5 months). The VAS, UCLA, and ASES scores at 12 months after operation significantly improved when compared with those before operation ( P<0.05). The ROMs of abduction and forward flexion and the internal rotation strength at 3 and 12 months significantly improved when compared with those before operation ( P<0.05); and the ROMs at 12 months significantly improved compared to that at 3 months ( P<0.05). However, there was no significant difference ( P>0.05) in the ROM of external rotation at 3 months compared to that before operation; but the ROM at 12 months significantly improved compared to that before operation and at 3 months after operation ( P<0.05). Thirty-one patients underwent MRI at 3-6 months, of which 28 patients possessed intact structural integrity, good tendon tension and tendon healing; 3 patients underwent tendon re-tear. At last follow-up, 41 patients (78.8%) were very satisfied with the effectiveness, 7 were satisfied (13.5%), and 4 were dissatisfied (7.7%). CONCLUSION Arthroscopic repair via modified viewing portal for Lafosse Ⅰsubscapularis tendon tears, which can achieve the satisfactory visualization and working space, can obtain good short-term effectiveness with low overall re-tear risk.
Male ; Female ; Humans ; Middle Aged ; Rotator Cuff/surgery* ; Rotator Cuff Injuries/surgery* ; Shoulder Pain ; Retrospective Studies ; Treatment Outcome ; Arthroscopy ; Shoulder Joint/surgery* ; Tendons/surgery* ; Range of Motion, Articular