Objective:To further investigate the safety and efficacy of Belimumab in the treatment of patients with systemic lupus erythematosus (SLE).Methods:All SLE patients treated with Belimumab from May 1, 2020 to February 1, 2022 in Peking Union Medical College Hospital were retrospectively collected and analyzed. The clinical manifestations, the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2000) score, and laboratory test such as levels of anti-dsDNA antibody, the medication before and after Belimumab treatment, adverse events were collected. Normally distributed data were tested using the t-test, otherwise the Wilcoxon paired signed rank test was used. Results:A total of 81 patients were enrolled in this study. The use of belimumab could significantly decrease the SLEDAI-2000 score [10.00(7.75, 12.00) vs. 4.00(3.75, 6.00), Z=-5.38, P<0.001], ESR of SLE patients [19.50(12.75, 32.25) mm/1 h vs. 14.00(7.75, 20.25) mm/1 h, Z=-3.71, P=0.003], anti-dsDNA titer detected by CLIFT [300.00 (117.00, 864.00) vs. 183.00(100.00, 471.00), Z=-4.15, P=0.001], meanwhile, increase the complement C3 [0.78 (0.62, 0.97)g/L vs. 0.69 (0.55, 0.84)g/L, Z=-4.68, P<0.001], and the complement C4 [0.12 (0.08, 0.19)g/L vs. 0.10 (0.05, 0.14)g/L, Z=-4.78, P<0.001]. We also observed that with the use of Belimumab, the dosage of Glucocorticoids decreased significantly, which were [10.00(7.50, 22.50) mg vs. 7.50(5.00, 10.00) mg, Z=-4.90, P<0.001]. In addition, the antibody of IgG, IgA and IgM decreased significantly. Only one patient stopped the administration of Belimumab due to the low level of immunoglobulin. Conclusion:Belimumab can alleviate disease activity of patients with SLE and help in safely tapering the daily dose of glucocorticoid with good safety.

Myotonic dystrophy type 1 (DM1, OMIM 160900) is a rare autosomal dominant hereditary disease. A case of DM1 patient with early onset diabetes and decreased muscle strength was treated in the Department of Endocrinology, Third Xiangya Hospital, Central South University. The peripheral blood of the patient was collected to extract DNA for gene detection. It was found that the triple nucleotide CTG repeat in the 3'-untranslated region (3'-UTR) of the dystrophia myotonica protein kinase (DMPK) gene was more than 100 times, and the diagnosis of DM1 was clear. For diabetes patients with multiple system abnormalities such as muscle symptoms, attention should be paid to the screening of DM1, a rare disease.
Humans ; Myotonic Dystrophy/genetics* ; Abnormalities, Multiple ; Hospitals ; Universities ; Diabetes Mellitus

Diabetic mellitus (DM) is a common degenerative chronic metabolic disease often accompanied by severe cardiovascular complications (DCCs) as major causes of death in diabetic patients with diabetic cardiomyopathy (DCM) as the most common DCC. The metabolic disturbance in DCM generates the conditions/substrates and inducers/triggers and activates the signaling molecules and death executioners leading to cardiomyocyte death which accelerates the development of DCM and the degeneration of DCM to heart failure. Various forms of programmed active cell death including apoptosis, pyroptosis, autophagic cell death, autosis, necroptosis, ferroptosis and entosis have been identified and characterized in many types of cardiac disease. Evidence has also been obtained for the presence of multiple forms of cell death in DCM. Most importantly, published animal experiments have demonstrated that suppression of cardiomyocyte death of any forms yields tremendous protective effects on DCM. Herein, we provide the most updated data on the subject of cell death in DCM, critical analysis of published results focusing on the pathophysiological roles of cell death, and pertinent perspectives of future studies.

Objective:To investigate the application value of fetal heart quantification (fetal HQ) in the evaluation of fetal heart size, morphology and function in fetuses with right ventricular outflow obstruction (RVOTO).Methods:Fifty-five fetuses diagnosed as RVOTO by fetal echocardiography in Sir Run Run Shaw Hospital Affiliated to Medical College of Zhejiang University from April 2020 to February 2021 were selected. They were divided into simple pulmonary artery stenosis (PS) group and conus arteriosus malformation (CTD) group according to whether they were combined with other cardiovascular malformations. On the standard four chamber view, the end diastolic basal apical length (4CV length) and transverse width (4CV width) were obtained by fetal HQ analysis technique, and the cardiac global spherical index (4cv-gsi) was calculated. The left and right ventricles (LV and RV) were divided into 24 segments from the base to the apex. The endocardial curve was obtained by total HQ tracking. The 24 segment transverse width (ED), spherical index (SI), short axis shortening (FS) and its Z-score were calculated. The LV and RV of RVOTO fetuses were compared and analyzed from the aspects of heart size, morphology and function.Results:The 4CV length of RVOTO fetal heart was in the normal range, 4CV width increased in varying degrees, GSI decreased, and the whole heart showed spherical changes. In PS group, LV-ED was larger than that of RV and the difference was statistically significant in 5-24 segments( P<0.05). LV was more spherical than RV. There was no significant difference in ED between LV and RV in CTD group( P>0.05), and RV was more spherical than LV. Twenty-four segment FS decreased in different degrees in RVOTO fetal heart, and the decrease of RV was more obvious than that of LV. There was significant difference between the LV and RV in PS group from S5 to 19 ( P<0.05), and there was significant difference between the left and right ventricles in CTD group from S1 to 11 ( P<0.05). Conclusions:Fetal HQ can provide new insights of cardiac size, morphology and function in fetuses with RVOTO.

Objective To explore the use of biological agents in Neuro-Beh(c)et's disease (NBD).Methods We retrospectively reviewed the clinical data of five NBD patients treated with biological agents who were in-patients at Peking Union Medical College Hospital between June 2009 and June 2016.The continuous variables were analyzed by t test.Results All five cases (4 male and 1 female) were severe and/or refractory patients with parenchymal involvement (pNBD).Their age at neurological onset was (31±12) years old.Four cases presented with multiple lesions.The brainstem,spinal cord,cerebral hemisphere and cerebellum involvement were presented in 4,3,3 and 2 patients,respectively.The Rankin score at the onset of NBD was (4.0±0.7).The biological agents were administrated when corticosteroids and immunosuppressant were ineffective.Three cases received tumor necrosis factor (TNF)-α inhibitors therapy,among whom one patient had gastrointestinal ulceration.One patient with refractory retinal vasculitis received interferon-α therapy.One patient treated with tocilizumab [interleukin (IL)-6R inhibitor] had high level IL-6 in the cerebrospinal fluid.All patients achievcd clinical improvements and the Rankin score significantly decreased to (2.2±0.8) when compared with the baseline (t=4.81,P＜0.01) after the treatment with biological agents.The corticosteroid dose was tapered in all cases and the numbers of immunosuppressants were reduced in most cases,indicating a potential steroid and immunosup-pressant-sparing effect.No serious adverse events were observed during the follow-up.Conclusion Neurological involvement is a severe complication of Behqet's disease.We can take appropriate biological agents such as TNF-α inhibitors or interferon-α into consideration when patients have severe/refractory pNBD.

BACKGROUND:There are many postmenopausal women taking hormone, which leads to much loss of bone mass, further inducing fragility fractures. The studies on the hormone exposure combined with ovariectomy-induced osteoporotic model are still immature, and the related molecular mechanism remains unclear. OBJECTIVE: To establish the rat osteoporotic model induced by ovariectomy combined with glucocorticoid exposure and to explore the underlying molecular mechanism. METHODS: Thirty 3-month-old female Sprague-Dawley rats were randomly divided into blank control, sham and model groups (n=10 per group). The rats in the blank control group received no intervention; rats in the sham group were clipped off a little of coeliac adipose tissue; the model rats received bilateral ovariectomy and 4-week administration of glucocorticoid. RESULTS AND CONCLUSION:At 4 weeks after modeling, compared with blank control and sham groups, the model group showed significantly lower bone mineral density of the femur, number of bone trabeculae and bone volume/total volume, and significantly wider bone trabecular spacing. Additionally, the model group revealed the damaged bone trabecular structure and thiner cortical bone. The expression level of Runx2 was downregulated whereas both collagen type 1α1 and peroxisome proliferators activated receptor γ mRNA were upregulated in the model group. These findings suggest that ovariectomized rats exposed to glucocorticoid rapidly develop femur osteoporosis, maybe by downregulating the expression of Runx2, as well as upregualting collagen type 1α1 and peroxisome proliferators activatedreceptor γ mRNA.

Objective:To observe and compare the clinical effect of single-incision and two-incision posterior chamber phakic intraocularlens implantation in the correction of extreme myopia.Methods:40 cases(80 eyes) of patients with extreme myopia underwent conventional two-incision posterior chamber phakic intraocularlens implantation in our hospital from January 2011 to June 2013 were selected as the control group and 40 cases(80 eyes) underwent single-incision posterior chamber phakic intraocularlens implantation from July 2013 to January 2016 were selected as observation group.The open hole before and after operation,best corrected visual acuity of vision,operation safety,effectiveness index,diopter (column mirror,equivalent ball for eyeglasses),intraocular pressure,ECD,anterior chamber depth and occurrence of complications were compared between two groups.Results:The uncorrected visual acuity (UCVA) of both groups at 6 months after operation were significantly higher than those before operation (P＜0.05),which was significantly higher in the observation group than that of the control group (P＜0.05);The operation safety and effectiveness index of observation group were significantly higher than those of the control group (P＜0.05);The cylinder and spherical equivalent degree of both groups at 6 months after operation were significantly better than those before operation(P＜0.05),which was significantly better in the observation group than that of the control group(P＜0.05).The corneal endothelial cell counts(ECL) of control group after operation was significantly lower than that before operation (P＜0.05),and no significant difference was found in the ECL of observation group before and after operation (P＞0.05).The ECL of observation group after operation was significantly higher than that of the control group (P＜0.05);The incidence rate of complication in observation group was significantly lower than that of the control group (P＜0.05).Conclusion:Compared with two-incision operation,the single-incision posterior chamber phakic intraocularlens implantation had remarkable clinical effect in the correction of extreme myopia with higher security.

Aim Paclitaxel(PTX)has shown an effect against human cancer. However, serious drawbacks hamper PTX clinical use.Overcoming paclitaxel limi-tations is one of the best approaches to enhance water solubility.Methods In this study,water-soluble pa-clitaxel prodrug was prepared,folic acid-polyethylene glycol-glutamic-paclitaxel (FA-PEG-Glu-PTX ) com-posed of folic acid (FA,target),amino acids (Glu, linker),and polyethylene glycol(PEG)in order to im-prove the solubilization and stability. The chemical structure and physicochemical property of prodrug were measured by LC-MS,solubility,drug release rate to e-valuate the antitumor activity and cytotoxicity of FA-PEG-Glu-PTX.MTT assays were conducted on MDA-MB-231,MCF-7,A549 and HELF cell lines.FA-PEG-Glu-PTX prodrugs were labeled with 5 amino flu-orescence visible fluorescent dye (5 AF ) for fluores-cence microscopy.Results The successful conjugation of FA-PEG-Glu-PTX was confirmed by LC-MS,and had better water solubility,release rate curve.In vitro studies indicated that foliate receptor(FR-α)mediated uptake of PTX-conjugated multi-small molecules carri-ers induced highly targeting ability,and antitumor ac-tivity,as well as reduced side toxicity effects of PTX. Conclusion FA-PEG-Glu-PTX has a good antitumor activity.

Objective To investigate the trend of liver function changes in untreated adult patients with Graves’ disease in China, and to analyze the associated factors. Methods Patients with newly diagnosed as well as recurrent Graves’ disease from January 2006 to August 2014 were enrolled. They were over 18 years old and did not receive any treatments, Examination of liver function, thyroid function, and thyroid related antibodies as well as tests regarding virus hepatitis were performed. Results A total of 1 254 patients were enrolled. 33 patients with virus hepatitis were ruled out. Ultimately, 1 221 patients matched the criteria of our trial, with 347 males and 874 females [(39. 3 ± 9. 5) year old]. After inclusion, they were assigned to 2 groups according to their liver function results(605 in normal group and 616 in abnormal group). Compared to normal group, patients in the abnormal group were older [(40. 1 ± 9. 2 vs 38. 5 ± 8. 7) year old, P<0. 05] and with higher proportion of females(81. 8% vs 61. 2% , P<0. 05). Regarding the thyroid function and related antibody tests, some patients yielded results that were extremely high so as to exceed the upper limit of the normal range. These patients were more frequently seen in the group with abnormal liver function. The patients whose thyroid function parameters exceeded the upper limit had higher level of alanine aminotransferase[ALT,(37. 69 ± 7. 51 vs 31. 90 ± 5. 95) U/ L, P<0. 05], aspartate aminotransferase[AST, (31. 97 ± 5. 09 vs 27. 88 ± 3. 82) U/ L, P<0. 05], direct bilirubin[DBiL, (5. 58 ± 0. 77 vs 4. 54 ± 0. 71) μmol/ L, P<0. 05]than the group whose thyroid function on the detected range. In the patients with all results detected, patients in abnormal liver function group had higher level of triiodthyronine[T3 , (5. 42 ± 0. 29 vs 4. 94 ± 0. 33) nmol/ L, P<0. 05], thyroxin[T4 ,(217. 53 ±14. 32 vs 204. 22 ±13. 54) nmol/ L, P<0. 05], free triiodthyronine[FT3 ,(15. 88 ± 2. 86 vs 14. 48 ±4. 83) pmol/ L, P<0. 05], free thyroxin[FT4 ,(48. 91 ±8. 45 vs 42. 95 ±6. 14) pmol/ L, P<0. 05], thyroid peroxidase antibody[ TPOAb, (402. 75 ± 89. 99 vs 210. 70 ± 44. 63) IU/ ml, P < 0. 05] and thyrotrophin receptor antibody[TRAb,(14. 08 ± 5. 24 vs 9. 04 ± 2. 58) IU/ L, P<0. 05]. Multivariate logistic regression analysis revealed that patients’ age(OR=0. 98, 95% CI 0. 97-0. 99), gender(OR=0. 94, 95% CI 0. 91-0. 97), level of FT4 (OR=3. 08, 95% CI 2. 19-4. 32), TPOAb(OR = 0. 98, 95% CI 0. 97-0. 99), and TRAb(OR = 1. 07, 95% CI 1. 01-1. 12) were independent risk factors of their liver dysfunction. Conclusion Graves’ disease may lead to liver dysfunction, which is much more common and severe in elder and female patients, as well as patients who are suffering from hyperthyroidism and raised level of thyroid related antibodies.

Objective To explore the effects of hyperbaric oxygen treatment on chronic stress and glucocorticoid receptor (GR) expression in the hippocampus.Methods A total of 60 male Wistar rats were randomly divided into a restraint group,an HBO (hyperbaric oxygen) group,an HBO-restraint group and a control group using a random number table,each group with 15 animals.All the rats in the restraint and HBO groups were constrained by immobilizing their fore-and hind-limbs on a self-made frame for 3h daily for 21 days,and those in the HBO group received HBO treatment once daily for the same 21 days.The HBO-restraint group was immobilized in the morning and treated with HBO in the afternoon.The control group was reared without any special intervention.On the 1st,11th and 21st day of treatment,rats from the different groups were assessed using the open field test.On the 21st day,all the animals were sacrificed and their brains were harvested to detect GR expression.Results In the open field test on the 11 th day,the restraint group scored (131.0 ± 20.6) in terms of motor level and (26.5 ± 4.6) for exploratory behavior,both significantly higher than before restraint and significantly higher than those in the HBO-restraint group at the same time point.Immunofluorescence assay showed that GR expression in the hippocampus of the restraint group was significantly decreased compared with the control group.There was no significant difference,however,between the HBO-restraint group and the control group.Conclusion Chronic restraint stress induces changes in behavior and GR expression in rats which can be alleviated by hypbaric oxygen treatment.