We report a case of a young female patient with fatigue, hypokalemia, and hyperglycemia. She had past-history of diabetes mellitus, and was admitted to hospital with a history of fatigue and hypokalemia for 5 years. The patient's examination indicated hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria, and SLC12A3 gene pathogenic mutation. The diagnosis was Gitelman syndrome. Potassium and magnesium supplements were given to improve the patient's fatigue. Serum potassium and magnesium were normal. The blood glucose reached standard after treatment with oral hypoglycemic drugs. This article incorporates literature review to sort out the diagnosis and treatment of Gitelman syndrome, in order to provide feasible reference for clinicians.

Objective To evaluate the efficacy of Broncho-Vaxom combined with physiological sea water nasal wash in the treatment of chronic rhinitis-rhinosinusitis in children. Methods A total of 179 children with chronic rhinitis-rhinosinusitis were randomly divided into observation group of 90 cases and control group of 89 cases. The observation group received treatment of oral administration of Broncho-Vaxom capsules at a dose of 3.5 mg once daily on an empty stomach in the morning for 10 consecutive days, with a 20-day drug-free period as one course of treatment, for a total of 3 courses. Additionally, they underwent nasal irrigation with physiological sea water twice daily in the morning and evening, for 10 consecutive days, with a 20-day break as one course of treatment, for a total of 3 courses. The control group underwent nasal irrigation with physiological sea water using the same method of the observation group. Both groups received symptomatic treatment such as anti-allergy therapy, and antibiotics were added when there presented obvious inflammatory changes. After treatment, the clinical total effective rate was compared between the two groups. Changes in the scores of Visual Analogue Scale (VAS) and Lund-Kenndy scale for nasal endoscopy, as well as changes in serum IgG, IgE, and T lymphocyte subsets were also compared. A six-month follow-up was conducted to assess the recurrence rate and average number of episodes of rhinosinusitis (times per person). Results The clinical total effective rate in the observation group was significantly higher compared to that in the control group(95.56% versus 86.52%). The scores of VAS and Lund-Kenndy scale in the observation group were significantly better than those in the control group. Serum IgG levels in the observation group were increased and higher than those in the control group, while serum IgE level in the observation group was decreased and lower than that in the control group. After 3 courses of treatment, the levels of CD3⁺, CD4⁺, and CD4⁺/CD8⁺ in the blood of the observation group were increased, while the level of CD8⁺ was decreased. The six-month follow-up after treatment showed that the recurrence rate of rhinitis-rhinosinusitis in the observation group was 17.05%, with an average of 0.28 episodes per person, which was lower than that in the control group (P < 0.05). Conclusion The combination of Broncho-Vaxom and physiological sea water nasal wash is effective in treating chronic rhinitis-rhinosinusitis in children, and can increase serum IgG level, decrease serum IgE level, optimize the structure of T lymphocyte subsets, enhance immune resistance, and improve allergic constitution. The six-month follow-up of the treatment reduces recurrence rate and average number of episodes of rhinitis-rhinosinusitis.

BACKGROUND: Imatinib mesylate (IM) resistance is an emerging problem for chronic myeloid leukemia (CML). Previous studies found that connexin 43 (Cx43) deficiency in the hematopoietic microenvironment (HM) protects minimal residual disease (MRD), but the mechanism remains unknown. METHODS: Immunohistochemistry assays were employed to compare the expression of Cx43 and hypoxia-inducible factor 1α (HIF-1α) in bone marrow (BM) biopsies of CML patients and healthy donors. A coculture system of K562 cells and several Cx43-modified bone marrow stromal cells (BMSCs) was established under IM treatment. Proliferation, cell cycle, apoptosis, and other indicators of K562 cells in different groups were detected to investigate the function and possible mechanism of Cx43. We assessed the Ca 2+ -related pathway by Western blotting. Tumor-bearing models were also established to validate the causal role of Cx43 in reversing IM resistance. RESULTS: Low levels of Cx43 in BMs were observed in CML patients, and Cx43 expression was negatively correlated with HIF-1α. We also observed that K562 cells cocultured with BMSCs transfected with adenovirus-short hairpin RNA of Cx43 (BMSCs-shCx43) had a lower apoptosis rate and that their cell cycle was blocked in G0/G1 phase, while the result was the opposite in the Cx43-overexpression setting. Cx43 mediates gap junction intercellular communication (GJIC) through direct contact, and Ca 2+ is the key factor mediating the downstream apoptotic pathway. In animal experiments, mice bearing K562, and BMSCs-Cx43 had the smallest tumor volume and spleen, which was consistent with the in vitro experiments. CONCLUSIONS Cx43 deficiency exists in CML patients, promoting the generation of MRD and inducing drug resistance. Enhancing Cx43 expression and GJIC function in the HM may be a novel strategy to reverse drug resistance and promote IM efficacy.
Animals ; Humans ; Mice ; Apoptosis ; Bone Marrow Cells ; Cell Communication ; Connexin 43/genetics* ; Gap Junctions/metabolism* ; Imatinib Mesylate/therapeutic use* ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology* ; Mesenchymal Stem Cells/metabolism* ; Tumor Microenvironment ; Calcium/metabolism*

ObjectiveTo explore the features and assessment for far space neglect in left spatial neglect patients after right brain stroke. MethodsFrom January to October, 2021, 30 left unilateral spatial neglect (USN) patients after right stroke (patients, n = 30) from Beijing Bo'ai Hospital and healthy volunteers matching with gender, age and level of education (controls, n = 30) were evaluated with line cancelation (LC), star cancelation (SC) and line bisection (LB) tests, nearly and far away. The 25 controls were evaluated with LB on the second day. ResultsNo line or star was omissed in the controls. Both the deviation and percentage were more in the patients than in the controls (|t| > 4.319, P < 0.001). Both the deviation and percentage were less different for all the test (|Z| < 1.638, t = -1.282, P > 0.05) between nearly and far away, except the deviation of LB (t = -4.994, P < 0.001). The ICC of test-retest was above 0.462 (P < 0.01). ConclusionRight brain stroke patients with USN may present far spatial neglect, which can be assessed with LB.

Objective:To investigate the effect of human umbilical cord mesenchymal stem cells (hUC-MSC) on the apoptosis of retinal ganglion cells (RGCs) in diabetic retinopathy (DR) model rats and on the regulation of p38 mitogen-activated protein kinase (p38MAPK) pathway.Methods:Forty-five SPF male 8-week old SD rats were selected.The DR rat model was established by intraperitoneal injection of streptozotocin (STZ) combined with a high-sugar and high-fat diet.The fasting blood glucose (FBG) and body weight of the rats were measured every week during the high-sugar and high-fat diet, and fundus angiography was used to observe the circulation and leakage of retinal blood vessels.Forty rats with successful modeling were randomly divided into model group and hUC-MSC injection group according to the random number table method, with 20 rats in each group.Another 20 normal rats fed routinely were served as control group, and intraperitoneally injected with the same amount of citric acid buffer.The hUC-MSC injection group was injected intravitreously with hUC-MSC, and the control group and model group were injected intravitreously with the same amount of phosphate buffer saline (PBS). Fluoro gold (FG) retrograde tracer labeling RGCs was used to observe the number of survived RGCs.Hematoxylin-eosin staining was used to observe the pathological changes of retina.TUNEL method was used to observe the apoptosis of RGCs.Western blot was used to detect B cell lymphoma /leukemia-2 (Bcl-2), Bcl-2 associated X protein (Bax), p38MAPK and phosphorylated (p-) p38MAPK protein expression in retinal tissues.The use and care of the rats complied with the ARVO statement.The study protocol was approved by an Animal Ethics Committee of Zhengzhou central Hospital Affiliated to Zhengzhou University (NO.2980316).Results:The FBG of control rats was maintained at a normal level, and the body weight gradually increased over time, and was gradually decreased as the course of disease prolonged.The retinal blood vessels ran normally without fluorescein leakage in the control group.In the modeling group, the FBG was maintained at a high level, and the body weight increased slowly and gradually decreased with the prolongation of the disease course since the second week after modeling.The distal retinal vessels were found twisted with large area of capillary fluorescein leakage in the modeling group.The density of RGCs in the control group, model group and hUC-MSC injection group were (2 136.10±215.17), (849.40±167.82), (1 549.20±183.26) cells/mm 2, with significant overall differences ( F=115.218, P<0.01). The density of RGCs in the model group and the hUC-MSC injection group were significantly lower than that of the control group, and the density of RGCs in the hUC-MSC injection group was significantly higher than that of the model group, and the differences were statistically significant (all at P<0.05). The retina in the control group was with clear structure, distinct layers, and a large number of complete RGCs.The number of RGCs in the model group was significantly reduced with nuclear pyknosis, thinned and atrophied RGC layer.The retinal structure was relatively complete, and there were more RGCs in the hUC-MSC injection group than the model group.The apoptosis rates of RGCs in the control group, model group and hUC-MSC injection group were (2.16±1.11)%, (43.47±2.26)%, (20.75±2.18)%, with significant overall difference ( F=445.159, P<0.01). The apoptosis rates of RGCs in the model group and hUC-MSC injection group were significantly higher than that of the control group, and the apoptosis rate of RGCs in the hUC-MSC injection group was lower than that of the model group, and the differences were statistically significant (all at P<0.05). There were statistically significant differences in the relative expression levels of Bax, Bcl-2 and p-p38MAPK proteins in the retina tissues among the three groups ( F=30.982, 12.526, 73.158, all at P<0.01). The relative expression of Bax and p-p38MAPK protein were significantly higher, and the relative expression of Bcl-2 protein was significantly lower in the hUC-MSC injection group and the hUC-MSC injection group than those of the control group, and the differences were statistically significant (all at P<0.05). The relative expression of Bax and p-p38MAPK protein was significantly lower, and the relative expression of Bcl-2 protein was significantly higher in the hUC-MSC injection group than those in the model group, and the differences were statistically significant (all at P<0.05). There was no significant difference in the relative expression of p38MAPK protein among the three groups ( F=1.182, P=0.322). Conclusions:Intravitreal injection of hUC-MSC can inhibit the apoptosis of RGCs in DR model rats and protect the retinal structure of rats, which may play an anti-apoptotic effect by inhibiting the p38MAPK signaling pathway.

Preclinical studies have shown that metformin, an activator of AMP-activated protein kinase (AMPK) , can inhibit the growth of lymphoma cells without affecting the function of normal lymphocytes, promote the apoptosis of lymphoma cells and improve the tumor immune environment. Clinical studies have shown that metformin can improve the efficacy of chemotherapy and prognosis of non-Hodgkin lymphoma (NHL) . Through the influence on glucose metabolism, it can improve blood glucose level and reduce the incidence of steroid diabetes. The main molecular mechanisms of metformin against NHL include activating AMPK in tumor cells, inhibiting mammalian target of rapamycin signal, inhibiting key cholesterol synthesis, improving glucose metabolism, enhancing highly cytotoxic T lymphocyte (CTL) activity and so on. Current research shows that metformin may become a new strategy for the treatment of NHL.

Objective:To investigate the risk factors associated with death among patients with coronavirus disease 2019 (COVID-19).Methods:A total of 217 COVID-19 patients admitted to Zhongnan Hospital, Wuhan University from December 29, 2019 to January 31, 2020 were enrolled. The general conditions, clinical symptoms, comorbidities, laboratory test indicators and clinical outcomes of the COVID-19 patients were analyzed. According to prognosis, the COVID-19 patients were divided into the death group and the survival group, and the clinical manifestations and laboratory examination results of the two groups were compared by t test and chi-square test. The binary logistics regression model was used to analyze the risk factors related to death. Results:Among the 217 COVID-19 cases, 124 were males and 93 were females, as of March 4, 2020, 25 died and 192 survived, with the mortality of 11.5%. Eighty-nine patients (41.0%) had confirmed history of exposure to the Huanan seafood market or had close contact with another patient with confirmed COVID-19. Among the patients who died, 21(84.0%) were male, 21(84.0%) had comorbidities, 15(60.0%) had more than three types of clinical symptoms, 14(56.0%) had alaine aminotransferase or aspartate aminotransferase>1.5 upper limit of normal (ULN), 13(52.0%) had creatinine (Cr) >104 μmol/L, and 18(72.0%) had procalcitonin (PCT) >0.05 μg/L, whereas the above indicators among the survival patients were 103(53.6%), 95(49.5%), 92(47.9%), 23(12.0%), 14(7.3%) and 47(24.5%), respectively. The differences of the above indicators between the two groups were all statistically significant ( χ2=11.506, 7.889, 14.897, 30.307, 40.585 and 23.807, respectively, all P<0.01). The multivariate analysis results showed that age≥65 years old (odds ratio ( OR)=5.968, 95% confidence interval ( CI)1.991-17.888, P=0.001), male ( OR=6.009, 95% CI 2.504-14.422, P<0.01), comorbidities ( OR=7.152, 95% CI 2.058-24.851, P=0.002), having more than three types of clinical symptoms ( OR=7.944, 95% CI 2.280-27.676, P=0.001), alanine aminotransferase or aspartate aminotransferase>1.5×ULN ( OR=9.552, 95% CI 3.760-24.269, P<0.01), Cr>104 μmol/L ( OR=11.458, 95% CI 4.289-30.613, P<0.01), lactic acid dehydrogenase (LDH)>243 U/L ( OR=7.591, 95% CI 1.683-34.249, P=0.008) and PCT>0.05 μg/L( OR=12.410, 95% CI 4.433-34.744, P<0.01) were risk factors for death among COVID-19 infection patients. Conclusion:For elderly male COVID-19 patients with comorbidities, impaired liver and kidney functions, elevated LDH and PCT are early warning signs for disease deterioration.

Objective:To investigate the risk factors of birth weight discordance in dichorionic diamniotic (DCDA) twins.Methods:This study retrospectively analyzed 1 757 cases of DCDA twin pregnancies from 11 Chinese hospitals from January 1, 2014, to December 31, 2017. Birth weight discordance was defined as ≥ 20% difference between the twins. All cases were divided into two groups: the concordant group ( n=1 520) and discordant group ( n=237). General information was compared and the high-risk factors of birth weight discordance were analyzed. Mann-Whitney U test, Chi-square test or Fisher's exact test, and logistic regression analysis were used as statistical methods. Results:Compared with the concordant group, the discordant group showed a higher incidence of hypertensive disorders of pregnancy [24.5% (58/237) vs 12.8% (194/1 520), χ2=22.882, P<0.05], fetal structural malformations [4.2% (10/237) vs 1.0% (15/1 520), χ2=15.160, P<0.05], fetal distress [6.3% (15/237) vs 1.4% (21/1 520), χ2=22.602, P<0.05], umbilical cord abnormalities [3.8% (9/237) vs 1.2% (18/1 520), χ2=7.607, P<0.05] and abnormal placental cord insertion [3.8% (9/237) vs 1.4% (21/1 520), χ2=34.904, P<0.05], but lower incidence of premature rupture of membranes [11.0% (26/237) vs 16.5% (250/1 520), χ2=4.645, P=0.034]. Logistic regression analysis showed that the independent risk factors of birth weight discordance in DCDA twins were hypertensive disorders of pregnancy ( OR=2.258, 95% CI: 1.620-3.184, P<0.001), fetal structural malformations ( OR=4.268, 95% CI: 1.892-9.631, P<0.001), umbilical cord abnormalities ( OR=2.889, 95% CI: 1.245-6.705, P=0.014) and abnormal placental cord insertion ( OR=2.318, 95% CI: 1.012-5.311, P=0.047). Conclusions:Hypertensive disorders of pregnancy, fetal structural malformations, umbilical cord abnormalities and abnormal placental cord insertion may be the risk factors of birth weight discordance in DCDA twins.

Objective    To summarize the clinical experience of Da Vinci robotic-assisted left upper lobectomy for treating lung cancer. Methods    We retrospectively analyzed the perioperative data of 33 patients with primary lung cancer who underwent Da Vinci robotic-assisted left upper lobectomy between December 2016 and December 2018 in our hospital. Meanwhile, the perioperative data of 41 patients with lung cancer who underwent video-assisted thoracoscopic left upper lobectomy during the same period by the same surgeon were studied as a control group. The resection was followed by the principle of "from back down to front up" way. Systemic lymph node dissection including No.4-9 was performed for all patients. Results    All patients received successful surgery with no case of conversion to thoracotomy and perioperative death. Comparing to video-assisted thoracoscopic surgery, the Da Vinci robotic-assisted left upper lobectomy had longer operating time (191.21±61.77 min vs. 154.51±38.81 min, P=0.003), more cost (82 307.75±11 859.03 yuan vs. 58 966.57±5 640.07 yuan, P=0.000), shorter chest tube duration (4.58±1.77 d vs. 5.41±1.52 d, P=0.031) and postoperative hospital stay (6.48±1.82 d vs. 7.66±2.12 d, P=0.014). However, there was no significant difference between the two groups regarding to blood loss, lymph node dissection, postoperative pain score, total chest drainage volume, chest drainage volume per day and the rate of pulmonary complications. Conclusion    The Da Vinci robotic-assisted left upper lobectomy for treating lung cancer is safe and more minimally invasive, but more expensive.

Objective: Chronic graft-versus-host disease (cGVHD) is a major long-term complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . It is important to study the changes of serum biomarkers expression in patients for early diagnosis and treatment. Methods: The expression levels of five serum protein markers (IL-1b, IL-16, CXCL9, CCL19, CCL17) in patients with or without cGVHD after allo-HSCT were detected by liquid suspension microarray. Results: Compared with the control group without cGVHD, the expression levels of CXCL9 and CCL17 in serum of patients with cGVHD were significantly increased (P<0.05) . CCL17 was correlated with the severity of cGVHD (P<0.001) . CXCL9 was significantly increased in the serum of patients with skin lesion (P<0.01) , and CCL17 was significantly expressed in cGVHD patients with liver as the target organ (P<0.01) . Conclusion The combination of CXCL9 and CCL17 can be used as serum biomarkers of cGVHD, which has certain reference value in assisting the diagnosis and evaluation of cGVHD severity.