[A multicenter study on the tolerance of intravenous low-dose cyclophosphamide in systemic lupus erythematosus].

OBJECTIVE: To compare the safety of low-dose cyclophosphamide and high-dose cyclophosphamide in the treatment of systemic lupus erythematosus (SLE). METHODS: A total of 1 022 patients with systemic lupus erythematosus from 24 hospitals in China between March 2017 to July 2018 were enrolled. Their clinical manifestations, laboratory tests, adverse events, reasons for stopping receiving intravenous cyclophosphamide and comorbidities were collected. Among them, 506 SLE patients received short-interval low-dose intravenous cyclophosphamide therapy (SILD IV-CYC, 400 mg every two weeks), and 256 patients underwent high-dose cyclophosphamide therapy (HD IV-CYC, 500 mg/m2 of body surface area every month), the side effects between the two groups were compared, the remaining 260 SLE patients were treated with IV-CYC irregularly. Moreover, a total of 377 patients in SILD IV-CYC group and 214 patients in HD IV-CYC group had medical records of the reasons for stopping recei-ving IV-CYC. The reasons for stopping receiving IV-CYC in these two groups were analyzed. RESULTS: In this study, only 40.27%(238/591)of the SLE patients stopped receiving intravenous cyclophosphamide for the causes of disease improvement, however, up to 33.67% (199/591) of the patients for the reason of drug-related side effects. There were 83 patients out of 214 (38.79%) with high-dose intravenous cyclophosphamide treatment who stopped receiving IV-CYC for the drug-related side effects, which was significantly higher than that in the low-dose cyclophosphamide group (30.77%, 116/337, P=0.048). Of theses 506 patients in SILD IV-CYC group, 88 (17.39%) patients experienced gastrointestinal reactions, 66 (13.04%) suffered from infections, 49 (9.68%) had myelosuppression and 68 (13.44%) had alopecia, respectively. Among the 256 patients in the HD IV-CYC group, 80 (31.25%) experienced gastrointestinal reactions, 57 (22.27%) suffered from infections, 51 (19.92%) had myelosuppression and 49 (19.14%) had alopecia. Moreover, 71 (25.18%) of 282 female patients with age between 16 to 45 years in SILD IV-CYC group had abnormal menstruation, while menstrual disorder occurred in 39.72% (56/141) patients of HD IV-CYC group. There was no difference of drug-induced hepatic injury, hemorrhagic cystitis and fatigue between the two groups. CONCLUSION: Low-dose cyclophosphamide showed a lower prevalence of adverse events than high-dose cyclophosphamide in systemic lupus erythematosus patients.

[Analysis of 8 cases of asparaginase related cerebral venous sinus thrombosis in children].

Objective: To summarize the clinical features, treatment and prognosis of asparaginase (ASP) related cerebral venous sinus thrombosis (CVST). Methods: Clinical profiles including age, sex, first symptoms, coagulation function, imaging findings, ASP type, treatment and prognosis of eight acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL) children with ASP related CVST at the Department of Pediatrics, First Affiliated Hospital of Zhengzhou University from November 2016 to October 2021 were analyzed retrospectively. Results: Eight CVST children were all male, including 6 ALL and 2 LBL, with the onset age ranged from 5 to 15 years, 6 cases occurred in the stage of first induction remission, and the initial symptom were mainly epileptic seizures (7 cases). Magnetic resonance imaging combined magnetic resonance venography (MRV) showed the most common site of venous sinus enlargement was superior sagittal sinus (8 cases). Secondary cerebral hemorrhage was found in 5 cases. D-dimer elevated on the day of onset in all cases. Three patients were treated with intravascular mechanical thrombectomy and thrombolysis combined with anticoagulant therapy, 3 patients were treated with continuous anticoagulant therapy only, 2 patients were not treated with anticoagulant therapy. MRV follow-up for 3 months showed that the thrombi in patients were almost completely absorbed except in 2 patients who were not treated with anticoagulant therapy. Thrombolysis combined with anticoagulant therapy was the fastest way for thrombosis absorption. Among 8 patients, 1 died of early recurrence of ALL, and 7 patients accepted further asparaginase and no CVST recurrence or progression was found. There were no sequelae of nervous system except 1 patient with left upper limb muscle strength impairment. Conclusions: ASP related CVST is more common in older male children and the prognosis is good. ASP related CVST occurred mostly in the stage of first induction remission, and most initial manifestation is epileptic seizure. The superior sagittal region is a common site of thrombus, magnetic resonance imaging combined with MRV is helpful for accurately diagnosis. Timely anticoagulant treatment can improve the prognosis, and mechanical thrombectomy and thrombolysis can quickly recanalize the vessel.

[Application of tracheotomy in the treatment of severe cases of COVID-19].

Objective: To discuss the the effects, indications and protective measures of tracheotomy for severe cases of coronavirus disease 2019 (COVID-19) patients. Methods: A retrospectively analysis was conducted to explore the clinical data of COVID-19 patients who received tracheotomy in February to March 2020, and descriptive statistics were used to analyze the indication of tracheotomy, particularity of intraoperative treatment and protective measures. Results: A total of 4 cases were included in this article. All patients were successfully operated. One case had postoperative incision continuous bleeding, there were not other complications and nosocomial infection among the medical staff. The patient's condition was relieved in different degrees after the operation, who remained hospitalized. Conclusion: Tracheotomy for severe cases of COVID-19 can achieve certain curative effect, but the occurrence of tracheotomy related complications and nosocomial infection should be effectively controlled, and the risk benefit ratio of tracheotomy should be carefully weighed before surgery.

[Application of tracheotomy in the treatment of severe cases of COVID-19].

Objective: Todiscuss the the effects, indications and protective measures of tracheotomy for severe cases of 2019 novel corona virus disease(COVID-19)patients. Methods: A retrospectively analyze was conducted to explore the clinical data of ofCOVID-19 patients who received tracheotomy in February to March 2020,descriptive statistics were used to analyze the indication of tracheotomy, particularity of intraoperative treatment and protective measures. Results: A total of 4 cases were included in this article, 3 cases were successfully operated, 1 case of postoperative incision continuous bleeding, there were not other complications and nosocomial infection among the medical staff.the patient's condition was relieved in different degrees after the operation, who remain hospitalized. Conclusion: Tracheotomy for severe cases of COVID-19 can achieve certain curative effect, but the occurrence of tracheotomy related complicationsand nosocomial infection should be effectively controlled, and the risk benefit ratio of tracheotomy should be carefully weighed before surgery.

[Morphological characteristic of anal canal in patients with dyssynergic defecation and its correlation with anorectal manometry].

Objective: To evaluate the diagnostic value of three-dimensional endoanal ultrasound (3D-EAUS) for dyssynergic defecation (DD). Methods: A case-control study was performed to retrospectively collectclinical data of 46 DD patients, including 16 males and 30 females with median age of 51 (20 to 70) years, at Nanjing Hospital of Chinese Medicine from February 2012 to April 2015.All the patients met the diagnostic criteria of functional constipation of Rome III. The paradoxical contraction of puborectalis (PR) muscle was found by both rectal examination and anorectal manometry. In the same period,45 healthy volunteers, including 22 males and 23 females with median age of 48 (21 to 72) years, without pelvic operation history, and with normal defecation in recent 6 months, were enrolled as the control group. No significant differences were observed in age and gender between two groups (both P>0.05). Cleveland constipation score of DD group was higher than that of control group [15(8-24) vs. 5(1-9), t=15.720, P<0.001]. 3D-EAUS examination was performed in all the subjects. Thickness and length of internal anal sphincter (IAS) (anterior side and posterior side), thickness of PR muscle, length of external anal sphincter (EAS) plus PR muscle, and puborectalis angle were measured and compared by using student t test between two groups. Correlation between these ultrasound parameters and anorectal manometry was examined by Pearson correlation analysis. Results: Both male and female in the DD group had the greater thickness of IAS, as compared to those in the control group [male: (1.7±0.5) mm vs.(1.5±0.2) mm, t=2.516, P=0.016; female: (1.9±0.4) mm vs.(1.6±0.5) mm, t=2.034,P=0.047]. No significant differences between the two groups were observed with respect to the posterior length of IAS, length of EAS plus PR muscle, and thickness of PR muscle (all P>0.05). Compared to the control group, male in the DD group had smaller puborectalis angle during straining [(87.0±3.6)° vs. (90.5±1.8)°,t=3.502,P=0.002];female in the DD group had smaller puborectalis angle both in resting and straining [resting:(86.5±3.8)° vs. (90.1±2.1)°,t=4.047, P<0.001;straining: (84.1±4.5)° vs. (90.2±2.3)°, t=5.938, P<0.001]. Correlation analysis showed that anterior length of IAS was positively correlated with anal resting pressure (r=0.321, P=0.030); the length of EAS plus PR muscle was positively correlated with anal squeeze pressure (r=0.415, P=0.004). There were no correlations between the thickness and the posterior length of IAS and the anal resting pressure, or between the thickness of PR muscle and the anal squeeze pressure (all P>0.05). Conclusions: The 3D-EAUS can accurately assess the morphological features of anal canal in DD patients. There is a certain positive correlation between 3D-EAUS and anorectal manometry.

Overexpressed microRNA-615-3p promotes progression of neonatal acute respiratory distress syndrome by inhibiting differentiation of mesenchymal stem cells to alveolar type II epithelial cells.

OBJECTIVE: To explore whether microRNA-615-3p participates in the progression of neonatal acute respiratory distress syndrome (ARDS) by inhibiting differentiation of mesenchymal stem cells (MSCs) to alveolar type II epithelial cells (ATII) via Wnt/ß-catenin pathway. PATIENTS AND METHODS: Expression levels of microRNA-615-3p and inflammatory factors (IL-1, IL-6, IL-8, and TNF-α) in peripheral blood of 24 neonatal ARDS patients and 14 healthy newborns were detected by qRT-PCR (quantitative Real-Time Polymerase Chain Reaction). MSCs were isolated from bone marrow of mice and identified by flow cytometry. The effect of microRNA-615-3p on regulating the differentiation of MSCs to ATII was analyzed. After altering expressions of microRNA-615-3p and DKK1 by plasmids transfection, Wnt/ß-catenin pathway-related genes were detected by Western blot. RESULTS: Higher expression levels of microRNA-615-3p and inflammatory factors (IL-1, IL-6, IL-8, and TNF-α) were observed in peripheral blood of neonatal ARDS patients than those of healthy newborns. ATII-specific genes were upregulated, and inflammatory factors were downregulated after the microRNA-615-3p knockdown in MSCs. Moreover, expressions of Wnt/ß-catenin pathway-related genes were downregulated after the microRNA-615-3p overexpression, which was partially reserved by the DKK1 knockdown. CONCLUSIONS: Overexpressed microRNA-615-3p promoted ARDS development through inhibiting differentiation of MSCs to ATII via Wnt/ß-catenin pathway.

[The pilot study of type â allergic reaction in Meniere's disease patients].

Objective: To evaluate the correlation between type Ⅰ allergic reaction and pathogenesis of Meniere's disease. Methods: A total of 35 (10 male vs. 25 female) patients aged between 21-66 years diagnosed with Meniere's disease were recruited to this study, mean age of them was (47.3±13.6) years. The control group consisted of 15 inpatients (5 male vs. 10 female) with pharyngolaryngeal diseases but without otologic and rhinologic abnormity, mean age was 45.4±12.8 years. Allergic prevalence, serous total immunoglobulin E( tIgE ) levels, serous specific immunoglobulin E( sIgE ) levels and subtypes of T lymphocytes were measured and compared in patients with Meniere's disease and the control group. Severity of vertigo, tinnitus and sensation of fullness were compared between Meniere's disease patients with or without allergy. Results: Allergic prevalence were significantly different (Pearson chi-square 5.832, P<0.05) between patients with Meniere's disease and the control group(57.1% vs. 20.0%). Patients with Meniere's disease report higher level of serous tIgE compared with controls, the difference is statistically significant (Z=168.000, P<0.05). However, positive rates of sIgE of food allergens and inhalant allergens were not significantly different between patients with Meniere's disease and the control group. Scores of vertiginous severity, dizziness handicap inventory (DHI) and tinnitus handicap inventory (THI) were significantly different between Meniere's disease patients with or without allergy (P<0.05). Treg and Treg/Th17 levels (Z=26.000) were much higher in Meniere's disease patients with allergy than in the controls(P<0.05). Conclusions: Patients with Meniere's disease report higher rate of allergy than the control group. Type Ⅰ allergic reaction is thought to be one of the possible reasons that may induce endolymphatic hydrops and lead to Meniere's disease.

Effect of CYP1A1 and GSTM1 genetic polymorphisms on bone tumor susceptibility.

Tumor gene polymorphisms are often associated with individual susceptibility to genetic diseases. Cytochrome P4501A1 (CYP1A1) and glutathione S-transferase mu 1 (GSTM1) gene polymorphisms are closely related to the susceptibility of the body to chemical carcinogens in the environment. Therefore, we explored the relationship between CYP1A1 and GSTM1 gene polymorphisms and susceptibility to bone tumors. Multiplex-polymerase chain reaction (PCR), allelic-specific PCR, and PCR-restriction fragment length polymorphism techniques were used to analyze CYP1A1 and GSTM1 gene polymorphisms in 52 bone tumor patients and 100 healthy subjects. The allelic variation frequency of the CYP1A1 gene at exon 7 (Ile 462 Val) in bone tumor patients was 0.462, which was significantly higher than that in the normal controls (0.223). The frequency of the absence of the GSTM1 homozygous genotype in the patients (0.65) was also markedly higher than that in the control group (0.41). Subjects with CYP1A1 Val/Val homozygous mutations and absence of the GSTM1 homozygous genotype were at markedly increased risk of developing bone tumors [ORs 4.15 (95%CI: 1.268-13.30) and 2.35 (95%CI: 1.15-4.85), respectively]. The OR for the combined effect of the CYP1A1 and GSTM1 gene polymorphisms was 8.55 (95%CI: 1.75-41.50). CYP1A1 and GSTM1 polymorphisms are genetic risk factors in patients with bone tumors, and the allelic variation of these genes increases the risk of bone tumor occurrence.

Correlation of CD4⁺ CD25⁺ Foxp3⁺ Treg with the recovery of joint function after total knee replacement in rats with osteoarthritis.

In this study, we observed changes in CD4(+) CD25(+) Foxp3(+) Treg expression in rats with osteoarthritis (OA) to explore the role that CD4(+) CD25(+) Foxp3(+) Treg plays in the decline in the condition of OA rats. Thirty rats were randomly divided into 2 groups equally and OA was induced in rats in the model group by injection of papain and l-cysteine into the right knee joint. Cartilage lesions were scored by the modified Mankin scale; pulmonary function was assessed by spirometry; interleukin (IL)-17 and IL-4 levels were evaluated by the enzyme-linked immunosorbent assay; and the levels of CD4(+) CD25(+) Foxp3(+) Treg in peripheral blood were measured by flow cytometry. The left knee joints of the model rats appeared palpable swelling and osteophytes, while the body weight, heart and lung function of these rats decreased. The serum IL-4 level was lower, whereas the serum IL-17 level was higher in the model group (P < 0.05). The peripheral blood CD4(+) CD25(+) Foxp3(+) Treg of CD4(+)T cells was significantly lower. Correlation of the changes in the levels of IL-4, IL-17, and Treg suggests that the underlying mechanism may be a reduction of the regulatory effect of Treg. The specific mechanism still requires further study.

Association of xeroderma pigmentosum group D (Asp312Asn, Lys751Gln) and cytidine deaminase (Lys27Gln, Ala70Thr) polymorphisms with outcome in Chinese non-small cell lung cancer patients treated with cisplatin-gemcitabine.

Xeroderma pigmentosum group D (XPD) plays a key role in the repair of DNA and platinum resistance lesions. Cytidine deaminase (CDA) genes determine the velocity of gemcitabine catalysis. This study aimed to investigate the relationship between XPD and CDA genotypes and outcome in non-small lung cancer (NSCLC) patients. We used polymerase chain reaction-restriction fragment length polymorphism to evaluate genetic polymorphisms of XPD (Asp312Asn and Lys751Gln) and CDA (Lys27Gln and Ala70Thr) in 93 NSCLC patients treated with a cisplatin-gemcitabine regimen. There were no significant correlations between the XPD polymorphisms Asp312Asn and Lys751Gln with clinical benefits (P>0.05). Time to progression (TTP) did not differ between patients with wild type genotypes and those heterozygous for the single nucleotide polymorphism loci of XPD. However, a significant difference was observed in overall survival (OS) between XPD Asp312Asp and XPD Asp312Asn individuals (20.0 vs 12.4 months, P=0.04). Furthermore, the OS of patients with wild type genotypes was longer (20.5 months) than that of patients carrying the XPD 751Lys/Gln polymorphism (11.5 months). No significant differences in TTP or OS were observed in patients carrying different genotypes of CDA Lys27Gln, and no mutations were observed at the CDA Ala70Thr site. These results provide suggestive evidence of a favorable effect for the XPD 312Asp/Asp and XPD 751Lys/Lys genotypes with respect to overall survival rates in platinum-treated NSCLC patients. However, the CDA 27 polymorphism does not appear to affect the efficacy of gemcitabine.

The role of traditional Chinese medicine in colorectal cancer treatment.

Surgery, chemotherapy and radiotherapy have been the mainstay of colorectal cancer treatment. There is however current intense research on traditional Chinese medicine (TCM) as novel or additional treatment methods for colorectal cancer. This article reviews the current use of TCM in colorectal cancer so as to increase the awareness of colorectal surgeons. The pathogenesis of colorectal cancer according to TCM is discussed. TCM has been used successfully during the perioperative period to relieve intestinal obstruction, reduce postoperative ileus and reduce urinary retention after rectal surgery. Good results have been reported in the treatment of the complications of chemotherapy and radiation enterocolitis. Favourable results have also been shown in the use of TCM either alone or in combination with chemotherapy to treat advanced colorectal cancer. Molecular studies have shown some TCM compounds to reduce tumour cell proliferation and induce apoptosis. Although the reported results of TCM have been exciting thus far, problems of lack of consensus on treatment regimes and questions on the reliability, validity and applicability of published studies prevent its widespread use. There is now an urgent need for colorectal surgeons to work with TCM physicians in the continuing research on this 6,000-year-old art so as to realize its full potential for our patients.

Evaluation and analysis of colonoscopy in the diagnosis of 186 cases of ulcerative colitis patients.

The objective of this study was to evaluate the diagnostic value of colonoscopy plus biopsy in patients with ulcerative colitis (UC). Retrospective analysis was performed on clinical data in 186 cases. Erosions, or ulcers, together with mucosal hyperemia and oedema were the most common manifestations of colonoscopy in 87% of patients. In about 56.4% of 186 cases, such manifestations occurred in the rectum and the sigmoid colon. Nearly 65.6% of the patients had a chronic intermittent clinical course. One case developed colon cancer, and another case had toxic megacolon; each case represents 0.05% of the total 186 patients. Therefore, prevalence of both malignancy and complication is low. Colonoscopy plus biopsy is considered to be the major means of the diagnosis of UC, demonstrating its value in differential diagnosis.