[Clinical study of the efficacies of ruxolitinib plus low-dose PTCY for acute GVHD prevention after haploidentical transplantation in malignant hematological diseases].

Objective: To investigate and verify a novel acute graft versus host disease (aGVHD) prevention protocol in the context of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: Patients who underwent haplo-HSCT in our center between January 2022 and December 2022 were included. All patients received reduced doses of cyclophosphamide, Rabbit anti-human tymoglobulin, ruxolitinib, methotrexate, cyclosporine, and MMF to prevent aGVHD. The transplantation outcomes, complications, and survival rate of all patients were investigated. Results: A total of 52 patients with haplo-HSCT were enrolled, 29 (55.8%) male and 23 (44.2%) female, with a median age of 28 (5-59) years. There were 25 cases of acute myeloid leukemia, 17 cases of acute lymphocyte leukemia, 6 cases of myelodysplastic syndrome, 2 cases of chronic myeloid leukemia and 2 cases of myeloproliferative neoplasms. 98.1% of patients had successful engraftment. The incidence of Ⅱ-Ⅳ aGVHD and Ⅲ-Ⅳ aGVHD was 19.2% (95% CI 8.2% -30.3% ) and 7.7% (95% CI 0.2% -15.2% ), respectively. No patients experienced severe gastrointestinal mucositis. The Epstein-Barr virus and CMV reactivation rates were 40.4% and 21.3%, respectively. 9.6% of patients relapsed during followup, with 1-year overall survival, progression-free survival, and non-relapse mortality rates of 86.5% (95% CI 76.9% -96.1% ), 78.8% (95% CI 67.4% -90.3% ) and 11.5% (95% CI 2.6% -20.5% ), respectively. Conclusion: Ruxolitinib combined with a low dose of PTCY is a safe and effective first-line aGVHD prevention strategy.

[Exploration of the method and efficacy of treatments for intractable pelvic pain caused by rectal or bladder fistula].

Objective: To explore the causes and therapeutic effects of pelvic pain caused by rectal fistula or bladder fistula after comprehensive treatment of cervical cancer and rectal cancer (radiotherapy, surgery, chemotherapy, and other treatments). Methods: A retrospective analysis was conducted on the clinical and pathological data of patients with pelvic tumors admitted to the First People's Hospital of Yinchuan City, Ningxia and the Affiliated Cancer Hospital of Zhengzhou University from June 2016 to June 2022. The causes of persistent pelvic pain in patients after comprehensive treatment was investigated, and the corresponding therapeutic effects after clinical treatment was observed. Results: Thirty-two tumor patients experienced persistent pain after comprehensive treatment, including 22 cases of cervical cancer and 10 cases of rectal cancer. The preoperative pain of the entire group of patients was evaluated using the digital grading method, with a pain score of (7.88±1.31) points. Among the 32 patients, there were 16 cases of rectovaginal fistula or ileovaginal fistula, 9 cases of vesicovaginal fistula, 5 cases of rectoperineal fistula, and 2 cases of vesicovaginorectal fistula. Thirty-two patients were initially treated with medication to relieve pain, and according to the ruptured organs, a fistula was made to the corresponding proximal intestinal canal and renal pelvis to intercept the intestinal contents and urine. However, the pain did not significantly be improved. The pain score of treatment with the above methods for one week was (8.13±1.13) points, and there was no statistically significant difference compared to preoperative treatment (P=0.417). In the later stage, based on a comprehensive evaluation of whether the tumor had recurred, the value of organ preservation, the benefits of surgery, the balance between survival time and improving quality of life, pathological organ resection or repair was performed. The surgical methods included repair of leaks, local debridement combined with irrigation of proximal intestinal fluid, distal closure of the sigmoid colon combined with proximal ostomy, posterior pelvic organ resection, anterior pelvic organ resection, and total pelvic organ resection. One week after surgery, the patients' pain completely relieved or disappeared, with the pain score of (1.72±1.37) points, which was significantly divergent from the preoperative and initial surgical treatments (P＜0.001). Conclusions: Palliative pyelostomy and proximal enterostomy cannot effectively alleviate persistent pelvic floor pain. The fundamental way to alleviate pain is complete blocking of the inflammatory erosion of the intestinal fluid and urine.

[Investigation of the effects and mechanisms of berberine on a mouse model of polycystic ovary syndrome: based on intestinal flora analysis].

Objective: To examine the impact of berberine on polycystic ovary syndrome (PCOS) in mice, and to investigate the effects of berberine on the intestinal flora and the intestinal flora on PCOS. Methods: A mouse model of PCOS was established by administering dehydroepiandrosterone in combination with high fat diet, and the mouse model was given a berberine treatment. The study consisted of a blank control group (C group), a PCOS model group (M group) and a berberine treatment group (T group). During the experiment, the mice were closely monitored through timed body weight measurements and estrous cycle monitoring; intraperitoneal glucose tolerance test and insulin tolerance test were done. Upon completion of the pharmacological intervention, the wet weights of liver, ovary and fat deposits of mice were assessed and subjected to HE staining to confirm the success of PCOS modeling and the efficacy of berberine. Additionally, fecal samples were analyzed for intestinal flora through 16S rRNA analysis. Results: The PCOS model was established successfully, berberine alleviated the disturbance of estrous cycle in mice, and significantly alleviated fat accumulation and metabolic abnormalities of glucose in mice. The cross-sectional area of fat pad cells in T group was (2 858±146) µm², which was significantly lower than that in M group [(9 518±347) µm²], and the difference was statistically significant (P<0.001). The blood glucose levels in T group were significantly lower than those in M group (P<0.05). The composition and structure of intestinal flora in mice of M group with PCOS (compared with C group) and in mice of T group after berberine intervention (compared with M group) were significantly altered. However, alpha diversity did not change significantly among three groups (P>0.05). Conclusion: Berberine could alleviate PCOS by intervening in the alterations of gut microbiota.

[A survey on the current situation of serum vitamin A and vitamin D levels among children aged 2-<7 years of 20 cities in China].

Objective: To investigate serum vitamin A and vitamin D status in children aged 2-<7 years in 20 cities in China. Methods: A cross-sectional study was conducted. A total of 2 924 healthy children aged 2-<7 years were recruited from September 2018 to September 2019 from 20 cities in China, categorized by age groups of 2-<3 years, 3-<5 years, and 5-<7 years. The demographic and economic characteristics and health-related information of the enrolled children were investigated. Body weight and height were measured by professional staff members. The serum vitamin A and vitamin D levels were detected by high-performance liquid chromatography-tandem mass spectrometry. Chi-square test and Logistic regression were applied to analyze the association between vitamin A and vitamin D deficiency and insufficiency as well as their underlying impact factors. Results: The age of the 2 924 enrolled children was 4.33 (3.42, 5.17) years. There were 1 726 males (59.03%) and 1 198 females (40.97%). The prevalences of vitamin A and vitamin D deficiency in enrolled children were 2.19% (64/2 924) and 3.52% (103/2 924), respectively, and the insufficiency rates were 29.27% (856/2 924) and 22.20% (649/2 924), respectively. Children with both vitamin A and vitamin D deficiencies or insufficiencies were found in 10.50% (307/2 924) of cases. Both vitamin A (χ2=7.91 and 8.06, both P=0.005) and vitamin D (χ2=71.35 and 115.10, both P<0.001) insufficiency rates were higher in children aged 3-<5 and 5-<7 years than those in children aged 2-<3 years. Vitamin A and vitamin D supplementation in the last 3 months was a protective factor for vitamin A and D deficiency and insufficiency, respectively (OR=0.68 and 0.22, 95%CI 0.49-0.95 and 0.13-0.40, both P<0.05). The rates of vitamin A and D insufficiency was higher in children with annual household incomes <60 000 RMB than in those with annual household incomes ≥60 000 RMB (χ2=34.11 and 10.43, both P<0.01). Northwest and Southwest had the highest rates of vitamin A and vitamin D insufficiency in children aged 2-<7 yeas, respectively (χ2=93.22 and 202.54, both P<0.001). Conclusions: Among 20 cities in China, children aged 2-<7 years experience high rates of vitamin A and vitamin D insufficiency, which are affected by age, family economic level, vitamin A and vitamin D supplementation, and regional economic level. The current results suggest that high level of attention should be paid to vitamin A and vitamin D nutritional status of preschool children.

[Clinical characteristics and surgical outcomes in pediatric progressive restrictive strabismus].

Objective: To investigate the clinical features, imaging manifestations, histopathological characteristics, and surgical outcomes in pediatric progressive restrictive strabismus. Methods: A retrospective case series study was conducted, including data from 9 cases (9 eyes) of pediatric progressive restrictive strabismus treated at Tianjin Eye Hospital from June 2017 to October 2022. The study compared the degree of globe protrusion in both eyes, changes in eyelid fissure height during internal and external rotation in the primary gaze, summarized clinical characteristics, and analyzed intraoperative conditions, surgical outcomes and postoperative histopathological results of strabismus correction surgery. Statistical analysis was performed using Wilcoxon signed-rank test and Friedman two-way analysis of variance. Results: All 9 cases involved unilateral onset, with 4 males and 5 females. Three cases affected the right eye, and six affected the left eye. Onset age ranged from 2 to 40 months. The degree of globe protrusion in the affected eyes was 13.00 (12.00, 13.00) mm for the right eye and 12.00 (12.00, 13.50) mm for the left eye, with no statistically significant difference (Z=-1.00, P=0.317). There were no significant changes in eyelid fissure height during internal rotation [8.00 (7.25, 8.00) mm], primary gaze [7.50 (7.00, 8.00) mm], and external rotation [8.00 (7.75, 8.00) mm] in the affected eyes (χ²=1.00, P=0.607). No apparent abnormalities were observed in head CT or MRI scans, serum, or immunological tests. However, orbital CT or MRI scans indicated thickening of different extraocular muscle bellies. Six out of nine cases underwent strabismus correction surgery, and postoperative examination revealed restriction in eye movement despite achieving orthophoria in the primary gaze. Tissue pathology of three cases showed increased collagen fiber proliferation in one, scattered bundles of smooth muscle fibers amid diffuse collagen fiber proliferation in another, and abnormal proliferation of striated muscle fibers with varying diameters, increased paired box (PAX)7-positive satellite cells expressing slow muscle myosin in the third case. Conclusions: Pediatric progressive restrictive strabismus presents with restrictive changes, without significant alterations in globe protrusion and eyelid fissure height. Imaging examinations reveal thickening of the extraocular muscle bellies in the affected eye. Although strabismus correction surgery improves eye position, postoperative eye movement remains restricted. Histopathological findings in some cases show abnormal proliferation of skeletal muscle fibers or collagen fibers.

[Clinical pathological and genetic mutation characteristics of conjunctival lymphoepithelial carcinoma].

Objective: To analyze the clinical pathological and genetic mutation characteristics of conjunctival lymphoepithelial carcinoma. Methods: A retrospective case series study was conducted. Data from three patients diagnosed with conjunctival lymphoepithelial carcinoma and treated with tumor resection surgery at Tianjin Eye Hospital from January 2006 to December 2022 were collected. Four paraffin specimens (including one patient undergoing two surgeries) were subjected to immunohistochemical staining for epithelial antigen and lymphocytic antigen. Epstein-Barr virus (EBV)-encoded RNA (EBER) was detected using in situ hybridization, and whole-exome sequencing was performed on three specimens from two patients using next-generation sequencing methods. Results: All three patients were males aged over 65, with a disease duration ranging from 3 to 44 months. The tumors were unilateral, located on the bulbar or limbal conjunctiva, appearing red, with a maximum diameter of 4-20 mm. Imaging examinations revealed anterior location of the tumors with no involvement of the orbital bone, extraocular muscles, optic nerve, or paranasal sinuses. No local lymph node metastasis was observed in any patient. Pathological findings included undifferentiated carcinoma nests with significant reactive lymphocytic and plasma cell infiltration. Tumor cells were positive for pan-cytokeratin (CK-pan), epithelial membrane antigen (EMA), tumor protein 40 (p40), and tumor protein 63 (p63), with a cell proliferation index (Ki67) exceeding 80%. Cluster of differentiation 20 (CD20), CD3, and CD8 were positive for lymphocytes. In situ hybridization showed partial tumor cell expression of EBER in two specimens of one patient. Whole-exome sequencing revealed 58, 50, and 36 mutated genes in the three specimens, with enriched signaling pathways including melanoma signaling pathway, Notch1 signaling pathway, and RHOQ GTP cycle; enriched biochemical processes included amino acid starvation response, programmed cell death, regulation of lipid synthesis, sodium ion transport, and chromosome segregation. The common mutated gene in all three specimens was SZT2, and SZT2 was involved in the amino acid starvation response. One patient underwent a second complete resection surgery 40 months after partial excision, while the other two underwent complete resection surgery without recurrence. Two patients did not undergo radiation or chemotherapy, and one was lost to follow-up. Conclusions: Conjunctival lymphoepithelial carcinoma is associated with prominent lymphocytic and plasma cell infiltration, some cases are associated with EBV infection, and SZT2 mutations are present in conjunctival lymphoepithelial carcinoma.

[Clinical application effect of pedunculated rectus abdominis muscle combined with bilateral ureters for repairing refractory bladder-vaginal stump fistula through external vesical drainage].

Objective: To investigate the efficacy and safety of pedunculated rectus abdominis combined with bilateral ureteral extravestheter drainage in the treatment of refractory bladder-vaginal stump fistula. Methods: The clinical data of 8 cases of the refractory bladder-vaginal stump fistula were admitted to the Second Hospital of Hebei Medical University and Henan Cancer Hospital and underwent the clinical treatment of bladder-vaginal stump from December 2019 to December 2022 were collected. The reason of refractory bladder-vaginal stump fistula was analyzed, the operation manner of pedunculated rectus abdominis combined with peduncle and bilateral ureter for the treatment of bladder-vaginal stump through extrabladder drainage was explored. The operation time, bleeding volume and clinical effect were record. Results: The median operation time of 8 patients was 150 minutes(120~180 min), and the median blood loss was 400 ml(200~600 ml). During the perioperative period, there were 2 cases of incision infection, delayed healing by debridement and dressing, 2 cases of incision rupture and suture wound healing after reoperation, and 2 cases of urinary tract infection were cured by anti-infection. When followed up for 6 months, 8 cases of vesicovaginal stump fistula were cured. Conclusion: Bilateral ureteral external drainage of the rectus abdominis muscle, has a practical effect in the treatment of refractory bladder-vaginal stump fistula, which can be one of the clinical repairing treatment.

[Clinical pathological characteristics analysis of ocular adnexal follicular lymphoma].

Objective: To investigate the clinical pathological characteristics of ocular adnexal follicular lymphoma (OAFL). Methods: A retrospective case series study was conducted. Clinical data of 10 OAFL patients diagnosed at Tianjin Eye Hospital from January 1990 to May 2022 were collected. The study analyzed general patient information, medical history, site of involvement, imaging, histopathology, and molecular detection. Among them, 7 cases underwent Epstein-Barr virus-encoded small RNA (EBER) and B-cell lymphoma protein 2 (BCL-2)/immunoglobulin heavy chain gene (IgH) translocation gene detection. Treatment and prognosis of patients were followed up. Results: All 10 patients (10 eyes) had unilateral involvement, including 5 males and 5 females, with an age range of 58 (43, 68) years. Clinical manifestations included eyelid swelling, pink conjunctival thickening, painless slow-growing masses in the lacrimal gland area, extraconal muscle cone, conjunctiva, lacrimal sac, or a combination of lacrimal sac and conjunctiva. Among them, 8 cases were primary, and 2 cases were secondary. According to the Ann Arbor staging, 8 cases were stage Ⅰ-Ⅱ E, and 2 cases were stage Ⅲ E. Histopathological grading revealed 6 cases of grade 1-2 and 3 cases of grade 3A. One case showed grade 3B in the lacrimal sac area and grade 1-2 in the conjunctiva. The predominant subtype was follicular in 4 cases, diffuse in 3 cases, and mixed in 2 cases. One case had a mixed subtype involving the lacrimal sac and conjunctiva. All patients expressed positivity for leukocyte differentiation antigens (CD) 20, CD21, and CD23. Nine cases were positive for CD10, with 1 case showing partial CD10 positivity. All patients were positive for B-cell lymphoma protein 6 (BCL-6), and 9 cases were positive for BCL-2. Specific markers CyclinD1 and Multiple Myeloma Oncogene Protein 1 (MUM-1) were negatively expressed in all cases. The Ki-67 proliferation index ranged from 10% to 90%. Molecular detection was performed in 7 patients, with none showing positive EBER in situ hybridization. However, 5 cases exhibited BCL2/IgH gene fusion. Among 7 patients with follow-up data, the median follow-up time was 17 (6, 34) months. Four patients achieved complete remission, 2 had partial remission, and 1 patient died due to lung infection. Conclusions: OAFL is a tumor originating from follicular center B-cells, characterized by positive expression of BCL-2, CD10, and BCL-6. It can involve the lacrimal gland, extraconal muscles, lacrimal sac, and conjunctiva. Patients generally have a favorable prognosis.

[Pay more attention to the management of burn wounds of special causes and sites].

The treatment of burn wounds of special causes and sites is a very challenging clinical work. In this paper, we briefly discussed the incidence rates of chemical burns, electric burns, facial burns, hand burns, and perineal burns, as well as the complexity and severity of pathological injury of the corresponding wound tissue. In addition, we briefly discussed the main principles and methods of clinical treatment, as well as the difficult problems to be solved. It is hoped to attract attention and provide reference for further improving the overall treatment ability of burns.

[Investigation of extrauterine growth restriction in very preterm infants in Chinese neonatal intensive care units].

Objective: To comprehensively assess the current status of extrauterine growth restriction (EUGR) in very preterm infants (VPI) and its associated factors in Chinese neonatal intensive care units (NICU). Methods: In this cohort study, 6 179 preterm infants born at <32 weeks' gestation were included, who were admitted to 57 hospitals in the China Neonatal Network in 2019 and hospitalized for ≥7 days. EUGR was evaluated by a cross-sectional definition (weight at discharge<10th percentile for postmenstrual age), a longitudinal definition (decline in weight Z score>1 from birth to discharge), and weight growth velocity. The comparison between infants with and without EUGR was conducted by t-test, Mann-Whitney U test or χ2 test as appropriate. Multivariable Logistic regression models were used to evaluate associations between EUGR with different definitions and maternal and neonatal factors, clinical practices, and neonatal morbidities. Results: A total of 6 179 VPI were enrolled in the study, with a gestational age of (29.8±1.5) weeks and birth weight of (1 365±304) g; 56.2% (3 474) of them were male. Among them, 48.4% (2 992 VPI) were cross-sectional EUGR and 74.9% (4 628 VPI) were longitudinal EUGR. Z score of weight was (0.13±0.78) at birth and decrease to (-1.35±0.99) at discharge. The weight growth velocity was 10.13 (8.42, 11.66) g/(kg·d). Multivariate Logistic regression analysis showed that among the influential factors that could be intervened after birth, late attainment of full enteral feeds (ORadjust=1.01, 95%CI 1.01-1.02, P<0.001; ORadjust=1.01, 95%CI 1.01-1.02, P<0.001), necrotizing enterocolitis≥Ⅱstage (ORadjust=2.64, 95%CI 1.60-4.35, P<0.001; ORadjust=1.62, 95%CI 1.10-2.40, P<0.001) and patent ductus arteriosus (ORadjust=1.94, 95%CI 1.50-2.51, P<0.001; ORadjust=1.63, 95%CI 1.29-2.06, P<0.001) were all associated with increased risks of both cross-sectional and longitudinal EUGR. In addition, late initiation of enteral feeds (ORadjust=1.06, 95%CI 1.02-1.09, P=0.020) and respiratory distress syndrome (ORadjust=1.45, 95%CI 1.24-1.69, P<0.001) were all associated with cross-sectional EUGR. Breast milk feeding (ORadjust=1.33, 95%CI 1.05-1.68, P<0.001) was associated with a higher risk of longitudinal EUGR. Conclusions: The incidence of EUGR in VPI in China is high. Some modifiable risk factors provide priorities to improve postnatal growth for VPI. Nutritional management of VPI and the efforts to decrease the incidence of complications are still the focus of clinical management in China.

Projections of temperature-associated mortality risks under the changing climate in an ageing society.

OBJECTIVES: This study aimed to project future temperature-associated mortality risk and additional deaths among Taiwan's elderly (aged >65 years) population. STUDY DESIGN: This study investigated retrospective temperature-mortality risk associations and future mortality projections. METHODS: A distributed lag non-linear model and random effect meta-analyses were employed to assess the risk of daily temperature-associated deaths in all-cause, circulatory, and respiratory diseases. Using the statistical downscaling temperature projections of the Representative Concentration Pathways (RCPs; i.e. RCP2.6, RCP6.0 and RCP8.5), future risk of mortalities were projected among the elderly for 2030-2039, 2060-2069 and 2090-2099, with a 30%, 40% and 50% expected increase in elderly population proportions, respectively. RESULTS: The baseline analysis from 2005 to 2018 identified that Taiwan's population is more vulnerable to cold effects than heat, with the highest cold-related mortality risk being attributed to circulatory diseases, followed by all-cause and respiratory diseases. However, future projections suggest a declining trend in cold-related mortalities and a significant rise in heat-related mortalities under different RCP scenarios. Heat-attributable mortalities under the RCP8.5 scenario by 2090-2099 would account for almost 170,360, 36,557 and 29,386 additional annual deaths among the elderly due to all-cause, circulatory and respiratory diseases, respectively. Heat-attributable all-cause mortalities among the elderly would increase by 3%, 11% and 30% under RCP2.6, RCP6.0 and RCP8.5, respectively, by 2090-2099. CONCLUSIONS: The findings of this study provide predictions on future temperature-related mortality among the elderly in a developed, ageing society with a hot and humid climate. The results from this study can guide public health interventions and policies for climate change and ageing society-associated health risks.

The Effectiveness of Frailty Intervention for Older Patients with Frailty during Hospitalization.

OBJECTIVES: This study aims to assess the effectiveness of a multidomain intervention program on the change in functional status of hospitalized older adults. DESIGN: This single-arm, prospective, non-randomized interventional study investigates the efficacy of a multidomain interventional program including cognitive stimulation activity, simple exercises, frailty education, and nutrition counseling. SETTING AND PARTICIPANTS: At a tertiary hospital in southern Taiwan, 352 eligible patients were sequentially enrolled. Included patients were aged ≥65 years (mean age, 79.6 ± 9.0 years; 62% male), scored 3-7 on the Clinical Frailty Scale (CFS), and were hospitalized in the geriatric acute ward. INTERVENTION: Those receiving standard care (physical rehabilitation and nutrition counseling) during January-July 2019 composed the historical control group. Those receiving the multidomain intervention during August-December 2019 composed the intervention group. MEASUREMENTS: The primary outcome was the change in activities of daily life (ADL) and frailty status, as assessed by Katz Index and Clinical Frailty Scale, with using the generalized estimating equation model. The length of hospital stay, medical costs, and re-admission rates were secondary outcomes. RESULTS: Participants undergoing intervention (n = 101; 27.9%) showed greater improvements in the ADL and CFS during hospitalization (ADL adjusted estimate, 0.61; 95% CI, 0.11-1.11; p = 0.02; CFS adjusted estimate, -1.11; 95% CI, -1.42- -0.80; p < 0.01), shorter length of hospital stay (adjusted estimate, -5.00; 95% CI, -7.99- -2.47; p < 0.01), lower medical costs (adjusted estimate, 0.58; 95% CI, 0.49-0.69; p < 0.01), and lower 30- and 90-day readmission rates (30-day adjusted OR [aOR], 0.12; 95% CI, 0.27-0.50; p < 0.01; 60-day aOR, 0.04; 95% CI, 0.01-0.33; p < 0.01) than did controls. CONCLUSIONS: Participation in the multidomain intervention program during hospitalization improved the functional status and decreased the hospital stay length, medical costs, and readmission rates of frail older people.

[Correction model of the sampling time error on the blood trough concentration of tacrolimus in non-sustained-release dosage form for renal transplant recipients].

Objective: To establish correction model of the sampling time error on the blood trough concentration of tacrolimus in non-sustained-release dosage form for renal transplant recipient and improve the accuracy of drug dose assessment and clinical adjustment in renal transplant recipients. Methods: Visit records of 206 outpatients in the Department of Transplantation, Nanfang Hospital, Southern Medical University were retrospectively collected from October 15, 2022 to October 30, 2022. The distribution of sampling time of tacrolimus blood drug concentration was described and the time range of correction was determined. Twenty inpatients after renal transplantation in the Department of Transplantation, Nanfang Hospital, Southern Medical University from October 1, 2022 to November 30, 2022 were prospectively included, and their demography data, laboratory test results during follow-ups, and CYP3A5 genotype were collected. The patients took tacrolimus in non-sustained-release dosage form every 12 h starting from 19∶30 on the day of admission. Peripheral blood samples were collected from the patients on the second day of admission at 7∶30 and on the third day at 6∶00-10∶00 every 30 minutes to test the blood concentration of tacrolimus. Using the collection time as the independent variable and the blood tacrolimus concentration as the dependent variable, a simple linear regression was performed to fitting a linear model of tacrolimus blood concentration-sampling time. Multiple linear regression was performed to analyze the influencing factors of the tacrolimus metabolic rate within a specific period and generate the regression equation. Results: The 206 outpatients aged (46±13) years, including 131 males (63.6%). The time gap [M (Q1, Q3)] between the sampling time of the follow-up outpatients and standard C12 was 24 (13.0, 46.5) min, and the maximum time gap was 135 min. The 20 enrolled inpatients aged (45±12) years, including 15 males (75.0%). There was no significant difference in the blood concentration of tacrolimus collected at 7∶30 on the second (7.87±2.21)ng/ml and third days (7.84±2.33)ng/ml after admission of the enrolled inpatients (P=0.917), and the blood tacrolimus concentration rhythm was stable in the trial. The plasma concentration of C10.5-C14.5 was linearly related to the time, with R2 [M (Q1, Q3)] 0.88 (0.85, 0.92) and all P<0.05. The metabolic rate of tacrolimus during C10.5-C14.5=0.984+0.090×basic concentration of tacrolimus (ng/ml)-0.036×body mass index+0.489×CYP3A5 genotype-0.007×hemolobin(g/L)-0.035×alanine aminotransferase (U/L)+0.143×total cholesterol (mmol/L)+0.027×total bilirubin (µmol/L), with R2=0.85. Conclusion: This study propose a correction model for tacrolimus (non-sustained-release dosage form) trough concentration around C12, which is helpful for clinicians to easily and accurately assess renal transplant recipients' tacrolimus exposure.

Development of a Novel Method for the Clinical Visualization and Rapid Identification of Multidrug-Resistant Candida auris.

Outbreaks of multidrug-resistant Candida auris infections, associated with a mortality rate of 30% to 60%, are of serious global concern. Candida auris demonstrates high transmission rates in hospital settings; however, its rapid and accurate identification using currently available clinical identification techniques is challenging. In this study, we developed a rapid and effective method for detecting C. auris based on recombinase-aided amplification combined with lateral flow strips (RAA-LFS). We also screened the appropriate reaction conditions. Furthermore, we investigated the specificity and sensitivity of the detection system and its ability to distinguish other fungal strains. Candida auris was accurately identified and differentiated from related species at 37°C within 15 min. The minimum detection limit was 1 CFU (or 10 fg/reaction) and was not affected by high concentrations of related species or host DNA. The simple and cost-efficient detection method established in this study exhibited high specificity and sensitivity and successfully detected C. auris in simulated clinical samples. Compared with other traditional detection methods, this method greatly reduces the time and cost of testing and is thus suitable for hospitals or clinics in remote underfunded areas for screening C. auris infection and colonization. IMPORTANCE Candida auris is a highly lethal, multidrug-resistant, invasive fungus. However, conventional methods of C. auris identification are time-consuming and laborious and have low sensitivity and high error rates. In this study, a new molecular diagnostic method based on recombinase-aided amplification combined with lateral flow strips (RAA-LFS) was developed, and accurate results could be obtained by catalyzing the reaction at body temperature for 15 min. This method can be used for rapid clinical detection of C. auris, consequently saving valuable treatment time for patients.

[Analysis of the causes of long-standing pelvic anterior sacral space infection and discussion of management techniques].

Objective: To investigate the causes and management of long-term persistent pelvic presacral space infection. Methods: Clinical data of 10 patients with persistent presacral infection admitted to the Cancer Hospital of Zhengzhou University from October 2015 to October 2020 were collected. Different surgical approaches were used to treat the presacral infection according to the patients' initial surgical procedures. Results: Among the 10 patients, there were 2 cases of presacral recurrent infection due to rectal leak after radiotherapy for cervical cancer, 3 cases of presacral recurrent infection due to rectal leak after radiotherapy for rectal cancer Dixons, and 5 cases of presacral recurrent infection of sinus tract after adjuvant radiotherapy for rectal cancer Miles. Of the 5 patients with leaky bowel, 4 had complete resection of the ruptured nonfunctional bowel and complete debridement of the presacral infection using an anterior transverse sacral incision with a large tipped omentum filling the presacral space; 1 had continuous drainage of the anal canal and complete debridement of the presacral infection using an anterior transverse sacral incision. 5 post-Miles patients all had debridement of the presacral infection using an anterior transverse sacral incision combined with an abdominal incision. The nine patients with healed presacral infection recovered from surgery in 26 to 210 days, with a median time of 55 days. Conclusions: Anterior sacral infections in patients with leaky gut are caused by residual bowel secretion of intestinal fluid into the anterior sacral space, and in post-Miles patients by residual anterior sacral foreign bodies. An anterior sacral caudal transverse arc incision combined with an abdominal incision is an effective surgical approach for complete debridement of anterior sacral recalcitrant infections.

[Clinical and pathological analysis of 35 cases of ocular adnexal solitary fibrous tumor].

Objective: To analyze the clinical and pathological characteristics and prognosis of 35 cases of solitary fibrous tumor of ocular adnexal (SFT). Methods: This was a retrospective case series study. The clinical data of 35 cases of ocular adnexal SFT was collected in Tianjin Eye Hospital from January 2000 to December 2020. The clinical manifestations, imaging examination results, pathological characteristics, treatment of patients were analyzed, and patients were followed up. All cases were classified according to the 2013 classification of World Health Organization of tumors of soft tissue and bone. Results: There were 21 males (60.0%) and 14 females (40.0%). The age range was 17 to 83 years, and the median age was 44 (35, 54)years. All patients were unilateral, with 23 (65.7%) in the right eye and 12 (34.3%) in the left eye. The course of disease ranged from 2 months to 11 years, with an a median duration of 12(6,36)months. Clinical manifestations included exophthalmos, limited eye movements, diplopia, and tearing. All patients underwent surgical treatment of complete resection of the tumor. Ocular adnexal SFT mostly occurred in the upper orbit (19 cases, 73.1%). On imaging examination, the tumor showed well-circumscribed space occupying lesion that heterogeneously enhanced with contrast, and abundant blood flow signals in the tumors. MRI showed isointensity or low signal on T1WI, and significantly enhanced on T2WI, presenting intermediate-to-high heterogeneous signals. The tumor diameter was 2.1 (1.5, 2.6) cm. There were 23 cases (65.7%) of classic subtype, 2 cases (5.7%) of giant cell subtype, 8 cases (22.9%) of myxoid subtype, and 2 cases (5.7%) of malignancy. Immunohistochemical staining showed that Vimentin, CD34 and STAT6 were positively expressed in all patients. Twenty-one cases (60.0%) showed positive expression of BCL-2, and Ki-67 positive index ranged from 1.0% to 10.0%. Tumors in this group were all low-risk according to the Demicco risk stratification. Follow-up was available for 25 patients with a duration of 2 years to 14 years and 7 months, and the median follow-up time was 88 (61, 124) months. Two patients relapsed, and no distant metastasis or death was observed. Conclusions: Ocular adnexal SFT mainly presents as a painless, slow-growing mass. And most of them are typical SFT. The imaging manifestations are varied Ocular adnexal SFT generally follows a benign course, with a good prognosis after complete excision. Recurrence could occur many years after surgery which requiring careful and long-term follow-up.

[Abnormal expression of CXCR5+CD8+ T cells and CXCL13 in severe aplastic anemia patients and their correlation with hematological parameters].

Objective: To analyze the expression of C-X-C chemokine receptor 5 (CXCR5)+CD8+ T cells and plasma C-X-C motif chemokine 13 (CXCL13) in severe aplastic anemia (SAA) patients and their correlations with hematological parameters. Methods: The clinical data of 35 SAA patients in the Hematology Department of Tianjin Medical University General Hospital from January 2018 to September 2021 were retrospectively analyzed. The patients were divided into two groups according to whether they had received the medication: untreated SAA group and recovery SAA group. In untreated group, there were 18 patients who had not received any medication, with 9 males and 9 females, and aged 51 (18-76) years. In recovery SAA group, there were 17 patients who were separated from component blood transfusion after the immunosuppressive treatment with anti-thymocyte globulin (ATG) combined with cyclosporine A (CsA), with 7 males and 10 females, and aged 46 (16-70) years. Meanwhile, 20 healthy controls were also selected, including 8 males and 12 females, and aged 45(15-72) years. Peripheral blood and bone marrow samples were collected from SAA patients, while peripheral blood samples were obtained from healthy controls. Flow cytometry was used to detect the percentage of CXCR5+CD8+ T cells in peripheral blood and bone marrow samples. The concentration of plasma CXCL13 was measured by enzyme-linked immunosorbent assay (ELISA). The correlations between the percentage of CXCR5+CD8+ T cells and the concentration of CXCL13, as well as the correlations between these two parameters and the hematological parameters were analyzed by Spearman correlation analysis. Results: The proportion of CXCR5+CD8+ T cells in the bone marrow of untreated SAA group was (4.9±2.9)%, which was higher than that of recovery SAA group (2.7±1.5)%, with a statistically significant difference (t=2.34, P=0.027). The proportion of CXCR5+CD8+ T cells in peripheral blood of untreated SAA group, recovery SAA group and healthy control group was (8.4±4.2)%, (3.8±2.3)% and (2.6±2.0)% respectively. The proportion of CXCR5+CD8+ T cells in peripheral blood of untreated SAA group was higher than that of recovery SAA group and healthy control group (both P<0.05). The plasma CXCL13 concentration in untreated SAA group was (97.2±46.8) ng/L, which was significantly higher than that in recovery SAA group [(54.9±20.9) ng/L] and healthy control group [(47.6±17.3) ng/L] (both P<0.05). The proportion of CXCR5+CD8+ T cells in peripheral blood of SAA patients was positively correlated with the concentration of plasma CXCL13 (r=0.545, P<0.001). The proportion of peripheral blood CXCR5+CD8+ T cells in SAA patients was negatively correlated with white blood cell count, platelets count, percentage of neutrophils, absolute neutrophils count, percentage of reticulocytes, absolute reticulocytes count, bone marrow myeloid cells, bone marrow erythroid cells and megakaryocytes count (r=-0.556, -0.392, -0.617, -0.615, -0.395, -0.543, -0.432, -0.484 and -0.523, all P<0.05). The proportion of peripheral blood CXCR5+CD8+ T cells was positively correlated with the percentage of peripheral blood lymphocytes and bone marrow lymphoid cells (r=0.593 and 0.556, both P<0.05). Meanwhile, the concentration of plasma CXCL13 in SAA patients was negatively correlated with white blood cell count, absolute neutrophils count, percentage of reticulocytes, absolute reticulocytes count and bone marrow myeloid cells (r=-0.447, -0.446, -0.498, -0.407 and -0.456, all P<0.05), but positively correlated with bone marrow lymphoid cells (r=0.384, P<0.05). Conclusions: The proportion of CXCR5+CD8+ T cells and the concentration of plasma CXCL13 increases in SAA patients. The proportion of CXCR5+CD8+ T cells in peripheral blood is positively correlated with the concentration of CXCL13. Moreover, the proportion of CXCR5+CD8+ T cells and the concentration of CXCL13 are correlated with many hematological parameters, which may play a critical role in the immune pathogenesis of SAA.

[Impact of different types of heart failure on long-term renal prognosis in patients with renal insufficiency and heart failure].

Objective: To investigate the effects of different types of heart failure on long-term renal prognosis in patients with renal insufficiency and heart failure. Methods: The patients with renal insufficiency [baseline estimated glomerular filtration rate < 60 ml·min-1·(1.73 m2)-1] and heart failure followed-up for more than 2 years and hospitalized in Beijing Anzhen Hospital, Capital Medical University from January 1, 2018 to June 30, 2019 were enrolled in this retrospective cohort study. The patients were divided into three groups based on the baseline left ventricular ejection fraction (LVEF): heart failure with reduced ejection fraction (HFrEF, LVEF < 40%) group, heart failure with mildly reduced ejection fraction (HFmrEF, 40% ≤ LVEF < 50%) group, and heart failure with preserved ejection fraction (HFpEF, LVEF ≥ 50%) group. Clinical data were collected and endpoint events (adverse renal outcome: the composite outcome of all-cause death or worsening renal function) were recorded through the electronic medical record system. Kaplan-Meier survival curve was used to analyze the incidence of endpoint events of different heart failure subgroups. Cox regression model was performed to analyze the risk factors of endpoint events. Results: A total of 228 patients with renal insufficiency complicated with heart failure were included, with age of (68.14±14.21) years old and 138 males (60.5%). There were 85 patients (37.3%) in the HFrEF group, 40 patients (17.5%) in the HFmrEF group, and 103 patients (45.2%) in the HFpEF group. There were statistically significant differences in age, proportion of age > 65 years old, sex distribution, systolic blood pressure, pulmonary artery pressure, serum sodium, serum calcium, hemoglobin, serum cholesterol, low-density lipoprotein cholesterol, serum uric acid, troponin I, hypersensitive C-reactive protein, LVEF, ventricular septal thickness, left ventricular end-diastolic diameter, B-type natriuretic peptide, estimated glomerular filtration rate, and proportions of using beta blockers, using spirolactone, myocardial infarction, hypertension, cardiomyopathy and atrial fibrillation (all P < 0.05). During the median follow-up of 36.0 (28.0, 46.0) months, 73 patients (32.0%) had adverse renal outcomes. The total incidences of adverse renal outcomes were 32.9% (28/85) in the HFrEF group, 35.0% (14/40) in the HFmrEF group, and 30.1% (31/103) in the HFpEF group. Kaplan-Meier survival curve showed that there was no significant difference in the incidence of endpoint events among the three groups (log-rank test χ2=0.17, P=0.680). Multivariate Cox regression analysis showed that HFpEF (HFrEF as reference, HR=2.430, 95% CI 1.055-5.596, P=0.037) was an independent influencing factor of endpoint events. Conclusions: The long-term renal prognosis of patients with renal insufficiency and heart failure is poor. Compared with HFrEF, HFpEF is an independent risk factor of poor long-term renal prognosis in renal insufficiency patients with heart failure.