BACKGROUND:Various proteins,signaling pathways,and inflammatory mediators are involved in the pathophysiological process of osteoarthritis.The development of small molecule drugs targeting these proteins,signaling pathways,and inflammatory mediators can effectively delay the progression of osteoarthritis and ameliorate its clinical manifestations. OBJECTIVE:To review the research progress of small molecule drugs in the treatment of osteoarthritis based on the pathogenesis of osteoarthritis. METHODS:PubMed,CNKI,and WanFang databases were searched with English search terms"osteoarthritis,arthritis,osteoarthrosis,degenerative,arthritides,deformans,small molecule drugs,small molecule inhibitors,small molecule agents"and Chinese search terms"osteoarthritis,small molecule drugs,small molecule inhibitors."A total of 68 articles were included for review according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)Currently,studies concerning the pathogenesis of osteoarthritis remain unclear.The occurrence and development of osteoarthritis are strongly associated with proteins,cytokines,and signal transduction pathways,so its therapeutic mechanism is relatively complex.Currently,targeting proteins,cytokines,and signal transduction pathways related to osteoarthritis with small molecule drugs has become a major research focus.(2)Small molecule drugs frequently possess visible intracellular or extracellular targets and efficacy,containing enhancing cartilage repair,resisting joint degradation,attenuating inflammation,and relieving pain.Other anti-osteoarthritis small molecule drugs have shown promise in promoting stem cell chondrogenic differentiation and cartilage matrix reconstruction.(3)At present,small molecule drugs targeting the pathophysiological process of osteoarthritis to delay the progression of osteoarthritis are still in the experimental stage,but most of these small molecule drugs have shown the expected results in the experimental process,and there are no relevant studies to illustrate the efficacy of small molecule drugs in the treatment of osteoarthritis.(4)Small molecule drugs for the treatment of osteoarthritis have reached the expected experimental results in the basic experimental stage.Numerous studies have exhibited that small molecule drugs can target the suppression of specific proteins,cytokines,and signal transduction pathways that cause osteoarthritis,so as to treat osteoarthritis.Nevertheless,its safety and effectiveness still need to be identified by further basic and clinical studies.This process needs to be investigated and studied by more scholars.(5)At present,many scholars in and outside China have made contributions to the treatment of osteoarthritis.Compared with traditional treatment methods,small molecule drugs reveal better efficacy and safety in the basic experimental stage,and it is expected to become an emerging method for the treatment of osteoarthritis in the future to rid patients of pain.

Objective:To investigate the efficacy and safety of en-bloc Holmium laser enucleation of the prostate (HoLEP) with an early apical mucosa dissection technique for the treatment of benign prostate hyperplasia (BPH).Methods:The clinical data of 215 patients treated with HoLEP for BPH from January 2020 to January 2023 in the Department of Urology, Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed. According to different treatment methods, the patients were divided into study group ( n=112) and control group ( n=103). Patients in the study group were treated by the en-bloc HoLEP with an early apical mucosa dissection technique, while patients in the control group were treated by the classical two or three-lobes HoLEP. The primary endpoints included the rates of urinary incontinence at 1-month, 3-month, and 6-month after surgery in two groups of patients. The secondary endpoints included operative time, hemoglobin decrease, dissected prostate weight, postoperative indwelling catheter time, postoperative hospital stay, and international prostate symptom score (IPSS), quality of life (QoL), Qmax, and postvoid residual urine (PVR) at 3-month and 6-month after surgery. The measurement data were tested by Shapiro-Wilk normality test. The normal distribution of the measurement data were expressed as mean ± standard deviation ( ± s), and independent sample t-test was used for comparison between two groups. Measurement data of skewness distribution were expressed as median (interquartile distance) [ M( Q1, Q3)], and Wilcoxon or Mann-Whitney U test were used for comparison between two groups. The count data in the two groups were compared by the Chi-square test. Results:The incidence of urinary incontinence in the study group was 9.0% (10/112) and 3.6% (4/112) at 1-month and 3-month after surgery, which was significantly lower than those in the control group [18.5% (19/103) and 11.7% (12/103)], and the differences were statistically significant ( P< 0.05). Urinary incontinence in two groups recovered completely 6-month after surgery. The operation time of the study group was (68.74±23.71) min, which was lower than that of the control group [(88.04±25.43) min], and the difference was statistically significant ( P<0.05). There were no significant differences in hemoglobin decrease, dissected prostate weight, postoperative indwelling catheter time, postoperative hospital stay in the two groups ( P> 0.05). The IPSS, QoL, Qmax and PVR of the two groups were significantly improved at 3-month and 6-month after surgery ( P< 0.05), but there was no significant difference between the two groups ( P> 0.05). Conclusion:En-bloc HoLEP with an early apical mucosa dissection technique is safe and reliable in treating BPH, and has advantages over classic HoLEP in terms of short-term urinary continence rates, shortening operation time.

Objective To understand the research status and development trend in the field of molecular and cell biology of thyroid cancer.Methods Relevant literature published in the field of molecular and cell biology of thyroid cancer from January 1,2013 to December 31,2022 was obtained in the web of science core collection(WoSCC)according to the search conditions,and bibliometric and visual analysis were performed using the bibliometric software VOSviewer and Excel.Results A total of 1 627 literatures were included.Among them,113 papers were published in 2013,and 214 were published in 2022.The annual number of publications was on the rise.There were 9 274 authors in total,of whom 6 published no less than 10 literatures.There were a total of 2 042 institutions,of which the top 10 institutions were mostly Chinese universities.There were 68 countries in total,and the largest number of publications was China,followed by the United States.There were 513 journals in total,and the top 10 journals with the largest number of literatures were mainly in the field of oncology,followed by the field of endocrinology and metabolism.A total of 62 563 references from 5 887 journals were cited.The most co-cited journal was Journal of Biological Chemistry(1 608 times),and the most co-cited references was Molecular Pathogenesis and Mechanisms of Thyroid Cancer(89 times).Conclusion The field of molecular and cell biology of thyroid cancer is currently developing steadily.Ferroptosis,glycosylation,telomerase reverse transcriptase and oxidative stress are the research frontiers in this field.

Objective:To explore the short-term efficacy of perioperative fecal microbiota transplantation combined with nutritional support in patients with radiation-induced enteritis complicated by intestinal obstruction.Methods:The cohort of this prospective cohort study comprised 45 patients (nine men and 36 women) with radiation-induced enteritis complicated by intestinal obstruction admitted to Shanghai Tenth People's Hospital Affiliated to Tongji University from January 2022 to October 2022. The median age was 53 (42–65) years. Thirty-five of the patients had gynecological tumors and 10 colorectal malignancies. The patients were randomly allocated to a fecal microbiota transplantation group of 20 patients who underwent fecal microbiota transplantation starting 2 weeks before surgery for 6 days, in addition to receiving conventional perioperative treatment, and a conventional treatment group of 25 patients who only received nutritional support during the perioperative period. There were no significant differences in baseline characteristics (sex, age, preoperative nutritional indices, and surgical procedure) between the two groups (all P>0.05). Postoperative recovery (time to passing flatus or a bowel movement, length of stay) and complications were compared between the two groups. Postoperative complications within 30 days after surgery classified in accordance with the international Clavien–Dindo classification of surgical complications (I–V) were statistically analyzed. Improvement in gastrointestinal symptoms, namely abdominal pain, distension, diarrhea, and rectal bleeding) and gastrointestinal quality of life scores (which include 36 problems rated 0–144 points related to physical, psychological, social activities and family life; the lower the score, the more severe the symptoms) were compared between the two groups. Nutritional recovery was assessed by body mass, body mass index, total protein, albumin, prealbumin, and hemoglobin. Results:Compared with the conventional treatment group, the postoperative hospital stay was shorter in the fecal microbiota transplantation group (8.0±4.3 days vs. 11.2±5.4 days, t=2.157, P=0.037) and the time to passage of flatus or having a bowel movement was earlier (2.2±3.2 days vs. 3.9±2.3 days, t=2.072, P=0.044). There were 26 postoperative complications in the fecal microbiota transplantation group and 59 in the conventional treatment group. There were 20 and 36 Grade I to II complications and no and three Grade III to V complications in the transplantation and conventional treatment group, respectively. The overall grade of complication did not differ significantly between the two groups ( P=0.544). However, the incidence of postoperative intestinal inflammatory obstruction was lower in the fecal microbiota transplantation than the conventional treatment group (10.0% [2/20] vs. 40.0% [10/25], P=0.040). One patient in the conventional treatment group died. This patient had complete intestinal obstruction complicated by severe malnutrition preoperatively, and an intestinal fistula complicated by abdominal infection postoperatively, and died despite active treatment. Nineteen and 23 patients in the transplantation and conventional treatment group, respectively, attended for follow-up 1 month after surgery; 19 and 21, respectively, attended for follow-up 3 months after surgery, and 17 and 20, respectively, attended for follow-up 6 months after surgery. There were no significant differences between the two groups in abdominal pain or rectal bleeding 1, 3, or 6 months after surgery (all P>0.05). One month after surgery, the incidence of abdominal distension and diarrhea was lower in the fecal microbiota transplantation than in the conventional treatment group (3/19 vs. 48.0% [11/23], P=0.048; 3/19 vs. 52.2% [12/23], P=0.023). However, at the 3 and 6 month follow-ups the incidence of abdominal distension and diarrhea had gradually decreased in both groups and the differences between the groups were not statistically significant ( P>0.05 for all). Scores for gastrointestinal quality of life improved significantly in both treatment groups compared with preoperative values ( F=71.250, P<0.001; F=79.130, P<0.001, respectively). Scores for gastrointestinal quality of life were higher in the fecal microbiota transplantation than the conventional treatment group at all follow-up time points ( P<0.05). One-way ANOVA showed that body mass, body mass index, and total protein, albumin and hemoglobin concentrations improved in both groups compared with preoperative values (all P<0.05). Prealbumin concentration improved significantly in the transplantation ( F=5.514, P=0.002), but not in the conventional, group ( F=1.535, P=0.211). The improvements in body mass, body mass index, total protein, and albumin were better in the fecal microbiota transplantation than conventional treatment group at 3 and 6 months of follow-up (all P<0.05). Conclusion:Perioperative fecal microbiota transplantation combined with nutritional support is effective in improving early postoperative nutritional status and quality of life in patients with radiation-induced enteritis complicated by intestinal obstruction.

Objective:To explore the short-term efficacy of perioperative fecal microbiota transplantation combined with nutritional support in patients with radiation-induced enteritis complicated by intestinal obstruction.Methods:The cohort of this prospective cohort study comprised 45 patients (nine men and 36 women) with radiation-induced enteritis complicated by intestinal obstruction admitted to Shanghai Tenth People's Hospital Affiliated to Tongji University from January 2022 to October 2022. The median age was 53 (42–65) years. Thirty-five of the patients had gynecological tumors and 10 colorectal malignancies. The patients were randomly allocated to a fecal microbiota transplantation group of 20 patients who underwent fecal microbiota transplantation starting 2 weeks before surgery for 6 days, in addition to receiving conventional perioperative treatment, and a conventional treatment group of 25 patients who only received nutritional support during the perioperative period. There were no significant differences in baseline characteristics (sex, age, preoperative nutritional indices, and surgical procedure) between the two groups (all P>0.05). Postoperative recovery (time to passing flatus or a bowel movement, length of stay) and complications were compared between the two groups. Postoperative complications within 30 days after surgery classified in accordance with the international Clavien–Dindo classification of surgical complications (I–V) were statistically analyzed. Improvement in gastrointestinal symptoms, namely abdominal pain, distension, diarrhea, and rectal bleeding) and gastrointestinal quality of life scores (which include 36 problems rated 0–144 points related to physical, psychological, social activities and family life; the lower the score, the more severe the symptoms) were compared between the two groups. Nutritional recovery was assessed by body mass, body mass index, total protein, albumin, prealbumin, and hemoglobin. Results:Compared with the conventional treatment group, the postoperative hospital stay was shorter in the fecal microbiota transplantation group (8.0±4.3 days vs. 11.2±5.4 days, t=2.157, P=0.037) and the time to passage of flatus or having a bowel movement was earlier (2.2±3.2 days vs. 3.9±2.3 days, t=2.072, P=0.044). There were 26 postoperative complications in the fecal microbiota transplantation group and 59 in the conventional treatment group. There were 20 and 36 Grade I to II complications and no and three Grade III to V complications in the transplantation and conventional treatment group, respectively. The overall grade of complication did not differ significantly between the two groups ( P=0.544). However, the incidence of postoperative intestinal inflammatory obstruction was lower in the fecal microbiota transplantation than the conventional treatment group (10.0% [2/20] vs. 40.0% [10/25], P=0.040). One patient in the conventional treatment group died. This patient had complete intestinal obstruction complicated by severe malnutrition preoperatively, and an intestinal fistula complicated by abdominal infection postoperatively, and died despite active treatment. Nineteen and 23 patients in the transplantation and conventional treatment group, respectively, attended for follow-up 1 month after surgery; 19 and 21, respectively, attended for follow-up 3 months after surgery, and 17 and 20, respectively, attended for follow-up 6 months after surgery. There were no significant differences between the two groups in abdominal pain or rectal bleeding 1, 3, or 6 months after surgery (all P>0.05). One month after surgery, the incidence of abdominal distension and diarrhea was lower in the fecal microbiota transplantation than in the conventional treatment group (3/19 vs. 48.0% [11/23], P=0.048; 3/19 vs. 52.2% [12/23], P=0.023). However, at the 3 and 6 month follow-ups the incidence of abdominal distension and diarrhea had gradually decreased in both groups and the differences between the groups were not statistically significant ( P>0.05 for all). Scores for gastrointestinal quality of life improved significantly in both treatment groups compared with preoperative values ( F=71.250, P<0.001; F=79.130, P<0.001, respectively). Scores for gastrointestinal quality of life were higher in the fecal microbiota transplantation than the conventional treatment group at all follow-up time points ( P<0.05). One-way ANOVA showed that body mass, body mass index, and total protein, albumin and hemoglobin concentrations improved in both groups compared with preoperative values (all P<0.05). Prealbumin concentration improved significantly in the transplantation ( F=5.514, P=0.002), but not in the conventional, group ( F=1.535, P=0.211). The improvements in body mass, body mass index, total protein, and albumin were better in the fecal microbiota transplantation than conventional treatment group at 3 and 6 months of follow-up (all P<0.05). Conclusion:Perioperative fecal microbiota transplantation combined with nutritional support is effective in improving early postoperative nutritional status and quality of life in patients with radiation-induced enteritis complicated by intestinal obstruction.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To investigate the efficacy and safety of en-bloc low-power (22.5 W) holmium laser for enucleation of prostate (LP-HoLEP) in the treatment of benign prostatic hyperplasia (BPH).Methods:The clinical data of 98 patients with BPH who underwent surgical treatment in the Department of Urology, Beijing Friendship Hospital, Capital Medical University from January 2020 to October 2022 were retrospectively analyzed. They were divided into LP-HoLEP group ( n=53) and TURP group ( n=45) according to different treatment methods. Patients in the LP-HoLEP group were treated with en-bloc holmium laser enucleation of prostate, and patients in the TURP group were treated with transurethral resection of prostate (TURP). Perioperative indexes of the two groups were compared, including operation time, postoperative hemoglobin changes, tissue resection amount, postoperative catheter indentation time, postoperative hospital stay, complications, and international prostate symptom score (IPSS), quality of life (Qol) score, maximum urine flow rate (Qmax), postvoid residual volume (PVR) and other indicators were obtained at 3 and 6 months after surgery. The measurement data were tested by Shapiro-Wilk normality test. The measurement data conforming to normal distribution were expressed as mean ± standard deviation ( ± s), independent sample t-test was used for comparison between groups, measurement data of skewness distribution were expressed as median (interquartile distance)[ M( Q1, Q3)], and Mann-Whitney U test was used for comparison between groups. The Chi-square test was used to compare the count data between groups. Results:In the LP-HoLEP group, the operative time was (65.74±22.82) min, the hemoglobin decreased 5.71(3.97, 9.01) g/L, the tissue resection volume was (60.59±24.40) g, and the catheter indinduration time was (3.03±0.91) d. The length of postoperative hospitalization was (4.14±1.05) d. TURP group was (77.04±27.33) min, 11.02(8.89, 16.51) g/L, (39.49±11.32) g, (4.80±0.91) d, (5.98±1.03) d, respectively. All the indexes of LP-HoLEP group were better than TURP group. The differences were statistically significant ( P<0.05). Compared with preoperative, IPSS, Qol score, Qmax and PVR of two groups were significantly improved at 3 months after surgery, but there were no statistical significance between groups ( P>0.05). Conclusion:En-bloc LP-HoLEP is safe and reliable in the treatment of BPH, and has advantages over TURP in terms of tissue resection volume, shortening hospitalization and indwelling catheter time, and reducing intraoperative bleeding.

Objective:To investigate the safety and efficacy of individualized transperineal prostate biopsy based on the segmentation of PI-RADS v2 for mpMRI.Method:The clinical data of patients undergoing prostate biopsy in Beijing Friendship Hospital from December 2018 to November 2021 were analyzed retrospectively . A total of 228 patients with a median age of 65(49-83)years underwent biopsy. There were 102(44.7%) with tPSA <10 ng / ml, 108(47.4%) with tPSA 10-20 ng /ml, and 18(7.9%) with tPSA >20 ng /ml, with the median tPSA of 9.87(4.1-89.0)ng /ml. There were 42(18.4%) cases without MRI results, and 32(14.0%)cases with PI-RADS score of 1-2, 47(20.6%)cases of PI-RADS 3, 66(28.9%)cases of PI-RADS 4 and 41(18.1%)cases of PI-RADS 5, respectively.Transrectal ultrasound-guided transperineal prostate targeted biopsy (TB) and systematic biopsy (SB) were performed under local anesthesia or intravenous anesthesia. SB was performed for those without MRI and PI-RADS score of 1-2 (SB group), and TB and SB were performed for those with PI-RADS score of 3-5 (TB+ SB group). Prostate image under ultrasound was cognitively fused according to PI-RADS v2. One needle per area was distributed in 10 areas of each layer(the transition zone anterior and posterior sectors, the peripheral zone anterior, lateral, and medial sectors or central zone in left and right lobe). For those whose prostate length was less than 3cm, 10 needles were punctured, and two needles were added to each lateral lobe of the apex with a total of 14 needles. For those whose prostate length was from 3 to 6 cm, selected two layers with a total of 20 needles. For those with a length greater than 6cm, selected three layers with a total of 30 needles. If there was a suspicious lesion with PI-RADS score of 3-5, two needles were targeted for each lesion.The detection rate and complication rate of prostate cancer and clinically significant prostate cancer (csPCa) in the overall samples were observed, and the difference of the detection rate of prostate cancer and csPCa between the two groups was compared.Results:Of the 228 cases, there were 46 cases undergoing biopsy of one layer, 148 cases of two layers, and 34 cases of three layers, detecting 131 prostate cancer (PCa) diagnosed by pathology, with a detection rate of 57.5%, including 40 cases (17.5%)of clinically insignificant PCa and 91 cases(39.9%)of csPCa. The detection rate of PCa in TB+ SB group was 61.0%(94/154), which was higher than that in SB group, but there was no significant difference ( P=0.114). However, the detection rate of csPCa in TB + SB group was higher than that in SB group, which was 46.8%(72/154)vs. 25.6%(19/74), respectively ( P=0.002). In the combined TB and SB group (TB + SB group), the detection rate of csPCa by TB was 44.8% (69/154), which was higher than that of 33.8%(52/154)by SB( P=0.047). In the TB+ SB group, 7(4.5%) PCa were missed by SB, which was less than 18 cases (11.7%) missed by TB( P=0.022), but csPCa were missed by SB more than that missed by TB( P<0.001). There were 37 cases suffered from complications, with Clavien Dindo classification grade 1 of 29 cases (12.7%), grade 2 of 7 cases (3.1%), and grade 3 of 1 case(0.4%). Conclusions:Individualized transperineal prostate biopsy based on the segmentation of PI-RADS v2 for mpMRI is safe and reliable. Target biopsy by cognitive fusion can improve the detection rate of significant PCa. Systematic biopsy is also an important and essential supplement, which can detect prostate cancer missed by TB. Combined TB and SB are the best choice.

Objective:To investigate the clinical value of the expression levels of biological protein markers regenerating islet-derived protein 3-alpha(REG3α), soluble tumor suppressor factor 2(sST2) and tumor necrosis factor receptor 1(TNFR1) in peripheral blood in the diagnosis and efficacy evaluation of intestinal acute graft-versus-host disease (aGVHD) in children after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:Retrospective analysis of 50 children who underwent allo-HSCT, in the Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University from January 2020 to February 2021 were enrolled, including 39 males and 11 females [median age: 8.5 (1-13) years]. The expression levels of above 3 biological proteins were detected before transplantation, 1 week, 2 weeks, 3 weeks, 5 weeks, 7 weeks, 9 weeks, 11 weeks and 13 weeks after transplantation, when intestinal aGVHD occured, and after treatment.Children with intestinal aGVHD were taken as the observation group, and children without intestinal aGVHD were taken as the control group.Whether differences in the expression levels of the 3 biological proteins in the peripheral blood of the 2 groups of children were statistically significant was analyzed.The receiver operating characteristic(ROC) curve was used to evaluate the diagnostic value of the above three biological proteins for intestinal aGVHD, and independent sample t test was performed to compare the expression levels of the 3 biological proteins before and after treatment in children with intestinal aGVHD. Results:(1) The concentrations of REG3α, sST2, and TNFR1 in the peripheral blood of the observation group were (33 985.42±24 631.33) ng/L, (139 899.66±115 825.65) ng/L, (3 041.65±2 418.72) ng/L, respectively, which were higher than the control group of (7 457.39±4 547.49) ng/L, (32 059.57±23 452.85) ng/L, (1 944.51±1 170.35) ng/L, the difference was statistically significant ( t=6.04, 5.19, 2.17, all P<0.05). (2) The area under ROC curve (AUC) of REG3α combined with sST2 in the diagnosis of intestinal aGVHD was 0.952 (95% CI: 0.851-0.992, P<0.001), the maximum Youden index was 0.894, the corresponding sensitivity was 83%, and the specificity was 99%.Its diagnostic value was better than REG3α, sST2 and TNFR1 ( Z=1.763, 1.332, 3.001, all P<0.05). (3) The concentrations of REG3α, sST2, and TNFR1 before treatment in the peripheral blood of children having received effective treatment were (31 343.01±25 364.71) ng/L, (146 629.52±110 501.04) ng/L and (2 489.00±859.70) ng/L, respectively, which were (12 104.37±11 704.60) ng/L, (93 539.55±81 920.93) ng/L and (2 048.15±813.47) ng/L after treatment, lower than those before treatment.The expression levels of REG3α and sST2 were significantly reduced ( t=-3.23, -2.10, all P<0.05), while the difference of the expression level of TNFR1 before and after treatment was not statistically significant ( P>0.05). Conclusions:REG3α and sST2 can be used as important reference indicators for clinical auxiliary diagnosis of intestinal aGVHD, and have good auxiliary diagnostic value.REG3α and sST2 can be used as objective indicators to evaluate the efficacy of clinical treatment of intestinal aGVHD.

Objective:To investigate the clinical efficacy, safety and compliance of Voriconazole suspension formula on the prevention and treatment of invasive fungal infection (IFI) in children with allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:Clinical data of 25 children treated Voriconazole suspension formula for the prevention and treatment of IFI during the period of allo-HSCT in the Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University from August 1, 2020 to April 30, 2021 were retrospectively analyzed.The plasma trough concentration of Voriconazole was detected by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and the genotype of CYP2C19 was detected by polymerase chain reaction-restriction fragment length polymorphism (RFLP). The effect of CYP2C19 genotype on Voriconazole trough concentration was analyzed by rank-sum test, and Fisher′ s accurate test was used to analyze the influence of severity of gastrointestinal mucositis on serum trough concentration of Voriconazole in children with allo-HSCT. Results:A total of 25 children, including 18 males and 7 females were recruited.The median age at allo-HSCT was 6 (2-13) years.After initial administration of conventional dose of Voriconazole suspension formula during transplantation, plasma trough concentration of Voriconazole was intermittently monitored.Only 13 cases (52.0%) reached the target plasma trough concentration, 11 cases(44.0%) reached the target plasma trough concentration after adjusting the dose according to the plasma concentration, and 1 cases(4.0%) failed to reach it after increasing the dose twice.Genotype detection of CYP2C19 was performed in 20 children, involving 4 cases of poor metabolizers (PM), 9 cases of intermediate metabolizers (IM), 6 cases of extensive metabolizers (EM), and 1 case of ultra extensive metabolizer (UEM). A significant difference in plasma trough concentration was detected among all groups ( F=24.012, P<0.01). During the transplantation, 12 cases developed mild to moderate gastrointestinal mucositis, and 7 cases had severe gastrointestinal mucositis.The stan-dard rate of plasma trough concentration in children with severe gastrointestinal mucositis (1/7 cases, 14.3%)was significantly lower than those with mild to moderate gastrointestinal mucositis (9/12 cases, 75.0%) ( P=0.02). Five children (71.4%) with severe gastrointestinal mucositis could reach the target trough concentration after increasing the drug dose, suggesting that severe gastrointestinal mucositis had a great influence on the plasma concentration of Vorico-nazole suspension.The incidence of IFI in 25 children with allo-HSCT was 0, and the compliance of children taking Voriconazole dry suspension was 100.0%.The incidence of adverse reactions was 24.0% and all adverse reactions were relieved after symptomatic treatment. Conclusions:The plasma concentration of Voriconazole varies greatly among children and in different states of the same patient.Therefore, it is necessary to monitor the trough concentration of the drug and adjust the drug dose.The use of Voriconazole suspension formula for the prevention and treatment of fungal infection during allo-HSCT in children is clinically safe and effective, with a good compliance in children.