Hiatt-Neu-Cooper neurodevelopmental syndrome(HINCONS),a rare neurodevelopmental disorder closely associated with a heterozygous mutation in the RALA gene on 7p14,is characterized by prominent in-tellectual disability or global developmental delay.Currently,no effective treatment options are available for this dis-ease.This article reports a case of HINCONS presenting with global developmental delay,particularly in language and motor development,along with decreased muscle tone,short stature,distinctive facial features,and congenital ventricular septal defect.No significant abnormalities were found in laboratory biochemical tests.Head MRI revealed enlarged ventricles and increased space in the subarachnoid and convexity regions.Trio-based whole exome sequen-cing testing identified a novel variant RALA gene c.475(exon4)A＞G(p.K159E)in the affected child.In this study,we performed a retrospective analysis of the clinical features of 12 reported cases of HINCONS from the litera-ture,with the aim of providing a reference for the clinical diagnosis and genetic counseling of HINCONS.

Objective:To explore the clinical and genetic characteristics of four children with Kabuki syndrome (KS) due to variants of KMT2D gene. Methods:Four children with KS diagnosed at the Children′s Hospital of Shanxi Province between January 2020 and December 2022 were selected as the study subjects. Whole exome sequencing was carried out for the children and their family members. Candidate variants were verified by Sanger sequencing and pathogenicity analysis.Results:The KS phenotype scores for the four children were 7, 8, 6, and 6, respectively. Child 2 also presented with a rare solitary kidney malformation. Genetic testing revealed that all children had harbored novel de novo variants of the KMT2D gene, including c. 16472_16473del, c. 858dup, c. 11899C>T, and c. 12844C>T, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), all of the variants were classified as pathogenic. Conclusion:For children showing phenotypes such as distinctive facial features, intellectual disability, developmental delay, cardiac abnormalities, and urinary system anomalies, KS should be considered. Early diagnosis and intervention can be achieved through genetic testing, especially in the presence of KMT2D gene mutations.

Objective:To explore the relationship between anhedonia and suicidal ideation and the effects of anhedonia on suicidal ideation in patients with first-episode untreated depressive disorder.Methods:Totally 106 in-patients who met the diagnostic criteria for depressive disorder of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5)were invited to participate in the study.Anhedonia,depressive symptoms and sui-cidal ideation were assessed with the Snaith-Hamilton Pleasure Scale(SHAPS),Hamilton Depression Scale(HAMD)and Beck Scale for Suicide Ideation(BSI),respectively.If both items 4 and 5 of BSI were 0,it indicated non-suicidal ideation,the subjects were divided into a group of suicidal ideation(n=66)and a group non-suicidal ideation(n=40).Spearman correlation analysis and multivariate binary logistic regression analysis were used for a-nalysis.Results:The correlation between the scores of SHAPS and HAMD was not statistically significant(P＞0.05).The SHAPS scores were positively correlated with the BSI scores(r=0.70,P＜0.01).Meanwhile,binary logistic regression analysis showed that anhedonia was one of a risk factor for suicidal ideation(OR=2.34,95％CI:1.58-3.47,P＜0.001).Conclusion:It suggests that anhedonia maybe partially independent of other depres-sive symptoms and it is one of the risk factors for suicidal ideation in first-episode untreated patients with depressive disorder.

Cyclodipeptide (CDP) composed of two amino acids is the simplest cyclic peptide. These two amino acids form a typical diketopiperazine (DKP) ring by linking each other with peptide bonds. This characteristic stable ring skeleton is the foundation of CDP to display extensive and excellent bioactivities, which is beneficial for CDPs' pharmaceutical research and development. The natural CDP products are well isolated from actinomycetes. These bacteria can synthesize DKP backbones with nonribosomal peptide synthetase (NRPS) or cyclodipeptide synthase (CDPS). Moreover, actinomycetes could produce a variety of CDPs through different enzymatic modification. The presence of these abundant and diversified catalysis indicates that actinomycetes are promising microbial resource for exploring CDPs. This review summarized the pathways for DKP backbones biosynthesis and their post-modification mechanism in actinomycetes. The aim of this review was to accelerate the genome mining of CDPs and their isolation, purification and structure identification, and to facilitate revealing the biosynthesis mechanism of novel CDPs as well as their synthetic biology design.
Actinobacteria/metabolism* ; Actinomyces/metabolism* ; Biological Products/metabolism* ; Bacteria/metabolism* ; Diketopiperazines/metabolism* ; Amino Acids

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

Objective:To explore the predictive value of peripheral blood cytokine models on organ functional impairment after chimeric antigen receptor T(CAR-T) cell therapy in children with B-lineage lymphocytic leukemia.Methods:The clinical data of 44 children with acute B-lineage lymphoblastic leukemia who received CAR-T cell therapy at Children′s Hospital of Soochow University from September 2018 to October 2020 were retrospectively analyzed.Peripheral blood cytokines, including interleukin(IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-α, interferon(IFN)-γ and IL-17A, were measured daily for 14 days after receiving CAR-T cell therapy.The trend of peripheral blood cytokine levels was analyzed at the endpoint of organ function recovery or death within 14 days after CAR-T cell treatment.Receiver operating characteristic curve was used to establish a mathematical prediction model to predict the occurrence of organ damage in the children.Results:Of the 44 children, 31 cases were boys and 13 cases were girls, with a median age of 7.96 (5.19, 11.48)years.Cytokine release syndrome(CRS) response occurred in 95.5% (42/44) children, with 88.1% (37/42) had a grade 1-3 CRS response, and 16.7% (7/42) had a severe grade 4-5 CRS response.Using IL-6>3 892.95 pg/mL as cut-off value, the area under the curve(AUC) for predicting acute respiratory failure was 0.818, with a sensitivity of 0.8 and a specificity of 0.735, while combining IFN-γ>414.4 pg/mL, IL-6>3 892.95 pg/mL and IL-2>27.05 pg/mL were the three cut-off values, with an AUC of 0.741, sensitivity of 0.6 and specificity of 0.912 for predicting acute respiratory failure. Using IFN-γ>1 699.5 pg/mL as cut-off value, the AUC for predicting shock was 0.908, with a sensitivity of 0.722 and a specificity of 1.With IL-6>4 607.3 pg/mL as cut-off value, the AUC for predicting liver injury was 0.964, with a sensitivity of 1 and a specificity of 0.906, while combining both IL-6>4 607.3 pg/mL and IFN-γ>1 446.2 pg/mL as cut-off values, the AUC for predicting liver injury was 0.977, with a sensitivity of 1 and a specificity of 0.906.Combining both IL-6>6 972.2 pg/mL and IFN-γ>3 981.5 pg/mL predicted a positive predictive value of 62.5% and a negative predictive value of 94.4% for grade 4-5 CRS response, with an AUC of 0.846, a predictive sensitivity of 0.714 and a specificity of 0.838, and all children had a combination of two or more organ function injuries.Conclusion:The combination of IL-6 and IFN-γ can effectively predict the incidence of liver injury and cytokine release syndrome.The combination of peripheral blood cytokines IFN-γ, IL-6 and IL-2 can be used to predict the incidence of acute respiratory failure after the treatment of CAR-T cells in children with acute B-lineage lymphoblastic leukaemia.IFN-γ single index can be used to predict the incidence of shock.The combination of IL-6 and IFN-γ can be used to predict the incidence of liver injury and the severity of CRS.

Objective:To systematically evaluate the intervention effect of exposure and response prevention (ERP) on obsessive compulsive disorder (OCD).Methods:PubMed, Web of Science Core Collection, EBSCO, Cochrane Library, Embase, Science Direct, Wanfang Data, China National Knowledge Infrastructure and VIP-CSTJ were used to collect randomized controlled studies related to ERP for OCD.Randomized controlled studies that met the criteria were included, with the score of Yale-Brown obsessive-compulsive scale as the primary outcome indicator and the scores of anxiety and depression scale as secondary outcome indicators, while the included literatures were evaluated for literature quality and data extraction.Review Manager 5.3 and Stata 16.0 softwares were used to conduct Meta-analysis on the extracted data.Results:Twenty-seven studies with a total of 1 239 patients were included, and 599 cases in the ERP group and 640 cases in the control group.Meta-analysis results showed that the efficacy of ERP group was significantly better than that of blank control group(MD=-6.55, 95% CI: -8.75--4.35, P<0.001) and significantly better than chlorpromazine control group treatment (MD=-5.88, 95% CI: -8.20--3.56, P<0.001) for improving patients' obsessive-compulsive symptoms, but not significantly different from CBT intervention (MD=0.21, 95% CI: -1.62-2.04, P=0.82), and the efficacy of ERP and CBT had no significant during the post-intervention follow-up period (MD=0.41, 95% CI: -2.45-3.27, P=0.78). For improving patients' depressed mood, ERP was effective in improving patients' depressed mood (SMD=-0.45, 95% CI: -0.74--0.17, P=0.002), but not significantly different from CBT (SMD=-0.05, 95% CI: -0.27-0.16, P=0.62). For improving anxiety, the efficacy of ERP group was not different from that of control group (SMD=-0.17, 95% CI: -0.56-0.23, P=0.41). Conclusion:ERP has good feasibility in improving obsessive-compulsive symptoms and depression in patients with OCD.However, long-term efficacy was not verified for improving anxiety and maintaining long-term efficacy during the follow-up period.

Objective:To investigate the efficacy of 3D-printed quantitative bone implants assisting second-stage Masquelet technique for the treatment of long-segment bone defect following Gustilo type IIIB and IIIC tibial fractures.Methods:A retrospective case series analysis was made on 26 patients with long-segment bone defect following Gustilo type IIIB and IIIC tibial fractures treated in Wuxi Ninth People′s Hospital from July 2015 to December 2020, including 20 males and 6 females; aged 19-63 years [(46.5±4.5)years]. Gustilo classification was type IIIB in 23 patients and type IIIC in 3. In the first stage, all patients had thoroughly emergent debridement, removal of all free bone pieces, restoration of the length and force line plus externally fixion, and vacuum sealing drainage (VSD) of the residual wound. After 2-7 days, the external fixation was removed and replaced by internal fixation, with the bone cement filling in the defect area and the free flap covering the wound. The length of tibial bone defect was 5-14 cm [(6.3±0.4)cm], and the tibial defect volume was 12.2-73.1 cm 3 [(33.6±9.2)cm 3]. In the second stage (6-19 weeks after injury), the bone cement was removed, followed by autologous bone grafting. Prior to bone grafting, digital technology was used to accurately calculate the bone defect volume, and an equal volume of bone harvesting area was designe to produce the 3D printed osteotomy template. Bone grafting was conducted after bone removal according to the osteotomy template during operation. The success rate of one-time iliac bone extraction, bone harvesting time, and bleeding volume were recorded. Pain in the bone extraction area was evaluated by visual analogue score (VAS) at 1 day and 1 month after operation and at the last follow-up. Wound healing, complications, and bone healing were observed. Life quality was evaluated by health survey brief form (SF-36) including scores of physical component summary (PCS) and mental component summary (MCS) before bone grafting and at the last follow-up. Results:All the patients were followed up for 13-53 months [(32.3±12.5)months]. One-time iliac bone extraction was successful in all the patients. Bone harvesting time was 15-30 minutes [(21.0±2.5)minutes]. The bleeding volume was 50-120 ml [(62.3±29.0)ml]. The VAS was 1-4 points [(1.2±0.9)points] at 1 day after operation, higher than these (0.0±0.0)points at 1 month after operation and at the last follow-up (all P<0.01). Totally, 25 patients obtained wound healing after operation, except for 1 patient with superficial wound infection after bone grafting that was healed by dressing change. There was 1 patient with bone infection after 3 months of bone grafting that was healed by repeated surgery with Masquelet technique in the first and second stage. Besides, 2 patients had symptoms of cutaneous nerve injury in the iliac donor area. The time of bone healing was 4-7 months [(5.8±0.8)months]. The scores of PCS and MCS in SF-36 at the last follow-up were (73.6±12.8)points and (83.6±13.2)points, significantly higher than those before bone grafting [(46.8±0.5)points, (60.7±2.0)points] (all P<0.01). Conclusion:Second-stage Masquelet technique with 3D printed quantitative bone implants for the treatment of long-segment bone defect following Gustilo type IIIB and IIIC tibial fractures is associated with shortened bone harvesting time, attenuated pain, reduced complications, accelerated bone healing and improved function.

Objective:To investigate the prevalence and risk factors of diabetic retinopathy (DR) in patients in Tibet.Methods:A total of 239 patients with DR who received treatment in Department of Endocrinology and Metabolism, Hospital of Chengdu Office of People's Government of Tibet Autonomous Region from December 2017 to December 2018 were included in this study. They were divided into Han nationality and Zang nationality groups according to ethnicity. The condition of DR was evaluated with nonmydriatic ocular fundus photography according to the staging criteria of the severity of retinopathy.Results:The prevalence of DR in Tibet was 18.0％. The prevalence of DR in Tibetan and Han patients with diabetes was 17.5% and 19.2%, respectively. There was no significant difference in the prevalence of DR between Tibetan and Han patients with diabetes ( χ2 = 0.10, P = 0.754). Logistic regression analysis revealed that the risk factors of developing DR in Tibet included diabetes duration ( OR = 1.14, 95% CI: 1.05-1.24, P < 0.05), insulin therapy ( OR = 2.74, 95% CI: 1.09-6.89, P < 0.05), fasting plasma glucose ( OR = 1.37, 95% CI: 1.07-1.75, P < 0.05) and hypertension ( OR = 1.98, 95% CI: 1.02-3.86, P < 0.05). Diabetes duration and fasting plasma glucose are independent risk factors of DR. However, although elevated glycated hemoglobin levels were high in Tibet, they could not be used to predict the risk for developing DR ( OR = 1.01, 95% CI: 0.82-1.25, P > 0.05). Conclusion:Hyperglycemia is an important risk factor of developing DR in Tibet. However, elevated glycated hemoglobin levels cannot be used to predict the risk of developing DR in Tibet. Findings from this study fill the gap in the research on DR prevalence and ethic difference of DR prevalence, providing scientific evidence for prevention and treatment of DR in high-altitude areas.

Objective:To compare the efficacy of concurrent and asynchronous radiochemotheray for early extranodal nasal natural killer/T-cell lymphoma (NKTCL).Methods:From 2007 to 2020, 278 patients with early NKTCL treated with comprehensive treatment in the Affiliated Tumor Hospital of Guizhou Medical University were recruited. According to the adjusted Nomogram-revised risk index (NRI) prognostic model, there were 49 cases in the good prognostic group without adverse prognostic factors (age>60 years old, increased serum lactate dehydrogenase (LDH), ECOG score ≥2, primary tumor invasion (PTI), Ann Arbor stage Ⅱ, and 229 cases in the poor prognostic group with any adverse prognostic factors. 145 of these cases were treated with concurrent radiochemotherapy, and 133 of them were treated with asynchronous radiochemotherapy.Results:The 5-year overall survival (OS) rate of the whole group was 71.0%, and the progression-free survival (PFS) rate was 67.6%. The 5-year OS rate in the good prognostic group was 95.6%, and 65.4% in the poor prognostic group ( P<0.001). In the poor prognostic group, the 5-year OS rates of patients with NRI=1(low-and moderate-risk group), NRI=2(moderate-and high-risk group), NRI≥3(high-risk group) were 72.1%, 61.1% and 47.7%, respectively ( P=0.007). There was no significant difference in curative effect between the concurrent and asynchronous radiochemotherapy groups. The 5-year OS rates were 70.6% and 69.8%( P=0.783), and the 5-year PFS rates were 67.6% and 65.2%( P=0.631). Further stratified analysis showed that the 5-year OS rates of patients with NRI=1 receiving concurrent and asynchronous radiochemotherapy were 73.1% and 76.5%( P=0.576), 62.6% and 69.3%( P=0.427) for those with NRI=2, and 58.1% and 42.3% for those with NRI≥3( P=0.954). Conclusions:Comprehensive treatment can significantly improve the prognosis of early NKTCL in the poor prognostic group. In the sequence of radiotherapy and chemotherapy, there is no significant difference in 5-year OS and PFS rates between concurrent and asynchronous radiochemotherapy. Sequential treatment with better tolerance can be adopted for early NKTCL with poor prognosis.