Objective To analyze the characteristics of time in range(TIR)and its relationship with oxidative stress(OS)and insulin resistance status(HOMA-IR)in patients with type 2 diabetes mellitus(T2DM)and sleep apnea-hypopnea syndrome(OSAHS).Methods According to apnea-hypopnea index(AHI),165 T2DM in patients were divided into simple T2DM group(AHI<5 times/h,n=43),T2DM combine OSAHS mild group(OSAHS-G,5≤AHI<15 times/h,n=51),T2DM combined OSAHS moderate group(OSAHS-M,15≤AHI≤30 times/h,n=40)and T2DM combine OSAHS severe group(OSAHS-S,AHI>30 times/h,n=31).TIR was calculated by dynamic blood glucose monitoring.Superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and other indexes were detected and analyzed.Results Compared with simple T2DM group,the levels of HOMA-IR,8-iso-PGF2a and Ox-LDL were higher in T2DM combined OSAHS-G,OSAHS-M or OSAHS-S group,while the levels of TIR,SOD and GSH-Px were lower(P<0.05).Pearson correlation analysis showed that TIR was positively correlated with the levels of SOD and GSH-Px(P<0.05 or P<0.01),and negatively correlated with the levels of 8-iso-PGF2a,Ox-LDL,HbA1c,HOMA-IR and the severity of OSAHS(P<0.01).Logistic regression analysis showed that TIR,SOD and GSH-Px were protective factors for severe OSAHS in T2DM patients,while 8-iso-PGE2a and Ox-LDL were the risk factors for severe OSAHS.Conclusions The glucose level fluctuates greatly in patients with T2DM and OSAHS.Insulin resistance and oxidative stress are factors that affect the normalization of TIR.

Objective:This study investigated the efficacy and safety of denosumab (DENOS) versus zoledronic acid (ZOL) in the bone disease treatment of newly diagnosed multiple myeloma.Methods:The clinical data of 80 patients with myeloma bone disease (MBD) at the Fifth Medical Center of PLA General Hospital between March 1, 2021 and June 30, 2023 were retrospectively reviewed. Eighteen patients with severe renal impairment (SRI, endogenous creatinine clearance rate<30 ml/min) were treated with DENOS, and 62 non-SRI patients were divided into DENOS (30 patients) and ZOL group (32 patients) .Results:Hypocalcemia was observed in 26 (33%) patients, and 22 patients developed hypocalcemia during the first treatment course. The incidence of hypocalcemia in the non-SRI patients of DENOS group was higher than that in the ZOL group [20% (6/30) vs 13% (4/32), P=0.028]. The incidence of hypocalcemia in SRI was 89% (16/18). Multivariate logistic regression analysis revealed that endogenous creatinine clearance rate<30 ml/min was significantly associated with hypocalcemia after DENOS administration ( P<0.001). After 1 month of antiresorptive (AR) drug application, the decrease in the serum β-C-terminal cross-linked carboxy-telopeptide of collagen type I concentrations of SRI and non-SRI patients in the DENOS group were significantly higher than that in the ZOL group (68% vs 59% vs 27%, P<0.001). The increase in serum procollagen type Ⅰ N-terminal propeptide concentrations of patients with or without SRI in the DENOS group were significantly higher than that in the ZOL group (34% vs 20% vs 11%, P<0.05). The level of intact parathyroid hormone in each group increased after AR drug treatment. None of the patients developed osteonecrosis of the jaw and renal adverse events, and no statistically significant differences in the overall response rate, complete remission and stringent complete remission rates were found among the groups ( P>0.05), and the median PFS and OS time were not reached ( P>0.05) . Conclusions:In the treatment of MBD, DENOS minimizes nephrotoxicity and has strong AR effect. Hypocalcemia is a common adverse event but is usually mild or moderate and manageable.

OBJECTIVE To study and analyze the relationship between serum levels of Endocan,Cyclophilic A (CyPA),and asprosin with the condition severity and cognitive function in patients with obstructive sleep apnea hypopnea syndrome(OSAHS). METHODS From November 2021 to December 2023,99 OSAHS patients who visited our hospital were collected and separated into mild group(n=29),moderate group(n=45),and severe group(n=25) based on the apnea hypopnea index(AHI). ELISA method was applied to detect serum levels of Endocan,CyPA,and asprosin. Multivariate logistic regression was used to analyze the influencing factors of severity of condition. ROC curve was plotted to analyze the diagnostic value of serum Endocan,CyPA,and asprosin for cognitive function in OSAHS patients. Spearman rank correlation was applied to analyze the correlation between serum Endocan,CyPA,asprosin,with severity of condition,cognitive function. RESULTS Compared with the mild group,the serum levels of Endocan,CyPA,and asprosin were obviously increased in the moderate and severe groups(P<0.05),and the serum levels of Endocan,CyPA,and asprosin in the severe group were obviously increased compared to the moderate group(P<0.05). There were statistically obvious differences in AHI,Epworth sleepiness scale(ESS) scores,and some sleep related parameters among the three groups(P<0.05). Further analysis revealed that mean blood oxygen saturation(MSaO2) was a protective factor affecting the severity of condition(P<0.05),while AHI,serum Endocan,CyPA,and asprosin levels were all risk factors affecting the severity of condition(P<0.05). The serum levels of Endocan,CyPA,and asprosin in patients with cognitive impaired were obviously higher than those in patients with normal cognition,and the MoCA score was lower than that in patients with normal cognition(P<0.05). The AUC of serum Endocan,CyPA,asprosin,and combined diagnosis for cognitive impairment in patients was 0.889,0.893,0.861,and 0.974,respectively,and the combined diagnosis was obviously better than individual diagnosis of Endocan(Z=2.832,P=0.005),CyPA(Z=2.907,P=0.004),and asprosin(Z=3.225,P=0.001). Serum Endocan,CyPA,and asprosin were positively correlated with AHI and negatively correlated with MoCA score(P<0.05). CONCLUSION In patients with severe OSAHS and cognitive impairment,serum Endocan,CyPA,and asprosin levels are all increased,and they have certain auxiliary diagnostic value for the severity of condition and cognitive function.

Objective To explore the evaluation value of serum levels of aquaporin 4(AQP4),decorin(DCN),and Apelin in the diagnosis and pathological staging of retinopathy of prematurity(ROP).Methods A total of 64 ROP children(128 eyes)who received treatment in the hospital from October 2021 to October 2022 were collected as the ROP group,while 64 premature infants of the same birth age without ROP((128 eyes)were regarded as the normal group.Enzyme linked immunosorbent assay(ELISA)was applied to meas-ure the levels of serum AQP4,DCN,and Apelin.Multivariate Logistic regression was applied to analyze the factors that affected the occurrence of ROP.Receiver operating characteristic(ROC)curve was applied to ana-lyze the diagnostic value of serum AQP4,DCN,and Apelin in the occurrence and pathological staging of ROP.Results Compared with the normal group,the birth weight in the ROP group was obviously reduced(P＞0.05).The serum levels of AQP4,DCN,and Apelin in the ROP group were obviously higher than those in the normal group(P＜0.05).The serum levels of AQP4,DCN,and Apelin in children with ROP at different pathological stages showed statistically significant differences(P＜0.05).According to multivariate Logistic regression analysis,AQP4,DCN,and Apelin were risk factors affecting the occurrence of ROP(P＜0.05),while birth weight was a protective factor affecting the occurrence of ROP(P＜0.05).The combination of se-rum AQP4,DCN,and Apelin had the largest area under the curve(AUC)for the diagnosis of ROP,which was superior to the individual diagnosis of serum AQP4,DCN,and Apelin(Zcombination-AQP4=3.018,P=0.003,Zcombination-DCN=2.306,P=0.021,Zcombination-Apelin=3.301,P=0.001).The combination of serum AQP4,DCN,and Apelin had the largest AUC for the diagnosis of pathological staging of ROP,which was superior to the indi-vidual diagnosis of serum AQP4,DCN,and Apelin(ZcombinationAQP4=2.735,P=0.006,Zcombination-DCN=2.228,P=0.026,Zcombination-Apelm=2.594,P=0.001).Conclusion The serum levels of AQP4,DCN,and Apelin in children with ROP are obviously increased,and the combination of the three could better diagnose the occurrence of ROP and evaluate the pathological staging.

Ulcerative colitis （UC） is a chronic non-specific digestive disease with abdominal pain， diarrhea， and blood and mucus in stool as the main clinical manifestations and inflammatory injury of colorectal mucosa and submucosa as the main pathological changes. With the change in living habits and dietary structure of people， the incidence and cancer morbidity in UC are rising rapidly all over the world， which has seriously reduced the quality of life and caused a huge social burden. Till now， the pathogenesis has not been elucidated. In western medicine， aminosalicylates， corticosteroids， and immunosuppressors are commonly used to relieve symptoms. However， the long-term application will lead to problems such as decreased efficacy and increased adverse reactions. There are more studies of traditional Chinese medicine （TCM） in the treatment of UC by reducing the inflammatory response， alleviating oxidative stress， protecting the intestinal mucosal barrier， and regulating intestinal microecological imbalance by virtue of the advantages of integrated regulation based on multiple links， levels， and targets. In view of this， the present study reviewed the effect and mechanism of active ingredients of TCM， TCM extracts， TCM pairs， classic TCM compounds， and TCM combined with chemical agents in the treatment of UC based on relevant research articles in recent 10 years to provide references for seeking effective drugs.

Objective:This study aimed to evaluate the efficacy and safety of daratumumab as a maintenance treatment after autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with newly diagnosed multiple myeloma (NDMM) .Methods:The clinical data, hematological and renal response, and safety of 15 post-transplant patients with NDMM who had received daratumumab maintenance between May 1, 2022 and June 30, 2023 were retrospectively analyzed.Results:Fifteen patients (11 males and 4 females) with a median age of 58 (41-72) years were included. Thirteen patients did not receive daratumumab during induction therapy and auto-HSCT, 6 patients had renal impairment, and nine patients had high-risk cytogenetics. The median infusion of daratumumab was 12 (6-17) times, and the median duration of maintenance was 6 (1.5-12) months. The treatment efficacy was evaluated in all 15 patients, and daratumumab maintenance therapy increased the rate of stringent complete response from 40% to 60%. The renal response rate and median estimated glomerular filtration rate of six patients with RI-NDMM were also improved. During daratumumab maintenance therapy, the most common hematological grade 3 adverse event (AE) was lymphopenia [4 of 15 patients (26.67%) ], whereas the most common nonhematologic AEs were infusion-related reactions [7 of 15 patients (46.67%) ] and grade 3 pneumonia [5 of 15 patients (33.33%) ]. The five patients with pneumonia were daratumumab naive [5 of 13 patients (38.46%) ], with a median of 8 (6-10) infusions. Among them, the chest computed tomography of three patients showed interstitial infiltrates, and treatment with methylprednisolone was effective. With a median follow-up of 12 months, the 1-year overall survival rate was 93.33%, and only one patient died (which was not related to daratumumab treatment) .Conclusions:Daratumumab was safe and effective as a maintenance agent for post-auto-HSCT patients with NDMM, and AEs were controllable. The most common nonhematologic AE was grade 3 pneumonia, and a less dose-intense maintenance regimen for the first 8 weeks could reduce the incidence of pneumonia.

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 clinical efficacy of distal pancreatectomy with celiac axis resection(DP-CAR).Methods:A total of 89 consecutive patients (50 males and 39 females) who were diagnosed with pancreatic body cancer and underwent DP-CAR in Pancreas Center,First Affiliated Hospital of Nanjing Medical University between September 2013 and June 2022 were retrospectively reviewed. There were 50 males and 39 females,with age( M(IQR)) of 63(12) years(range:43 to 81 years). Perioperative parameters,pathology results and follow-up data of these patients were analyzed, χ2 or Fisher′s test for categorical data while the Wilcoxon test for quantitative data. Survival results were estimated by the Kaplan-Meier survival method. Results:Among 89 cases,cases combined with portal vein-superior mesenteric vein or organ resection accounted for 22.5% (20/89) and 42.7% (38/89),respectively. The operative time,blood loss and postoperative hospital stay were 270 (110) minutes,300 (300) ml and 13 (10) days,respectively. The overall morbidity rate was 67.4% (60/89) while the major morbidity was 11.2% (10/89). The increase rate in transient liver enzymes was 42.7% (38/89),3.4% (3/89) for liver failure,53.9% (48/89) for clinically relevant postoperative pancreatic fistula,1.1% (1/89) for bile leak,3.4% (3/89) for chylous leak of grade B and C,11.2% (10/89) for abdominal infection,9.0% (8/89) for postoperative hemorrhage of grade B and C,4.5% (4/89) for delayed gastric emptying,6.7% (6/89) for deep vein thrombosis,3.4% (3/89) for reoperation,4.5% (4/89)for hospital mortality,7.9% (7/89) for 90-day mortality. The pathological type was pancreatic cancer for all 89 cases and pancreatic ductal adenocarcinoma made up 92.1% (82/89). The tumor size was 4.8(2.0) cm, ranging from 1.5 to 12.0 cm. The number of lymph nodes harvested was 14 (13)(range:2 to 33),with a positive lymph node rate of 13.0% (24.0%). The resection R0 rate was 30.0% (24/80) and the R1 (<1 mm) rate was 58.8% (47/80). The median overall survival time was 21.3 months (95% CI: 15.6 to 24.3) and the median disease-free survival time was 19.1 months (95% CI: 11.7 to 25.1). The overall survival at 1-year and 2-year were 69.60% and 39.52%. The median survival time of 58 patients with adjuvant chemotherapy was 24.3 months (95% CI: 17.8 to 32.3) while that of 13 patients without any kind of adjuvant therapy was 8.4 months (95% CI: 7.3 to 22.3). Seven patients accepted neoadjuvant chemotherapy and there was no significant morbidity among them,with a resection rate of R0 of 5/7. Conclusion:DP-CAR is safe and feasible for selective cases,which could be more valuable in improving long-term survival when combined with (neo) adjuvant therapy.

Objective:To investigate the clinical efficacy of distal pancreatectomy with celiac axis resection(DP-CAR).Methods:A total of 89 consecutive patients (50 males and 39 females) who were diagnosed with pancreatic body cancer and underwent DP-CAR in Pancreas Center,First Affiliated Hospital of Nanjing Medical University between September 2013 and June 2022 were retrospectively reviewed. There were 50 males and 39 females,with age( M(IQR)) of 63(12) years(range:43 to 81 years). Perioperative parameters,pathology results and follow-up data of these patients were analyzed, χ2 or Fisher′s test for categorical data while the Wilcoxon test for quantitative data. Survival results were estimated by the Kaplan-Meier survival method. Results:Among 89 cases,cases combined with portal vein-superior mesenteric vein or organ resection accounted for 22.5% (20/89) and 42.7% (38/89),respectively. The operative time,blood loss and postoperative hospital stay were 270 (110) minutes,300 (300) ml and 13 (10) days,respectively. The overall morbidity rate was 67.4% (60/89) while the major morbidity was 11.2% (10/89). The increase rate in transient liver enzymes was 42.7% (38/89),3.4% (3/89) for liver failure,53.9% (48/89) for clinically relevant postoperative pancreatic fistula,1.1% (1/89) for bile leak,3.4% (3/89) for chylous leak of grade B and C,11.2% (10/89) for abdominal infection,9.0% (8/89) for postoperative hemorrhage of grade B and C,4.5% (4/89) for delayed gastric emptying,6.7% (6/89) for deep vein thrombosis,3.4% (3/89) for reoperation,4.5% (4/89)for hospital mortality,7.9% (7/89) for 90-day mortality. The pathological type was pancreatic cancer for all 89 cases and pancreatic ductal adenocarcinoma made up 92.1% (82/89). The tumor size was 4.8(2.0) cm, ranging from 1.5 to 12.0 cm. The number of lymph nodes harvested was 14 (13)(range:2 to 33),with a positive lymph node rate of 13.0% (24.0%). The resection R0 rate was 30.0% (24/80) and the R1 (<1 mm) rate was 58.8% (47/80). The median overall survival time was 21.3 months (95% CI: 15.6 to 24.3) and the median disease-free survival time was 19.1 months (95% CI: 11.7 to 25.1). The overall survival at 1-year and 2-year were 69.60% and 39.52%. The median survival time of 58 patients with adjuvant chemotherapy was 24.3 months (95% CI: 17.8 to 32.3) while that of 13 patients without any kind of adjuvant therapy was 8.4 months (95% CI: 7.3 to 22.3). Seven patients accepted neoadjuvant chemotherapy and there was no significant morbidity among them,with a resection rate of R0 of 5/7. Conclusion:DP-CAR is safe and feasible for selective cases,which could be more valuable in improving long-term survival when combined with (neo) adjuvant therapy.

Objective:To explore the effect of play-based communication and behavior intervention (PCBI) on internalizing and externalizing behaviors in children with autism spectrum disorder (ASD).Methods:From November 2018 to November 2021, 90 ASD children aged 8-30 months who registered in the Child Mental Health Research Center of the Affiliated Brain Hospital of Nanjing Medical University for PCBI ultra-early intervention training were selected and randomly assigned to the intervention group( n=60) and the waiting group( n=30) according to the ratio of 2∶1.Behavioral videos of free play between children and caregivers were collected before and after the 12-week intervention and the behavioral observation and analysis system (Observer XT) was used to code the parent-child interaction status and children's internalizing and externalizing behaviors.SPSS 23.0 statistical software were used and the data were analyzed by t-test, chi-square test, Pearson correlation analysis and multiple linear stepwise regression analysis. Results:After the intervention, the children in the intervention group had improved internalizing and externalizing behaviors (2.43±2.22, 1.88±1.91) compared with those before the intervention (4.82±3.37, 3.68±5.68), and the difference was statistically significant ( t=4.66, 2.60, both P<0.05). The children in the waiting group had no significant difference in internalizing and externalizing behaviors before (4.23±2.47, 4.00±2.18) and after intervention (4.37±2.57, 4.67±3.72) ( t=-0.23, -0.83, both P>0.05). After intervention, the children in the intervention group had fewer internalizing and externalizing behaviors than those in the waiting group, and the difference was statistically significant ( t=-3.70, -4.71, both P<0.05). The differences in internalizing behaviors (2.38±3.96, 1.80±5.37) and externalizing behaviors (1.80±5.37, -0.67±4.38) between the two groups before and after the intervention were statistically significant ( t=3.03, 2.18, both P<0.05). The results of multiple linear stepwise regression showed that the negative interaction of caregivers ( β=0.29, P<0.01) was a risk factor for internalizing behaviors.The negative interaction of children ( β=0.45, P<0.01) was a risk factor for externalizing behaviors, and the child's object status ( β=-0.30, P<0.01) and binary interaction ( β=-0.39, P<0.01) were protective factors for externalizing behaviors.In the intervention group, active child interaction, active caregiver interaction, and binary interaction increased after the intervention ( t=-6.77, -4.58, -7.72, all P<0.05), while the child's object status and the caregiver's negative interaction decreased ( t=3.37, 4.30, both P<0.05). Conclusion:The PCBI ultra-early intervention can effectively improve the internalizing and externalizing behaviors of ASD children.Improvements in internalizing behaviors may work by reducing negative caregiver interactions, and improvements in externalizing behaviors may work by increasing parent-child binary interactions.