OBJECTIVES: To study genotype-phenotype correlations in children with FGFR3 variants and to improve clinical recognition of related disorders. METHODS: Clinical data of 95 patients aged 0-18 years harboring FGFR3 variants, confirmed by whole‑exome sequencing at Shanghai Children's Medical Center from January 2012 to December 2023, were retrospectively reviewed. Detailed phenotypic characterization was performed for 22 patients with achondroplasia (ACH) and 10 with hypochondroplasia (HCH). RESULTS: Among the 95 patients, 52 (55%) had ACH, 24 (25%) had HCH, 9 (9%) had thanatophoric dysplasia, 3 (3%) had syndromic skeletal dysplasia, 2 (2%) had severe achondroplasia with developmental delay and acanthosis nigricans, and 5 (5%) remained unclassified. A previously unreported FGFR3 variant, c.1663G>T, was identified. All 22 ACH patients presented with disproportionate short stature accompanied by limb dysplasia, commonly with macrocephaly, a depressed nasal bridge, bowed legs, and frontal bossing; complications were present in 17 (77%). The 10 HCH patients predominantly exhibited disproportionate short stature with limb dysplasia and depressed nasal bridge. CONCLUSIONS ACH is the most frequent phenotype associated with FGFR3 variants, and missense variants constitute the predominant variant type. The degree of FGFR3 activation appears to correlate with the clinical severity of skeletal dysplasia.
Humans ; Receptor, Fibroblast Growth Factor, Type 3/genetics* ; Child ; Male ; Child, Preschool ; Female ; Infant ; Adolescent ; Dwarfism/genetics* ; Achondroplasia/genetics* ; Lordosis/genetics* ; Infant, Newborn ; Retrospective Studies ; Genetic Association Studies ; Bone and Bones/abnormalities* ; Phenotype ; Limb Deformities, Congenital

Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of digestive system(DS)cancers,but results remain conflicting rather than conclusive.Here,we performed a case-control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk. Methods A total of 1,727 patients with cancer(gastric/liver/colorectal:460/480/787)and 800 healthy controls were recruited.Genotyping of rs1137101 was conducted using a polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)assay and confirmed using Sanger sequencing.Twenty-four eligible studies were included in the meta-analysis. Results After Bonferroni correction,the case-control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population.The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS,gastric,and liver cancer in the Chinese population. Conclusion The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers(especially liver and gastric cancer)in the Chinese population.

Objective To investigate the prognosis of patients with hepatitis B virus(HBV)-related intrahepatic cholangiocarcinoma(ICC)whose HBV DNA was negative before surgical.Methods A retrospective analysis was conducted on the clinical data of 97 ICC patients who underwent surgery resection at the Fifth Medical Center of Chinese PLA General Hospital between October 2010 and January 2017.All patients were divided into HBV-related ICC(HBV-ICC)group(n=62)and non-HBV-related ICC(Con-ICC)group(n=35).HBV-ICC group included 34 patients with HBV core antigen positive(HBcAb+)and HBV surface antigen positive(HBsAg+),and 28 patients with HBcAb positive and HBsAg negative.Kaplan-Meier analysis was used to plot survival curves and compare the overall survival(OS)and postoperative recurrence-free survival(RFS)among patients in Con-ICC,ICC patients with HBsAg+/HBcAb+,and ICC patients with HBsAg-/HBcAb+.Univariate and multivariate Cox proportional hazard models were used to analyze independent influencing factor for OS,RFS and early postoperative recurrence among gender,age,pathogenic factor,liver cirrhosis,Child-Pugh grade,carbohydrate antigen 19-9(CA199),alpha-fetoprotein(AFP),glutamine transferase(GGT),alkaline phosphatase(ALP),total bilirubin(TBil),direct bilirubin(DBil),American Joint Committee on Cancer(AJCC)stage,tumor size,tumor number,tumor differentiation,microvascular invasion,lymph node metastasis,hepatectomy procedure,cholecystectomy,and follow-up treatment.Results Of the 97 patients,the median age was 56 years,and 79(81.4%)of them were male.The median follow-up time was 92.2 months.Eighty-eight(90.7%)patients presented with tumor recurrence and 73(75.3%)died.In multivariate analyses,HBV-ICC and CA199>37 kU/L were independent predictors of OS(HR=0.45,95%CI 0.26-0.77,P=0.003;HR=2.10,95%CI 1.24-3.57,P=0.006),RFS(HR=0.43,95%CI 0.27-0.68,P<0.001;HR=1.78,95%CI 1.12-2.81,P=0.014),and postoperative early recurrence(HR=0.42,95%CI 0.26-0.70,P=0.001;HR=2.02,95%CI 1.20-3.39,P=0.008).AJCC stage Ⅲ was an independent risk factor for postoperative RFS(HR=1.81,95%CI 1.04-3.14,P=0.037).Multiple tumor lesions was an independent risk factor for postoperative RFS and early recurrence(HR=1.73,95%CI 1.07-2.77,P=0.024;HR=1.90,95%CI 1.12-3.24,P=0.017).There was no statistically significant difference in OS,RFS,and early recurrence between HBV-ICC patients with HBsAg-/HBcAb+and Con-ICC patients(P<0.05),whereas HBsAg+/HBcAb+was a significant factor affecting postoperative OS(HR=0.32,95%CI 0.16-0.62,P=0.001),RFS(HR=0.32,95%CI 0.18-0.55,P<0.001),and early recurrence(HR=0.29,95%CI 0.15-0.54,P<0.001)in ICC patients.Conclusions The prognosis of HBV-ICC patients with preoperative HBV-DNA-is better than that of Con-ICC patients.The prognosis of HBV-ICC patients with HBcAb+/HBsAg-is worse than that of HBV-ICC patients with HBcAb+/HBsAg+,but similar to Con-ICC patients.Therefore,the postoperative stratified management of HBV-ICC patients should be emphasized.

Objective:To study the risk of malignant tumor in medical X-ray workers in Shanghai and provide scientific data for the study on occupationally exposed population.Methods:A retrospective cohort study was conducted to investigate the risk of cancer. Totally, 715 physicians in radiology departments during 1950-1980 in Shanghai were selected as exposure group, while 738 with non-radiology departments in the same hospital in the same time period as control group. The basic information on the selected physicians and associated cancer incidence were collected. The comulative number of individuals with cancer from 1980 to 2021 was calculated. The relative risk ( RR) of cancer was analyzed using logistic regression model in terms of gender, birth year, and work starting year. As well, stratified analysis based on confounding factors was conducted. Results:A total of 1 369 individuals were followed up, including 668 in exposure group and 701 in control group. The cumulative person-year of observed individuals was 52 980. As of 31 December 2021, a total of 199 patients with various malignant tumors were identified. The results of the logistic regression analysis showed that the risk of malignant tumors in exposure group was significantly higher than that in control group. The adjusted RR of solid cancer and total cancer was 1.49 (95% CI: 1.08-2.05, P=0.015) and 1.40 (95% CI: 1.02-1.92, P=0.036), respectively. In addition, the risk of thyroid cancer in exposure group was significantly higher than that in control group ( RR=10.06, 95% CI: 2.05-49.62, P=0.005). Stratified analysis showed that the exposure group had a higher risk of total cancer both for femals and workers taking their jobs at age of 21-25. Conclusions:The risk of thyroid cancer, solid cancer and total cancer in the medical X-ray workers was significantly higher than that in control group. It is suggested that radiation protection in medical practice should be strengthened for the occupationally exposed workers, especially for femals and workers taking their jobs at low age.

The 3-succinate-30-stearyl glycyrrhetinic acid(18-GA-Suc) was inserted into glycyrrhetinic acid(GA)-tanshinone Ⅱ_A(TSN)-salvianolic acid B(Sal B) liposome(GTS-lip) to prepare liver targeting compound liposome(Suc-GTS-lip) mediated by GA receptors. Next, pharmacokinetics and tissue distribution of Suc-GTS-lip and GTS-lip were compared by UPLC, and in vivo imaging tracking of Suc-GTS-lip was conducted. The authors investigated the effect of Suc-GTS-lip on the proliferation inhibition of hepatic stellate cells(HSC) and explored their molecular mechanism of improving liver fibrosis. Pharmacokinetic results showed that the AUC_(Sal B) decreased from(636.06±27.73) μg·h·mL~(-1) to(550.39±12.34) μg·h·mL~(-1), and the AUC_(TSN) decreased from(1.08±0.72) μg·h·mL~(-1) to(0.65±0.04) μg·h·mL~(-1), but the AUC_(GA) increased from(43.64±3.10) μg·h·mL~(-1) to(96.21±3.75) μg·h·mL~(-1). The results of tissue distribution showed that the AUC_(Sal B) and C_(max) of Sal B in the liver of the Suc-GTS-lip group were 10.21 and 4.44 times those of the GTS-lip group, respectively. The liver targeting efficiency of Sal B, TSN, and GA in the Suc-GTS-lip group was 40.66%, 3.06%, and 22.08%, respectively. In vivo imaging studies showed that the modified liposomes tended to accumulate in the liver. MTT results showed that Suc-GTS-lip could significantly inhibit the proliferation of HSC, and RT-PCR results showed that the expression of MMP-1 was significantly increased in all groups, but that of TIMP-1 and TIMP-2 was significantly decreased. The mRNA expressions of collagen-I and collagen-Ⅲ were significantly decreased in all groups. The experimental results showed that Suc-GTS-lip had liver targeting, and it could inhibit the proliferation of HSC and induce their apoptosis, which provided the experimental basis for the targeted treatment of liver fibrosis by Suc-GTS-lip.
Humans ; Liposomes ; Hepatic Stellate Cells ; Glycyrrhetinic Acid/pharmacology* ; Liver ; Liver Cirrhosis/genetics* ; Collagen/pharmacology*

OBJECTIVES: To study the clinical characteristics of plastic bronchitis (PB) in children and investigate the the risk factors for recurrence of PB. METHODS: This was a retrospective analysis of medical data of children with PB who were hospitalized in Children's Hospital of Chongqing Medical University from January 2012 to July 2022. The children were divided into a single occurrence of PB group and a recurrent PB group and the risk factors for recurrence of PB were analyzed. RESULTS: A total of 107 children with PB were included, including 61 males (57.0%) and 46 females (43.0%), with a median age of 5.0 years, and 78 cases (72.9%) were over 3 years old. All the children had cough, 96 children (89.7%) had fever, with high fever in 90 children. Seventy-three children (68.2%) had shortness of breath, and 64 children (59.8%) had respiratory failure. Sixty-six children (61.7%) had atelectasis and 52 children (48.6%) had pleural effusion. Forty-seven children (43.9%) had Mycoplasma pneumoniae infection, 28 children (26.2%) had adenovirus infection, and 17 children (15.9%) had influenza virus infection. Seventy-one children (66.4%) had a single occurrence of PB, and 36 cases (33.6%) had recurrent occurrence of PB (≥2 times). Multivariate logistic regression analysis showed that involvement of ≥2 lung lobes (OR=3.376) under bronchoscopy, continued need for invasive ventilation after initial removal of plastic casts (OR=3.275), and concomitant multi-organ dysfunction outside the lungs (OR=2.906) were independent risk factors for recurrent occurrence of PB (P<0.05). CONCLUSIONS Children with pneumonia accompanied by persistent high fever, shortness of breath, respiratory failure, atelectasis or pleural effusion should be highly suspected with PB. Involvement of ≥2 lung lobes under bronchoscopy, continued need for invasive ventilation after initial removal of plastic casts, and concomitant multi-organ dysfunction outside the lungs may be risk factors for recurrent occurrence of PB.
Female ; Male ; Child ; Humans ; Child, Preschool ; Multiple Organ Failure ; Retrospective Studies ; Bronchitis/etiology* ; Dyspnea ; Pleural Effusion ; Pulmonary Atelectasis ; Plastics ; Respiratory Insufficiency

ObjectiveThrough a randomized， double-blind， double-simulation， positive-control， multicenter design， this study aimed to analyze the relationship between the dosage， efficacy， and safety of Pudilan anti-inflammatory oral liquid in treating acute pharyngitis/tonsillitis in adults caused by bacterial infection and validate the regulatory effect of Pudilan anti-inflammatory oral liquid on inflammatory markers such as serum amyloid A （SAA）， C-reactive protein （CRP）， white blood cells （WBC）， neutrophil percentage （NE%）， and erythrocyte sedimentation rate （ESR）， thereby exploring the feasibility of using Pudilan anti-inflammatory oral liquid as a substitute for antibiotics in the treatment of infectious diseases and providing a basis for rational clinical medication. MethodUsing a stratified randomized， double-blind， double-simulation， positive-control， multicenter design， 220 participants were enrolled from nine centers. The participants were randomly divided into three groups at 1∶1∶1 — a Pudilan anti-inflammatory oral liquid 20 mL group （73 cases）， a Pudilan anti-inflammatory oral liquid 10 mL group （73 cases）， and a control group （amoxicillin group， 74 cases）. The treatment course was 7 days. The study observed parameters including the total effective rate of sore throat， onset and disappearance time of sore throat， health status score， treatment time， and inflammation markers. Result①Dataset division： The 211 cases were included in the full analysis dataset （FAS）， 208 cases were included in the per-protocol dataset （PPS）， and 218 cases were included in the safety dataset （SS）. ② Efficacy evaluation： There were statistically significant differences （P<0.05） in the comparison of the three groups regarding the total effective rate of sore throat， disappearance time of sore throat， and health status. Both the 20 mL and 10 mL groups were non-inferior to the control group， and there was a statistically significant difference between the 20 mL and 10 mL dosage groups （P<0.05）. There was no statistically significant difference in the comparison of onset time of sore throat among the groups. CRP， WBC， and NE% of patients in all three groups significantly decreased on the 7^th day of treatment compared with those before treatment （P<0.01）. ③Safety evaluation： Adverse events mainly occurred in various examination indicators. There were no statistically significant differences in the comparison between groups， and no adverse reactions or serious adverse events occurred. ④Economic evaluation： The increased cost of the 10 mL and 20 mL dosage groups was entirely justified as compared with that in the control group. When comparing the 10 mL and 20 mL dosage groups， the 10 mL dosage group was deemed less advantageous. ConclusionPudilan anti-inflammatory oral liquid can be used alone as an alternative to antibiotics in the treatment of acute pharyngitis/tonsillitis caused by bacterial infection. It demonstrates good safety and can lower inflammation markers such as CRP， WBC， and NE%， suggesting its potential to reduce the body's inflammatory response. Its mechanism of action may be related to its multi-target regulatory mechanism.

Objective: To understand the associations between internet addiction, screen time (computer/mobile devices use and television watching time) and depressive symptoms in adults. Methods: A total of 6 932 adults aged <60 years from the Tianjin Chronic Low-grade Sgstemic Inflammation and Health (TCLSIH) Cohort of 2013-2019 were surveyed. The information about their computer/mobile devices use and television watching time were collected by using a self-reported questionnaire. The depressive symptoms were assessed using the self-rating depression scale (SDS). The adults surveyed were divided into two groups: non-depressive symptom group (SDS score <45) and depressive symptom group (SDS score ≥45). The associations between internet addiction, screen time and depressive symptoms were estimated using Cox proportional hazard regression models, with adjusting for multiple confounders. Results: After adjusting for confounding factors, the hazard ratios (HRs) of depressive symptom in the adults who had internet addiction before, had light internet addiction and had moderate or severe internet addiction were 0.83 (95%CI: 0.56-1.23) , 1.20 (95%CI: 1.03-1.41) for light and 1.48 (95%CI: 1.16-1.89), respectively, compared with those without internet addiction. The linear trend test results of the association between internet addiction and depressive symptoms was significant (trend P<0.001). Compared with the adults who used computer/mobile devices for <1 hour/day, the HRs of depressive symptoms in those who used computer/mobile devices for >1 hour, >3 hours, >5 hours and >10 hours were 0.59 (95%CI: 0.40-0.88), 0.58 (95%CI: 0.40-0.85), 0.52 (95%CI: 0.36-0.76) and 0.69 (95%CI: 0.45-1.05) respectively, a U-shaped association was found between computer/mobile devices use time and depressive symptoms (trend P<0.001). Compared with the adults who never watch TV, the HR of depressive symptoms was 1.36 (95%CI:1.09-1.69) for those watching TV for ≥3 hours/day in crude model and 1.34 (95%CI: 1.07-1.68) for those watching TV for ≥3 hours/day in adjusted model (trend P<0.001). Conclusion: Our findings suggested that internet addiction and television watching time were associated with an increased risk of depressive symptoms, while computer/mobile device use time was associated with a reduced risk of depressive symptoms.
Adult ; Humans ; Screen Time ; Internet Addiction Disorder ; Self Report

Objective:To investigate the effect of Jiaomu Gualou Decoction combined with bisoprolol on myocardial microcirculation and oxidative/antioxidant balance in patients with heart failure.Methods:A total of 128 patients with heart failure who met the inclusion criteria from March 2020 to February 2021 in Dagang Hospital of Traditional Chinese Medicine, Binhai New Area, Tianjin were divided into 2 groups by random number table method, with 64 in each group. On the basis of conventional treatment, the control group was given oral bisoprolol, and the study group was given Jiaomu Gualou Decoction and oral bisoprolol. Both groups were treated continuously for 4 weeks. TCM syndrome scores were performed before and after treatment. The left ventricular ejection fraction (LVEF), left ventricular end-systolic diameter (LVESD), and left ventricular end-diastolic diameter (LVEDD) were detected by ultrasonic diagnostic equipment, and the frequency, duration and total myocardial ischemia load of the 24-hour ECG were recorded. Lipid peroxide (LPO) was detected by fluorescence method, SOD, MDA and GSH-Px were detected by colorimetric method. The adverse events were recorded and clinical response was evaluated.Results:The response rate was 93.75% (60/64) in the study group and 79.69% (51/64) in the control group, and the difference between the two groups was statistically significant ( χ2=5.49, P=0.019). After treatment, the scores of shortness of breath, phlegm, sternocostal fullness, and fatigue in the study group were significantly lower than those in the control group ( t values were 8.48, 8.15, 8.86, and 6.88, respectively, all Ps<0.001). After treatment, the LVEF of the study group [(53.26±5.18)% vs. (48.65±5.27)%, t=4.99] was significantly higher than that of the control group, and the LVESD [(42.59±3.26) mm vs. (46.98±3.55) mm, t=7.29], LVEDD [(52.79±4.15) mm vs. (57.48±4.60) mm, t=6.06] significantly lower than the control group ( P<0.01). After treatment, frequency of ST segment fall [(2.51±0.42) times/24 h vs. (3.79±0.55) times/24 h, t=14.80], duration [(15.26±3.45) min/24 h vs. (22.65±3.71) min/24 h, t=11.67] and total myocardial ischemia load [(25.79±5.13) mm/min vs. (38.02±5.44) mm/min, t=13.09] were significantly lower than those in the control group ( P<0.01). After treatment, the levels of serum GSH-Px and SOD in the study group were significantly higher than those in the control group ( t values were 10.97, 14.37, respectively, all Ps<0.001), while the levels of LPO and MDA were significantly lower than those in the control group ( t values were 7.50, 11.04, respectively, all Ps<0.001). During the treatment period, the incidence of adverse events was 4.69% (3/64) in the study group and 7.81% (5/64) in the control group, with no significant difference between the two groups ( χ2=0.13, P=0.715). Conclusion:The Jiaomu Gualou Decoction combined with bisoprolol can improve the cardiac function and myocardial microcirculation in patients with heart failure, promote the body's oxidation/antioxidant balance, relieve the clinical symptoms of patients, and improve the response effect safely.