AIM: To analyze the clinical outcomes of cyclosporine combined with lacrimal plug in the treatment of dry eye in patients with primary Sjögren's syndrome.METHODS: The clinical data of 60 patients(120 eyes)who were admitted to the ophthalmology department and rheumatology and immunology department of Baoding No.1 Central Hospital and were diagonosed with siogren's syndrome dry eye after multidisciplinary consultation from June 2022 to September 2023 were retrospectively analyzed. All the patients received regular treatment of primary Sjögren's syndrome, and they were divided into three groups according to treatment methods: A, B and C, with 20 cases(40 eyes)in each group. The group A received 0.3% sodium hyaluronate eyedrops, the group B received 0.3% sodium hyaluronate eyedrops plus 0.05% cyclosporine eyedrops, and the group C received 0.3% sodium hyaluronate eyedrops plus 0.05% cyclosporine eyedrops combined with binocular lacrimal plugs. The ocular surface disease index(OSDI)score, conjunctival hyperemia score, tear film breakup time(BUT), tear meniscus height(TMH), corneal fluorescein staining(FL)score and tear secretion of the three groups of patients were compared before and at 4, 8 and 12 wk after treatment. The contents of inflammatory factors such as interleukin-6(IL-6), tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in tears were detected before and at 12 wk after treatment.RESULTS: At 4, 8 and 12 wk after treatment, the scores of OSDI, conjunctival hyperemia score and FL in the three groups of patients were lower than those before treatment, and the BUT, TMH and tear secretion were higher than those before treatment(all P<0.001). The OSDI score of the group C was lower than that of the group A and B, and the group B was lower than the group A(all P<0.001). The BUT, TMH and tear secretion of the group C were higher than those of the group A and B, with the group B higher than the group A(all P<0.001). At 12 wk after treatment, the levels of IL-6, TNF-α and IL-1β in the tears of the three groups of patients were lower than those before treatment, with the group C lower than the group A and B, and the group B lower than the group A(all P<0.001). There was no statistical significant difference in the incidence of adverse reactions among the three groups of patients(P>0.05).CONCLUSION: The combined use of cyclosporine and lacrimal plug is safe and effective in improving the clinical symptoms of patients with moderate and severe dry eye, promoting the function of tear film and cornea, increasing tears secretion, and reducing the level of tear inflammatory factors.

Background::Adamantinomatous craniopharyngioma (ACP) is the commonest pediatric sellar tumor. No effective drug is available and interpatient heterogeneity is prominent. This study aimed to identify distinct molecular subgroups of ACP based on the multi-omics profiles, imaging findings, and histological features, in order to predict the response to anti-inflammatory treatment and immunotherapies.Methods::Totally 142 Chinese cases diagnosed with craniopharyngiomas were profiled, including 119 ACPs and 23 papillary craniopharyngiomas. Whole-exome sequencing (151 tumors, including recurrent ones), RNA sequencing (84 tumors), and DNA methylome profiling (95 tumors) were performed. Consensus clustering and non-negative matrix factorization were used for subgrouping, and Cox regression were utilized for prognostic evaluation, respectively.Results::Three distinct molecular subgroups were identified: WNT, ImA, and ImB. The WNT subgroup showed higher Wnt/β-catenin pathway activity, with a greater number of epithelial cells and more predominantly solid tumors. The ImA and ImB subgroups had activated inflammatory and interferon response pathways, with enhanced immune cell infiltration and more predominantly cystic tumors. Mitogen-activated protein kinases (MEK/MAPK) signaling was activated only in ImA samples, while IL-6 and epithelial-mesenchymal transition biomarkers were highly expressed in the ImB group, mostly consisting of children. The degree of astrogliosis was significantly elevated in the ImA group, with severe finger-like protrusions at the invasive front of the tumor. The molecular subgrouping was an independent prognostic factor, with the WNT group having longer event-free survival than ImB (Cox, P = 0.04). ImA/ImB cases were more likely to respond to immune checkpoint blockade (ICB) therapy than the WNT group ( P <0.01). In the preliminary screening of subtyping markers, CD38 was significantly downregulated in WNT compared with ImA and ImB ( P = 0.01). Conclusions::ACP comprises three molecular subtypes with distinct imaging and histological features. The prognosis of the WNT type is better than that of the ImB group, which is more likely to benefit from the ICB treatment.

OBJECTIVE To investigate the effect and mechanism of action of KRT8 small interfering RNA(si-KRT8)in exosomes derived from patient serum with hypopharyngeal carcinoma on chemosensitivity to 5-fluorouracil(5-FU)in human pharyngeal squamous cell carcinoma FaDu cell line.METHODS The cancerous tissues of hypopharyngeal cancer patients and The serum,cancerous tissues and paracancerous tissues of drug-resistant patients after treatment were collected.A 5-FU-resistant cell line of FaDu(FaDu/R)was constructed for subsequent experiments.Exosomes were isolated from patient serum by ultrafast gradient centrifugation,identified using transmission electron microscopy and Western blot(WB)techniques.si-KRT8 was encapsulated into exosomes(Exosome@si-KRT8)using electroporation technology and subsequently used to treat cells.Real-time fluorescence quantitative PCR(RT-qPCR)and WB were used to detect the expression levels of KRT8 in different tissues,exosomes after electroporation of si-KRT8,and FaDu cells,respectively.Cell counting kit-8(CCK-8),terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay,migration invasion technique and WB were used to detect the effects of Exosome@si-KRT8 on viability,apoptosis,and epithelial-mesenchymal transition of FaDu/R cells.RESULTS The expression level of KRT8 in drug-resistant tissues of hypopharyngeal carcinoma and FaDu/R cells was elevated compared with that in paraneoplastic tissues,cancer tissues and normal FaDu cells(t=15.79,P＜0.01).Isolated patient serum exosomes showed a double membrane structure and expressed both CD63 and TSG101 proteins,and KRT8 expression in exosomes was decreased after electro-transfection with si-KRT8(t=6.70,P＜0.01).Exosome@si-KRT8 inhibited KRT8 protein expression levels in FaDu/R cells(t=123.50,P＜0.01).Compared with the 5-FU group and the 5-FU+Exosome group,Exosome@si-KRT8 was able to inhibit the viability of FaDu/R cells(t=17.07,P＜0.01),promote the level of apoptosis in FaDu/R cells,and inhibit the expression of drug-resistance-associated proteins in FaDu/R cells(P-gp:t=103.20,MDR1:t=238.60,P＜0.01),and Exosome@si-KRT8 was able to suppress the expression of metastasis of FaDu/R cells(t=42.30,t=122.00,P＜0.01)and promoted the expression of E-cadherin while inhibiting the expression level of N-cadherin(t=130.80,t=83.90,P＜0.01).CONCLUSION Serum-derived exosome encapsulation of si-KRT8 enhances chemosensitivity of hypopharyngeal carcinoma cells and its mechanism of action may be related to inhibition of epithelial-mesenchymal transition.

By searching the literature on the application of entrustable professional activities in college education in China and globally, this article comprehensively analyzes the concept of entrustable professional activities, the development of evaluation items, the effectiveness of clinical application, the problems to be improved, and research prospects, so as to provide a useful reference for the reform and evaluation of competency-oriented medical education in China and the application of entrustable professional activities that can be repeated and promoted in clinical teaching.

Abstract OBJECTIVE Linezolid(LZD) is a synthetic oxazolidone antibacterial drug that has activity against most Gram positive bacteria. LZD is widely used in pediatric patients, and its common adverse reactions include gastrointestinal reactions and bone marrow suppression, etc. In recent years, LZD-induced hyperlactatemia has gradually attracted attention. LZD-induced hyperlactatemia can exacerbate the condition of pediatric patients and is associated with high mortality rates in children. However, there is currently a lack of data on the risk factors for LZD-induced hyperlactatemia in pediatric patients. METHODS Therefore, this paper collected and retrospectively analyzed the information of hospitalized pediatric patients who received LZD treatment at the Children's Hospital of Chongqing Medical University from October 2012 to February 2023, including demographic characteristics of pediatric patients and clinical treatment related records, etc. According to the inclusion and exclusion criteria, this paper identified whether the included pediatric patients had developed hyperlactatemia and evaluated the causal relationship between LZD and hyperlactatemia using the Naranjo's Scale. The risk factors were analyzed using univariate and multivariate logistic regression, and the dose-response relationship between risk factors and LZD-induced hyperlactatemia was further analyzed using a restricted cubic spline(RCS) model. RESULTS A total of 331 pediatric patients were included, of which 145 pediatric patients(43.8%) developed LZD-induced hyperlactatemia, including 122 cases of mild hyperlactatemia and 23 cases of severe hyperlactatemia; the causal relationship score of LZD-induced hyperlactatemia was “possibly related” in 87 cases(60.0%) and “highly likely related” in 58 cases(40.0%). The median age of pediatric patients was 3(0.92, 9) years old, with 55.29% males, 25.38% patients with liver disease, 8.76% pediatric patients with kidney disease, and 36.56% pediatric patients with cardiovascular disease; the median number of treatment days for pediatric patients receiving LZD was 13(8, 22) d, with pediatric patients with hyperlactatemia having a longer median number of LZD treatment days than those without hyperlactatemia[16(10, 28) vs 11(7, 18)]; 41.09% of pediatric patients used P-glycoprotein inducers in combination, with more pediatric patients(57.4%) experiencing hyperlactatemia; 53.47% of pediatric patients used P-glycoprotein inhibitors in combination; the median values of lactic acid baseline, creatinine baseline, and baseline estimated glomerular filtration rate(eGFR) were 0.92(0.80, 0.92)mmol·L-1, 26(18.25, 34.90) μmol·L-1, 179.97(137.23, 222.70)mL·min-1·(1.73 m)-2, respectively. Multivariate logistic regression analysis showed that pediatric patients received longer LZD treatment duration(OR=1.026, P=0.004), and the combination of P-glycoprotein inducers(OR=2.023, P=0.004), higher lactic acid baseline levels(OR=2.408, P=0.022), and lower eGFR(OR=0.997, P=0.047) were independent risk factors for LZD-induced hyperlactatemia. The RCS model showed that as the number of days of LZD treatment increases, the risk of LZD-induced hyperlactatemia increased nonlinearly(P-non-linear=0.041); when the lactic acid baseline value was -1, the risk of LZD-induced hyperlactatemia dramatically increased as the lactic acid baseline value increased, when it was >0.92 mmol·L-1, the risk of LZD-induced hyperlactatemia slowly increased as the lactic acid baseline value increased(P-non-linear=0.013). CONCLUSION This study explores for the first time the risk factors of LZD-induced hyperlactatemia in pediatric patients, including the impact of the interaction between LZD and drugs that affect mitochondrial function, P-glycoprotein inducers, and P-glycoprotein inhibitors on hyperlactatemia. RCS models are used to analyze the dose-response relationships between LZD treatment days, lactic acid baseline values, and the occurrence of LZD-induced hyperlactatemia. When LZD is combined with P-glycoprotein inducers(mainly isoniazid, rifampicin, and ethambutol), the risk of LZD-induced hyperlactatemia increases, and its related mechanisms still need further research. In addition, pediatric patients with renal insufficiency may need to adjust the LZD dosage appropriately to avoid the occurrence of hyperlactatemia. In conclusion, when pediatric patients receive LZD treatment, attention should be paid to risk factors such as lactic acid baseline value, duration of LZD use, combined use of P-glycoprotein inducers, and renal dysfunction, in order to prevent the occurrence of LZD-induced hyperlactatemia based on the pediatric patient's treatment needs.

Objective:To summarize the clinical manifestations and gene mutation features of patients with nucleotide excision repair (NER) disorders.Methods:A retrospective analysis was made on clinical data of patients with NER disorders who were admitted to the Chinese People′s Liberation Army General Hospital from October 2008 to February 2022 and diagnosed in the Outpatient Department of Beijing Children′s Hospital, Capital Medical University from October 2015 to February 2022.Literature on previously reported Chinese patients with NER disorders was reviewed.Results:(1)A total of 16 patients with NER disorders were enrolled, including 6 males and 10 females.The onset age was 7.5 (4.0, 12.0) months and the age at diagnosis was 42.0 (21.5, 77.0) months.There were 3 types of NER disorders: Cockayne syndrome (CS) in 13 cases, Xeroderma Pigmentosum (XP) in 2 cases and Cerebro-Oculo-Facio-Skeletal syndrome (COFS) in 1 case.Four disease-causing genes were detected: CSA gene in 11 cases, CSB gene in 3 cases, XPG gene in 1 case, and XPD gene in 1 case.The first symptoms of the 16 patients were photosensitivity and developmental delay, and neurological symptoms were observed in all the 3 NER disorder types.XP and CS patients had skin symptoms.CS patients presented typical facial features, visual and auditory impairment, microcephaly and changes in neuroimaging features.COFS patients showed intrauterine growth retardation.(2)Results of literature review: a total of 96 Chinese patients reported were retrieved, involving 6 disease types, including CS in 45 cases, XP in 44 cases, trichothiodystrophy in 4 cases, COFS in 1 case, XP-CS in 1 case, and ultraviolet sensitive syndrome in 1 case.Nine mutated genes were identified: CSA in 33 cases, XPA in 15 cases, CSB in 13 cases, XPV in 10 cases, XPC in 9 cases, XPG in 7 cases, XPD in 7 cases, XPF in 1 case, and MPLKIP in 1 case.The common symptoms were growth failure (62 cases), skin photosensitivity (61 cases), typical facial features (52 cases), mental retardation (49 cases) and microcephaly (48 cases). Among 36 cases had imaging data 33 cases(91.7%)had calcification of basal nucleus or globus pallidus.Three cases had intrauterine growth retardation and microcephaly during pregnancy. Conclusions:Patients with such prenatal manifestations as intrauterine growth retardation and microcephaly or with typical symptoms like skin photosensitivity, typical facial features, growth failure, mental retardation, hypertonia, and calcifications of basal ganglia should be suspected of NER disorders.Early genetic testing is recommended to confirm the diagnosis.

【Objective】 To understand the current situation of blood components distribution in domestic prefecture-level blood stations through analyzing the components distribution data of 24 prefecture-level blood stations in China. 【Methods】 The data of components distribution of 24 blood stations from 2017 to 2020 as well as the data of blood deployment of 24 blood stations from 2019 to 2020 were collected and analyzed. 【Results】 From 2017 to 2020, positive annual growth in red blood cells, plasma and cryoprecipitate was observed in 22, 19 and 15 out of the 24 blood stations, and the annual growth median rate of above three components was 5.24%, 3.80% and 3.25%, respectively. Among the 24 prefecture-level blood stations, 23 carried out the preparation of cryoprecipitate. 【Conclusion】 The distribution of red blood cells, cryoprecipitate and plasma in prefecture-level blood stations is increasing year by year. However, there is a overstock of plasma, and most blood stations need blood employment.

Birth cohort is an important platform to study the effect of early-life exposure on health outcome, but large cohorts to investigate the effect of preconception exposure, especially paternal exposure, on reproductive health and birth outcome are limited. The Preconception Reproductive Health and Birth Outcome Cohort (PREBIC) is a prospective birth cohort study which pays equal attention to the contribution of environmental, psychological, behavioral as well as other factors to reproductive health and adverse birth outcomes in both men and women in Chongqing, China. PREBIC started in 2019 and plans to recruit 20 800 reproductive-age couples with child-bearing willingness. Followed up was conducted to understand the conception status of the women within two years. Women in pregnancy would be visited at first, second, third trimesters and after delivery. The offspring would be monitored until 2 years old to understand the incidences of preterm birth, low birth weight, birth defects, neurodevelopmental disorders and other outcomes. Related information and biospecimen collections (including semen, peripheral blood, urine, placenta, umbilical cord, cord blood and oral swab) were scheduled in each period. By January 2022, PREBIC had recruited 8 698 participants from all 38 districts in Chongqing. The goal of PREBIC is to establish one of the largest prospective preconception birth cohorts covering both men and women, which might provide a unique insight to understand the effects of the full reproductive cycle on reproductive health and adverse outcomes, with especial emphasis on preconception exposures.

Objective:To explore the associations of platelet parameters platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (PCT) with the risk for stroke in people with different blood pressure levels.Methods:All the participants were from Dongfeng-Tongji cohort, including 38 295 retired employees from Dongfeng Motor Corporation at the first follow-up survey. After excluding participants with coronary heart disease, stroke, cancer, history of platelet influential drug use and those with missed data of platelet parameters or blood pressure or lost to follow-up, finally a total of 21 294 participants were included in this study. All the participants completed baseline questionnaires, physical examinations, clinical biochemical tests, and blood sample collection. Cox proportional hazard models were used to estimate the hazard ratios ( HRs) and the corresponding 95% confident intervals ( CIs) for the associations between platelet parameters and risk for stroke in people with different blood pressure levels. Results:After a mean follow-up of 8.0 years, 1 578 participants developed incident stroke [1 266 ischemic stroke (IS) cases and 312 hemorrhagic stroke (HS) cases]. Compared with the participants with PLT<188×10 9/L, those with PLT≥188×10 9/L among hypertension cases were significantly associated with higher risks for stroke and IS (stroke: HR=1.27, 95% CI: 1.12-1.44; IS: HR=1.39, 95% CI: 1.21-1.60). Among hypertension group, compared with participants with PCT<0.165%, PCT≥0.165% were significantly associated with higher risk for stroke ( HR=1.15, 95% CI: 1.01-1.30) and lower risk for HS ( HR=0.70, 95% CI: 0.53-0.93); Among non-hypertension and hypertension group, PCT ≥0.165% were significantly associated with higher risks of IS ( HR=1.27, 95% CI: 1.05-1.54; HR=1.31, 95% CI: 1.14-1.50). MPV and PDW were not significantly associated with risk for stroke. Risk for stroke increased significantly in hypertension cases with different platelet parameters levels compared with non-hypertension cases with lower levels of each platelet parameters. Conclusion:Higher levels of PLT and PCT could increase the risks for stroke and IS in middle-aged and elderly hypertension patients, and lower levels of PCT could decrease the risk for HS in hypertension patients.

Objective:To describe the characteristics and the survival status of pneumoconiosis cases reported in Guangzhou City from 1958 to 2018, and to investigate the epidemiological trends of pneumoconiosis. This study is aiming to provide basic data for formulating the guidelines and policies for control of pneumoconiosis, and for evaluating the control effects of pneumoconiosis.Methods:From July 2019 to January 2020, based on the data collected in the pneumoconiosis case cards and database as well as the retrospective follow-up investigate of pneumoconiosis cases, we conducted a descriptive analysis for all the new cases of pneumoconiosis reported from 1958 to 2018 in Guangzhou City. The statistical indices included the number of new pneumoconiosis cases in each decade, types of pneumoconiosis, regional and industrial distributions, survival status, and the change tendency of the diagnosis age and the dust exposure time of pneumoconiosis cases.Results:From 1958 to 2018, a total of 1194 new cases of pneumoconiosis were reported in Guangzhou City, including 1147 males (96.1%) and 47 females (3.9%) . Silicosis (60.1%, 718/1194) and welder's pneumoconiosis (21.5%, 257/1194) were the main types of pneumoconiosis. The top three districts for reporting new cases were Huangpu District (29.0%, 346/1194) , Nansha District (12.6%, 151/1194) and Baiyun District (11.1%, 132/1194) , respectively. The top three industries for reporting new cases were civil engineering construction industry (25.0%, 298/1194) , railway ship aerospace and other transportation equipment manufacturing industry (16.1%, 192/1194) and non-metal mining industry (15.7%, 187/1194) . The diagnosis age for new cases was 47.8 (23.6-79.1) years old, and the dust exposure time was 12.3 (0.4-49.1) years. Both of these two statistical indicators rose first and fell later from 1958 to 2018. As of December 31, 2019, a total of 963 new cases of pneumoconiosis were followed up, of which 467 (48.5%) survived, mainly silicosis (41.3%, 193/467) and welder's pneumoconiosis (43.3%, 203/467) . 496 cases (51.5%) died, and the age of death was 69.9 (32.4-96.9) years old.Conclusion:According to the epidemiological characteristics of pneumoconiosis in Guangzhou, we should focus on key districts and industries in the prevention and control of pneumoconiosis. Besides, the staffs in the occupational disease diagnosis institutions should try the best to collect the complete dust exposure data of new cases of pneumoconiosis. Moreover, the health administrative departments should pay more attention to the management of pneumoconiosis death case reports.