Purpose: This study was aimed to investigate long-term survivals and toxicities of early-stage nasopharyngeal carcinoma (NPC) in endemic area, evaluating the role of chemotherapy in stage II patients. Materials and Methods: Totally 187 patients with newly diagnosed NPC and restaged American Joint Committee on Cancer/ International Union Against Cancer 8th T1-2N0-1M0 were retrospectively recruited. All received intensity-modulated radiotherapy (IMRT)±chemotherapy (CT) from 2001 to 2010. Results: With 15.7-year median follow-up, 10-year locoregional recurrence-free survival, distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were 93.3%, 93.5%, 92.9% and 88.2%, respectively. Multivariable analyses showed cervical lymph nodes positive and pre-treatment prognostic nutritional index ≥ 52.0 could independently predict DMFS (p=0.036 and p=0.011), DSS (p=0.014 and p=0.026), and OS (p=0.002 and p < 0.001); Charlson comorbidity index < 3 points could predict DSS (p=0.011); age > 45 years (p=0.002) and pre-treatment lactate dehydrogenase ≥ 240 U/L (p < 0.001) predicted OS. No grade 4 late toxicity happened; grade 3 late toxicities included subcutaneous fibrosis (4.3%), deafness or otitis (4.8%), skin dystrophy (2.1%), and xerostomia (1.1%). No differences on survivals were shown between IMRT+CT vs. IMRT alone in stage II patients, even in T2N1M0 (p > 0.05). Unsurprising, patients in IMRT+CT had more acute gastrointestinal reaction, myelosuppression, mucositis, late ear toxicity, and cranial nerve injury (all p < 0.05) than IMRT alone group. Conclusion Superior tumor control and satisfying long-term outcomes could be achieved with IMRT in early-stage NPC with mild late toxicities. As CT would bring more toxicities, it should be carefully performed to stage II patients.

OBJECTIVE: To explore the relationship between drug treatment and outcomes in patients with late-onset severe pneumonia (LOSP) after allogeneic stem cell transplantation (allo-SCT). METHODS: We retrospectively analyzed the effects of the initiation time of treatment drugs, especially antiviral drugs and glucocorticoids on the clinical outcomes in 82 patients between January 2016 and August 2021 who developed LOSP after allo-SCT in Peking University People's Hospital. Univariate analysis was performed by Mann-Whitney U test and χ² test, and multivariate analysis was performed by Logistic regression. When multiple groups (n>2) were involved in the χ² test, Bonferroni correction was used for the level of significance test. RESULTS: Of all 82 patients in this study, the median onset time of LOSP was 220 d (93-813 d) after transplantation, and the 60-day survival rate was 58.5% (48/82). The median improvement time of the survival patients was 18 d (7-44 d), while the median death time of the died patients was 22 d (2-53 d). Multivariate analysis showed that the initiation time of antiviral drugs from the onset of LOSP (< 10 d vs. ≥10 d, P=0.012), and the initiation time of glucocorticoids from antiviral drugs (< 10 d vs. ≥10 d, P=0.027) were the factors affecting the final outcome of the patients with LOSP at the end of 60 d. According to the above results, LOSP patients were divided into four subgroups: group A (antiviral drugs < 10 d, glucocorticoids ≥10 d), group B (antiviral drugs < 10 d, glucocorticoids < 10 d), group C (antiviral drugs ≥10 d, glucocorticoids ≥10 d) and group D (antiviral drugs ≥10 d, glucocorticoids < 10 d), the 60-day survival rates were 91.7%, 56.8%, 50.0% and 21.4%, respectively. CONCLUSION Our study demonstrated that in patients who developed LOSP after allo-SCT, the initiation time of antiviral drugs and glucocorticoids were associated with the prognosis of LOSP, and the survival rate was highest in patients who received antiviral drugs early and glucocorticoids later. It suggested that for patients with LOSP of unknown etiology should be highly suspicious of the possibility of a secondary hyperimmune response to viral infection.
Antiviral Agents/therapeutic use* ; Glucocorticoids/therapeutic use* ; Hematopoietic Stem Cell Transplantation/methods* ; Humans ; Pneumonia/etiology* ; Prognosis ; Retrospective Studies ; Transplantation, Homologous/adverse effects*

Objective Focused cardiac ultrasound (FCU) and lung ultrasound (LU) are increasingly being used in critically ill patients. This study aimed to investigate the effect of FCU in combination with LU on these patients and to determine if the timing of ultrasound examination was associated with treatment change. Methods This is a multicenter cross-sectional observational study. Consecutive patients admitted to the intensive care unit (ICU) were screened for enrollment. FCU and LU were performed within the first 24 h, and treatment change was proposed by the performer based on the ultrasound results and other clinical conditions. Results Among the 992 patients included, 502 were examined within 6 h of ICU admission (early phase group), and 490 were examined after 6 h of admission (later phase group). The early phase group and the later phase group had similar proportions of treatment change (48.8%
Critical Illness ; Cross-Sectional Studies ; Echocardiography ; Humans ; Intensive Care Units ; Lung/diagnostic imaging* ; Retrospective Studies

Whether direct manipulation of Parkinson's disease (PD) risk genes in the adult monkey brain can elicit a Parkinsonian phenotype remains an unsolved issue. Here, we used an adeno-associated virus serotype 9 (AAV9)-delivered CRISPR/Cas9 system to directly co-edit PINK1 and DJ-1 genes in the substantia nigras (SNs) of two monkey groups: an old group and a middle-aged group. After the operation, the old group exhibited all the classic PD symptoms, including bradykinesia, tremor, and postural instability, accompanied by key pathological hallmarks of PD, such as severe nigral dopaminergic neuron loss (>64%) and evident α-synuclein pathology in the gene-edited SN. In contrast, the phenotype of their middle-aged counterparts, which also showed clear PD symptoms and pathological hallmarks, were less severe. In addition to the higher final total PD scores and more severe pathological changes, the old group were also more susceptible to gene editing by showing a faster process of PD progression. These results suggested that both genetic and aging factors played important roles in the development of PD in the monkeys. Taken together, this system can effectively develop a large number of genetically-edited PD monkeys in a short time (6-10 months), and thus provides a practical transgenic monkey model for future PD studies.
Animals ; Brain ; CRISPR-Cas Systems/genetics* ; Dependovirus/genetics* ; Haplorhini ; Phenotype ; Protein Kinases/genetics*

Whether direct manipulation of Parkinson’s disease (PD) risk genes in the adult monkey brain can elicit a Parkinsonian phenotype remains an unsolved issue. Here, we used an adeno-associated virus serotype 9 (AAV9)-delivered CRISPR/Cas9 system to directly co-edit PINK1 and DJ-1 genes in the substantia nigras (SNs) of two monkey groups: an old group and a middle-aged group. After the operation, the old group exhibited all the classic PD symptoms, including bradykinesia, tremor, and postural instability, accompanied by key pathological hallmarks of PD, such as severe nigral dopaminergic neuron loss (>64%) and evident α-synuclein pathology in the gene-edited SN. In contrast, the phenotype of their middle-aged counterparts, which also showed clear PD symptoms and pathological hallmarks, were less severe. In addition to the higher final total PD scores and more severe pathological changes, the old group were also more susceptible to gene editing by showing a faster process of PD progression. These results suggested that both genetic and aging factors played important roles in the development of PD in the monkeys. Taken together, this system can effectively develop a large number of genetically-edited PD monkeys in a short time (6–10 months), and thus provides a practical transgenic monkey model for future PD studies.

Whether and how garlic-derived -allylmercaptocysteine (SAMC) inhibits hepatocellular carcinoma (HCC) is largely unknown. In the current study, the role of low-density lipoprotein receptor (LDLR)-related protein 6 (LRP6) in HCC progression and the anti-HCC mechanism of SAMC was examined in clinical sample, cell model and xenograft/orthotopic mouse models. We demonstrated that SAMC inhibited cell proliferation and tumorigenesis, while induced apoptosis of human HCC cells without influencing normal hepatocytes. SAMC directly interacted with Wnt-pathway co-receptor LRP6 on the cell membrane. LRP6 was frequently over-expressed in the tumor tissue of human HCC patients (66.7% of 48 patients) and its over-expression only correlated with the over-expression of -catenin, but not with age, gender, tumor size, stage and metastasis. Deficiency or over-expression of LRP6 in hepatoma cells could partly mimic or counteract the anti-tumor properties of SAMC, respectively. administration of SAMC significantly suppressed the growth of Huh-7 xenograft/orthotopic HCC tumor without causing undesirable side effects. In addition, stable down-regulation of LRP6 in Huh-7 facilitated the anti-HCC effects of SAMC. In conclusion, LRP6 can be a potential therapeutic target of HCC. SAMC is a promising specific anti-tumor agent for treating HCC subtypes with Wnt activation at the hepatoma cell surface.

Objectives: This study aimed to observe the change of arachidonic acid-induced platelet aggregation rate (AA-Ag) and short-term adverse reactions after taking 50 or 100 mg/d aspirin(enteric-coated sustained-release formulation) or 100 mg/d aspirin (enteric-coated aspirin tablet)in the elderly Chinese population (aged 60 years or older). Methods: A total of 1 194 participants aged 60 or older, who should be recommended to take aspirin therapy due to medical reasons, were recruited and randomly assigned into three groups to receive enteric-coated sustained-release aspirin tablet (50 mg, once daily, group A), or 100 mg, once daily (group B) or enteric-coated aspirin tablet 100 mg once daily (group C), respectively. AA-Ag was measured after (14±3)days of aspirin treatment. Adverse events and bleeding events were recorded during the (28±3)days of follow-up. Results: The AA-Ag in group A (n=347), B (n=338) and C (n=332) post 14-day aspirin therapy were 6.65 (4.03,10.84)%, 5.89(3.22,10.03) % and 6.00(3.68,10.09) %, respectively (P>0.05). During the 28 days follow-up, the adverse events rate of group A (n=388), B (n=387) and C (n=385) was 3.87%,3.36%, and 7.95%, and the mild bleeding events rate was 3.09%, 2.33%, and 6.23%, respectively. Adverse events rate and mild bleeding events rate were significantly higher in group C than in group A and B (P<0.05). Conclusions: Compared with 100 mg-dose aspirin, 50 mg-dose aspirin achieves similar anti-platelet aggregation effect in this elderly Chinese population. The short-term adverse events and mild bleeding risk of aspirin with enteric-coated sustained-release formulation were fewer than that of enteric-coated formulation.

Objective: To investigate the current status of depression and anxiety among female staff in a maternal and child health hospital, and to provide a basis for developing related prevention and intervention measures and promoting the mental health of female staff. Methods: The female staff from a provincial maternal and child health hospital completed a psycho-health questionnaire survey on Internet from June to October, 2016. The questionnaires used in the survey consisted of Patient Health Questionnaire (PHQ-9) , Generalized Anxiety Disorder Scale (GAD-7) , and Symptom Checklist-90 (SCL-90) . The distribution features of mental health problems such as depression and anxiety were analyzed according to the results: of the questionnaire survey. Results Of all female staff surveyed, 42.04% showed depression symptoms, 28.90% showed anxiety symptoms, and 26.12% showed comorbid symptoms of depression and anxiety. Moderate or severe depression (anxiety) was mainly distributed among the female staff with comorbid symptoms (90.63% and 97.01%, respectively) . There were significant differences in the distribution of moderate or severe anxiety symptoms between the medical staff and nursing staff (χ²= 5.81, P=0.05) and between those with intermediate and junior professional titles (χ²=7.99, P=0.018) . As for SCL-90 results, the total score, total average score, and scores on factors of somatization, compulsion, interpersonal sensitivity, depression, and anxiety in the female staff with comorbid symptoms, moderate or severe depression, and moderate or severe anxiety were significantly higher than the national norm (P<0.01) , while the scores on paranoid and psychotic factors were significantly lower than the national norm (P<0.01) . The numbers of cases of positive factors were significantly higher in the female staff with comorbid symptoms than in the female staff with a single symptom and asymptomatic female staff (both P<0.01) , and positive cases were mainly distributed in depression, interpersonal sensitivity, compulsion, anxiety, and somatic factors. Conclusion The prevalence of depression and anxiety is high among female staff in the maternal and child health hospital, mainly characterized by comorbid symptoms of moderate or severe depression and anxiety. Comorbidity is accompanied by mental health problems such as interpersonal sensitivity, obsessive compulsion, and physical discomfort. Corresponding measures are needed for the prevention and intervention of mental health problems among female staff in the maternal and child health hospital.

Objective: To investigate the current status of reproductive health among the female medical staff in a provincial maternal and child health hospital and analyze the occupational influencing factors for reproductive health, particularly the effects of high-intensity work, work shift, chemical poisons, and physical and biological factors on reproductive health, and to provide a scientific basis for developing related intervention measures and promoting the reproductive health of professional females. Methods: A reproductive health questionnaire was designed in terms of age, type of work, professional title, education level, working hours, working strength, and the reproductive health of female staff to analyze the current status of reproductive health, working strength, and occupational hazardous factors. The female medical staff in the provincial maternal and child health hospital completed the questionnaire on the internal network of the hospital voluntarily. Results: Of all respondents, 19.46% had a history of miscarriage, 5.90% visited the hospital due to infertility, 21.31% had irregular menstruation within the last 3 months, and 30.57% had reproductive system disease; 72.28% of the investigated medical staff often worked at night, 47.25% often worked overtime (more than 3 days a week) , and 22.27% worked over 8 hours daily. The respondents who often worked overtime had a significantly higher prevalence of reproductive system disease than those who did not often work overtime (χ²= 58.65, P<0.01) . The respondents who often worked at night had a significantly higher rate of miscarriage than those who did not work at night (χ²=41.57, P<0.01) . In all respondents, 87.08% were often exposed to chemical injuries such as disinfectants, and 78.15% had contact with noise, radiation, and other physical injuries; the medical staff exposed to chemical and physical injuries had a significantly higher proportion of individuals with a history of miscarriage than the unexposed staff (χ²=10.04, P<0.01; χ²=13.30, P<0.01) . Conclusion Much attention should be paid to the reproductive health of female medical staff in the provincial maternal and child health hospital, who have high working strength. The occupational hazard factors can be avoided by reasonably arranging the work schedule and creating a supportive environment to improve the reproductive health of female medical staff.

Objective To understand the pathogenic distribution and epidemiological trend of hand-foot-and-mouth disease (HFMD),and provide evidence for the prevention and control of HFMD.Methods Children who were diagnosed with HFMD in a hospital between January and December 2015 were investigated,real time fluorescence PCR was used to detect enterovirus universal type EV,enterovirus 71 (EV71),and Coxsackievirus A16 (CoxA16) in specimens from children with HFMD.Positive rates and distribution of various types of EV among children of different months,genders,age groups,and infection types were analyzed.Results A total of 837 throat swab specimens from HFMD children were collected in 2015,380 (45.40％) of which were EV positive specimens.Virus typing showed that 110 (28.95 ％),7 (1.84 ％),6(1.58 ％),and 257(67.63 ％) were positive specimens for EV71,CoxA16,EV71 + CoxA16,and other types of EV.HFMD had a high prevalence since April,reached a peak in May-June,and remained high incidence in July-December.Positive rates of EV in children of different months were statistically different (P＜0.05).The age of onset was mainly in children under 3 years.Positive rates of EV and constitute ratios of different types of EV in children of different age groups were all statistically different (all P＜0.05).The positive rate of EV in severe HFMD cases was higher than common cases (65.34％ vs 27.06％,P＜0.001).The proportion of severe cases in children with EV71 infection and other types of EV infection were 90.00％ and 60.70％ respectively;children with EV71 + CoxA16 double infection were all severe cases.Constitute of EV types in children with different infection types was statistically different(P＜0.001).Conclusion In 2015,EV infection in hospitalized children with HFMD in this hospital was mainly caused by other types of EV (nonEV71 and non-CoxA16),the high prevalence season,high-risk population under 3 years of age,and severe cases should be paid high attention,prevention and treatment should be performed well.