Objective:To systematically evaluate the clinical efficacy of melatonin for neonatal hypoxic-ischemic encephalopathy (HIE).Methods:From the inception of the databases to December 1, 2022, randomized controlled trials (RCTs) and cohort studies on the use of melatonin for HIE were searched in the following databases: PubMed, Web of Science, Cochrane library, Embase, Chinese Medical Journal Full-text Database, CNKI, Wanfang Database and VIP Database. Meta-analysis, literature risk assessment and sensitivity analysis were conducted using R4.2.2 software and RevMan5.4 software.Results:A total of 4 eligible RCTs were found, including 155 patients. Meta-analysis showed that melatonin could reduce the mortality rate ( RR=0.336, 95% CI0.157-0.718, P=0.005) and white blood cell count in HIE infants ( MD=-1.74, 95% CI -3.404--0.079, P=0.040). Sensitivity analysis showed that the Meta-analysis results were generally stable after excluding the studies one by one. Conclusions:Current evidence shows that melatonin can reduce mortality in HIE infants. However, the included studies have high risk of bias and small sample sizes. More high-quality studies are still needed.

OBJECTIVES: The aim of this study was to evaluate the disease burden of prostate cancer (PC) and assess key influencing factors associated with the disease expenditures of PC in the United States. METHODS: The total deaths, incidence, prevalence, and disability-adjusted life-years of PC were obtained from the Global Burden of Disease Study 2019. The Medical Expenditure Panel Survey was used to estimate healthcare expenditures and productivity loss and to investigate patterns of payment and use of healthcare resources in the United States. A multivariable logistic regression model was conducted to identify key factors influencing expenditures. RESULTS: For patients aged 50 and older, the burden for all age groups showed a modest increase over the 6-year period. Annual medical expenditures were estimated to range from US$24.8 billion to US$39.2 billion from 2014 to 2019. The annual loss in productivity for patients was approximately US$1,200. The top 3 major components of medical costs were hospital inpatient stays, prescription medicines, and office-based visits. Medicare was the largest source of payments for survivors. In terms of drug consumption, genitourinary tract agents (57.0%) and antineoplastics (18.6%) were the main therapeutic drugs. High medical expenditures were positively associated with age (p=0.005), having private health insurance (p=0.016), more comorbidities, not currently smoking (p=0.001), and patient self-perception of fair/poor health status (p<0.001). CONCLUSIONS From 2014 to 2019, the national real-world data of PC revealed that the disease burden in the United States continued to increase, which was partly related to patient characteristics.

Alzheimer's disease （AD） is a common degenerative disease of the central nervous system in the elderly， with memory impairment and behavioral changes as the main clinical manifestations. Modern research has demonstrated that many herbs with both medicinal and edible values have anti-oxidation and anti-aging activities. In addition， these herbs are naturally safe and play a role in disease prevention and health care. The 110 medicinal and edible herbs announced by the National Health Commission of the People's Republic ofChina in 2021 were studied. The relevant papers published in the last five years were searched against CNKI， VIP， Wanfang Data， PubMed and other databases. The effects， mechanism， and active ingredients of the medicinal and edible herbs against Alzheimer's disease were summarized. The results showed that more than 30 herbs including Ginseng Radix et Rhizoma， Curcumae Longae Rhizoma， Astragali Radix， Corni Fructus， Gastrodiae Rhizoma， Angelicae Sinensis Radix， Cistanches Herba， Croci Stigma， Glycyrrhizae Radix et Rhizoma， Ganoderma and their active ingredients were effective in the prevention and treatment of Alzheimer's disease. Among them， ten herbs that met the requirements were screened out for analysis. The medicinal and edible herbs and their active ingredients can act on multiple targets and treat Alzheimer's disease via multiple signaling pathways such as nuclear factor-κB （NF-κB）， mitogen-activated protein kinase 5 （MEK5）/extracellular signal-regulated kinase 5 （ERK5）， cytochrome C （CytC） and cysteine aspartate-specific protease （Caspase）-3/（Caspase）-9， Wnt/β-catenin， and brain-derived neurotrophic factor （BDNF）/tyrosine kinase receptor B （TrkB）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）， thus improving learning， cognitive ability， and memory ability. Most of the medicinal and edible herbs have the tropism to the heart， spleen， liver， and kidney meridians and tonifying effect.

Objective:To investigate the effects of osteocalcin (BGP) on bone growth and development and the expression levels of related hormones in offspring rats under the intervention of sodium fluoride.Methods:Twenty-four clean female SD rats and 24 clean male SD rats were selected, weighing 180-220 g, and the rats were mated in a 1∶1 cage for 10 d. The fluorosis rat model was established by drinking the fluorosis water method, female rats were divided into 3 groups according to body weight by random number table method, each group of 8 rats, including the high-dose, low-dose and control groups, with sodium fluoride of 200, 100, 0 mg/L in drinking water. The female rats were exposed to fluoride from the 0th day of pregnancy to the 3rd week after the offspring rats were born (before weaning). After weaning, 10 male offspring rats were selected from each group and continued to be exposed to fluoride in the same amount and manner until the 12th week after birth. The body weight and length of the offspring rats were measured every week before weaning and every two weeks after weaning. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum BGP, parathyroid hormone (PTH), calcitonin (CT), and alkaline phosphatase (ALP) contents in the offspring rats of each group exposed to fluoride for 12 weeks.Results:In the 2nd week of fluoride exposure, the body weights [(27.25 ± 3.57), (26.27 ± 4.48) g] and body lengths [(6.92 ± 0.46), (6.50 ± 0.54) cm] of the low-dose and high-dose groups were lower than those of the control group [(31.32 ± 3.62) g, (7.19 ± 0.26) cm, P < 0.05], but there were no significant differences in body weights and lengths between the high-dose group and the low-dose group ( P > 0.05). From the 3rd week of fluoride exposure, the body weight and length of the high-dose group were lower than those of the low-dose group and the control group ( P < 0.05). Serum BGP, PTH and ALP contents [(5.42 ± 0.26) mg/L, (157.53 ± 32.21) ng/L, (36.62 ± 6.01) U/L] in the control group were lower than those of the low-dose group [(6.15 ± 0.29) mg/L, (212.26 ± 51.97) ng/L, (50.68 ± 6.11) U/L] and high-dose group [(7.31 ± 0.77) mg/L, (274.21 ± 60.32) ng/L, (74.99 ± 9.08) U/L], and CT content [(182.40 ± 17.39) ng/L] was higher than those of the low-dose and high-dose groups [(135.77 ± 14.06), (70.09 ± 13.49) ng/L], and the differences were statistically significant ( P < 0.05); serum BGP, PTH and ALP contents in the high-dose group were higher than those in the low-dose group, and the CT content was lower than that in the low-dose group ( P < 0.05). Conclusion:Sodium fluoride may be involved in regulating the expression of related hormones by promoting the secretion of BGP, thereby affecting the bone growth and development of offspring rats.

Objective:To investigate the effects of different doses of fluoride on vascular endothelial injury in rats.Methods:Thirty clean male SD rats of 2 - 3 months old were selected, with body mass of 180 - 220 g. According to body mass, they were divided into three groups by random number table. The rat model of fluorosis was established by drinking water intoxication. According to the concentration of sodium fluoride in drinking water, the three dosage groups were blank control group (0 mg/L of sodium fluoride), low dose group (100 mg/L of sodium fluoride), and high dose group (200 mg/L of sodium fluoride), with 10 rats in each group. The rats were continuously exposed to fluoride for 12 weeks, and their body mass was measured every 2 weeks. After 12 weeks of fluoride exposure, the levels of serum osteocalcin (BGP), endothelin-1 (ET-1), intercellular adhesion factor-1 (ICAM-1), interleukin-6 (IL-6) and adiponectin (APN) were measured by enzyme-linked immunosorbent assay (ELISA). The ultrastructure of vascular endothelium in rats was observed by transmission electron microscopy.Results:At the 4th week of fluoride exposure, the body mass of rats in the blank control group was higher than that of the fluoride-exposed groups [(306.90 ± 19.13), (280.31 ± 18.44), (269.03 ± 17.47) g, P < 0.05], but there was no significant difference between the low dose group and the high dose group ( P > 0.05). From the 6th week of fluoride exposure, the body mass of rats in the blank control group was higher than that in the fluoride-exposed groups [(377.40 ± 23.72), (329.50 ± 21.78), (306.75 ± 27.09); (422.89 ± 32.23), (368.90 ± 23.79), (343.00 ± 18.41); (450.00 ± 29.26), (395.17 ± 28.22), (362.99 ± 21.77); (473.20 ± 28.43), (409.27 ± 29.95), (371.76 ± 21.65) g, P < 0.05], while that in the high dose group was lower than that in the low dose group ( P < 0.05). After 12 weeks of fluoride exposure through drinking water, the levels serum BGP, ET-1, ICAM-1 and IL-6 in blank control group were lower than those in fluoride-exposed groups ( P < 0.05), and the serum APN was higher than that in fluoride-exposed groups ( P < 0.05); while the levels of serum BGP, ET-1, ICAM-1 and IL-6 in high dose group were higher than those in low dose group, and the level of serum APN was lower than that in low dose group ( P < 0.05). Compared with the blank control group, the external processes of vascular endothelial cells in the low dose group were not standardized, the endothelial cells were not closely connected with the basement membrane, and the vacuoles were obvious. In the high dose group, the endothelial cells became short or detached; the content of heterochromatin increased significantly, the endothelial cells dropped into the vascular cavity, and with endothelial cells apoptosis. Conclusion:High fluoride can cause vascular endothelial injury.

Objective Parkinson's disease (PD) is a common degenerative disease of the central nervous system.The main pathological feature is the reduction of dopaminergic neurons,which induces motion symptoms such as resting tremor,muscle rigidity,bradykinesia,and postural disorder.The etiology and pathogenesis of PD are complex and related to a variety of factors.The current pathogenesis is related to mitochondrial dysfunction,oxidative stress,neuroinflammatory response,apoptosis,and autophagy.The early onset of PD is occult and the rate of misdiagnosis is high.It requires a new simple,safe,and effective early diagnosis method.The current methods of early diagnosis mainly include clinical non-motor symptoms,biomarkers,and imaging examination methods.

Objective To evaluate the safety and efficacy of the combined treatment with an optimized intense pulsed light (IPL) and a non-ablative fractional laser (NAFL) for facial rejuvenation.Methods A prospective,split-face,randomized,controlled study was conducted.A total of 22 testees with facial photoaging,who aged from 35 to 55 years,were enrolled into this study from the Department of Dermatology of Peking University First Hospital between March and June in 2017.By a random number table,the two sides of each testee's face were randomized to receive combined treatment with optimized IPL immediately followed by non-ablative 1 565 nm Erbium:Glass fractional laser (combined treatment group) or non-ablative 1 565 nm Erbium:Glass fractional laser alone (NAFL group) once every month for 3 sessions.Before the treatment,60 and 90 days after the treatment (1 month after the second and third treatment respectively),photos of the treatment regions were taken,skin physiology parameters (including skin melanin,erythema indices,water content of the stratum corneum,transepidermal water loss [TEWL],skin flexibility and glossiness) were measured,and subjective and objective clinical evaluation was carried out.After each treatment,adverse reactions were assessed by two dermatologists independently,including facial erythema,swelling and crusting,desquamation,pigmentation and pains.Results During the treatment course,1 testee dropped out due to pains,another 1 testee dropped out for personal reasons,and 20 testees completed the treatment and follow-up.The combined treatment group showed significantly decreased melanin indices on days 60 and 90 (152.9 ± 36.9 and 155.0 ± 38.1,respectively) compared with that before the treatment (168.4 ± 41.3,F =5.321,P ＜ 0.05).On day 60,the melanin index was significantly lower in the combined treatment group than in the NAFL group (159.4 ± 35.3,P ＜ 0.05).However,the melanin indices on days 60 and 90 in the NAFL group (159.4 ± 35.3,156.7 ± 36.3) did not significantly differ from that before the treatment (165.9 ± 35.4,P ＞ 0.05).No significant difference was observed between the pre-and post-treatment erythema indices in either of the two groups (both P ＞ 0.05).The water content of the stratum corneum on days 60 and 90 significantly increased compared with that before the treatment in both the combined treatment group (F =21.795,P ＜ 0.001) and NAFL group (F =21.798,P ＜ 0.001),while the TEWL on days 60 and 90 significantly decreased compared with that before the treatment in both the combined treatment group (F =8.848,P =0.001) and NAFL group (F =5.833,P ＜ 0.05).However,there were no significant differences in either of the water content of the stratum corneum or TEWL on days 60 and 90 between the two groups (P ＞ 0.05).On days 60 and 90,the combined treatment group and NAFL group both showed significantly increased skin flexibility (P＜ 0.05,0.001,respectively) and glossiness (both P ＜ 0.001) compared with those before the treatment.On day 90,the skin glossiness in the combined treatment group was higher than that in the NAFL group (P ＜ 0.05).The short-term adverse reactions included transient pain,erythema and swelling which lasted 2-3 days,and slight desquamation.The main adverse reaction was mild local pigmentation,which lasted 2-3 months and then subsided gradually.Conclusion The 3 sessions of treatment with an optimized IPL immediately followed by a 1 565 nm NAFL is clinically superior to those with the NAFL alone for improving the facial pigmentation and skin glossiness,and the adverse reactions are usually transient and mild.

Objective:To analyze the time consumption in the review of multicenter clinical trials and to explore the methods of improving the approval efficiency.Methods:We retrospectively analyzed 246 multicenter clinical trials approved by our hospital from 2012.Group A were trials that our hospital was the leading site while group B were those not.In group B,trials were divided into group B1 (conference review) and B2 (expeditedreview)according to the ethical review methods.Each group's ethical review time,contract signature time,starting experiment time,the total time consumption of review,and the time from the leading site approving to the participating site submitting application were analyzed.Results:In the review of multicenter clinical trials,contract signature cost the most time,accounting for 41％.There was no significant difference in terms of whether to be the leading site.The total time consumption of group B1 and group B2 was 180.94 days and 140.36 days (P ＜0.05),respec tively.The average ethical review time of group B1 was about 20 days longer than group B2 (P ＜ 0.01).There were 96.54 days that the leading site submitted review materials to the participating site after approved.Conclusions:In multicenter clinical trials,for those the leading site has already approved,immediate submission to participating site and choosing the expedited review method may improve the ethical review efficiency,thereby shorten the total approval time consumption.

Objective:To study the changes and significance of Th17 and Treg cells as well as their associated cytokines in pe-ripheral blood of patients with chronic hepatitis C and cirrhosis in order to investigate their role in the pathogenesis of chronic hepatitis C and hepatitis C cirrhosis. Methods:Flow cytometry and ELSIA assay were used to detect the expression ratio of Th17 and Treg cells and the serum levels of IL-10,TGF-β,IL-6 and IL-17 in peripheral blood of healthy human and patients with chronic hepatitis C and hepatitis C cirrhosis. Than we analyzed the differences of the above detection index between the healthy and patients with chronic hepatitis C and hepatitis C cirrhosis. Results:The expression ratio of Th17 cells (1. 33%±0. 30%) in peripheral blood of patients with chronic hepatitis C and IL-6[(8. 10±2. 42)ng/L] and IL-17[(16. 70±4. 73)ng/L] serum levels were significantly higher than those in the healthy (Th17:1. 14%±0. 19%) and IL-6[(1. 72±6. 70)ng/L],IL-17[(12. 29±1. 88)ng/L],P<0. 05;The expression ratio of Treg cells in peripheral blood of patients with hepatitis C cirrhosis and chronic hepatitis C patients was significantly higher than that in the healthy (6. 21%±0. 76%,5. 89%±0. 85% vs 5. 51%±0. 59% ),P<0. 05,The ratio of Th17/Treg in patients with cirrhosis was significantly lower than that in patients with chronic hepatitis C and the healthy(0. 19±0. 02 vs 0. 22±0. 03,0. 21±0. 03),P<0. 05;the levels of IL-1[(16. 21±3. 76)ng/L] and TGF-β[(5. 15±0. 83)ng/L] in peripheral blood of patients with hepatitis C cirrhosis were significantly higher than those in chronic hepatitis C[(14. 36±2. 78)ng/L;(4. 47±0. 87)ng/L] and the healthy[(14. 01±3. 01)ng/L;(4. 43±0. 98)ng/L)],P<0. 05. Conclusion:Th17 and Treg cells and their related cytokines involved in the process of chronicity of hepatitis C and cirrhosis,Th17 and Treg cells and their related cytokines in the treatment and prevention of chronicity of hepatitis C and cirrhosis may have important significance.

Objective To explore the relationship between cervical bone age and male juvenile mandibular second molar (Msm) root growth ,and to provide evidence for the development of bone and teeth in patients with orthodontic treatment . Methods The CBCT and lateral cephalometric radiographs of 114 cases of 9 .5 to 15 .5 years old children in Chongqing city and ad‐olescents cervical vertebral bone and MSM root length were measured ,using statistical analysis to explore the relationship between cervical vertebral bone ,tooth root length change of age and Msm .Results By Pearson correlation analysis ,Msm root length chan‐ges and cervical vertebral bone were positively correlated(r= 0 .737 ,P< 0 .01) .Msm root length changes showed a positive correla‐tion with age(r= 0 .681 ,P< 0 .01) .Msm root length changes was positively related with dental age(r = 0 .795 ,P< 0 .01) .Conclu‐sion The root growth of the mandibular second molar was highly correlated with cervical vertebral bone in male children .When the growth and development of patients were judged by orthodontic treatment ,we can adopt the mandibular second molar root length forecast growth level of male adolescents .