Objective: To examine the association between sleep and frailty using the bidirectional two-sample Mendelian randomization (MR) approach, so as to provide the basis for the prevention and intervention of frailty. Methods: The data on single nucleotide polymorphisms (SNP) related to sleep duration, insomnia and morning chronotype were collected from genome-wide association studies (GWAS) and meta-analysis of GWAS, involving 446 118, 1 331 010 and 697 828 participants, respectively. The frailty was evaluated using the frailty index, and the relevant SNP data were collected from a meta-analysis of GWAS involving 175 226 participants. A bidirectional MR analysis was performed using the inverse-variance weighted method. Sensitivity analyses employed the weighted median method, the maximum likelihood-based method, the MR-Egger regression, and the MR-PRESSO test. Results: Forward MR analysis showed that longer sleep duration (β=-0.170, 95%CI: -0.255 to -0.085) and morning chronotype (β=-0.036, 95%CI: -0.058 to -0.014) decreased the risk of frailty, while insomnia increased the risk of frailty (β=0.167, 95%CI: 0.149-0.184). Reverse MR analysis showed that frailty increased the risk of insomnia (OR=1.645, 95%CI: 1.278-2.117). Both bidirectional MR results were robust, which excluded the impact of heterogeneity and horizontal pleiotropy. Conclusion Sleep duration, insomnia, and morning chronotype are associated with frailty.

Objective:To explore the effects of nutrition management based on Patient-Generated Subjective Global Assessment (PG-SGA) on nutritional idicators,quality of life and other indicators in patients with pancreatic cancer undergoing chemotherapy, to provide guidance for the implementation of the intervention plan for pancreatic cancer patients undergoing chemotherapy.Methods:This was a randomized controlled study. From January 2021 to December 2022, 96 patients with pancreatic cancer who received chemotherapy in Shanghai Changzheng Hospital and Affiliated Cancer Hospital of Fudan University were selected using convenience sampling method and divided into the observation group and the control group according to the random number table, with 48 cases in each group. The control group was given routine nursing intervention, and the observation group was given PG-SGA-based nutrition management intervention. Patients in both groups continued the intervention until discharge. Nutritional indexes, quality of life, the score of cancer-related fatigue, sleep quality and mental state before and after intervention, intervention compliance and satisfaction after intervention, and complications during intervention of both groups were compared.Results:There were 48 patients in each group ultimately. In the control group, there were 28 males, 20 females, aged (63.33 ± 4.31) years old; in the observation group, there were 27 males, 21 females, aged (63.15 ± 4.25) years old. After intervention, the PG-SGA score, serum triacylglycerol level, and scores of Revised Piper ′s Fatigue Scale and Arsens Insomnia Scale, Self-rating Anxiety Scale and Self-rating Depression Scale in the observation group were (3.87 ± 1.16) points, (1.35 ± 0.52) mmol/L, (3.79 ± 0.67) points, and (5.31 ± 2.05), (44.55 ± 5.14), (45.15 ± 5.08) points respectively, lower than the control group ′s (5.77 ± 1.58) points, (2.04 ± 0.35) mmol/L, (4.82 ± 0.88) points, and (7.29 ± 2.14), (51.74 ± 5.18), (52.26 ± 5.11) points, the differences were statistically significant ( t values were 4.63-7.63, all P<0.05); the serum levels of retinol binding protein and transferrin were (18.13 ± 2.41) mg/L and (61.25 ± 5.34) ng/L, respectively, higher than the control group ′s (15.29 ± 2.33) mg/L and (48.31 ± 5.28) ng/L, with statistical significance ( t=5.87, 11.94, both P<0.05). The symptom domain score in the observation group after intervention was (56.17 ± 5.25) points, lower than (66.22 ± 5.57) points in the control group, while the cognitive, social, emotional, role, and physical scores were (76.35 ± 5.71 ), (77.55 ± 6.51 ), (75.87 ± 6.45), (77.38 ± 6.61), (75.75 ± 6.37) points, higher than (66.29 ± 5.39), (65.74 ± 6.34 ), (64.22 ± 6.18), (66.56 ± 6.26), (65.74 ± 6.11) points in the control group ( t values were 7.86 to 9.10, all P<0.05). Conclusions:Nutritional management based on PG-SGA could reduce the degree of cancer-induced fatigue, relieve negative emotions, improve the overall nutritional status, improve intervention compliance, reduce the occurrence of complications; improve sleep quality, quality of life, and patient ′s satisfaction.

Hematopoietic stem cell (HSC) transplantation is the only curative therapy for many diseases. HSCs from umbilical cord blood (UCB) source have many advantages over from bone marrow. However, limited HSC dose in a single CB unit restrict its widespread use. Over the past two decades, ex vivo HSC expansion with small molecules has been an effective approach for obtaining adequate HSCs. Till now, several small-molecule compounds have entered the phase I/II trials, showing safe and favorable pharmacological profiles. As HSC expansion has become a hot topic over recent years, many newly identified small molecules along with novel biological mechanisms for HSC expansion would help solve this challenging issue. Here, we will give an overview of HSC biology, discovery and medicinal chemistry development of small molecules, natural products targeting for HSC expansion, and their recent clinical progresses, as well as potential protein targets for HSC expansion.

Objective:To evaluate the efficacy of long-pulsed 1 064-nm Nd:YAG laser combined with a topical emulsion containing Camellia reticulata and Radix Notoginseng in the treatment of melasma. Methods:A total of 80 patients with melasma were enrolled from Department of Dermatology, People′s Hospital of Ningxia Hui Autonomous Region from June 2019 to June 2020, and randomly and equally divided into control group and observation group by using a random number table: 40 patients in the control group were treated with long-pulsed 1 064-nm Nd:YAG laser once every 2 weeks for 6 sessions as a course of treatment; another 40 in the observation group were treated with the same laser therapy as the control group and a topical emulsion containing Camellia reticulata and Radix Notoginseng twice a day for 3 months as a course of treatment. Melasma area and severity index (MASI), clinical efficacy, patient satisfaction rate and safety were compared between the 2 groups before and/or after treatment. Results:After 4- and 8-week treatment, there was no significant difference in the MASI score between the observation group (14.57 ± 3.22 points, 10.00 ± 2.94 points, respectively) and control group (14.74 ± 3.11 points, 11.31 ± 3.00 points, respectively; both P>0.05). After 12-week treatment, the MASI score was significantly lower in the observation group (4.80 ± 2.78 points) than in the control group (7.07 ± 3.22 points, t = -3.38, P<0.01). After 3-month treatment, the response rate was significantly higher in the observation group (36 cases, 90%) than in the control group (31 cases, 77.5%; χ2 = 4.58, P < 0.001) ; however, there was no significant difference in the patient satisfaction rate between the observation group (87.5%) and control group (72.5%, χ2 = 7.26, P = 0.06). In addition, no significant difference in the occurrence of adverse reactions was observed between the observation group (5 cases, 12.5%) and control group (7 cases, 17.5%; P > 0.05) . Conclusion:Compared with the long-pulsed 1 064-nm Nd:YAG laser alone, the topical emulsion containing Camellia reticulata and Radix Notoginseng in combination with the long-pulsed 1 064-nm Nd:YAG laser is more effective for the treatment of melasma, with higher patient satisfaction and less adverse reactions.

Objective:To explore the dynamic change of platelet count and related factors in HIV-infected patients with access to antiretroviral therapy (ART) in Dehong Dai and Jingpo autonomous prefecture of Yunnan province.Methods:A longitudinal analysis was used to analyze the dynamic change of platelet count in HIV-infected patients with access to ART. Linear mixed model (LMM) was used to analyze factors associated with the dynamic change of platelet count. Stratified analysis and sensitivity analysis were also conducted.Results:A total of 761 HIV-infected patients were recruited and 608 cases had at least one follow-up record (80.0%,608/761). 374, 555 and 233 cases were investigated in follow-up visits at month 6, 12 and 24, respectively. The mean platelet count and the proportion of higher platelet count (>300×10 9/L) were significantly higher in women than in men at both baseline survey and each follow-up visit ( P<0.05). Among patients with no obvious liver fibrosis, the mean platelet count was significantly higher in women than in men at baseline survey and each follow-up visit; while in the patients with liver fibrosis, the mean baseline platelet count was still significantly higher in women than in men, but the difference had no significance at follow-up visits. Results of LMM revealed that follow-up platelet count was positively correlated with gender ( β=5.90, 95% CI: 1.09-10.70, P=0.016), baseline platelet count ( β=0.82, 95% CI: 0.79-0.86, P<0.001) and time ( β=1.76, 95% CI: 1.52-2.01, P<0.001). Sensitivity analysis among 220 cases who had both 12- and 24-month follow-up visits further confirmed that follow-up platelets count was still positively associated with gender ( β=10.50, 95% CI: 2.24-18.74, P=0.013), baseline platelet count ( β=0.71, 95% CI: 0.65-0.77, P<0.001) and time ( β=1.60, 95% CI: 1.20-1.99, P<0.001) but negatively associated with age ( β=-0.42, 95% CI: -0.78--0.06, P=0.021). Conclusions:The platelet count of HIV-infected patients gradually increased after ART. The mean platelet count was consistently higher in women than in men. Attention should be paid to the gender specific difference in platelet count in HIV-infected patients and timely intervention should be given to reduce the morbidity and mortality of platelet-related diseases.

OBJECTIVE：To compare the protective effects model mice between the aboveground and underground parts of Astragalus membranaceus on immunosuppression ，and to provide reference for further utilization and development of A. membranaceus. METHODS ：A total of 240 ICR mice were divided into 4 batches，60 mice in each batch ，with half male and half female. Each batch of mice were randomly divided into blank group ，model group ，A. membranaceus aboveground part and undergroud part low-dose and high-dose groups （3，6 g/kg，by crude drug ）according to body weight and sex ，with 10 mice in each group. Blank group and model group were given normal saline intragastrically. A. Membranaceus groups were given corresponding concentration of drug intragastrically ，10 mL/kg，once a day ，for consecutive 30 days. Except for blank group ， other groups were intraperitoneally injected with cyclophosphamide 40 mg/（kg·d）for consecutive 3 days，since 24th day of treatment，to establish immunosuppression model. The levels of serum immunoglobulin （IgG，IgM，IgA），inflammation factors [nitric oxide ，interleukin-2（IL-2），IL-6，tumor necrosis factor-α] and half hemolysis value were detected in each group. Body weight ，thymus index ，spleen index ，phagocytic index ，activity of natural killer （NK）cell，splenic lymphocyte proliferation ability，dinitrofluorobenzene-induced delayed metamorphosis reaction in mice （by weight difference between left and right ears ） and the number of hemolytic plaque were determined. RESULTS ： Compared with blank group ， the serum levels of immunoglobulin，body weight ，thymus index ，spleen index ，phagocytic index ，NK cell activity ，the proliferation ability of splenic lymphocyte，the number of hemdytic plaque and half hemolysis value were decreased significantly in model group （P＜0.05）， while inflammation factor level as well as weight difference between left and right ears were increased significantly （P＜0.05）. Compared with model group ，above indexes of mice in A. membranaceus groups were improved significantly ，in dose-dependent manner（P＜0.05）. Compared with A. membranaceus undergroud part group ，above indexes of A. membranaceus aboveground part group were improved significantly （P＜0.05）. CONCLUSIONS ：Aboveground and underground part of A. membranaceus both have pretective effect on immunosuppression model mice ，and the effect of aboveground part of A. membranaceus is stronger than underground part of A. membranaceus .

Objective:To analyze influencing factors of instant antiretroviral therapy (ART) and explore associution between strategies of ART and immunological effects among HIV/AIDS patients in Taizhou city during 2006-2019.Methods:A retrospective cohort study was conducted on HIV/AIDS patients under ART, and a logistic regression model was used to analyze factors of instant ART. The student t-test and chi-square test were used to compare immunological effect of different ART strategies while the Kaplan-Meier method was used to generate a survival curve. Results:A total of 2 971 HIV/AIDS patients were enrolled with 1 786 cases (60.1%) having instant ART strategy. The proportion of instant ART were 77.8% (1 170/1 504) during 2016 to 2019. The treatment success rate of the instant ART group (87.4%, 1 561/1 786) were higher than the delayed ART group (84.4%, 1 000/1 185). The results of multivariate logistic regression model indicated that male (a OR=1.28, 95 %CI: 1.03-1.59), married (a OR=1.71, 95 %CI: 1.33-2.19) and baseline CD 4+T lymphocyte cells (CD 4) counts ≤200 cells/μl (a OR=1.60, 95 %CI: 1.27-2.02) were factors positively related to instant ART while 31-40 years old (a OR=0.63, 95 %CI: 0.48-0.84), infected through heterosexual transmission(a OR=0.60, 95 %CI: 0.49-0.74) and diagnosed before 2015 (a OR=0.20, 95 %CI: 0.17-0.23) were inversely related to instant ART. The increase of the CD 4/CD 8 ratio was greater, and the cumulative ART success rate was higher each year in the instant ART group than in the delayed ART group ( P<0.05). Conclusions:The instant ART strategy has been well implemented in Taizhou city during 2006-2019, and the immunological effect was better in instant ART group. The proportion of instant ART were more than 60.0% among HIV/AIDS patients. Instant ART strategy needs to be strengthened for those who are 31-40 years old, women, unmarried, and infected through heterosexual transmission in an attempt to further increase treatment level and improve treatment effect.

OBJECTIVE:To provide reference for ration use of TCM injection. METHODS:The utilization of TCM injections in 39 hospitals from Chongqing area during 2012-2014 was analyzed statistically in respects of consumption sum,DDDs,DDC and B/A. RESULTS:The total consumption sum of TCM injections increased slowly in 39 hospitals from Chongqing area during 2012-2014,increasing from 767 581 thousand yuan to 911 759 thousand yuan,with annual growth rate of 8.98%. Total sum of consumption sum of top 10 drugs was 1 326 019.7 thousand yuan,accounting for 51.11% of total. The consumption sum of Hong-hua injection and Shenxiong glucose injection always took up the first 2 places in those years. DDDs of Xuesaitong injection, Shenxiong glucose injection glucose,Honghua injection and Shuxuetong injection always took up the first 4 places in those years. DDC of Xuebijing injection and Kanglaite injection always took up the first and second places in those years. Among top 10 TCM injection in the list of consumption sum,most of B/A was lower than 1.00;B/A of Shuxuetong injection,Xingnaojing injection, Shenqiong glucose injection and Xueshuantong injection were close or equal to 1.00. Xuesaitong injection was the one that B/A>1.00 from beginning to end. CONCLUSIONS:Total use of TCM injection increased steadily and drug use relatively concentrated in 39 hospitals from Chongqing area during 2012-2014,and rationality of drug use by physicians had been improved gradually.

OBJECTIVE:To provide reference for rational use of anti-tumor essential medicine in the clinic. METHODS:The application of anti-tumor essential medicine in 39 hospitals from Chongqing area during 2012-2014 was analyzed statistically in re-spects of consumption sum,DDDs,DDC and B/A. RESULTS:The total consumption sum of anti-tumor essential medicine in 39 hospitals from Chongqing area during 2012-2014 increased from 10 083.65 ten thousand yuan to 15 186.65 ten thousand yuan,with annual increase rate of 22.72%. 3-year total consumption sum was 37 952.45 ten thousand yuan,and the sum of consumption sum of top 10 medicines was 36 742.24 ten thousand yuan,accounting for 96.81%;top 3 medicines were paclitaxel,oxaliplatin and flu-orouracil. During 2012-2014,DDDs had changed to certain extent,and the front medicines contained tegafur,paclitaxel and cyclo-phosphamide,etc;the most increment medicine was paclitaxel (oral),whose annual growth rate was 59.63%;that of tamoxifen decreased year by year,with annual decrease rate of 5.14%. DDC of paclitaxel,oxaliplatin and etoposide were the higher others. Annual B/A of oxaliplatin,fluorouracil and cytosine arabinoside were all lower than 1.00. CONCLUSIONS:The lonsumption sum and DDDs of anti-tumor essential medicine had increased reasonably in 39 hospitals from Chongqing area during 2012-2014,while their DDC had kept stable. Main medicines used in the clinic are suitable for numerous indications,and are expensive.

In order to affirm the cardioactive components in Fuzi, we identified a group of aminoalcohol- diterpenoid alkaloids in Fuzi using ultra high-performance liquid chromatography coupled with electrospray ionization mass spectrometer (UPLC-ESI-MS) method. Among a total of forty-one isolated ingredients, thirteen major aminoalcohol-diterpenoid alkaloids were identified by comparing their retention times and MS spectra with those of the reference substances. Moreover, Fuzi samples from different places of origin and with different processing methods were examined and their components displayed a pattern of high similarity, though the relative abundance varies probably due to their different processing methods. Furthermore, the cardiac effect of each identified alkaloid was individually evaluated using the isolated bullfrog heart perfusion experiment. Among the thirteen aminoalcohol diterpenoid alkaloids tested, six of them significantly enhanced the amplitude rates. Taken together, we affirm that the cardioactive components in Fuzi are aminoalcohol-diterpenoid alkaloids, shedding light on future studies of the mechanisms and development of these cardioactive compounds.