Development and validation of the patient-reported outcome for older people living with HIV/AIDS in China (PROHIV-OLD).

BACKGROUND: The involvement of quality of life as the UNAIDS fourth 90 target to monitor the global HIV response highlighted the development of patient-reported outcome (PRO) measures to help address the holistic needs of people living with HIV/AIDS (PLWHA) beyond viral suppression. This study developed and tested preliminary measurement properties of a new patient-reported outcome (PROHIV-OLD) measure designed specifically to capture influences of HIV on patients aged 50 and older in China. METHODS: Ninety-three older people living with HIV/AIDS (PLWHA) were interviewed to solicit items and two rounds of patient cognitive interviews were conducted to modify the content and wording of the initial items. A validation study was then conducted to refine the initial instrument and evaluate measurement properties. Patients were recruited between February 2021 and November 2021, and followed six months later after the first investigation. Classical test theory (CTT) and item response theory (IRT) were used to select items using the baseline data. The follow-up data were used to evaluate the measurement properties of the final instrument. RESULTS: A total of 600 patients were recruited at the baseline. Of the 485 patients who completed the follow-up investigation, 483 were included in the validation sample. The final scale of PROHIV-OLD contained 25 items describing five dimensions (physical symptoms, mental status, illness perception, family relationship, and treatment). All the PROHIV-OLD dimensions had satisfactory reliability with Cronbach's alpha coefficient, McDonald's ω, and composite reliability of each dimension being all higher than 0.85. Most dimensions met the test-retest reliability standard except for the physical symptoms dimension (ICC = 0.64). Confirmatory factor analysis supported the structural validity of the final scale, and the model fit index satisfied the criterion. The correlations between dimensions of PROHIV-OLD and MOS-HIV met hypotheses in general. Significant differences on scores of the PROHIV-OLD were found between demographic and clinical subgroups, supporting known-groups validity. CONCLUSIONS: The PROHIV-OLD was found to have good feasibility, reliability and validity for evaluating health outcome of Chinese older PLWHA. Other measurement properties such as responsiveness and interpretability will be further examined.

[Effect of acupuncture on microglia activation in prefrontal cortex of chronic stress-induced depression rats].

OBJECTIVE: To observe the effect of acupuncture on the expression of proinflammatory cytokines interleukin-1ß (IL-1ß), interleukin-6 (IL-6), microglia marker ion calcium adaptor protein (Iba-1) and triggering receptor expressed on myeloid cells 2 (TREM2) in the prefrontal cortex of chronic stress-induced depression rats, so as to explore its antidepressant mechanism. METHODS: Thirty-two SD rats were randomly divided into normal control, model, acupuncture and fluoxetine groups, with 8 rats in each group. The depression model was established by using chronic mild unpredictable stress methods for 6 weeks. Manual acupuncture stimulation was applied to "Baihui" (GV20) and "Yintang" (GV29) for 10 min before modeling for 6 weeks. Fluoxetine (10 mg/kg, 1 mg/mL) was given to rats of the fluoxetine group by gavage before stress stimulation, once every day for 6 weeks. The open field test was used to evaluate the behavioral changes of rats. The contents of IL-1ß, IL-6 in the prefrontal cortex were determined by enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was used to determine the expression of Iba-1 in the prefrontal cortex. The TREM2 gene expression in the prefrontal cortex was determined by real time fluorescent quantitative polymerase chain reaction (RT-PCR). RESULTS: After modeling, the crossing numbers and rearing times were significantly decreased in the model group relevant to the control group (P<0.05). After the treatment, the crossing numbers were significantly increased in the acupuncture and fluoxetine groups (P<0.05), while the rearing times in the acupuncture group were significantly increased (P<0.05). Compared with the control group, the contents of IL-1ß, IL-6 and the expression of Iba-1 positive cells in the prefrontal cortex were significantly increased in the model group (P<0.05), while the expression of TREM2 gene in the prefrontal cortex was significantly decreased (P<0.05). After the treatment, the increased levels of IL-1ß, IL-6 and Iba-1 positive cells and the decreased TREM2 gene expression were considerably reversed in both acupuncture and fluoxetine groups compared with the model group (P<0.05). CONCLUSION: Acupuncture intervention plays a positive role in anti-depression in rats, which may be related to its effects in inhibiting the activation of microglia, reducing the expression of proinflammatory cytokines, and increasing TREM2 expression in the prefrontal cortex.

[Effect of moxibustion on IL-6/STAT3 signaling in frontal cortex of fatigue rats].

OBJECTIVE: To observe the effect of moxibustion on interleukin-6(IL-6)/signal transduction and transcriptional activator 3(STAT3) signaling pathway in the frontal cortex of fatigue rats, so as to reveal its mechanisms underlying alleviation of fatigue. METHODS: Twenty-one male SD rats were randomly divided into normal control, model, and moxibustion groups (n＝7 rats in each group). The fatigue model was established by forcing the rats to have an exhausted swim under load condition, once daily for 21 days. Moxibustion was applied to bilateral "Zusanli"(ST36) for about 15 min, once every other day for 21 days. The level of IL-6 in the frontal cortex was detected by ELISA, and the expression of Janus kinase 2 (JAK2), phosphorylated JAK2 (p-JAK2), signal transduction and transcriptional activator 3(STAT3) and phosphorylated STAT3 (p-STAT3) proteins in the frontal cortex was detected by Western blot. RESULTS: After modeling, the levels of IL-6 content and p-STAT3 protein expression and ratio of p-STAT3/STAT3 were significantly increased in the model group relevant to the normal control group (P<0.01). Follo-wing moxibustion, the duration of load swimming on the 21st day was significantly prolonged (P<0.01), content of IL-6 and levels of p-STAT3 protein expression and ratio of p-STAT3/STAT3 were significantly down-regulated in the moxibustion group compared with the model group (P<0.05). No significant differences were found between the model and control, and between moxibustion and model groups in the expression levels of JAK2, p-JAK2, STAT3 and p-JAK2/JAK2 (P>0.05). CONCLUSION: Moxibustion intervention can relieve fatigue in fatigue rats, which is associated with its function in inhibiting IL-6/STAT3 signaling pathway to reduce inflammatory injury.

[Effects of acupuncture on Nod-like receptor protein 3 inflammasome signal pathway in the prefrontal cortex of rat with depression].

OBJECTIVE: To observe the influence of acupuncture on the expression of pivotal molecules of Nod-like receptor protein 3(NLRP3) inflammasome signal pathway in the prefrontal cortex of rats with depression, so as to explore the underlying mechanism of acupuncture on treatment of depression. METHODS: SD rats were randomly divided into 4 groups (8 rats/group)，namely control, model, acupuncture and fluoxetine groups. The depression model was established by using chronic unpredictable mild stress for 6 weeks. During modeling, acupuncture (10 min)was applied to "Baihui"(GV20) and "Yintang"(EX-HN3) for rats of the acupuncture group once a day, with 1 day interval after consecutive 6 day-period for 36 days. Fluoxetine was given (10 mg/kg，1 mg/mL) by gavage to rats of the fluoxetine group every day during modeling for 42 days. The novelty-suppressed feeding test was used to observe feeding behavior of rats. The expressions of NLRP3 and apoptosis associated speck like protein containing a CARD (ASC), Caspase-1, and contents of IL-1ß in the prefrontal cortex were detected by Western blot, immunohistoche-mistry and ELISA, separately. RESULTS: Compared with the control group, the latency of the novelty-suppressed feeding, and the expressions of NLRP3, ASC, Caspase-1 and IL-1ß content in the prefrontal cortex of the model group were significantly increased (P<0.01). Following the interventions, the latency of the noveltysuppressed feeding，and the expressions of NLRP3, ASC, Caspase-1 and IL-1ß content in the prefrontal cortex in the acupuncture and fluoxetine groups were significantly decreased (P<0.05，P<0.01). There was no significant differences in the above indicators between the acupuncture group and the fluoxetine group (P>0.05). CONCLUSION: Acupuncture could inhibit the expression of NLRP3 inflammasome signal pathway in the pre-frontal cortex, and reduce the inflammation in the brain, which may mediate the anti-depressant effect of acupuncture.

[Protective effect of Longxue Tongluo capsule on oxidized low-density lipoprotein damage to human umbilical vein endothelial cells].

To observe the protective effect of Longxue Tongluo capsule (LTC) on human umbilical vein endothelial cells (EAhy.926 cells) injury induced by oxidized low-density lipoprotein (ox-LDL, 100 mg·L⁻¹). The effect of the cell viability of LTCin alleviating OX-LDL-induced endothelial cell injury was determined by MTT and LDH assay. The effect of LTC on lactic dehydrogenase (LDH), nitric oxide (NO), super oxide dlsmutase (SOD) and malondialdehyde (MDA) levels were detected by corresponding assay kits according to manufacturer's instruction. The effect of LTC on the protein expressions of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), p65, p-p65, IKB and p-IKB were detected by Western blot. The results showed that compared with the normal control group, the activity of EAhy.926 cells was significantly decreased, LDH leakage (P<0.01) increased, NO content and SOD activity significantly decreased (P<0.01, P<0.05), and the expressions of ICAM-1, VCAM-1, p-p65/p65 and p-IKB(P<0.05)increased.This study demonstrated that LTC had no significant effect on the growth of normal cells. The treatment with LTC significantly promoted the proliferation of vascular endothelial cells damagedby ox-LDL, decreased MDA content and LDH release, andincreased the activity of SOD and NO content. Meanwhile, ox-LDL significantly increased the expressions of ICAM-1, VCAM-1, p-p65/p65, p-IKB/IKB in Eahy.926 cells; these effects were suppressed by LTC at 1, 2 mg·L⁻¹. In conclusion, LTC has a significant protective effect on human umbilical vein endothelial cells caused by ox-LDL. This study suggested that LTC has a certain therapeutic effect on AS.

Interaction between Saikosaponin D, Paeoniflorin, and Human Serum Albumin.

Saikosaponin D (SSD) and paeoniflorin (PF) are the major active constituents of Bupleuri Radix and Paeonia lactiflora Pall, respectively, and have been widely used in China to treat liver and other diseases for many centuries. We explored the binding of SSD/PF to human serum albumin (HSA) by using fluorospectrophotometry, circular dichroism (CD) and molecular docking. Both SSD and PF produced a conformational change in HSA. Fluorescence quenching was accompanied by a blue shift in the fluorescence spectra. Co-binding of PF and SSD also induced quenching and a conformational change in HSA. The Stern-Volmer equation showed that quenching was dominated by static quenching. The binding constant for ternary interaction was below that for binary interaction. Site-competitive experiments demonstrated that SSD/PF bound to site I (subdomain IIA) and site II (subdomain IIIA) in HSA. Analysis of thermodynamic parameters indicated that hydrogen bonding and van der Waals forces were mostly responsible for the binary association. Also, there was energy transfer upon binary interaction. Molecular docking supported the experimental findings in conformation, binding sites and binding forces.

[Development and identification of monoclonal antibodies of cape jasmine proteins in Reduning injection].

Liposoluble cape jasmine proteins were used to immunize BALB/C mice. Indirect ELISA was utilized to develop one monoclonal antibody by integrating SP2/0 cells and spleen cells from immunized BALB/C mice. The subclass of the monoclonal antibody was identified as IgG2b, with Kappa chain as its light chain. The ascite titer of 2H8 monoclonal antibody was 1:204 080. Western-blot analysis proved that 2H8 reacted with cape jasmine proteins to identify specific liposoluble protein with molecuar weight of around 58.5 kDa. Dot-ELISA was established with 2H8 ascites as the primary antibody, showing the minimum detectable amount of 19.5 ng. This study lays a foundation for the development of protein kits of Reduning injection.

[Effect of Shuganlipi decoction on Th1/Th2 cytokines in patients with chronic hepatitis B].

OBJECTIVE: To investigate the effect of Shuganlipi decoction on Th1/Th2 cytokines, liver function and HBV replication in patients with chronic hepatitis B (CHB). METHODS: Eighty-six confirmed CHB cases were randomly divided into control group (n=42) and experimental group (n=44) for treatment with routine western medication and additional treatment with Shuganlipi decoction, respectively. The production of IFN-γ, IL-2, IL-6, IL-10 and liver function, HBV DNA, and HBeAg were detected in all the patients. RESULTS: The total response rate to the treatment was significantly higher in the experimental group than in the control group (78.13% vs 57.14%, P<0.01). ALT, AST, TBIL and ALB were all improved obviously in the two groups after the treatments (P<0.01). In terms of ALT and ALB, the experimental group showed more obvious improvement than the control group(P<0.05). The treatments also resulted in significant increases of IFN-γ and IL-2 levels and reductions of IL-6 and IL-10 levels in the two groups (P<0.01). CONCLUSION: Shuganlipi decoction can improve the liver function and activity of Th1/Th2 cytokines to promote the clearance of liver cell HBV infection.

[Observation on therapeutic effect of electroacupuncture combined with local blocking therapy on acute gouty arthritis].

OBJECTIVE: To search for a new method for treatment of acute gouty arthritis. METHODS: One hundred cases of acute gouty arthritis were randomly divided into an observation group and a control group. The observation group were treated with local blocking and electroacupuncture at Yinbai (SP 1), Taichong (LR 3), Sanyinjiao (SP 6), Zusanli (ST 36), Fenglong (ST 40), Yinlingquan (SP 9) and Ashi points, and the control group were treated with oral administration of 25 mg Indomethacin, thrice each day, and 100 mg Allopurinol, thrice daily. The therapeutic effects and changes of pain score, serum uric acid were observed in the two groups. RESULTS: The effective rate was 96.4% in the observation group and 84.1% in the control group, the former being better than the later (P < 0.05). Before and after treatment, pain scores were 3.48 +/- 1.05 and 0.94 +/- 10.85, 3.45 +/- 1.07 and 2.11 +/- 0.91, and serum uric acid contents were (539.16 +/- 34.49) micromol/L and (376.30 +/- 52.85) micromol/L, and (552.29 +/- 46.15) micromol/L and (425.79 +/- 48.69) micromol/L in the two group, respectively. After treatment, pain score and serum uric acid content very significantly decreased in the two groups (both P < 0.01) and the observation group in the analgesic effect and the effect in decreasing serum uric acid content was better than the control group (both P < 0.01). CONCLUSION: Electroacupuncture combined with local blocking is an effective method for treatment of acute gouty arthritis and it can decrease blood uric acid level.

[Evaluation of relationship between early brain response and neurodevelopment in newborns by using near infrared spectroscopy].

OBJECTIVE: To study the relationship between early brain response to extrinsic stimulation and neurodevelopment in preterm infants, assess the brain function of preterm infants in the early stage, and thereby to provide objective evidence for the degree of neurodevelopment in preterm infants and to evaluate prognosis. METHODS: Using near infrared spectroscopy (NIRS), the brain response to sound stimulation of 90 preterm infants at different gestational age was observed and compared with the result obtained from 20 full term infants. The neonatal behavioral neurological assessment (NBNA) was performed at corrected age of 40 weeks, and the infants were followed up for 2 years. The effect of gestational age and brain damage on preterm infants, the relation between early brain response in preterm infants and their neurodevelopment was evaluated. RESULTS: All the preterm infants responded to different degrees to auditory stimulation after birth. The time to beginning to react and the time to appearance of the peak reaction were attained after auditory stimulation and the time to beginning to resume when the auditory stimulation was stopped was (278 +/- 94) s, (446 +/- 67) s and (199 +/- 52) s, respectively, which were significantly longer than those observed in the full term infants (107 +/- 30) s, (264 +/- 51) s and (131 +/- 46) s, respectively. The maximum reactions of hemoglobin, oxyhemoglobin and regional oxygen saturation in the infants after gestational age 32 weeks was (0.3 +/- 0.3)%, (0.7 +/- 0.5)% and (0.3 +/- 0.3)%, respectively, which were significantly lower than those in the full term infants (1.7 +/- 0.7)%, (1.7 +/- 0.8)% and (1.6 +/- 0.7)%, respectively. When the brain response of preterm infants was compared with that in infants without brain damage, the speed of the reaction was slow, the maximum reaction was low. The brain response in preterm infant was correlated with NBNA at corrected age of 40 weeks. It was found during the following-up that abnormal neurodevelopment was associated with poor brain reaction. CONCLUSIONS: NIRS can be used to evaluate brain response of infants. Preterm infants display brain response to auditory stimulation. Early brain response is correlated with neurodevelopment.