Application of metabolomics in urolithiasis: the discovery and usage of succinate.

Urinary stone is conceptualized as a chronic metabolic disorder punctuated by symptomatic stone events. It has been shown that the occurrence of calcium oxalate monohydrate (COM) during stone formation is regulated by crystal growth modifiers. Although crystallization inhibitors have been recognized as a therapeutic modality for decades, limited progress has been made in the discovery of effective modifiers to intervene with stone disease. In this study, we have used metabolomics technologies, a powerful approach to identify biomarkers by screening the urine components of the dynamic progression in a bladder stone model. By in-depth mining and analysis of metabolomics data, we have screened five differential metabolites. Through density functional theory studies and bulk crystallization, we found that three of them (salicyluric, gentisic acid and succinate) could effectively inhibit nucleation in vitro. We thereby assessed the impact of the inhibitors with an EG-induced rat model for kidney stones. Notably, succinate, a key player in the tricarboxylic acid cycle, could decrease kidney calcium deposition and injury in the model. Transcriptomic analysis further showed that the protective effect of succinate was mainly through anti-inflammation, inhibition of cell adhesion and osteogenic differentiation. These findings indicated that succinate may provide a new therapeutic option for urinary stones.

Procyanidins-crosslinked small intestine submucosa: A bladder patch promotes smooth muscle regeneration and bladder function restoration in a rabbit model.

Currently the standard surgical treatment for bladder defects is augmentation cystoplasty with autologous tissues, which has many side effects. Biomaterials such as small intestine submucosa (SIS) can provide an alternative scaffold for the repair as bladder patches. Previous studies have shown that SIS could enhance the capacity and compliance of the bladder, but its application is hindered by issues like limited smooth muscle regeneration and stone formation since the fast degradation and poor mechanical properties of the SIS. Procyanidins (PC), a natural bio-crosslinking agent, has shown anti-calcification, anti-inflammatory and anti-oxidation properties. More importantly, PC and SIS can crosslink through hydrogen bonds, which may endow the material with enhanced mechanical property and stabilized functionalities. In this study, various concentrations of PC-crosslinked SIS (PC-SIS) were prepared to repair the full-thickness bladder defects, with an aim to reduce complications and enhance bladder functions. In vitro assays showed that the crosslinking has conferred the biomaterial with superior mechanical property and anti-calcification property, ability to promote smooth muscle cell adhesion and upregulate functional genes expression. Using a rabbit model with bladder defects, we demonstrated that the PC-SIS scaffold can rapidly promote in situ tissue regrowth and regeneration, in particular smooth muscle remodeling and improvement of urinary functions. The PC-SIS scaffold has therefore provided a promising material for the reconstruction of a functional bladder.

[Studies on chemical constituents of the extract of Lonicera japonica].

OBJECTIVE: To isolate and elucidate the structure of the constituents of the extract of Lonicera japonica. METHODS: The compounds were isolated and repeatedly purified on TLC, silica gel column chromatography, and gel column chromatography. The structures were elucidated by physico-chemical properties, MS and NMR. RESULTS: Seven compounds were obtained and elucidated as luteolin (I), luteoloside (II), quercetin (III), quercetin-3-0-beta-D-glucoside (IV), quercetin-7-0-beta-D-glucoside (V), rutin (VI), chlorogenic acid (VII). CONCLUSION: Compound V is isolated from this genus for the first time.

[Effect of auricular-point pressure combined with personalized music therapy on perioperative stress response in primipara].

OBJECTIVE: To explore the effect of auricula-point pressure combined with personalized music therapy on perioperative stress response in primipara. METHODS: A total of 1000 primiparas who were elective for cesarean section were randomly divided into an observation group and a control group, 500 cases in each one. 1 h before surgery and 3 h, 6 h, 12 h and 24 h after surgery, individualized music relaxation intervention was given for 1 h in the two groups. On the basis of the treatment, auricular-point pressure was added at Pizhixia (AT4), Shenmen (TF4), Xin (CO15), Zigong (uterus), Luanchao (ovary), Neishengzhiqi (TF2) in the observation group. Each point was pressed for 1 min each time, repeated once every 15 min, the force is from light to heavy, and it is better to have a feeling of distension, sourness and radiation in the auricle. The scores of anxiety self-rating scale, visual analog scale (VAS), heart rate, systolic blood pressure, thyroid stimulating hormone, cortisol and blood glucose levels were observed in the two groups. RESULTS: A total of 973 primiparas completed the clinical study in the end, including 488 patients in the observation group and 485 patients in the control group. Compared to enrollment, the scores of anxiety self-rating scale before entering the operating room in the two groups were significantly improved (P<0.05), and the observation group was superior to the control group (P<0.05). Entering the operating room and tracheal extubation, the heart rate and systolic blood pressure of the primiparas in the observation group were more stable than those in the control group, and the differences were statistically significant (P<0.05). Entering the operating room, 1 h into the surgery and 3 h after surgery, the thyroid stimulating hormone, cortisol and blood glucose levels of the primiparas in the observation group were significantly better than those in the control group (P<0.05). The VAS scores in the observation group at 6 h, 12 h and 24 h after surgery were lower than those in the control group (P<0.05). CONCLUSION: Auricular-point pressure combined with personalized music therapy can reduce the perioperative stress response in primipara and promote the improvement of psychological, physiological and emotional.

[Effect of auricular acupuncture on postpartum rehabilitation of primipara with cesarean].

OBJECTIVE: To explore the postoperative effect of auricular acupuncture on primipara with cesarean in order to promote postpartum rehabilitation. METHODS: A total of 120 primiparas with cesarean were randomly divided into an observation group and a control group, 60 cases in each group. The routine treatment and care after surgery were given in the two groups. On the basis treatment, auricular acupuncture was applied at penqiang (TF5), shenmen (TF4), jiaogan (AH6a), pizhixia (AT4), neishengzhiqi(TF2), pi(CO13), wei(CO4) in the observation group, even-needling technique at all points. The needles were retained for 30 min, 3 times a day, the acupuncture was alternately every other day for 5 days continuously. The postpartum pain, anus exhaust time, incidence of postpartum hemorrhage, urinary retention and constipation, and postpartum average hospitalization day were recorded and compared between the two groups. RESULTS: Twenty-seven cases of postpartum uterine contraction pain (45.0%), 25 cases of wound pain (41.7%), 19 cases of breast distending pain (31.7%) and 11 cases of muscle soreness (18.3%) in the observation group, which was significantly lower than 38 cases (63.3%), 36 cases (60.0%), 30 cases (50.0%) and 21 cases (35.0%) respectively in the control group (P<0.05). The anus exhaust time in the observation group was earlier than that in the control group (P<0.05), and the average hospitalization time was shorter than that in the control group (P<0.05). The incidence of postpartum hemorrhage, urinary retention and constipation in the observation group was lower than that in the control group (P<0.05). CONCLUSION: Auricular acupuncture can effectively relieve postpartum pain in primipara with cesarean, promote postpartum exhaust and shorten hospitalization days, and reduce the incidence of postpartum complications such as postpartum hemorrhage, urinary retention and constipation, it is conducive to postpartum rehabilitation.

[Effect of auricular point pressing combined with electroacupuncture on postoperative pain and inflammatory cytokines in children with hernia].

OBJECTIVE: To explore the clinical efficacy and action mechanism of auricular point pressing combined with electroacupuncture (EA) on postoperative pain in children with hernia. METHODS: A total of 93 children with inguinal hernia were randomly divided into an auricular point group, an EA group and a combination group, 31 cases in each group. All the three groups were treated with routine postoperative treatment and nursing, and analgesic and sedative drugs were used when necessary. After awaking, the children in the auricular point group were treated with auricular point pressing at Shenmen (TF4), Jiaogan (AH6a) and Pizhixia (AT4); the seeds of cowherb were placed at the auricular points and the same nurse used index finger and thumbs to press the points for 2 min, and repeated after 30 min. The pressing time was 8-11 AM and 14-17 PM for 3 days. The children in the EA group were treated with EA at Sanyinjiao (SP 6) and Zusanli (ST 36); the needles were perpendicularly inserted with mild reinforcing-reducing method; EA instrument was connected with needles and the current intensity was under the maximal tolerance of children; the needles were retained for 20 min, three times a day for continuous 3 days. The children in the combination group were treated with auricular point pressing and EA for 3 days. The Wong-Baker facial expression evaluation method was used to observe the pain scores 1-3 h, 4-24 h, 25-48 h and 49-72 h after operation; the contents of TNF-α, IL-6 and IL-8 were compared 1 day, 2 days and 3 days after operation; the number of cases using sedative drugs and average hospitalization days were compared among the three groups. RESULTS: ①Among the children aged 8-15 years old, the pain scores 4-24 h and 25-48 h after operation in the combination group were lower than those in the auricular point group and the EA group (all P<0.05); among the children aged 4-7 years old, differences of the pain scores in each time after operation were not significant statistically among the three groups (all P>0.05). ②The contents of TNF-α, IL-6 and IL-8 in serum 1 day, 2 days and 3 days after operation in the combination group were lower than those in the auricular point group and the EA group (all P<0.05). ③The number of cases using analgesic and sedative drugs after operation in the combination group was fewer than that in the auricular point group and the EA group (all P<0.05). ④The average hospitalization days in the combination group were shorter than those in the auricular point group and the EA group (all P<0.05). CONCLUSION: Compared with auricular point pressing or EA alone, the combination of auricular point pressing and EA could not only effectively relieve the postoperative pain, but also reduce the expression of inflammatory cytokines in children with hernia, improving the clinical efficacy.