[Stepwise treatment of complex intestinal fistulas and strategies of nutritional support treatment].

Intestinal fistula is one of the common diseases and complications in abdominal surgery. It does not only cause severe abdominal infections but also leads to obstruction, bleeding, malnutrition, and may develop into complex intestinal fistulas, resulting in increased challenges in treatment, elevated treatment costs, and increased risk of patient mortality. At present, the treatment of intestinal fistula mainly adopts a three-stage approach: (1) early diagnosis, (2) mid-term nutritional support treatment, and (3) definitive surgical treatment. Nutritional support treatment can significantly reduce patient mortality and improve recovery. Due to the difficulty, complexity, and diversity of intestinal fistula treatment, and the fact that complex intestinal fistulas are currently a challenge in the treatment of intestinal fistulas, this article will introduce the progress and difficulties at different stages, and explore the future treatment direction of intestinal fistulas from the perspective of interdisciplinary cooperation.

[Correlation between fluid parameter and cardiovascular events in hemodialysis patients based on repeated body composition analyses].

Objective: To explore the correlation between fluid load index and cardiovascular events in hemodialysis patients based on repeated body composition analyses. Methods: A prospective cohort study was conducted to collect the clinical data of patients undergoing maintenance hemodialysis (MHD) in the Department of Nephrology, Hangzhou Hospital of Traditional Chinese Medicine from July to September 2020. The pre-dialysis fluid overload (FO) index-overhydration (OH) was measured by bioelectrical impedance method, and the follow-up monitoring was conducted every 6 months. According to the baseline OH value, patients were divided into non-FO group (OH≤2.5 L) and FO group (OH>2.5 L). Moreover, according to the repeated measurements, the patients were divided into continuous non-FO group, continuous FO group and intermittent FO group. All patients were followed up until October 1, 2022, and the outcomes were recorded. The end point of follow-up was cardiovascular events. The cumulative incidence of cardiovascular events was calculated by the Kaplan-Meier method, and the risk factors of cardiovascular events were analyzed by Cox proportional hazards regression model. Results: A total of 289 patients were included, including 88 patients (30.4%) with FO and 201 patients (69.6%) with non-FO. There were 168 males (58.1%) and 121 (41.9%) females, with an average age of (58±13) years and an average follow-up time of (22.0±6.5) months. Kaplan-Meier analysis showed that the incidence of cardiovascular events in the baseline FO group was higher than that in the non-FO group (log-rank χ2=14.44, P<0.001). The incidence of cardiovascular events in both the continuous FO group and the intermittent FO group was higher than that in the continuous non-FO group (log-rank χ2=41.47, P<0.001; log-rank χ2=18.36, P<0.001). After adjustment for gender, age, comorbidities, and biochemical indicators, the incidence of cardiovascular events in the baseline FO group was 1.850 times of the non-FO group (95%CI: 1.046-3.271, P=0.034). The incidence of cardiovascular events in the continuous FO group was 4.679 times of the continuous non-FO group (95%CI: 2.189-10.002, P<0.001). The incidence of cardiovascular events in the intermittent FO group was 3.410 times of the continuous non-FO group (95%CI: 1.696-6.857, P=0.001). Conclusions: OH value measured by bioelectrical impedance can be used as an important reference index for clinical monitoring of cardiovascular events in MHD patients. Continuous chronic and intermittent exposures to FO are risk factors for cardiovascular events in hemodialysis patients.

[Correlational verification of drug-induced liver injury with HLA-B*35:01 allele due to Polygonum multiflorum].

In order to verify the correlation between Polygonum multiflorum-induced liver injury and HLA-B*35 : 01 alleles, six hospitalized patients diagnosed with Polygonum multiflorum-induced liver injury (PM-DILI) were selected, and their clinicopathological data were collected. Simultaneously, blood HLA-B* 35 : 01 allele detection was performed. Among the six PM-DILI cases, 4 were male, aged 38.83 ± 10.13 years old. The types of liver injury were hepatocellular injury types in all, and the severity of liver injury in five cases was grade 3. The histological presentations were acute hepatitis and acute cholestatic hepatitis. PM-DILI cases were all HLA-B*35:01 carriers, with a carrier rate of 100%. This finding indicates that PM-DILI is significantly correlated with HLA-B*35:01 alleles. Therefore, HLA-B*35 : 01 alleles can be used as an important predictive indicator for PM-DILI.

A novel FGFR1-binding peptide attenuates the degeneration of articular cartilage in adult mice.

OBJECTIVE: We previously reported that genetic ablation of (Fibroblast Growth Factors Receptors) FGFR1 in knee cartilage attenuates the degeneration of articular cartilage in adult mice, which suggests that FGFR1 is a potential targeting molecule for osteoarthritis (OA). Here, we identified R1-P1, an inhibitory peptide for FGFR1 and investigated its effect on the pathogenesis of OA in mice induced by destabilization of medial meniscus (DMM). DESIGN: Binding ability between R1-P1 and FGFR1 protein was evaluated by enzyme-linked immuno sorbent assay (ELISA) and molecular docking. Alterations in cartilage were evaluated histologically. The expression levels of molecules associated with articular cartilage homeostasis and FGFR1 signaling were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry (IHC). The chondrocyte apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay. RESULTS: R1-P1 had highly binding affinities to human FGFR1 protein, and efficiently inhibited extracellular signal-regulated kinase (ERK)1/2 pathway in mouse primary chondrocytes. In addition, R1-P1 attenuated the IL-1ß induced significant loss of proteoglycan in full-thickness cartilage tissue from human femur head. Moreover, this peptide can significantly restore the IL-1ß mediated loss of proteoglycan and type II collagen (Col II) and attenuate the expression of matrix metalloproteinase-13 (MMP13) in mouse primary chondrocytes. Finally, intra-articular injection of R1-P1 remarkably attenuated the loss of proteoglycan and the destruction of articular cartilage and decreased the expressions of extracellular matrix (ECM) degrading enzymes and apoptosis in articular chondrocytes of mice underwent DMM surgery. CONCLUSIONS: R1-P1, a novel inhibitory peptide for FGFR1, attenuates the degeneration of articular cartilage in adult mice, which is a potential leading molecule for the treatment of OA.

Reactivity of patients with maintenance hemodialysis to erythropoietin in the treatment of renal anemia.

To explore the reactivity of patients with renal anemia (MHD) to erythropoietin (EPO) in maintenance hemodialysis (HD), 31 patients were enrolled in this study. According to the level of serum ferritin (SF), they were divided into two groups; one group received treatment using recombinant human erythropoietin (rHuEPO) and the other group was given iron sucrose. Taking terminal EPO dosage, terminal erythropoietin resistance index (ERI) and rate of change of ERI (ΔERII) as target indexes, the influence of SF level on dosage of EPO was evaluated after usage conditions of relevant substances in a 3-month period. The results revealed that differences of dialysis age, albumin (ALB), blood calcium, initial and terminal SF, variable quantity of hemoglobin (Hb), terminal EPO and ERI between two groups had statistical significance. Furthermore, SF level and terminal EPO (r = -0.37, P < 0. 05) as well as SF level and terminal ERI (r = - 0.39, P <0.05) were negatively correlated. Difference of terminal ERI between the two groups had statistical significance. It can therefore be summarized that supplementing an iron agent intravenously to maintain SF level between 500 ng/ml and 1200 ng/ml may improve reactivity of patients with MHD to EPO. In addition, rHuEPO therapy in treating anemia of patients with MHD has the same effect with intravenous drug delivery, less side effects and is easy to administer.

Effects of sodium ferrous chlorophyll treatment on anemia of hemodialysis patients and relevant biochemical parameters.

This study explores the effects of sodium ferrous chlorophyll treatment on the anemia of maintenance hemodialysis (MHD) patients, as well as the relevant biochemical parameters. We selected 72 patients who had received regular MHD treatment two or three times a week for more than 3 months in the Hospital of Traditional Chinese Medicine of Zhengzhou City of Henan Province from March 2014 to March 2016. They were equally divided into a treatment group and a control group. Haemoglobin (HB) and hematocrit (HCT) of the treatment group increased significantly after treatment (p < 0.01), but less in the control group (p < 0.05); Also serum ferritin (SF) and transferrin saturation (TAST) of the treatment group increased significantly after treatment (p < 0.01); SF of the control group also increased significantly (p < 0.01) and TAST of the control group increased (p < 0.05) but less than in the treatment group. No obvious changes of serum creatinine (SCR), blood urea nitrogen (BUN), C-reactive protein (CRP) and superoxide dismutase (SOD) were found in either groups after treatment (p>0.05). Albumin (ALB) dosage of the treatment group increased after treatment (p < 0.05) while hemopoietin (EPO) decreased significantly (p < 0.01). ALB and EPO of the control group had no obvious changes after treatment (p>0.05). ALB level of the treatment group increased more significantly than in the control group (p < 0.05), while EPO dosage decreased more significantly than in the control group (p <0.05). Therefore, the combination of conventional western medicine and sodium ferrous chlorophyll can effectively improve anemia conditions of MHD patients and their quality of life.

The flavonoid from Polygonum perfoliatum L. inhibits herpes simplex virus 1 infection.

Herpes simplex virus 1 (HSV-1) is one of the most prevalent human pathogens in both industrialized and developing countries. This study was performed to analyze the antiviral activity of purified flavonoid from Polygonum perfoliatum L. against HSV-1 infection in vitro and in vivo. Flavonoid showed no inhibitory effect, when treated before virus infection, but it strongly inhibited viral replication and cell-to-cell spread which was vital for the virus's propagation. The therapeutic effect of the flavonoid in treating HSV-1 induced encephalitis was also investigated in mice. A dose-dependent increase of survival rate and mean survival time (MST) were observed in the flavonoid-treated mice. These results suggested that the flavonoid may be a viable therapeutic option for recurrent HSV-1 infection.

[Frequency-specific responses of human brain to peripheral transcutaneous electric nerve stimulation: a functional magnetic resonance imaging study].

The purpose of the present investigation was to determine the responses of human brain to transcutaneous electric nerve stimulation (TENS) at different frequencies by functional magnetic resonance imaging (fMRI) examinations covering the whole brain of eleven healthy volunteers. Each subject received TENS at acupoints ST36 and SP6 of the left leg at the frequencies of 2 and 100 Hz. Frequency-specific responses were found in motor-related areas, thalamus, limbic system and associated cortex to stimulation of the two frequencies, while the primary somatosensory areas were activated by both. Therefore, it appears that 2 and 100 Hz TENS act through different neuro-pathways in the central nervous system.

[Progress in the study of pain by brain imaging].

This review deals with the recent functional brain imaging studies of pain. In summary, the sensory-discriminative component of pain is related with the lateral thalamus, primary and secondary somatosensory area and insular cortices, while the posterior parietal and prefrontal cortices seem to play a role in the cognitive-attentional process of nociceptive information. Different parts of anterior cingulate gyrus are correlated with cognitive and emotional aspects of pain. Brain imaging data obtained from clinical patients suffering from various kinds of pain especially neuropathic pain, were discussed at the end of this article.

Peripheral electric stimulation inhibits morphine-induced place preference in rats.

Conditioned place preference (CPP) is a commonly used model to detect rewarding effect of drugs. To observe the effect of peripheral electric stimulation (PES) on morphine-induced CPP, we trained the rats with morphine in a CPP paradigm. Twelve hours before the testing phase, rats were given PES via stainless-steel needles with frequencies of 2, 100, or 2/100 Hz, respectively. PES of 2 and 2/100 Hz significantly decreased CPP in morphine-trained animals in a naloxone reversible manner, while PES of 100 Hz, foot shock, needle insertion, or plain restraining, showed no effect. Thus, PES with a low-frequency component (2 Hz) could specifically inhibit the expression of morphine-induced CPP, presumably via activation of opioid receptors.

[Cell cycle analysis and pathological changes of malignant tumors treated with electrochemical therapy].

To investigate the mechanism and to observe the effectiveness of electrochemical therapy(ECT), 33 patients of late stage cancers which treated by ECT were included in this study. Flow cytometry (FCM) and pathology were used to observe the changes of tumor cells before and after ECT. Tumor cells of G1, G2/M, S phases and aneuploid cells were found to be killed almostly and the ratio of apoptosis was elevated greatly after ECT. Also, pathological evidence proved the death of tumor cells and some characters of apoptosis. So, ECT can non-selectively kill tumor cells and induce the apoptosis of them, and FCM was a way to evaluate the effectiveness of ECT.

[Treatment of 121 heroin addicts with Han's acupoint nerve stimulator].

OBJECTIVE: To observe the Han's Acupoint Nerve Stimulator (HANS) for the treatment of heroin addicts. METHODS: One hundred and eighty-one cases of heroin addiction with obvious withdrawal syndrome were selected. Among them, 121 cases were randomly assigned to be treated with HANS, and the other 60 cases was taken as the control group. In the HANS group, patients were treated with HANS from the second day of their admission in the treatment center (when the withdrawal symptoms were obvious), they were given 4 treatments (30 min each) a day at the first 3 days, twice a day for 3 more days, and once a day 7 days later. The total treatment lasted 15 days. The acupoints selected were Hegu (LI4) and Laogong (PC 8) on one hand, Neiguan (PC 6) and Waiguan (SJ 5) on the other hand, and Zusanli (ST 36), Sanyinjiao (SP 6) on both legs. The frequency was 2/100 Hz, the intensities of the stimulations were 12-16 mA on arms and 16-26 mA on legs. All the manipulations in the control group were the same as in the HANS group, except that electrodes were placed at the acupoints without any electrical stimulation. RESULTS: There was no significant difference (P < 0.05) on the 8 indices (heart rate, body weight, sleeping time, chilling, pain, anxiety, catarrh and craving) observed between the 2 groups before treatment. After the HANS treatment, all the 8 indices improved significantly as compared with those observed before treatment (P < 0.01), while in the control group only a moderate improvement was observed. CONCLUSION: HANS is obviously effective in relieving the withdrawal syndrome in heroin addicts.

Tea polyphenols as inhibitors of mutagenicity of major classes of carcinogens.

Previous research suggested that the mutagenicity of some genotoxic carcinogens, mainly heterocyclic amines, was decreased by green or black tea extracts, or tea polyphenol fractions. Thus, it seemed important to test a variety of genotoxic carcinogens with distinct chemical structures and means of biochemical activation as regards modification of mutagenicity in appropriate strains of Salmonella typhimurium by 3 concentrations of polyphenols 60, 100, or B, standard commercial polyphenol preparations from green or black tea. Polyphenols sharply decreased the mutagenicity of a number of aryl- and heterocyclic amines, of aflatoxin B1, benzo[a]pyrene, 1,2-dibromoethane, and more selectively, of 2-nitropropane, all involving an induced rat liver S9 fraction. Good inhibition was found with 2 nitrosamines that required a hamster S9 fraction for biochemical activation. No effect was found with 1-nitropyrene, and with the direct-acting (no S9) 2-chloro-4-methyl-thiobutanoic acid. Thus, with some exceptions, polyphenols considerably decreased the mutagenicity of diverse types of carcinogens.

[A study on the cumulative effect of repeated electroacupuncture on chronic pain].

Clinical and animal studies were performed to evaluate the effect of repeated transcutaneous electric nerve stimulation (TENS) applied on acupoints of pain patients and the effect of repeated electroacupuncture (EA) at acupoints of the rat on experimental arthritic pain models. Attempts were also made to evaluate whether substance P (SP), cholecystokinin octopeptide (CCK-8), and met5-enkephalin (MEK) are involved in the mechanism of the cumulative effect of repeated EA on experimental arthritis using neuropharmacological (receptor antagonists) and neurochemical (radioimmunoassay, RIA) approach. The main results show that repeated TENS of 100 Hz relieves spinal spasticity in a cumulative manner, while TENS of 2/15 Hz is effective in relieving chronic pain. In animal chronic pain models, repeated EA suppressed the hyperalgesia in arthritic rats in a cumulative manner. Further studies revealed that in pain patients there was a plastic change in the release and metabolic rate of spinal opioid peptides. In arthritic rats there was also a change in the releasing rate of spinal SP, CCK-8, and MEK as compared to control rats, an effect modulated by repeated EA. These plastic changes occured under chronic pain condition and their modulation by repeated acupoint stimulation may explain the mechanisms of the cumulative effect of acupuncture on chronic pain.

[Influence of cerebral traumatic dementia treated with acupuncture at houxi and shenmen].

Sixty-two cerebral traumatic dementia patients were randomly divided into two groups acupuncture treatment group (Group A, 32 cases) and physical treatment group (Group B, 30 cases). The changes of MMSE scores and auditory P300 were observed before and after the treatment. It were found that the indexes in group A changed significantly (P < 0.05-0.001), and the indexes in group B didn't change significantly (P > 0.1-0.4). The therapeutic effect in group A was better than that in group B(P < 0.001). The results confirmed that the cognitive function of cerebral traumatic dementia patients was increased effectively with acupuncture at Houxi and Shenmen.

Detection of K-ras mutation in colonic effluent samples from patients without evidence of colorectal carcinoma.

BACKGROUND: K-ras gene mutation appears in more than 50% of patients with colon tumors. Both its frequency and early appearance may qualify this mutation as a potential biomarker. To enable early detection of mutant K-ras alleles, we had previously developed a sensitive polymerase chain reaction (PCR)-based assay, i.e., enriched PCR, which enables detection of one mutant K-ras allele present within 10,000 normal alleles. Using the enriched PCR, we were able to detect mutant K-ras alleles in "normal-appearing" colonic mucosa in patients with colorectal cancer. PURPOSE: A study was initiated to determine whether mutant K-ras alleles could be identified in colonic effluent samples of patients who may be at risk to develop colorectal cancer. METHODS: Over 9 years, colonic effluent samples were collected prior to routine colonoscopy from 39 patients who were apparently free of colorectal cancer. These samples were collected from patients with a family history of colorectal cancer (n = 7), adenomatous polyps (n = 7), previously resected colorectal cancer (n = 5), inflammatory bowel disorders (n = 13), normal colonoscopic examination (n = 6), and familial adenomatous polyposis (n = 1). All of the samples were double coded and analyzed for K-ras gene mutation. RESULTS: Of the 39 patients, seven were found to harbor mutant K-ras codon 12 alleles. Mutations were found in patients with a family history of colorectal cancer (three of seven), adenomatous polyps (one of seven), previously resected colorectal carcinoma (two of five), and familial adenomatous polyposis (one of one). In one case, effluent was found to harbor a mutant K-ras allele 4 years before the patient was diagnosed with colorectal cancer. CONCLUSIONS: (a) Effluent samples contain enough DNA to be detected with enriched PCR. Such samples may well be representative of the entire colon in general as opposed to a localized area such as that usually analyzed during colonoscopy. (b) K-ras gene mutation can be identified in routinely obtained colonic washings of patients who are at risk of developing colorectal cancer. Such mutations were absent in patients with inflammatory bowel disorders and in those who had undergone normal colonoscopic examinations. Detection of K-ras mutation in colonic washings may assist in identifying patients who may be at high risk for developing adenocarcinoma of the colon. IMPLICATIONS: The ability to examine colonic effluents provides a powerful and convenient source of sampling and may be adapted for future large-scale screening.

[Enkephelinase inhibitors acetorphan and SCH34826 potentiate the analgesic effect of low frequency electroacupuncture in rats].

Influence of two novel enkephelinase inhibitors, Acetorphan and SCH34826, on the effect of electroacupuncture analgesia (EAA) has been observed in rats. Administered Acetorphan (2.0-4.0 mg/kg, i.p.) or SCH34826 (30-100 mg/kg, p.o.) potentiated and prolonged the effect of 2 Hz EAA significantly in the nonresponder in which an evident analgesic effect can not be induced by 2 Hz electroacupuncture. This means that che non-responder of 2 Hz EAA can be converted into the responder with these two drugs. The non-responder of 100 Hz EAA, however, can not be changed into the responder with Acetorphan. These results again support our previous reports that enkephelin plays an important role in low frequency EAA. Meanwhile, this suggests us a probable route for potentiating acupuncture analgesia in clinical practice.