Microglia in drug addiction:A perspective from neuroimmunopharmacology

Drug addiction refers to a state of dependence that arises from habitual drug intake and can result in specific withdrawal symptoms upon cessation.The most commonly abused substances include psychostimulants,cannabinoids,and opioids.When drugs are consumed,they stimulate the release of dopamine,a neurotransmitter crucial for the pleasure and reward centers of the brain.With repeated drug use,the brain undergoes various changes,leading to tolerance,dependence,and addiction(Lüscher et al.,2020).The mechanisms involved in drug addiction are highly complex and involve diverse cell types within the brain.

Superficial femoral artery pseudoaneurysm at implantation site of drug eluting stent discovered due to bacteremia:A case report

BACKGROUND Drug-eluting stents(DES)are used to treat lower extremity arterial disease.During DES treatment,aneurysmal degeneration occasionally occurs,especially with fluoropolymer-based DES.However,the incidence of pseudoaneurysms after DES placement is rarely reported in the lower extremity region,although there have been several reports on pseudoaneurysm formation after DES placement in the coronary artery region.CASE SUMMARY We report the case of a 64-year-old man who presented with fever and pain in his left hand after dialysis.Bacteremia was diagnosed by blood culture,and after admission,he developed pain on the medial side of the right thigh.A pseudoaneurysm was observed in the right superficial femoral artery(SFA)at the proximal end of a previously placed DES.The bacteremia was thought to have been caused by a pseudoaneurysm of the left superficial brachial artery,and the pseudoaneurysm of the left superficial brachial artery was removed after antibiotic treatment.The pseudoaneurysm of the right SFA rapidly expanded after admission,but the expansion rate was reduced after infection control.Seven months after the first admission,the pseudoaneurysm of the left SFA was re-moved and in situ revascularization performed using a rifampicin-soaked Dacron graft.CONCLUSION Although pseudoaneurysm after DES placement in the lower extremity region is rare,it must be considered in patients with bacteremia.

Interpeduncular cistern intrathecal targeted drug delivery for intractable postherpetic neuralgia: A case report

BACKGROUND Intractable postherpetic neuralgia(PHN)can be difficult to manage even with aggressive multimodal therapies.Patients who experience uncontrolled refractory cranial PHN despite conservative treatment may benefit from an intrathecal drug delivery system(IDDS).For craniofacial neuropathic pain,the traditional approach has been to place the intrathecal catheter tip below the level of the cranial nerve root entry zones,which may lead to insufficient analgesia.CASE SUMMARY We describe a 69-year-old man with a 1-year history of PHN after developing a vesicular rash in the ophthalmic division of cranial nerve V(trigeminal nerve)distribution.The pain was rated 7-8 at rest and 9-10 at breakthrough pain(BTP)on a numeric rating scale.Despite receiving aggressive multimodal therapies including large doses of oral analgesics(gabapentin 150 mg q12 h,oxycodone 5 mg/acetaminophen 325 mg q6 h,and lidocaine 5%patch 700 mg q12 h)and sphenopalatine ganglion block,there was no relief of pain.Subsequently,the patient elected to have an implantable IDDS with the catheter tip placed at the interpeduncular cistern.The frequency of BTP episodes decreased.The patient’s continuous daily dose was adjusted to 0.032 mg/d after 3 mo of follow-up and stopped 5 mo later.He did not report pain or other discomfort at outpatient follow-up 6 mo and 1 year after stopping intracisternal hydromorphone.CONCLUSION The use of interpeduncular cistern intrathecal infusion with low-dose hydromorphone by IDDS may be effective for severe craniofacial PHN.

Pembrolizumab-induced psoriatic arthritis treated with disease-modifying anti-rheumatic drugs in a patient with gastric cancer:A case report

BACKGROUND Immune checkpoint inhibitor(ICI)-induced rheumatic immune-related adverse events(ir AEs)have been infrequently reported,and the treatment of severe or refractory arthritis as ir AEs has not been established yet.CASE SUMMARY The patient was a 67-year-old man with a history of well-controlled foot psoriasis who presented with polyarthralgia.He had received pembrolizumab for metastatic gastric adenocarcinoma 2 mo previously.Physical examination revealed erythematous swelling in the distal interphalangeal joints,left shoulder,and both knees.He had plaque psoriasis with psoriatic nail dystrophy and dactylitis in the distal joints of the fingers and toes.Inflammatory markers including C-reactive protein and erythrocyte sedimentation rate were elevated but rheumatoid factor and anticyclic citrullinated peptide antibody were negative.The patient was diagnosed with psoriatic arthritis(PsA)and started on methylprednisolone 1 mg/kg/day after pembrolizumab discontinuation.However,despite 1 wk of methylprednisolone treatment,PsA worsened;hence,leflunomide and methotrexate were started.After 4 wk of steroid treatment,PsA worsened and improved repeatedly with steroid tapering.Therefore,the therapy was intensified to include etanercept,a tumor necrosis factor inhibitor,which ultimately resulted in adequate PsA control.CONCLUSION This is the first report of ICI-induced PsA in a gastric cancer patient.Some rheumatic ir AEs with refractory severe arthritis may require disease-modifying anti-rheumatic drugs and long-term management.

Drug induced autoimmune hepatitis:An unfortunate case of herbal toxicity from Skullcap supplement:A case report

BACKGROUND The surge in traditional herbal dietary supplement(HDS)popularity has led to increased drug-induced liver injuries(DILI).Despite lacking evidence of efficacy and being prohibited from making medical claims,their acceptance has risen over sevenfold in the last two decades,with roughly 25%of United States(US)adults using these supplements monthly.An estimated 23000 emergency room visits annually in the US are linked to HDS side effects.NIH-funded research suggests HDS contribute to 7-20%of DILI cases,with similar trends in Europe—Spain reporting 2%and Iceland up to 16%.Patients with acute liver failure from HDS undergo liver transplantation more frequently than those from prescription medicines.Here we describe a case of drug-induced autoimmune hepatitis due to Skullcap supplements,this association appears to be the first documented instance in literature.CASE SUMMARY A middle-aged Caucasian woman,previously healthy,presented with sudden jaundice.Four months earlier,her liver enzymes were normal.She mentioned recent use of Skullcap mushroom supplements.Tests for chronic liver disease were negative.The first liver biopsy indicated severe resolving drug-induced liver injury.Despite treatment,she was readmitted due to worsening jaundice.Followup tests raised concerns about autoimmune hepatitis.A subsequent biopsy confirmed this diagnosis.The patient responded as expected to stopping the medication with improvement in liver enzymes.CONCLUSION This scenario highlights an uncommon instance of DILI caused by Skullcap supplements.It's crucial for hepatologists to recognize this connection due to the increasing prevalence of herbal supplements.

Comparison of drug concentrations in blood and gastric lavage fluid before and after gastric lavage:A case report

BACKGROUND Gastric lavage(GL)is one of the most important early therapies to remove unabsorbed toxins from the gastrointestinal tract.However,the details of performing gastric lavage remain to be established.There is controversy in clinical practice regarding individual choice of the timing of GL and its efficiency.CASE SUMMARY We report the case of a young woman who presented to the Emergency Department with drug intoxication for four hours.We used the latest toxicological screening techniques to compare drug concentrations in the patient's blood and gastric lavage fluid before and after gastric lavage.The results confirmed that gastric lavage was effective in reducing drug concentrations in the stomach;a small amount of drug remained in the stomach at the end of gastric lavage.CONCLUSION Gastric lavage is effective in reducing drug concentrations in the stomach,with a small amount of drug remaining in the stomach at the end of gastric lavage.

Problematic Internet use in drug addicts under treatment in public rehab centers

BACKGROUND Problematic Internet use(PIU)or Internet addiction has been recognized to be a behavioral addiction characterized by excessive or poorly controlled preoccupations,urges,or behaviors regarding computer use and Internet access that leads to impairment or distress resembling substance abuse.AIM To investigate the prevalence and characteristics of Internet use and abuse in a group of drug addicts from Southern Italy,by means of a specific questionnaire[“Questionario sull’Utilizzo delle Nuove Tecnologie”(QUNT)].METHODS All subjects(183)were heavy smokers,almost 50%of them used heroin and/or opioid compounds,30%alcohol,10%cannabis,8%cocaine,and 5%were polydrug users.Almost 10%of the individuals were also suffering from gambling disorder.RESULTS The time spent online was more than 4 hours a day in the total sample,with a slight prevalence in male subjects.Cocaine and cannabis users spent more than 6 hours online,significantly more than opioid and alcohol abusers.Distribution of the QUNT factors was not different in both sexes.Cocaine users showed higher scores at the“loss of control”,“pornography addiction”,and“addiction to social networks”factors,for the stimulant effect of this substance.Moreover,15 out of the total 17 cocaine users were pathological gamblers.Positive and statistically significant relationships were observed between some QUNT factors and body mass index.CONCLUSION These findings indicate that PIU is less severe in subjects taking sedative substances,such as heroin/opioids and alcohol,than in subjects taking stimulants.Alternatively,it may be used as a“stimulant”trigger in cocaine and cannabis users.Flattening effect of abuse drugs was noted on possible sex-related differences in QUNT items.We observed a sort of“protective”effect of a love relationship and/or living together with a partner,as those engaged subjects showed lower scores on different items than single subjects or those living alone.The relationship between time spent online(and related sedentary lifestyle)and body mass index would suggest that Internet use might be a contributing factor to increasing weight gain and obesity amongst adolescents and young adults worldwide.Our findings also highlighted the specific vulnerability of drug addicts who use stimulants,rather than sedative compounds,to other kinds of behavioral addictions,such as gambling disorder.

Comparison of brain functions between healthy participants and methamphetamine users with various addiction histories:Data analysis based on EEG and fNIRS

The electroencephalogram(EEG)rhythm and functional near-infrared spectroscopy(fNIRS)activation levels have not been compared between a healthy control group(HCG)and methamphetamine user group(MUG)with different addiction histories.This study used 64-electrode EEG and fNIRS to conduct an experiment that analyzed the resting and craving states.The EEG and fNIRS data of 56 participants were collected,including 14 healthy participants,14 methamphetamine users with an addiction history of 0.5–5 years,14 users with an addiction history of 5–10 years,and 14 users with an addiction history of 10–15 years.Isolated effective coherence(iCoh)within the brain network was used to process the EEG data.Statistical analysis was performed to compare differences in iCoh among the delta,theta,alpha,beta,and gamma bands and explore oxyhemoglobin activation levels in the ventrolateral prefrontal cortex,dorsolateral prefrontal cortex,orbitofrontal cortex,and frontopolar prefrontal cortex(FPC)of the control group.Finally,the Kmeans,Gaussian mixed model(GMM),linear discriminant analysis(LDA),support vector machine(SVM),Bayes,and convolutional neural networks(CNN)algorithms were used to classify methamphetamine users based on drug and neutral images.A 3-class accuracy was achieved.Changes in EEG and fNIRS activation levels of HCG and MUG with varied addiction histories were demonstrated.

Effect of Ultrasound-Guided Transversus Abdominis Plane Block Combined with Lornoxicam on Pain and Recovery Quality After Abdominal Surgery in Patients with Drug Addiction

Objective:This paper aims to analyze the analgesic effect of ultrasound-guided transversus abdominis plane block(TAPB)combined with non-steroidal anti-inflammatory analgesic drug lornoxicam on abdominal surgery in patients with a history of drug addiction.Methods:32 patients aged 18-60 who underwent lower abdominal surgery in the First People's Hospital of Liangshan Yi Autonomous Prefecture and Butuo County People's Hospital of Liangshan Yi Autonomous Prefecture from January 2022 to March 2023 were selected,the patients must have drug abuse history for more than 1 year,with a history of drug withdrawal and relapse.The patients were divided into observation group and control group by the envelope method,with 16 cases in the observation group and 16 cases in the control group.Two groups of patients underwent ultrasound-guided bilateral transversus abdominis plane block after the operation.The observation group was treated with dexmedetomidine hydrochloride 1μg/kg+0.25%ropivacaine hydrochloride 40ml,and the control group was treated with 40ml 0.9%sodium chloride injection,the two groups of patients returned to the ward after operation and given intravenous infusion of lornoxicam for relieving the pain.The visual analogue scale(VAS)score of postoperative pain,the times of rescue analgesia,the time of postoperative anal exhaust,the time of ambulation,nausea and vomiting,withdrawal symptoms,related adverse reactions,and hospitalization days were compared between the two groups.Results:The VAS score of postoperative pain in the observation group was significantly lower than that in the control group,P<0.05.Patients in the observation group used less postoperative rescue analgesics than those in the control group,P<0.05.For postoperative anal exhaust time,the difference between the two groups of patients was relatively small,and the time in the observation group was shorter,P>0.05.The time to get out of bed and the length of hospital stay were not significantly different between the control group and the observation group,P>0.05.The withdrawal symptoms of the patients in the observation group were better,P<0.05,nausea and vomiting,and other adverse reactions were lower in the control group,P<0.05.Conclusion:Ultrasound-guided transversus abdominis plane block combined with lornoxicam can be used to relieve pain in abdominal surgery for patients with drug addiction,which can effectively improve the therapeutic effect of patients and reduce the number of postoperative rescue analgesia.Thus,it has high clinical application value.

Conversion therapy in advanced perihilar cholangiocarcinoma based on patient-derived organoids:A case report

BACKGROUND Patient-derived organoids(PDOs)have been demonstrated to predict the response to drugs in multiple cancer types.However,it remains unclear about its application in cholangiocarcinoma.CASE SUMMARY A 59-year-old woman was admitted to the hospital due to upper abdominal pain for over 8 months.According to relevant examinations,she was diagnosed as perihilar cholangiocarcinoma(pCCA)with intrahepatic metastasis and perihilar lymphatic metastasis.After multidisciplinary team discussion,percutaneous transhepatic cholangiodrainage was performed to relieve biliary obstruction,and puncture biopsy was conducted to confirm the pathological diagnosis.Transarterial chemoembolization with nab-paclitaxel was used in combination with toripalimab and lenvatinib,but the levels of tumor markers including alpha fetal protein,carcinoembryonic antigen,carbohydrate antigen 15-3 and cancer antigen 125 were still raised.The PDO for drug screening showed sensitive to gemcitabine and cisplatin.Accordingly,the chemotherapy regimen was adjusted to gemcitabine and cisplatin in combination with toripalimab and lenvatinib.After 4 cycles of treatment,the tumor was assessed resectable,and radical surgical resection was performed successfully.One year after surgery,the patient was still alive,and no recurrence or occurred.CONCLUSION PDOs for drug sensitivity contribute to screening effective chemotherapy drugs for advanced pCCA,promoting conversion therapy and improving the prognosis.

Advanced Lung Adenocarcinoma with EGFR 19-del Mutation Transformed into SCC after EGFR-tyrosine Kinase inhibitors Treatment:A Case report

BACKGROUND Epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)significantly improve the survival of patients with Epidermal growth factor receptor(EGFR)sensitive mutations in non-small cell lung cancer(NSCLC).CASE SUMMARY A 67-year-old female patient in advanced lung adenocarcinoma suffered from drug resistance after EGFR-TKIs treatment.Secondary pathological tissue biopsy confirmed squamous cell carcinoma(SCC)transformation.Patients inevitably encountered drug resistance issues after receiving EGFR-TKIs treatment for a certain period of time,while EGFR-TKIs can significantly improve the survival of patients with EGFR-sensitive mutations in NSCLC.Notably,EGFR-TKIs resistance includes primary and acquired.Pathological transformation is one of the mechanisms of acquired resistance in EGFR-TKIs,with SCC transformation being relatively rare.Our results provide more detailed results of the patient’s diagnosis and treatment process on SCC transformation after EGFR-TKIs treatment for lung adenocarcinoma.CONCLUSION Squamous cell carcinoma transformation is one of the acquired resistance mechanisms of EGFR-TKIs in advanced lung adenocarcinoma with EGFR mutations.

The Effectiveness of Mindfulness Therapy in Controlling under Treatment Addicts’ Drug Cravings

The present study aimed to examine the effectiveness of mindfulness therapy in controlling under treatment addicts’ drug cravings. This was a quasi-experimental study with pretest and posttest. The sample of this study included 30 under treatment male addicts whom were selected through applying random sampling method and were placed in two groups, experimental and control. After holding a preliminary session aiming at aiding the experimental group to become familiar with the procedure, 8 sessions of the mindfulness-based therapy were administered. Assessment tools were Craving Beliefs Questionnaire (CBQ) and the Depression Anxiety Stress Scale (DASS-21). After calculating mean and standard deviation, the obtained data were analyzed using covariance. The results indicated that the mindfulness therapy was significantly effective in controlling drug cravings, decreasing stress, anxiety, and depression of under treatment addicts (p < 0.05).

The“1＋1”Therapy for Drug Addicts

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KAP Survey of Turkish University Students on Sexuality,reproductive Health,Drug Addiction and Violence

Objective To investigate the attitudes, behaviours and reflections of the university students, on sexuality, reproductive health, violence, smoking, alcohol and drug use, and to find out their expectations from a youth health service. Methods A total of 5 300 students （1 880 girls, 3 420 boys）from various Jaculties of Kyrykkale University were enrolled into this cross-sectional study. Students completed the self-administered questionnaire as one of the researchers was present at the classroom. Research monitors five categories of priority health-risk behaviours among youth and young adults. Results Mean age of 3 420 male （64.5%） and 1 880female （35.5%） students were 20.3 years. Among all 4 380 （82,9%） students [1 350 girls （71.8%）, 3 030 boys （88.5%）] had some kinds of information about sexuality, however this dropped to 2 730 students （51.5%） within the context of adequacy. Friends were the major source （34%） for the first information on sexuality. Using a condom was the mostly heard method of contraception （46.9%） and interestingly 1.1% of the students had no knowledge on any of the protection methods. Among all 25.3% of the students （33.0% boys, 11.4% girls） had some kind of sexual intercourse, and within this group 58.8% experienced his/her first sexual relationship at 18 years of age and over; 53.9% were protected in all intercourses. Using a condom was the main way of protection for boys （63.7%） and pills were for the girls （73.9%）. None of the female students mentioned having an abortion but 8% had friends who had undergone abortion. Tobacco use was 35.1% among the group, and 8. 7% of the male and 3.6% of the female students were using drugs. Although 67. 4% students claimed they never witnessed violence between their parents, 43.2% witnessed violence among their siblings, 67.0% beween friends, 72.6% in the streets and 64.2% in the school. About 30.0% of the students reported having weight problems, and 14.7% admitted visiting a doctor for that problem. If there would be a service providedfor the adolescents in the university, 67% of the students would attend in case of a problem. Past experiences were important for us and we saw that among all 8% of the participants had some kind of sexual problem, within this group 50.7% felt uncomfortable during the visit and only 60.4% were satisfied with the care of the physician. Conclusion Our study results show the current situation of adolescents in Kyrykkale University and will be used to improve policies and programs to reduce priority healthrisk behaviours among youth of our and surrounding provinces and establish a youth friendly service in Kyrykkale University within this purposes.

Reliability and Validity of Addiction Severity Index in Drug Users with Methadone Maintenance Treatment in Guizhou Province, China

Objective To evaluate the reliability and validity of the Chinese version of addiction severity index （ASI）-5th version （ASI-C-5）, in illegal drug users receiving methadone maintenance treatment （MMT） in China. Methods One hundred and eighty-six heroin addicts （144 men and 42 women） receivihg MMT at three clinics in Guizhou province, southwest China, were recmited. They were all interviewed with a questionnaire of ASI-C-5 and 35 were re-interviewed at an interval of seven days to assess its test-retest reliability. Results Cronbach＇s alpha for internal consistency of CSs varied from 0.60 to 0.81 in all domains. Test-retest reliability of composite scores （CSs） of ASI-C-5 were satisfactory （r=0.38-0.97）. Based on item analysis and expert＇s suggestions, five items were deleted and one item was modified in ASI-C-5. Criterion validity of ASI-C-5 was found acceptable, as compared to addicts＇ self-rating anxiety scale （SAS） and self-rating depression scale （SDS） （r=0.59 and 0.45） except for social support rating scale （SSRS）. Conclusions ASI-C-5 can be used for heroin addicts receiving MMT with acceptable reliability and validity.

Neurotransmitter-precursor-supplement Intervention for Detoxified Heroin Addicts

This study examined the effects of combined administration of tyrosine, lecithin, L-glutamine and L-5-hydroxytryptophan （5-HTP） on heroin withdrawal syndromes and mental symptoms in detoxified heroin addicts. In the cluster-randomized placebo-controlled trial, 83 detoxified heroin addicts were recruited from a detoxification treatment center in Wuhan, China. Patients in the intervention group （n=41） were given the combined treatment with tyrosine, lecithin, L-glutamine and 5-HTP and those in the control group （n=42） were administered the placebo. The sleep status and the withdrawal symptoms were observed daily throughout the study, and the mood states were monitored pre- and post-intervention. The results showed that the insomnia and withdrawal scores were significantly improved over time in participants in the intervention group as compared with those in the control group. A greater reduction in tension-anxiety, depression-dejection, anger-hostility, fatigue-inertia and total mood disturbance, and a greater increase in their vigor-activity symptoms were found at day 6 in the intervention group than in the control group （all P〈0.05）. It was concluded that the neurotransmitter-precursor-supplement intervention is effective in alleviating the withdrawal and mood symptoms and it may become a supplementary method for patients＇ recovery from heroin addiction.

Non-human primate models in drug addiction deserve more attention

Dear Editor, The process of relapse involves firm or aberrant memories of environmental cues associated with drug craving or addiction. To date, it is not known where these memories are stored in the brain, what kinds of regulatory biological factors or molecules are involved, nor why it is so difficult to stop addiction psychologically. Currently, rodent animal models, such as the self-administration and conditioning place preference / aversion paradigm are still widely used in the studies of drug withdrawal syndromes or drug-associate memories. However, the differences between humans and rodents--particularly in terms of genetics, and pathology and pharmacology--have significantly limited the application of further studies on this topic. Essentially, rodents lack the longterm or life-time memories humans possess and lose their drug-associated memory only after a few weeks of withdrawal.

Incidence of Interpersonal Violence among Individuals with Drug Addiction Receiving Compulsory Treatment: A Survey at Two Drug Detention Centers in Hunan, China

Drug dependence is a serious global health problem.To assist individuals with drug addiction,China alone has established 678 Compulsory Detoxification Detention Centers （CDDCs） that treat over300,000i ndividuals who are required by national law to receive compulsory treatment;because community-based outpatient treatment failed.

BCI+VR Rehabilitation Design of Closed-Loop Motor Imagery Based on the Degree of Drug Addiction

After abusing drugs for long,drug users will experience deteriorated self-control cognitive ability,and poor emotional regulation.This paper designs a closed-loop virtual-reality(VR),motorimagery(MI)rehabilitation training system based on brain-computer interface(BCI)(MI-BCI+VR),aiming to enhance the self-control,cognition,and emotional regulation of drug addicts via personalized rehabilitation schemes.This paper is composed of two parts.In the first part,data of 45 drug addicts(mild:15;moderate:15;and severe:15)is tested with electroencephalogram(EEG)and near-infrared spectroscopy(NIRS)equipment(EEG-NIRS)under the dual-mode,synchronous signal collection paradigm.Using these data sets,a dual-modal signal convolutional neural network(CNN)algorithm is then designed based on decision fusion to detect and classify the addiction degree.In the second part,the MIBCI+VR rehabilitation system is designed,optimizing the Filter Bank Common Spatial Pattern(FBCSP)algorithm used in MI,and realizing MI-EEG intention recognition.Eight VR rehabilitation scenes are devised,achieving the communication between MI-BCI and VR scene models.Ten subjects are selected to test the rehabilitation system offline and online,and the test accuracy verifies the feasibility of the system.In future,it is suggested to develop personalized rehabilitation programs and treatment cycles based on the addiction degree.

Sex differences in exercise and drug addiction:A mini review of animal studies

Growing literature has demonstrated that exercise may be an effective prevention and treatment option for drug addiction. In the past few years, many studies have suggested that there were sex differences in all phases of drug addiction. However, very limited research has investigated sex differences in the effectiveness of exercise intervention in drug addiction and rehabilitation. In this mini review, we summarize the effect of sex on the results of using exercise to prevent and treat drug addiction. The studies we consider span various animal models and use multiple types of exercise to examine the effectiveness of exercise on the neurobiological mechanism of exercise rehabilitation. We believe that exercise as an adjuvant intervention strategy can be applied better in drug addiction prevention and recovery. Copyright 2014, Shanghai University of Sport. Production and hosting by Elsevier B.V. All rights reserved.