A series of chemotherapeutic drugs that induce DNA damage, such as cisplatin (DDP), are standard clinical treatments for ovarian cancer, testicular cancer, and other diseases that lack effective targeted drug therapy. Drug resistance is one of the main factors limiting their application. Sensitizers can overcome the drug resistance of tumor cells, thereby enhancing the antitumor activity of chemotherapeutic drugs. In this study, we aimed to identify marketable drugs that could be potential chemotherapy sensitizers and explore the underlying mechanisms. We found that the alcohol withdrawal drug disulfiram (DSF) could significantly enhance the antitumor activity of DDP. JC-1 staining, propidium iodide (PI) staining, and western blotting confirmed that the combination of DSF and DDP could enhance the apoptosis of tumor cells. Subsequent RNA sequencing combined with Gene Set Enrichment Analysis (GSEA) pathway enrichment analysis and cell biology studies such as immunofluorescence suggested an underlying mechanism: DSF makes cells more vulnerable to DNA damage by inhibiting the Fanconi anemia (FA) repair pathway, exerting a sensitizing effect to DNA damaging agents including platinum chemotherapy drugs. Thus, our study illustrated the potential mechanism of action of DSF in enhancing the antitumor effect of DDP. This might provide an effective and safe solution for combating DDP resistance in clinical treatment.
Female ; Male ; Humans ; Cisplatin/pharmacology* ; Disulfiram/pharmacology* ; Testicular Neoplasms/drug therapy* ; Fanconi Anemia/drug therapy* ; Alcoholism/drug therapy* ; Drug Resistance, Neoplasm ; Cell Line, Tumor ; Substance Withdrawal Syndrome/drug therapy* ; Apoptosis ; Antineoplastic Agents/therapeutic use* ; Cell Proliferation

OBJECTIVE: To compare the clinical effect of SUN 's abdominal acupuncture and conventional acupuncture in the treatment of depression after methamphetamine withdrawal. METHODS: A total of 80 female patients with depression after methamphetamine withdrawal were randomly divided into an observation group (40 cases, 1 case dropped off) and a control group (40 cases, 2 cases dropped off). The control group was treated with conventional acupuncture at Baihui (GV 20), Yintang (GV 29), Taichong (LR 3), Shenmen (HT 7), Neiguan (PC 6), Danzhong (GV 17), and the observation group was treated with SUN 's abdominal acupuncture at area 1 of the abdomen and area 8 of the abdomen. Both groups were treated once a day, 30 min each time, 6 days as a course of treatment, 1 day rest between treatment courses, a total of 4 courses of treatment. The scores of withdrawal symptoms, Hamilton depression scale (HAMD), Pittsburgh sleep quality index (PSQI) scale and serum serotonin (5-HT) level were compared between the two groups before and after treatment. RESULTS: After treatment, the scores of withdrawal symptoms, HAMD and the various scores and total score of PSQI scale in the two groups were all lower than before treatment (P<0.01), and the scores of withdrawal symptoms, HAMD and the sleep quality, time to fall asleep, sleep time scores and total score of PSQI in the observation group were lower than the control group (P<0.05, P<0.01). After treatment, the serum 5-HT level of the two groups was increased (P<0.01), and that in the observation group was higher than the control group (P<0.05). CONCLUSION SUN 's abdominal acupuncture can improve withdrawal symptom, depression and sleep quality, increase serum 5-HT content in treatment of depression after methamphetamine withdrawal, and has better effect than conventional acupuncture.
Abdomen ; Acupuncture Points ; Acupuncture Therapy ; Depression/therapy* ; Female ; Humans ; Methamphetamine/adverse effects* ; Sleep Quality ; Substance Withdrawal Syndrome/therapy* ; Treatment Outcome

OBJECTIVES: To investigate the effect of sequential sedative and analgesic drugs in preventing delirium and withdrawal symptoms in children after ventilator weaning. METHODS: A retrospective analysis was performed on 61 children who were admitted and received mechanical ventilation support for ≥5 days in the Pediatric Intensive Care Unit of Dongguan Children's Hospital Affiliated to Guangdong Medical University from December 2019 to September 2021. The children were divided into a control group (30 children with no maintenance of analgesic and sedative drugs after ventilator weaning) and an observation group (31 children with sequential sedative and analgesic drugs maintained for 48 hours after ventilator weaning). The two groups were compared in terms of the Sophia Observation Withdrawal Symptoms Scale (SOS) score, the Pediatric Delirium Scale (PD) score, the Richmond Agitation-Sedation Scale (RASS) score, and the incidence rates of delirium or withdrawal symptoms at 24 and 72 hours after ventilator weaning. RESULTS: There was no significant difference in the incidence rate of delirium at 24 hours and 72 hours after ventilator weaning between the two groups (P>0.05). Compared with the control group, the observation group had significantly lower incidence rate of withdrawal symptoms and scores of SOS, PD, and RASS scales at 24 hours and 72 hours after ventilator weaning (P<0.01). CONCLUSIONS Sequential sedation and analgesia after ventilator weaning can reduce the incidence of withdrawal symptoms within 72 hours after ventilator weaning, but it cannot reduce the incidence rate of delirium.
Analgesia ; Analgesics/therapeutic use* ; Child ; Delirium/prevention & control* ; Humans ; Hypnotics and Sedatives/therapeutic use* ; Intensive Care Units, Pediatric ; Pain ; Prospective Studies ; Respiration, Artificial/adverse effects* ; Retrospective Studies ; Substance Withdrawal Syndrome/prevention & control* ; Ventilator Weaning

OBJECTIVE: To compare the clinical efficacy between auricular point sticking combined with transcutaneous electrical acupoint stimulation (TEAS) and nicotine patch for smoking cessation. METHODS: Two hundred patients who voluntarily quit smoking were randomly divided into a combination group and a nicotine patch group, 100 cases in each group. In the combination group, auricular point sticking (Shenmen [TF₄], Neifenmi [CO₁₈], Pizhixia [AT₄], Jiaogan [AH_6a], etc., once every other day) combined with TEAS（Lieque [LU 7] and Zusanli [ST 36], with continuous wave, 20 Hz in frequency, 1 mA in current intensity, 30 min each time, once a day) were applied. In the nicotine patch group, nicotine patch was applied. Both groups were treated for 8 weeks. The immediate withdrawal rate and persistent withdrawal rate 8 weeks into treatment and in follow-up of 16 weeks after treatment in the two groups were compared; before treatment, 8 weeks into treatment and in follow-up of 16 weeks after treatment, the degree of nicotine dependence was evaluated by using Fagerström test for nicotine dependence (FTND); 1 week into treatment, 8 weeks into treatment and in follow-up of 16 weeks after treatment, the withdrawal symptoms and smoking craving were evaluated by using Minnesota nicotine withdrawal scale (MNWS); the safety and compliance (dropped off rate and treatment completeness) were evaluated in the two groups. RESULTS: There was no statistical significance of the differences in the immediate withdrawal rate and persistent withdrawal rate 8 weeks into treatment and during follow-up between the two groups (P>0.05). The FTND scores were decreased 8 weeks into treatment and during follow-up in the two groups compared with those before treatment (P<0.01); the FTND score during follow-up in the combination group was lower than the nicotine patch group (P<0.05). The MNWS scores were decreased 8 weeks into treatment and during follow-up in the two groups compared with those 1 week into treatment (P<0.05); the changes of MNWS scores 8 weeks into treatment and during follow-up in the combination group were greater than the nicotine patch group (P<0.05, P<0.01). There were no serious adverse reactions in either group. Eight weeks into treatment and during follow-up, the dropped off rates were all 16.0% (16/100) in the combination group, which were 20.0% (20/100) and 23.0% (23/100) in the nicotine patch group, there was no statistical significance of the differences in the two groups (P>0.05). There was no significant difference in treatment completeness between the two groups (P>0.05). CONCLUSION Auricular point sticking combined with TEAS could effective decrease the degree of nicotine dependence, improve withdrawal symptoms in smokers, its effect is superior to nicotine patch.
Humans ; Smoking Cessation ; Tobacco Use Disorder ; Acupuncture Points ; Administration, Cutaneous ; Nicotine ; Substance Withdrawal Syndrome/drug therapy*

The purpose of this study was to investigate the effects of α₂ adrenergic receptor agonist dexmedetomidine on withdrawal symptoms in alcohol-dependent rats and the underlying mechanism, so as to provide a scientific basis for the treatment of alcohol withdrawal syndrome (AWS). Adult Sprague-Dawley (SD) male rats were orally administered with 6% aqueous alcohol continuously for 28 d to establish alcohol drinking model, and then stopped drinking to induce AWS. Enzyme-linked immunosorbent assay (ELISA) was used to determine the content of norepinephrine (NE) in the locus coeruleus and hippocampus of rats. Dexmedetomidine (5, 10, and 20 μg/kg) was intraperitoneally injected respectively when the rats showed significant AWS. In some rats, α₂ adrenergic receptor antagonist yohimbine was injected into hippocampus in advance. The results showed that, compared with the control group, the 6 h withdrawal group exhibited significantly increased AWS score and amount of repeat drinking. The NE contents in hippocampus and locus coeruleus of the last drinking and the 6 h withdrawal groups were significantly increased compared with those of the control group. Dexmedetomidine intervention significantly decreased AWS score and hippocampus NE content in the 6 h withdrawal group, while yohimbine could reverse these effects of dexmedetomidine. These results suggest that dexmedetomidine might improve the withdrawal symptoms in alcohol-dependent rats via activating α₂ adrenergic receptor.
Adrenergic alpha-2 Receptor Agonists/therapeutic use* ; Alcoholism/drug therapy* ; Animals ; Dexmedetomidine/therapeutic use* ; Hippocampus/metabolism* ; Male ; Norepinephrine ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic, alpha-2/metabolism* ; Substance Withdrawal Syndrome/drug therapy* ; Yohimbine/pharmacology*

Clinical studies published over the past two decades have consistently demonstrated the therapeutic efficacy and safety of anti-craving medications. To use anti-craving agents more effectively in clinical settings, it is important to set clear treatment goals. Because alcoholic patients have lost control of drinking alcohol, it is recommended to set ‘abstinence’ as a goal rather than ‘controlled drinking’. Indeed, the therapeutic effects of anti-craving medication are higher when abstinence is set as the target. On the other hand, if abstinence is the sole criterion, it is difficult to elicit the motivation of a patient who lacks motivation in clinical practice. In the case of patients who have not yet gained insight, the initial goal might be set to gradually reduce the amount of alcohol consumed and prevent at-risk heavy drinking. Even in this case, anti-craving can help clinically. To increase the effectiveness of anti-craving medications, it is best to start at least four to seven days after the patient has stopped drinking. If the patient has alcohol withdrawal symptoms, they should be treated first.
Alcoholics ; Craving ; Drinking ; Hand ; Humans ; Motivation ; Naltrexone ; Substance Withdrawal Syndrome ; Therapeutic Uses

Alcohol use disorder is a kind of chronic illness that is difficult to treat. The disorder often recurs easily and patients visit the outpatient clinic while intoxicated. Therefore, is often too difficult to treat all people of concern, i.e., the caregiver, patient, and doctor, due to the frequent helpless and hopeless relapse. If the patient has severe withdrawal symptoms or poor physical condition, it is very difficult to maintain treatment at an outpatient clinic. On the other hand, many patients abstain or reduce drinking and go on to live a sober life by outpatient-based management. In addition, psychosocial treatment techniques and efficient medications are available at the level of a psychiatric outpatient clinic. Under the scope and limitations of outpatient-based approaches, patients with alcohol use disorder can develop a new life called ‘recovery’ with the help of psychiatrists, by the way of motivating changes, correcting cognitive errors, establishing effective coping skills, utilizing external resources actively, and facilitating healthy roles with their families.
Adaptation, Psychological ; Alcoholism ; Ambulatory Care Facilities ; Caregivers ; Chronic Disease ; Drinking ; Drug Therapy ; Hand ; Humans ; Outpatients ; Psychiatry ; Psychotherapy ; Recurrence ; Substance Withdrawal Syndrome

PURPOSE: This study investigates pediatric nurses' knowledge and attitudes regarding iatrogenic narcotic analgesic withdrawal symptoms management (INAWSM).METHOD: In this cross-sectional study, 253 pediatric nurses working at a tertiary hospital in Seoul participated. Instruments were the inventory consisting questionnaires on 35 items knowledge and 12 items attitude for INAWSM. Further, descriptive statistics, t-test, and analysis of variance were used to evaluate the nurses' knowledge and attitudes.RESULTS: The correct answers rate of knowledge toward INAWSM was 44.9%. With respect to the pediatric nurses' attitudes, the participants scored an average value of 2.83±0.25 out of 4 points. The factor related to the knowledge and attitude level was age, pediatric nursing experience, educational experience, and educational needs.CONCLUSION: Results revealed that pediatric nurses had inadequate knowledge and attitude on INAWSM despite a compulsory education. Therefore, it is necessary to develop an efficient INAWSM educational program.
Analgesics ; Child ; Cross-Sectional Studies ; Education ; Humans ; Methods ; Narcotics ; Pediatric Nursing ; Seoul ; Substance Withdrawal Syndrome ; Tertiary Care Centers

Objective: To investigate the prevalence of diphenoxylate abuse and related factors of forced drug abstainer in Gansu province. Methods: By using a self-designed questionnaire, an epidemiologic investigation was carried out among 2 108 forced drug abstainer selected from the compulsory isolation detoxification center of Gansu province. A case-control study was conducted to analyze the factors related with diphenoxylate abuse. Results: The diphenoxylate abuse rate among forced drug abstainer in Gansu was 19.8% (406/2 046), ranking first in medical drug abuse. Multiple logistic regression analysis showed that factors as relieving withdrawal symptoms (OR=2.08, 95%CI: 1.01- 4.32), ways to obtain diphenoxylate (other ways: OR=1.00; regular clinic: OR=27.67, 95%CI: 2.64-289.82; friend: OR=0.01, 95%CI: 0.01-0.03), degree of euphoria (high: OR=1.00; medium: OR =3.36, 95%CI: 1.18-9.55; low: OR=26.16, 95%CI: 10.30-66.42), years of drug abuse (<5 years: OR=1.00; 10-15 years: OR=2.48, 95%CI: 1.02-6.04), abuse at home or in friend's house (OR=3.04, 95%CI: 1.08-8.68), abuse in car (OR=0.05, 95%CI: 0.00-0.68) and detoxification for the first time (OR=0.61, 95%CI: 0.43-0.86) were the possible influencing factors for diphenoxylate abuse. Conclusions: The prevalence of diphenoxylate abuse in forced drug abstainer in Gansu was relatively high. Reasons of abusing, the way to obtain diphenoxylate, whether using drug together with friends, degree of euphoria, years of abuse, abuse place and times for detoxification were related factors influencing the abuse of diphenoxylate.
Analgesics, Opioid/supply & distribution* ; Case-Control Studies ; China ; Diphenoxylate/supply & distribution* ; Humans ; Substance Withdrawal Syndrome ; Substance-Related Disorders/psychology* ; Surveys and Questionnaires

PURPOSE: Oral naloxone is combined with oxycodone to alleviate or prevent opioid-induced constipation in cancer pain patients. However, there is still concern that oral naloxone may precipitate opioid withdrawal symptoms in patients on opioids. We retrospectively investigated clinical characteristics of cancer patients who experienced opioid withdrawal symptoms. METHODS: We reviewed medical records of all patients who were prescribed with oral oxycodone/naloxone at a tertiary cancer center from January 1, 2012 through December 31, 2016. Eligible patients were screened based on demographics, opioid and naloxone dosages, clinical manifestation and pain intensity. RESULTS: Among a total of 1,641 patients, 10 patients were selected. Seven patients were male, and the average age was 68.1 years. The median dose of naloxone that induced withdrawal symptoms was 20 mg. Most common withdrawal symptom was shivering (seven patients) followed by cold sweating (five), and muscle twitching (five). Other symptoms included restlessness, fever, dizziness, and yawning. Pain was exacerbated from the median intensity of numeric rating scale (NRS) 3 to NRS 6. CONCLUSION: Opioid withdrawal symptoms may occur when switching to oral oxycodone/naloxone for cancer patients who have been treated with other strong opioids. A prospective, multicenter study on this issue should be conducted in future.
Analgesics, Opioid* ; Constipation ; Demography ; Dizziness ; Fever ; Humans ; Male ; Medical Records ; Naloxone ; Oxycodone ; Prospective Studies ; Psychomotor Agitation ; Retrospective Studies ; Shivering ; Substance Withdrawal Syndrome* ; Sweat ; Sweating ; Yawning