[Effective dose and adverse reactions analysis of Remimazolam for sedation in elderly patients undergoing gastroscopy].

Objective: To explore the 50% effective dose (ED50) and 95% effective dose (ED95) of Remimazolam during gastroscopic sedation in elderly patients, and to observe the adverse reactions during anesthesia. Methods: From July to November 2020, 39 elderly patients, of which there were 18 males and 21 females, aged from 65 to 82 (72±5) years, were examined by gastroscopy in the Second Affiliated Hospital of Hainan Medical University, who American Society of Anesthesiologists (ASA) was grade Ⅰ or Ⅱ. Sufentanil 0.1 µg/kg and test dose Remimazolam were injected intravenously, and the initial dose of Remimazolam was 0.17 mg/kg. The dose of the next patient was determined according to the modified Dixon sequential method. If the former patient had a positive reaction during gastroscopy, such as cough, nausea, vomiting and/or body movement reaction occurred when the gastroscope was placed into the pharynx or in the 2 min, the next patient would increase the dose, otherwise, the dose would be reduced. The dose increase and decrease gradient of Remimazolam was 0.01 mg/kg, and the test was stopped after 12 times of return. At the same time, the occurrence of adverse reactions during anesthesia was observed. Results: A total of 39 elderly patients completed the trial, of which 21 were effective and 18 were ineffective. When the elderly patients were sedated by gastroscopy, the ED50 of single intravenous injection of Remimazolam was 0.153 mg/kg (95%CI:0.151-0.154 mg/kg) and the ED95 was 0.164 mg/kg (95%CI:0.160-0.166 mg/kg). The total dose of Remimazolam was (10.6±2.8) mg, the recovery time was (10.0±3.4) min, and the stay time in resuscitation room was (8.2±2.6) min. During anesthesia, nausea and vomiting occurred in 1 case, transient hypotension in 4 cases, and no other adverse reactions were found. Conclusion: The ED50 of Remimazolam during gastroscopic sedation in elderly patients is 0.153 mg/kg, ED95 is 0.162 mg/kg, and the incidence of adverse reactions is low.

[Re-evaluation of the diagnostic value and optimal cutoff point of captopril challenge test in diagnosis of primary aldosteronism].

Objective: The aim of the present study was to re-evaluate the diagnostic value and optimal cutoff point of captopril challenge test (CCT) in diagnosis of primary aldosteronism (PA). Methods: This is a retrospective study. All patients with a high risk for PA underwent screening test, and then proceeded to CCT and fludrocortisone suppression test (FST) on different days. The FST was used as a reference standard for PA. The plasma renin concentration (PRC) and plasma aldosterone concentration (PAC) were measured with an automated chemiluminescence immunoassay. Random number method was performed in the patients with unilateral primary aldosteronism (UPA), in order to make the proportion of the analyzed UPA in PA was 35%. Receiver operating characteristic (ROC) analyses were performed to compare diagnostic accuracy. Results: A total of 543 patients with 400 PA patients and 143 essential hypertension (EH) patients were enrolled. The diagnostic value of post-CCT PAC was significantly higher than that of the post-CCT plasma aldosterone-renin ratio (ARR), and that of the PAC suppression percentage, respectively. The area under the ROC curve (AUCROC) was 0.86 (0.83, 0.89) for PAC, 0.78 (0.74, 0.82) for ARR, and 0.62 (0.56, 0.67) for the PAC suppression percentage (all P<0.01), respectively. The optimal cutoff point of post-CCT PAC for PA was 110 ng/L, in which the sensitivity and specificity were 73.25% and 79.02%, respectively. The diagnostic efficiency of post-CCT PAC was not improved either in combination with PAC suppression percentage or in combination with post-CCT ARR. Conclusions: CCT is a useful test for the confirmation of PA. PAC level of 110 ng/L at 2 h after 50 mg of captopril is recommended as an optimal cutoff point for the diagnosis of PA.

[Prevalence and clinical characteristics of obstructive sleep apnea in patients with primary hyperaldosteronism].

Objective: To explore the proportion of obstructive sleep apnea (OSA) in primary aldosteronism (PA) in Chinese population and compare the clinical characteristics between PA patients with OSA and those without. Methods: A total of 96 patients diagnosed with PA from September 2015 to November 2018 were recruited in this study. OSA was screened by cardio-respiratory polygraphy. According to the apnea hypopnea index (AHI), the patients were divided into PA with OSA group (AHI ≥5 times) and PA without OSA group (AHI<5 times). Results: Among all patients (96), 69 (71.9%) were with OSA, among them 22 patients (22.9%) were with mild OSA, 17 patients (17.7%) were with moderate OSA and 30 patients (31.3%) were with severe OSA. Compared with the patients without OSA, the patients with OSA were elder, and had higher levels of body mass index (BMI), waist circumference (WC), hip circumference (HC), creatinine (CR) and glycosylated haemoglobin (HbA1c) (P<0.05), but lower concentrations of plasma aldosterone (PAC), supine aldosterone renin concentration ratio(ARR) and the PAC after the diagnosis test (P<0.05). Spearman correlation analyses showed that BMI, WC, HC, CR and HbA1c were positively correlated with AHI (P<0.05), while high-density lipoproteincholesterol (HDL-C), supine-PAC and saline infusion test(SIT)-post PAC were negatively correlated with AHI (P<0.05). Conclusions: The proportion of OSA in PA patients is relatively high (71.9%). Metabolic abnormalities are more common in PA patients with OSA, indicating that screening for OSA should be carried out routinely in PA patients.

Influence of Cilostazol on Changes in Cyclin D1 Expression in Cerebral Cortex of Rats with Chronic Cerebral Ischemia.

The influence of cilostazol on learning and memory, and cyclin D1 expression in the cerebral cortex of rats with chronic cerebral ischemia were investigated. A chronic cerebral ischemia model was established using the permanent bilateral common carotid artery occlusion method (2VO), learning and memory capacity was detected using the Morris water maze, and expression changes in apoptosis regulating gene cyclin D1 were tested by RT-PCR. Results of the Morris water maze indicated that significant extensions were found in the escape latent period and swimming path of rats in the ischemia group (2VO group), learning and memory results in the cilostazol group was obviously superior compared to the 2VO group (P<0.05), and the expression of cyclin D1 was observed to increase in both the ischemia and cilostazol intervention groups at the 9th week of ischemia. A significant difference was observed, compared with the sham operation group (P<0.05), the expression level decreased in the ischemia group compared with the cilostazol group, and a significant difference was identified compared with the ischemia group (P<0.05). Cilostazol can reduce nerve function impairment and improve learning and memory functions by affecting changes in apoptosis regulating genes.

[A pilot study of transcranial alternating current stimulation in the treatment of drug-naive adult patients with major depressive disorder].

Objective: To explore the efficacy, adverse reactions, feasibility, and acceptability of transcranial alternating current stimulation (tACS) treating drug-naive adult patients with major depressive disorder (MDD), and provide basis for further study with a large sample. Methods: The study was performed in the Neuromodulation laboratory, Department of Neurology of Xuanwu Hospital, Capital Medical University (Beijing, China) from July, 2017 to June, 2018. Thirty Eligible first-episode MDD outpatients were randomized 1∶1 to receive active tACS or sham intervention. The tACS was administered in a 40 minute, 77.5 Hz frequency, 15 mA session with one forehead (Fp1, Fpz, and Fp2, in the 10/20 international placement system, 4.45 cm×9.53 cm) and two mastoid (3.18 cm×3.81 cm) stimulation for 20 times in 4 consecutive weeks at fixed day time frame once daily from Monday through Friday, with weekends off (week 4), followed by 4 weeks with no tACS treatment (week 8). By utilizing the Hamilton rating scale for depression-17 item (HRSD-17) to assess the depressive severity of MDD patients, adverse events were administered by the treatment-emergent adverse events, the Young mania rating scale, and the self-made common questionnaire on cranial electrical stimulation. The primary efficacy outcome was the remission rate defined as HRSD-17 score ≤7 at week 8. Secondary outcomes included the rates of remission at week 4 and response at weeks 4 and 8. Safety was assessed by evaluation of adverse events. Also the proportions of participants accepting the intervention and this study procedure were evaluated at weeks 4 and 8. Results: Thirty MDD patients completed the study, and both groups had no statistical differences on their demographic characteristics (P>0.05). At week 8, the active group had a remission rate of 10/15, which was higher than 3/15 in the sham group (P<0.05). Also, the remission rate (14/15) in the active group was higher than 5/15 of the sham group at week 4 (P<0.05). For the response rates, significant differences were found between groups at week 8. For safety, both groups showed no severe adverse events and no mania/hypomania. One participant per group had 2 times of tinnitus cerebri during the intervention days. All patients accepted the intervention and the study procedure. Conclusions: The pilot study indicated that tACS with 77.5 Hz and 15 mA may have a therapeutic effect on depressive symptoms. It is well-tolerated and safe, as well as feasible and acceptable for adults with MDD.

Nodal mitigates cerebral ischemia-reperfusion injury via inhibiting oxidative stress and inflammation.

OBJECTIVE: Nodal is a member of the transforming growth factor ß (TGF-ß) family, which induces the activation of the cytoplasmic Smad2 and Smad3, both of which play a neuroprotective role against cerebral ischemia-reperfusion (I/R) injury. However, the  role of Nodal in cerebral I/R is unclear. Thus, the aim of the present study was to shed light on the function of Nodal in cerebral I/R injury. MATERIALS AND METHODS: Cerebral I/R injury was induced in the Sprague Dawley (SD) rats by middle cerebral artery occlusion (MCAO) and reperfusion and in murine hippocampal neuronal cells (HT22) by oxygen-glucose deprivation/reperfusion (OGD/R) stimulation. The lentivirus vectors (Nodal overexpressing lentivirus vector [OE-Nodal] and the short hair RNA of Nodal [sh-Nodal]) were used to upregulate and downregulate Nodal in SD rats or cells. RESULTS: Nodal expression increased in the cerebral I/R models and reached a peak after 12 h of reperfusion. OE-Nodal administration to the cerebral I/R rats significantly reduced the cerebral infarction volume and inhibited the brain cell apoptosis. It also increased the level of superoxide dismutase (SOD), an antioxidant enzyme, and decreased the levels of the lipid peroxides (malondialdehyde [MDA] and lactate dehydrogenase [LDH]), in addition to those of the proinflammatory factors. Consistently, the upregulation of Nodal in HT22 by OGD/R significantly increased the SOD level and decreased the levels of MDA, LDH, interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α). CONCLUSIONS: This study revealed that Nodal exerted a protective role during cerebral I/R by inhibiting excessive oxidative stress and inflammation.

[Evaluation of peer support education mode for type 2 diabetes control in rural residents].

Objective: To evaluate the intervention effects of peer support education mode for type 2 diabetes control in rural residents. Methods: A random cluster sampling method has been used, including 300 rural residents aged above 18 years old from three villages (184 in control group, 116 in intervention group), in order to proceed the physical check-up and health education programs. Unchanged rate, transfer rate of patients, rate of impaired glucose tolerance, turn normal rate and other biochemical indicators of patients and people with impaired glucose tolerance from control group and intervention group were analyzed, to evaluate the intervention effects of peer support education mode. Results: The glycemic control rate of intervention group for patients and people with impaired glucose tolerance (72.2% and 71.4%) were higher than control group (43.6% and 26.7%), but the unchanged rate of intervention group (13.9% and 0.0%) were lower than control group (42.3% and 73.3%). Patients with diabetes or glucose intolerance in the education group improved significantly in waist-to-hip ratio, uric acid, total cholesterol and HDL-C. Glycemic hemoglobin level also improved significantly in diabetes patients of the education group. Conclusion: Peer support for education intervention seemed beneficial for diabetic control. The combination of education and effect evaluation was important in the evaluation of diabetes prevention and control. Peer support education also benefited the blood glucose control in general population.

[Clinical study of aged patients with secondary benign paroxysmal positional vertigo].

Objective: To investigate the clinical features and evaluate the efficacy of manual reduction in treatment of age patients with secondary benign paroxysmal positional vertigo (s-BPPV). Methods: Thirty-two cases of aged patients ( the s-BPPV group: including 19 cases of female and 13 males, age from 60 to 86 years old)with secondary benign paroxysmal positional vertigo from Jul. 2013 to Sep. 2015 in our hospital were retrospectively analyzed. The results were compared with 121 patients( the primary group: including 82 cases of female and 39males, aged from 60 to 86 years old)with aged primary benign paroxysmal positional vertigo(p -BPPV). All the patients were followed up for 12 months. Statistical data analysis was carried out with SPSS 19.0. Results: 20.92%(32/153)of all the observed elderly patients with BPPV was the aged s-BPPV. The sex ratio and onset age had no significant difference between the two groups(χ(2)=0.79, P>0.05; t=0.37, P>0.05). The rate of two or more semicircular canal involvement in the secondary group(21.88%) was higher than that in primary group(6.61%)(χ(2)=6.67, P<0.05). Bilateral semicircular canals were involved in 5 of the 32 cases in secondary group(15.63%) and 4 of the 121 cases in aged primary group(3.31%), The difference was significant(χ(2)=6.94, P<0.05). The effective rate after first manual reduction was 57.50%(23/40)in secondary group and 82.31%(107/130)in primary group, the difference was significant(χ(2)=10.46, P<0.05). The total effective rate were 87.50%(35/40) after more than once manual reduction in secondary group and 91.54%(119/130) in primary group, the difference was not significant(χ(2)= 0.59, P>0.05). The numbers of circulation of the first successful manual reduction management were (3.9±1.3)times in secondary group and (2.1±1.1)times in primary group, the difference was significant(t=3.15, P<0.05). The recurrence rate was 37.50%(15/40) in the secondary group and 16.15%(21/130)in primary group after during follow-up for 12 months, the difference was statistically significant(χ(2)=8.35, P<0.05). Conclusions: It's shown that the aged patients with secondary BPPV is not rare in clinical practice, sudden deafness and head trauma are frequent more than other reasons. The aged patients with secondary BPPV are prone to injury in multi-semicircular and bilateral canal compared with the primary BPPV. The effective rate after first manual reduction of secondary BPPV is lower than primary BPPV, it's needed more circulation of first success in manual reduction management. The total effective rates are not significant in two groups and recurrence rate is relatively high in secondary group.

Tea Polyphenols as Inhibitors of Furan Formed in the Maillard Model System and Canned Coffee Model.

In this article, the effects of sugars and amino acids on furan formation via the Maillard reaction in low-moisture model systems were investigated. Glucose and alanine are important furan precursors, and the effects of the heating temperature, heating time, and molar ratio of glucose to alanine on furan formation were studied in glucose/alanine model system by response surface methodology. The heating temperature greatly affected furan formation. The maximum furan concentration was obtained with a glucose-to-alanine molar ratio of 0.83:1.00, by heating at 151 °C for 41 min. Tea polyphenols effectively inhibited furan formation in the glucose/alanine model and a canned coffee model. A high inhibition rate of 42.4% ± 1.5% was obtained in the canned coffee model during sterilization procedure with addition of 84 mg (the mass fraction is 12.1%) of tea polyphenols (99%). However, the content of aromatic components in the canned coffee model was significantly reduced at the same time. This study provides evidence for a good furan inhibitor that can be used in food processing.

[Immune checkpoint inhibitor therapy in advanced head and neck cancer].

Immune checkpoint inhibitor therapy, which targets regulatory pathways in T cells to enhance antitumor immune responses, improves the life quality of cancer patients and has joined the ranks of surgery, radiation, and chemotherapy to become a major choice for cancer therapy. Over the past few years, multiple exciting results have been obtained on checkpoint inhibitor therapy in advanced head and neck cancer. However, questions such as patient selection and biomarkers for assessing the therapy are largely unsolved. Herein, we briefly review recent findings in checkpoint inhibitor therapy for advanced head and neck cancer. We will also discuss possible mechanism, safety, combination therapy, and side effects for the therapy. Checkpoint inhibitor therapy has led to important clinical advances and will provide a new weapon against cancer.

LKB1 inhibits HPV-associated cancer progression by targeting cellular metabolism.

Liver kinase B1 (LKB1) is mutationally inactivated in Peutz-Jeghers syndrome and in a variety of cancers including human papillomavirus (HPV)-caused cervical cancer. However, the significance of LKB1 mutations in cervical cancer initiation and progress has not been examined. Herein, we demonstrated that, in mouse embryonic fibroblasts, loss of LKB1 and transduction of HPV16 E6/E7 had an additive effect on constraining cell senescence while promoting cell proliferation and increasing glucose consumption, lactate production and ATP generation. Knockdown of LKB1 increased and ectopic expression of LKB1 decreased glycolysis, anchorage-independent cell growth, and cell migration and invasion in HPV-transformed cells. In the tumorigenesis and lung metastasis model in syngeneic mice, depletion of LKB1 markedly increased tumor metastatic colonies in lungs without affecting subcutaneous tumor growth. We showed that HPV16 E6/E7 enhanced the expression of hexokinase-ll (HK-II) in the glycolytic pathway through elevated c-MYC. Ectopic LKB1 reduced HK-II along with glycolysis. The inverse relationship between HK-II and LKB1 was also observed in normal and HPV-associated cervical lesions. We propose that LKB1 acts as a safeguard against HPV-stimulated aerobic glycolysis and tumor progression. These findings may eventually aid in the development of therapeutic strategy for HPV-associated malignancies by targeting cell metabolism.

Effect of compound Maqin decoction on TGF-ß1/Smad proteins and IL-10 and IL-17 content in lung tissue of asthmatic rats.

In this research, compound Maqin decoction (CMD) has been shown to positively affect in airway inflammation of asthma models. We evaluated the effects of CMD on the expression of transforming growth factor (TGF)-ß1/Smad proteins, interleukin (IL)-17, and IL-10 in lung tissue of asthmatic rats. Asthma was induced in a rat model using ovalbumin. After a 4-week treatment with CMD, rats were killed to evaluate the expression of TGF-ß1 and Smad proteins in lung tissue. IL-10 and IL-17 levels in lung tissue homogenates were determined by ELISA. The expression of TGF-ß1 and Smad3 protein increased, whereas expression of Smad7 protein decreased upon high-dose or low-dose treatment with CMD or by intervention with dexamethasone, compared to the control. There was a significant difference between treatment with a high dose CMD and the control treatment, but no significant difference was found between high-dose CMD treatment and dexamethasone intervention. The expression of TGF-ß1 and Smad7 protein increased, whereas the expression of Smad3 protein decreased in the model group compared to other groups. In the CMD high-dose group, low-dose group, and dexamethasone intervention group, the IL-17 concentrations in lung tissue homogenates were decreased, while IL-10 levels were increased. Again, there was a significant difference between CMD high-dose and control treatment, but not between CMD high-dose treatment and dexamethasone intervention. Thus, positive effects of CMD against asthmatic airway remodeling may be due to its regulatory effect on TGF-ß1, Smad3, and Smad7 protein levels and on cytokines such as IL-10 and IL-17.

Effects of c-Jun N-terminal kinase on Activin A/Smads signaling in PC12 cell suffered from oxygen-glucose deprivation.

Activin A (Act A), a member of transforming growth factor-ß (TGF-ß) superfamily, is an early gene in response to cerebral ischemia. Growing evidences confirm the neuroprotective effect of Act A in ischemic injury through Act A/Smads signal activation. In this process, regulation networks are involved in modulating the outcomes of Smads signaling. Among these regulators, crosstalk between c-Jun N-terminal kinase (JNK) and Smads signaling has been found in the TGF-ß induced epithelial-mesenchymal transition. However, in neural ischemia, the speculative regulation between JNK and Act A/Smads signaling pathways has not been clarified. To explore this issue, an Oxygen Glucose Deprivation (OGD) model was introduced to nerve-like PC12 cells. We found that JNK signal activation occurred at the early time of OGD injury (1 h). Act A administration suppressed JNK phosphorylation. In addition, JNK inhibition could elevate the strength of Smads signaling and attenuate neural apoptosis after OGD injury. Our results indicated a negative regulation effect of JNK on Smads signaling in ischemic injury. Taken together, JNK, as a critical site for neural apoptosis and negative regulator for Act A/Smads signaling, was presumed to be a molecular therapeutic target for ischemia.

LKB1 reduces ROS-mediated cell damage via activation of p38.

Liver kinase B1 (LKB1, also known as serine/threonine kinase 11, STK11) is a tumor suppressor mutated in Peutz-Jeghers syndrome and in a variety of sporadic cancers. Herein, we demonstrate that LKB1 controls the levels of intracellular reactive oxygen species (ROS) and protects the genome from oxidative damage. Cells lacking LKB1 exhibit markedly increased intracellular ROS levels, excessive oxidation of DNA, increased mutation rates and accumulation of DNA damage, which are effectively prevented by ectopic expression of LKB1 and by incubation with antioxidant N-acetylcysteine. The role of LKB1 in suppressing ROS is independent of AMP-activated protein kinase, a canonical substrate of LKB1. Instead, under the elevated ROS, LKB1 binds to and maintains the activity of the cdc42-PAK1 (p21-activated kinase 1) complex, which triggers the activation of p38 and its downstream signaling targets, such as ATF-2, thereby enhancing the activity of superoxide dismutase-2 and catalase, two antioxidant enzymes that protect the cells from ROS accumulation, DNA damage and loss of viability. Our results provide a new paradigm for a non-canonical tumor suppressor function of LKB1 and highlight the importance of targeting ROS signaling as a potential therapeutic strategy for cancer cells lacking LKB1.

Liver kinase B1 regulates the centrosome via PLK1.

Liver kinase B1 (LKB1) is a tumor suppressor mutationally inactivated in Peutz-Jeghers syndrome (PJS) and various sporadic cancers. Although LKB1 encodes a kinase that possesses multiple functions, no individual hypothesis posed to date has convincingly explained how loss of LKB1 contributes to carcinogenesis. In this report we demonstrated that LKB1 maintains genomic stability through the regulation of centrosome duplication. We found that LKB1 colocalized with centrosomal proteins and was situated in the mitotic spindle pole. LKB1 deficiency-induced centrosome amplification was independent of AMP-activated protein kinase (AMPK), a well-defined substrate of LKB1. Cells lacking LKB1 exhibited an increase in phosphorylated and total Polo-like kinase 1 (PLK-1), NIMA-related kinase 2 (NEK2), and ninein-like protein (NLP). Overexpression of active PLK1 (T210D) reversed the inhibition of LKB1 on centrosome amplification. In contrast, depletion of PLK1 with siRNA or suppression of PLK1 kinase activity with BTO-1 (5-Cyano-7-nitro-2-benzothiazolecarboxamide-3-oxide) abrogated LKB1 deficiency-induced centrosome amplification. We further characterized that LKB1 phosphorylated and activated AMPK-related kinase 5 (NUAK1 or ARK5) that in turn increased the phosphorylation of MYPT1, enhanced the binding between MYPT1-PP1 and PLK1, and conferred an effective dephosphorylation of PLK1. More importantly, we noted that LKB1-deficient cells exhibited multiple nuclear abnormalities, such as mitotic delay, binuclear, polylobed, grape, large, and micronuclear. Immediate depletion of LKB1 resulted in the accumulation of multiploidy cells. Expression of LKB1 is reversely correlated with the levels of PLK1 in human cancer tissues. Thus, we have uncovered a novel function of LKB1 in the maintenance of genomic stability through the regulation of centrosome mediated by PLK1.

Piperlongumine induces autophagy by targeting p38 signaling.

Piperlongumine (PL), a natural product isolated from the plant species Piper longum L., can selectively induce apoptotic cell death in cancer cells by targeting the stress response to reactive oxygen species (ROS). Here we show that PL induces cell death in the presence of benzyloxycarbonylvalyl-alanyl-aspartic acid (O-methyl)-fluoro-methylketone (zVAD-fmk), a pan-apoptotic inhibitor, and in the presence of necrostatin-1, a necrotic inhibitor. Instead PL-induced cell death can be suppressed by 3-methyladenine, an autophagy inhibitor, and substantially attenuated in cells lacking the autophagy-related 5 (Atg5) gene. We further show that PL enhances autophagy activity without blocking autophagy flux. Application of N-acetyl-cysteine, an antioxidant, markedly reduces PL-induced autophagy and cell death, suggesting an essential role for intracellular ROS in PL-induced autophagy. Furthermore, PL stimulates the activation of p38 protein kinase through ROS-induced stress response and p38 signaling is necessary for the action of PL as SB203580, a p38 inhibitor, or dominant-negative p38 can effectively reduce PL-mediated autophagy. Thus, we have characterized a new mechanism for PL-induced cell death through the ROS-p38 pathway. Our findings support the therapeutic potential of PL by triggering autophagic cell death.

Two new alleles, HLA-B*35:226 and HLA-B*40:233 identified by sequence-based typing in Chinese individuals.

HLA-B*35:226 differs from HLA-B*35:28, and HLAB*40:233 differs from HLA-B*40:01:01, both by a nonsynonymous mutation.