Minimally invasive interventional therapy for pain

Pain interventional therapy,known as the most promising medical technology in the 21st century,refers to clinical treatment technology based on neuroanatomy,neuroimaging,and nerve block technology to treat pain diseases.Compared with traditional destructive surgery,interventional pain therapy is considered a better and more economical choice of treatment.In recent years,a variety of minimally invasive pain interventional therapy techniques,such as neuroregulation,spinal cord electrical stimulation,intervertebral disc ablation,and intrasheath drug infusion systems,have provided effective solutions for the treatment of patients with post-herpetic neuralgia,complex regional pain syndrome,cervical/lumbar disc herniation,and refractory cancer pain.

Novel multimodal analgesia regimen improves post-TACE pain in patients with hepatocellular carcinoma

Backgroud: Transarterial chemoembolization(TACE) is the primary palliative treatment for patients with unresectable hepatocellular carcinoma(HCC). However, it is often accompanied by postoperative pain which hinder patient recovery. This study was to examine whether preemptive parecoxib and sufentanilbased patient controlled analgesia(PCA) could improve the pain management in patients receiving TACE for inoperable HCC. Methods: From June to December 2016, 84 HCC patients undergoing TACE procedure were enrolled. Because of the willingness of the individuals, it is difficult to randomize the patients to different groups. We matched the patients’ age, gender and pain scores, and divided the patients into the multimodal group( n = 42) and control group( n = 42). Patients in the multimodal group received 40 mg of parecoxib, 30 min before TACE, followed by 48 h of sufentanil-based PCA. Patients in the control group received a routine analgesic regimen, i.e., 5 mg of dezocine during operation, and 100 mg of tramadol or equivalent intravenous opioid according to patient’s complaints and pain intensity. Postoperative pain intensity, percentage of patients as per the pain category, adverse reaction, duration of hospital stay, cost-effectiveness, and patient’s satisfaction were all taken into consideration when evaluated. Results: Compared to the control group, the visual analogue scale scores for pain intensity was significantly lower at 2, 4, 6, and 12 h(all P < 0.05) in the multimodal group and a noticeably lower prevalence of post-operative nausea and vomiting in the multimodal group(31.0% vs. 59.5%). Patient’s satisfaction in the multimodal group was also significantly higher than that in the control group(95.2% vs. 69.0%). No significant difference was observed in the duration of hospital stay between the two groups. Conclusion: Preemptive parecoxib and sufentanil-based multimodal analgesia regime is a safe, efficient and cost-effective regimen for postoperative pain control in HCC patients undergoing TACE.

Stretch-induced Expression of CYR61 Increases the Secretion of IL-8 in A549 Cells via the NF-κβ/Iκβ Pathway

Mechanical ventilation （MV） with large tidal volumes can increase lung alveolar permeability and initiate inflammatory responses, resulting in ventilator-induced lung injury （VILI）. The mechanisms of the injurious effects of MV and the genetic susceptibility remain unclear. VILI-related genes such as cysteine-rich angiogenic inducer 61 （Cyr61） have been demonstrated to play a detrimental role in the aggressive ventilation strategies. In the present study, we investigated the involvement of Cyr61 in the VILI and the underlying mechanism. A549 cells were exposed to cyclic stretch of varying durations and then the mRNA and protein levels of Cyr61 were measured by real-time PCR and Western blotting, respectively. Additionally, after exposure ofA549 cells to cyclic stretch for 5 min to 1 h, the expression levels of nuclear factor kappaB （NF-κβ） and IL-8 were detected by ELISA and Western blotting. Thereafter, Cyr61 expression was depressed in A549 cells with the siRNA pGenesill. 1-Cyr61-3 before the cyclic stretch, and IL-8 secretion and the activation of NF- κB pathways were probed by ELISA and Western blotting, respectively. Moreover, a NF- κB inhibitor （PDTC） and an activator （TNF） were used before mechanical stretch. Realtime PCR and ELISA were performed to detect the mRNA and protein of IL-8, respectively. The results showed that the mechanical cyclic stretch led to increased Cyr61 expression at mRNA and protein levels in A549 cells. Additionally, cyclic stretch also mobilized NF- κB from the cytoplasm to the nucleus and increased IL-8 secretion in A549 cells. The inhibition of Cyr61 blocked the NF-κB activation and IL-8 secretion in response to cyclic stretch. Inhibition of NF-κB attenuated the mRNA and protein expression of IL-8 in A549 cells transfected with Cyr61 siRNA. It was suggested that Cyr61/NF-κB signaling pathway mediates the upregulation of IL-8 in response to cyclic stretch in A594 cells. These findings support the hypothesis that Cyr61 plays a critical role in acute lung inflammation triggered by mechanical strain.

Effect of intraoperative fluid administration on perioperative outcomes in patients undergoing McKeown esophagogastrectomy

Objective: Fluid therapy is one of the key components of perioperative management. However, evidence of intraoperative fluid(IOF) administration affecting clinical outcomes following McKeown esophagogastrectomy remains limited. This study investigated the impact of IOF on clinical outcomes after McKeown esophagogastrectomy.Methods: Patients who underwent McKeown esophagogastrectomy between July 2013 and July 2016 were identified. Preoperative, intraoperative and postoperative variables for each eligible patient were retrospectively collected from our electronic medical records and anesthetic records. IOF rates were determined and their relationships to postoperative clinical outcomes were compared.Results: A total of 546 patients were enrolled in the analysis. The median IOF rate was 8.87 mL/kg/h. We divided the patients into two groups: a low fluid volume group(LFVG <8.87 mL/kg/h, n=273) and a high fluid volume group(HFVG ≥8.87 mL/kg/h, n=273). No statistically significant differences in postoperative clinical outcomes were found between LFVG and HFVG either before or after propensity score matching.Conclusions: No effect of IOF administration on clinical outcomes in patients undergoing McKeown esophagogastrectomy was identified. Further high-quality studies examining the influence of IOF administration on clinical outcomes following McKeown esophagogastrectomy are still needed.

Identification of Differentially Expressed Proteins and Validation of the Changes of N-Ethylmaleimide-sensitive Factor in Rats with Focal Cerebral Ischemia after Transection of the Cervical Sympathetic Trunk

Stellate ganglion blockade （SGB） protects patients from focal cerebral ischemic injury, and transection of the cervical sympathetic trunk （TCST） in a rat model can mimic SGB in humans. The purpose of this study was to investigate the mechanisms underlying the neuroprotective effects of TCST on neuronal damage in the hippocampus in a rat model of middle cerebral artery occlusion （MCAO） in an attempt to elucidate the neuroprotective effects of SGB. The modified method of Zea Longa was used to establish the permanent MCAO model. Male Wistar rats were randomly divided into three groups： sham-operated group, MCAO group, and TCST group. The animals in TCST group were sacri- ficed 48 h after TCST which was performed after the establishment of the MCAO model. Proteins were extracted from the ipsilateral hippocampus and analyzed by two-dimensional difference gel electropho- resis （2D-DIGE） and peptide mass fingerprinting （PMF）. The levels of N-ethylmaleimide-sensitive fac- tor （NSF） were measured as well. The results showed that 11 types of proteins were identified by 2D- DIGE. The expressions of eight proteins were changed both in the sham-operated and TCST groups, and the expressions of the other three proteins were changed in all three groups. Moreover, the expres- sion of NSF was higher in the TCST group than in the MCAO group but lower in the MCAO group than in sham-operated group. The ratio of NSF expression between the MCAO group and sham- operated group was -1.37 （P〈0.05）, whereas that between the TCST group and MCAO group was 1.35 （P〈0.05）. Our results imply that TCST increases the expression of NSF in the hippocampus of adult rats with focal cerebral ischemia, which may contribute to the protection of the injured brain. Our study pro- vides a theoretical basis for the therapeutic application of SGB to patients with permanent cerebral ischemia.

Effect of overexpression of hypoxia-inducible factor-1α induced by hyperoxia in vivo in LNCaP tumors on tumor growth rate

Objective:To study effect of overexpression of hypoxia-inducible factor-1_α induced by hyperoxia in vivo in LNCaP tumors on tumor growth rate.Methods:The prostate cancer LNCaP cells were inoculated in the abdomen of mice.All the mice were randomly placed in the gas chamber with different oxygen content.The groups were divided as follows:twelve mice in hypoxia group,sixteen mice in normoxia group,ten mice in hyperoxia group.After 28 d of treatment,the mice were weighed,the blood samples were taken from the left ventricle,and the tumor was isolated and weighed.Tumor growth,angiogenesis and vascularization,HIF-1_α expression and intracellular signal transduction molecules expression in each group of xenografts were detected and analyzed by using Western blotting and immunofluorescence and determination of hemoglobin.Results:Comparison of the growth of xenografts in each group showed that,the xenografts growth of hypoxia group was more quickly than that of normoxia group.The difference was statistically significant(P=0.Q04).The difference in xenografts growth between hyperoxia group compared and normoxia group was not statistically significant(P>0.05).The expressions of HIF-1_α,VEGF and VEGF-R of xenografts in hyperoxia group were significantly higher than those of normoxia group(P<0.05).The expression of HIF-1_α of xenografts in hypoxia group and normoxia group were similar.The blood growth rate of xenografts in hypoxia group(170%) was significantly higher than that of normoxia group(40%)(P<0.05).The expression of Nrf2 of xenografts in hyperoxia group was significantly higher than that of normoxia group(P<0.05).Conclusions:When hyperoxia induces the overexpression of HIF-1_α in LNCaP tumor,it will not affect tumor growth.It provides a new ideas and theoretical basis for the clinical treatment of prostate cancer.

Nerve coblation for treatment of trigeminal neuralgia: A case report

BACKGROUND Trigeminal neuralgia(TN) is a severe type of neuropathic pain which is often inadequately managed using conventional therapies. In this report, we present the first case of TN treated with gasserian ganglion nerve coblation(NC).CASE SUMMARY A 58-year-old man presented with right facial pain, mostly localized in the right zygomatic zone, alveolar region, and jaws. Similar to acupuncture and shock pain, the pain lasted about five seconds after each attack before resolving unaided. A diagnosis of TN was made, after which treatment with acupuncture therapy and oral carbamazepine was given. However, the pain was not satisfactorily controlled. Subsequently, gasserian ganglion NC of the right trigeminal nerve guided by computed tomography(CT) was performed on the patient. Following this procedure, the right zygomatic, alveolar, submandibular,and cheek pain disappeared completely. The right zygomatic and alveolar areas experienced mild numbness(level II). At 1-, 2-, 3-, and 6-mo follow-ups after surgery, the patient was painless and the numbness score was level I.CONCLUSION CT-guided gasserian ganglion(NC) is an effective treatment for TN and is associated with less or no postoperative numbness or hypoesthesia in comparison with current standard-of-care approaches.

Treatment of Popliteal Cyst through Radiofrequency Thermocoagulation under Ultrasound Guidance

Objective: The purpose of this study was to explore the clinical efficacy and security of the treatment of popliteal cyst through radiofrequency thermocoagulation (RFT) under ultrasound guidance. Methods: The clinical data of 35 patients with popliteal cyst, who were treated by RFT under ultrasound guidance from June 2019 to June 2020, were retrospectively analyzed. The Visual Analogue Scores (VAS) and the size of cyst before and after treatment were recorded at the first month, the third month, the sixth month. After six months, the recovery rate of Rauschning and Lindgren classification (R-L classification) level 0, 0 - I were counted. All the complications of the patients were observed. Results: 32 patients were followed up for six months. The scores and cyst sizes of each patient before and after the treatment were on a normal distribution curve. There was no significant difference in VAS scores before and after the treatment (P > 0.05). However, there was a significant difference in cyst sizes before and after the treatment (P < 0.05). Moreover, there was no significant difference in VAS scores and cyst sizes in each period after treatment (P > 0.05). According to the R-L classification in 6 months after treatment: the recovery rate of class 0 was 62.5% and class 0 - I level was 87.5%. There were no serious complications in the process. Conclusion: Treatment of popliteal cyst through RFT under ultrasound guidance is a simple, easy, reliable method that is worthy of clinical promotion.

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.

Chemogenetic and Optogenetic Manipulations of Microglia in Chronic Pain

Chronic pain relief remains an unmet medical need.Current research points to a substantial contribution of glia-neuron interaction in its pathogenesis.Particularly,microglia play a crucial role in the development of chronic pain.To better understand the microglial contribution to chronic pain,specific regional and temporal manipulations of microglia are necessary.Recently,two new approaches have emerged that meet these demands.Chemogenetic tools allow the expression of designer receptors exclusively activated by designer drugs(DREADDs)specifically in microglia.Similarly,optogenetic tools allow for microglial manipulation via the activation of artificially expressed,light-sensitive proteins.Chemo-and optogenetic manipulations of microglia in vivo are powerful in interrogating microglial function in chronic pain.This review summarizes these emerging tools in studying the role of microglia in chronic pain and highlights their potential applications in microglia-related neurological disorders.

Thalamocortical Circuit Controls Neuropathic Pain via Up-regulation of HCN2 in the Ventral Posterolateral

The thalamocortical(TC)circuit is closely asso-ciated with pain processing.The hyperpolarization-activated cyclic nucleotide-gated(HCN)2 channel is predominantly expressed in the ventral posterolateral thalamus(VPL)that has been shown to mediate neuropathic pain.However,the role of VPL HCN2 in modulating TC circuit activity is largely unknown.Here,by using optogenetics,neuronal trac-ing,electrophysiological recordings,and virus knockdown strategies,we showed that the activation of VPL TC neurons potentiates excitatory synaptic transmission to the hindlimb region of the primary somatosensory cortex(S1HL)as well as mechanical hypersensitivity following spared nerve injury(SNI)-induced neuropathic pain in mice.Either pharmaco-logical blockade or virus knockdown of HCN2(shRNA-Hcn2)in the VPL was sufficient to alleviate SNI-induced hyperalgesia.Moreover,shRNA-Hcn2 decreased the excitability of TC neurons and synaptic transmission of the VPL-S1HL circuit.Together,our studies provide a novel mechanism by which HCN2 enhances the excitability of the TC circuit to facilitate neuropathic pain.

Bilateral thigh pyomyositis in an otherwise healthy middle-aged woman:A case report

BACKGROUND Pyomyositis generally occurs in otherwise healthy young men.Because this condition is unusual among otherwise healthy women in temperate climates,we present the following case.CASE SUMMARY An otherwise healthy 43-year-old woman presented with bilateral pain in her lower extremities and fever.Magnetic resonance imaging(MRI)findings were indicative of myositis with a possible abscess.We initiated empirical antibiotic therapy with ceftriaxone.However,the swelling and pain in her legs persisted even after 7 d of treatment.Contrast MRI revealed multiple pockets of pus in the vastus lateralis and gluteal muscles.We performed needle aspiration of these abscesses with ultrasound guidance and local anesthesia.Upon culturing,the purulent material was positive for Staphylococcus aureus.We diagnosed her with S.aureus-induced pyomyositis of the vastus lateralis muscle and gluteus region.Based on the antibiotic sensitivity report,ceftriaxone was administered for an additional 7 d.By day 15 post-drainage,the patient was able to start walking.Oral antibiotic therapy was continued for 1 wk following her discharge from hospital,after which her symptoms resolved completely.CONCLUSION Pyomyositis may present with muscle pain,swelling,and fever.Ultrasoundguided percutaneous puncture and drainage may enable timely diagnosis and treatment.

Transcutaneous electrical acupoint stimulation in adult patients receiving gastrectomy/colorectal resection:A randomized controlled trial

BACKGROUND Acupuncture promotes the recovery of gastrointestinal function and provides analgesia after major abdominal surgery.The effects of transcutaneous electrical acupoint stimulation(TEAS)remain unclear.AIM To explore the potential effects of TEAS on the recovery of gastrointestinal function after gastrectomy and colorectal resection.METHODS Patients scheduled for gastrectomy or colorectal resection were randomized at a 2:3:3:2 ratio to receive:(1)TEAS at maximum tolerable current for 30 min immediately prior to anesthesia induction and for the entire duration of surgery,plus two 30-min daily sessions for 3 consecutive days after surgery(perioperative TEAS group);(2)Preoperative and intraoperative TEAS only;(3)Preoperative and postoperative TEAS only;or(4)Sham stimulation.The primary outcome was the time from the end of surgery to the first bowel sound.RESULTS In total,441 patients were randomized;405 patients(58.4±10.2 years of age;247 males)received the planned surgery.The time to the first bowel sounds did not differ among the four groups(P=0.90;log-rank test).On postoperative day 1,the rest pain scores differed significantly among the four groups(P=0.04;Kruskal–Wallis test).Post hoc comparison using the Bonferroni test showed lower pain scores in the perioperative TEAS group(1.4±1.2)than in the sham sti-mulation group(1.7±1.1;P=0.04).Surgical complications did not differ among the four groups.CONCLUSION TEAS provided analgesic effects in adult patients undergoing major abdominal surgery,and it can be added to clinical practice as a means of accelerating postoperative rehabilitation of these patients.

Post-stroke pain hypersensitivity induced by experimental thalamic hemorrhage in rats is region-specific and demonstrates limited efficacy of gabapentin

Intractable central post-stroke pain（CPSP） is one of the most common sequelae of stroke, but has been inadequately studied to date. In this study, we first determined the relationship between the lesion site and changes in mechanical or thermal pain sensitivity in a rat CPSP model with experimental thalamic hemorrhage produced by unilateral intra-thalamic collagenase IV（ITC） injection. Then, we evaluated the efficacy of gabapentin（GBP）, an anticonvulsant that binds the voltage-gated Ca2＋ channel α2δ and a commonly used anti-neuropathic pain medication. Histological case-by-case analysis showed that only lesions confined to the medial lemniscus and the ventroposterior lateral/medial nuclei of the thalamus and/or the posterior thalamic nucleus resulted in bilateral mechanical pain hypersensitivity. All of the animals displaying CPSP also had impaired motor coordination, while control rats with intra-thalamic saline developed no central pain or motor deficits. GBP had a dose-related anti-allodynic effect after a single administration（1, 10, or 100 mg/kg） on day 7 post-ITC, with significant effects lasting at least 5 hfor the higher doses. However, repeated treatment, once a day for two weeks, resulted in complete loss of effectiveness（drug tolerance） at 10 mg/kg, while effectiveness remained at 100 mg/kg, although the time period of efficacious analgesia was reduced. In addition, GBP did not change the basal pain sensitivity and the motor impairment caused by the ITC lesion, suggesting selective action of GBP on the somatosensory system.

Endoscopic joint capsule and articular process excision to treat lumbar facet joint syndrome:A case report

BACKGROUND Lumbar facet joint syndrome(LFJS)is a pain condition arising from lumbar facet joint diseases.Treatments of LFJS includes patient education,oral medication,bed rest,physical therapy,and procedural interventions.For some refractory cases that fail conservative therapies,dorsal ramus medial brunch radiofrequency ablation is warranted.However,as nerve fibers can regenerate,their efficacy is impermanent,and the recurrence rate is relatively high.Considering synovial impingement is a paramount pathogenesis of LFJS,in this case,we removed the culprit hyperplastic articular capsule and the articular process partially through a spinal endoscope.As the culprit hyperplastic joint capsule was excised,it is supposed to generate more prolonged efficacy and a lower recurrence rate than radiofrequency treatment.CASE SUMMARY A 40-year-old female patient was diagnosed with LFJS.She complained of low back pain and right buttock pain for half a year.The patient was placed in the prone position.After disinfection and draping,a 25-cm 18-gauge needle was inserted into the dorsal surface of the right L5 articular process.Subsequently,a guidewire,dilating tubes,and a working cannula was inserted successively.The spinal endoscope was positioned in the working cannula.Under the endoscope,the microvascular tissue,muscle tissue attached on the L5 inferior articular process and S1 superior articular process,as well as the capsule and minor portion of the inferior articular process were removed.After the joint space was clear and no bleeding points existed,the endoscope and working cannula were shifted,and the incision was sutured.After treatment,the symptoms were completely relieved.The patient was pain-free during the follow-up period of 6 mo.CONCLUSION The endoscopic partial joint capsule and articular process excision is an effective procedure for LFJS,especially for cases caused by synovial impingement.

Mortality in patients with COVID-19 requiring extracorporeal membrane oxygenation:A meta-analysis

BACKGROUND Coronavirus disease 2019(COVID-19)has become a worldwide pandemic and significant public health issue.The effectiveness of extracorporeal membrane oxygenation(ECMO)in treating COVID-19 patients has been called into question.AIM To conduct a meta-analysis on the mortality of COVID-19 patients who require ECMO.METHODS This analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes 2020(PRISMA)and has been registered at the International Prospective Register of Systematic Reviews(number CRD42020227414).A quality assessment for all the included articles was performed by the Newcastle-Ottawa Scale(NOS).Studies with tenor more COVID-19 patients undergoing ECMO were included.The random-effects model was used to obtain the pooled incidence of mortality in COVID-19 patients receiving ECMO.The source of heterogeneity was investigated using subgroup and sensitivity analyses.RESULTS We identified 18 articles with 1494 COVID-19 patients who were receiving ECMO.The score of the quality assessment ranged from 5 to 8 on the NOS.The majority of patients received veno-venous ECMO(93.7%).Overall mortality was estimated to be 0.31[95%confidence interval(CI):0.24-0.39;I2=84.8%]based on random-effect pooled estimates.There were significant differences in mortality between location groups(33.0%vs 55.0%vs 37.0%vs 18.0%,P<0.001),setting groups(28.0%vs 34.0%,P<0.001),sample size(37.0%vs 31.0%,P<0.001),and NOS groups(39.0%vs 19.0%,P<0.001).However,both subgroup analyses based on location,setting,and sample size,and sensitivity analysis failed to identify the source of heterogeneity.The funnel plot indicated no evident asymmetry,and the Egger’s(P=0.95)and Begg’s(P=0.14)tests also revealed no significant publication bias.CONCLUSION With more resource assessment and risk-benefit analysis,our data reveal that ECMO might be a feasible and effective treatment for COVID-19 patients.

The Anatomical Research on the Mental Foramen Related to the Mental Nerve Block

Objective: The aim of this study was to observe and investigate the location of mental foramen, providing scientific and reasonable anatomic basic for clinical mental nerve block. Methods: The shape, orientations, relationship with teeth and number of accessory mental foramina in 50 (100 side) adult mental foramina were observed. The long and short diameters of the mental foramen and the distance between the mental foramen and the peripheral anatomical markers were measured by a vernier caliper, and statistical analysis of the data was performed to obtain the final results. Results: The probability of mental foramen being elliptical in shape accounted for 27%, circular for 73%;10% of the mental foramen openings are outward and 90% are outward and upward;The mental foramina were located under the first premolars in 20%, under the second premolars in 75%, and 5% situated in the bottom of the first molars. The incidence of accessory mental foramina was 1%;the long diameter of the mental foramen was (2.42 ± 0.71) mm, and the short diameter of the mental foramen was (2.15 ± 0.14) mm;the vertical distance from the mental foramen center to the alveolar crest and the lower margin of the mandible were (14.09 ± 3.23) mm and (14.56 ± 1.74) mm;the distance between the midpoints of the vertical line to the center of the mental foramen was (1.26 ± 0.97) mm;the horizontal distance from the center of the mental foramen to the anterior median line was (23.57 ± 1.82) mm. Conclusion: The point of mental nerve block was selected below and behind the second premolars, above the midline of the mandible. The distance from the anterior median line was 2.5 cm, and the mental foramen was explored forward and downward after the insertion.

Hemoglobin within normal range is negatively related to hemoglobin A1c in a nondiabetic American population aged 16 years and older

BACKGROUND Protein glycosylated hemoglobin,hemoglobin A1c(HbA1c)binds hemoglobin(Hb)in red blood cells to blood glucose.However,the relationship between Hb and HbA1c remains unclear.AIM To elucidate their relationship in a nondiabetic population aged≥16 years in the United States,using data from the 1999-2018 National Health and Nutrition Examination Survey.METHODS This study was based on data from 44560 adults aged≥16 years,excluding those with diabetes.The relationship was estimated using a multivariate regression.We also used piecewise linear regression for subgroup analysis based on age and sex stratification and analysis of the threshold effects of Hb on HbA1c.RESULTS Hb and HbA1c levels were negatively correlated in the unadjusted model(β=-0.01;95%CI:-0.01,-0.01).The correlation was significantly negative when the regression model was minimally regulated and stratified by age and sex,and remained negative when the model was further regulated(more than 10%)to identify covariates with the HbA1c level influence estimates.In subgroup analyses based on age and sex stratification,the association remained negative when the covariates were controlled.A nonlinear relationship was observed between them when the Hb levels reached the tipping point(13.2 g/dL)(adjusted odds ratio,-0.04;95%CI:-0.05,-0.03)and when the Hb levels exceeded 13.2 g/dL(adjusted odds ratio,-0.10;95%CI:-0.10,-0.09).CONCLUSION Our study shows that normal Hb levels are negatively correlated with HbA1c in nondiabetic Americans aged≥16 years.

Metastatic urothelial carcinoma harboring ERBB2/3 mutations dramatically respond to chemotherapy plus anti-PD-1 antibody:A case report

BACKGROUND Immune checkpoint inhibitors(ICIs)targeting the programmed death(PD)-1 pathway have substantially changed the clinical management of metastatic urothelial carcinoma(m UC);however,the response rate remains low.There are ongoing efforts to identify robust biomarkers that can effectively predict the treatment response to ICIs.Previous studies have suggested that ERBB2/3 mutations are associated with the efficacy of ICIs in gallbladder carcinoma.CASE SUMMARY We present a 59-year-old man with m UC harboring ERBB2/3 mutations(in-frame insertion of ERBB2 and ERBB3 amplification),negative PD-ligand 1 expression,and low tumor mutation burden.He received anti-PD-1 antibodies and paclitaxel as second-line treatment.After two cycles of treatment,the lung metastases had significantly shrunk,achieving good partial remission.After six cycles of combination therapy,the patient received sindilimab 200 mg once every 3 wk as maintenance monotherapy.At the last follow-up,the patient continued to exhibit a partial response and progression-free survival for as long as 19 mo.CONCLUSION ERBB2/3 mutations may represent a predictive biomarker for selecting a subgroup of m UC patients who will benefit from ICIs.