A 71-year-old male presented with esophageal cancer and severe aortic valve regurgitation. Treatment strategies for such patients are controversial. Considering the risks of cardiopulmonary bypass and potential esophageal cancer metastasis, we successfully performed transcatheter aortic valve implantation and minimally invasive three-incision thoracolaparoscopy combined with radical resection of esophageal cancer (McKeown) simultaneously in the elderly patient who did not require neoadjuvant treatment. This dual minimally invasive procedure took 6 hours and the patient recovered smoothly without any surgical complications.

Objective To evaluate the role of distortion product otoacoustic emissions (DPOAE) testing in evaluating early hearing loss among noise-exposed workers. Methods A total of 174 noise-exposed workers in a metal shipbuilding enterprise were selected as the research subjects by the convenience sampling method. Pure tone audiometry (PTA), DPOAE and the level of noise exposure were conducted on the workers. The rank correlation analysis was used to analyze the correlation between DPOAE amplitude and PTA threshold. The multilevel model was used to analyze the effects of gender, age, noise exposure intensity, cumulative noise exposure (CNE), hearing loss classification and PTA threshold on DPOAE results. Results At the frequencies of 0.50, 1.00, 2.00, 3.00, 4.00, 6.00 and 8.00 kHz, the DPOAE amplitude was negatively correlated with the PTA threshold (rank correlation coefficients were -0.12, -0.48, -0.47, -0.18, -0.23, -0.44, -0.19, respectively, all P<0.01). At the most frequencies, DPOAE amplitude was negatively correlated with age and CNE (all P<0.05). The results of multilevel model analysis showed that there were significant differences in DPOAE amplitudes at certain frequencies across gender, age, noise intensity, CNE, and hearing loss classification (all P<0.05). Significant differences in DPOAE responses were found among different CNE and hearing loss groups (all P<0.01). Conclusion DPOAE testing can objectively reflect the hearing status of noise-exposed workers and could be considered for inclusion in routine hearing monitoring to facilitate early detection of noise-induced hearing loss.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

The voltage-gated sodium channel subtype Nav1.7 is highly expressed in nociceptive sensory neurons and is a key pathogenic target in several human hereditary pain syndromes. In recent years, a large number of studies have shown that Nav1.7 plays an important role in inflammatory, neuropathic, and nociceptive pain. Therefore, targeting Nav1.7 is a new strategy and hotspot for the development of novel analgesics. This review introduces the structure and function of Nav1.7, its regulatory role in pain, highlights the development progress of small-molecule Nav1.7 inhibitors in clinical trials, and analyzes the preclinical development of highly specific Nav1.7 inhibitors, with a view to providing reference for the development of Nav1.7 analgesic drugs.

ObjectiveTo evaluate the clinical efficacy and safety of Xianqi Qinglong Formula （仙芪青龙方， XQF） in the treatment of cough variant asthma （CVS） patients with lung and kidney deficiency and exuberant wind-induced spasm and tension syndrome. MethodsA randomized， positive-controlled， non-inferiority clinical trial was designed. Totally， 102 CVS patients with lung and kidney deficiency and exuberant wind-induced spasm and tension syndrome were randomly divided into a treatment group （52 cases） and a control group （50 cases）. The treatment group was given XQF granules orally， 1 dose per day， 2 bags each time （9.25 g/bag）， twice a day， after breakfast and dinner； the control group was given XQF granules placebo orally combined with inhaled fluticasone propionate inhalation aerosol （125 μg each time， twice a day）. Both groups were treated for 12 weeks and followed up for 12 weeks， with a total of 24 weeks. The primary outcome was the cough symptom score （including daytime， nighttime and total score）， evaluated before treatment （at enrollment）， during treatment （after the 6th week of enrollment）， at the end of treatment （after the 12th week of enrollment）， and at the end of follow-up （after the 24th week of enrollment）. The non-inferiority was determined by the lower limit （LCL） of the unilateral 95% confidence interval. The secondary outcomes included cough relief and disappearance， total score of TCM syndrome， cough visual analogue （VAS） score， Leicester Cough Questionnaire （LCQ） score， and lung function indicators including forced expiratory volume in 1 second （FEV1）， percentage of predicted forced expiratory volume in 1 second （FEV1%pred）， forced vital capacity （FVC）， and peak expiratory flow （PEF）. Blood routine and liver and kidney function were tested before and after treatment， and the adverse events were recorded. ResultsA total of 101 patients were included in the full analysis set （FAS）， including 52 cases in the treatment group and 49 cases in the control group. After treatment， the daytime， nighttime and total cough symptom scores during treatment， at the end of treatment and at the end of follow-up all decreased in both two groups （P＜0.01）. The unilateral 95% LCL of the total cough symptom scores during treatment， at the end of treatment and at the end of follow-up of the two groups were -0.14， -0.47 and -0.27 （95% LCL all＞-0.6）. There were no significant differences in the cough relief rate， cough disappearance rate， cough relief days and cough disappearance days between the two groups at each time point （P＞0.05）. Compared to those before treatment， the TCM syndrome scores and cough VAS scores during treatment， at the end of treatment and at the end of follow-up decreased in both groups， while the LCQ scores increased （P＜0.01）， but there were no significant differences in FEV1， FEV1%， FVC and PEF before and after treatment （P＞0.05）. There were no significant differences in TCM syndrome scores， cough VAS scores， LCQ scores， FEV1， FEV1%， FVC， and PEF between the two groups at each time point （P＞0.05）. No clinically significant abnormal liver and kidney function were found in the two groups before and after treatment. ConclusionXQF is not inferior to fluticasone propionate inhalation aerosol in relieving cough symptoms， reducing cough scores， decreasing the number of cough attack days， and improving the quality of life when treating CVS patients with lung and kidney deficiency and exuberant wind-induced spasms and tension syndrome， and relatively safe.

Two methods including gas chromatography tandem mass spectrometry (GC-MS/MS) and high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) were established to detect common alkyl sulfonates and aryl sulfonates genotoxic impurities. Four alkyl sulfonates and methyl benzenesulfonate were determined by GC-MS/MS using butyl methanesulfonate as the internal standard, the chromatographic column was HP-5MS UI (30 mm × 0.25 mm, 0.25 µm), the carrier gas was helium, the flow rate was 1.0 mL·min^-1 in a constant flow mode, the sample inlet temperature was set to 250 ℃, the split ratio was 10∶1, and the initial temperature of the heating program was 80 ℃, maintained for 1 minute, and then increased to 240 ℃ at a heating rate of 30 ℃·min^-1 for 2 minutes. The mass spectrometry detector was an electron bombardment ion source (EI source), the data collection condition was multi reaction monitoring mode (MRM), and method validation using the raw material of clinical drug citalopram hydrobromide as a sample. The results showed that the linear range of four alkyl sulfonates and methyl benzenesulfonate were good at 3-50 ng·mL^-1 and 9-150 ng·mL^-1, with a correlation coefficient of r > 0.999, The spiked recovery was 80%-120%. The detection limits were 1 and 3 ng·mL^-1; Ten aryl sulfonates determined by LC-MS/MS, the chromatographic column was CSH Fluoro phenyl (100 mm × 2.1 mm, 1.7 µm), the mobile phase was methanol (B)-5 mmol·L^-1 ammonium formate (D), with a flow rate of 0.2 mL·min^-1, and gradient elution was performed. The gradient program (T/% B) was set as 0/20, 25/90, 35/90, 42/20. The mass spectrometer detector was electro spray ionization with positive ionization mode (ESI⁺), the data collection was in dynamic multi reaction monitoring mode (dMRM), and the method was validated using the raw material of the clinical drug citalopram hydrobromide as a sample. The results showed that the linear range of aryl sulfonates were good at 9-2 000 ng·mL^-1, 3-100 ng·mL^-1 and 0.9-30 ng·mL^-1, respectively. The correlation coefficient r > 0.999, the spiked recovery was 80%-120%. The detection limits were 30, 1 and 0.3 ng·mL^-1. Two detection methods did not detect potential sulfonate genotoxicity impurities in the above APIs. The established analytical methods are reliable and effective, which can provide reference for drug quality control and detection.

ObjectiveTo evaluate the reliability and validity of the Dampness Syndrome Scale of Chinese Medicine （DSSCM） among patients with persistent asthma， and to explore the correlation between dampness syndrome and clinical characteristics of persistent asthma. MethodsA cross-sectional survey was conducted. Basic information， examination results， DSSCM， Asthma Control Test （ACT）， Generalized Anxiety Disorder-7 （GAD-7）， and Patient Health Questionnaire-9 （PHQ-9） scores were collected from 206 patients with persistent asthma to evaluate the reliability and validity of DSSCM and to explore the correlation between dampness syndrome and clinical characteristics. ResultsThe mean score of DSSCM among 206 patients was 14.59 ± 10.53. The overall Cronbach α coefficient and Spearman-Brown split-half reliability coefficient of the scale were both greater than 0.8， and the success rate of scale convergent and discriminant validity calibration were greater than 80%. The confirmatory factor analysis showed that the χ²/df was 2.309， and the root mean square error of approximation （RMSEA） was 0.08； the root mean square residual （RMR） was 0.049， whereas the comparative fit index （CFI）， the goodness of fit index （GFI）， the adjusted goodness of fit index （AGFI）， the normed fit index （NFI） and the incremental fit index （IFI） were less than 0.9. Correlation analysis showed that DSSCM scores were positively correlated with disease duration， GAD-7 scores， and PHQ-9 scores （P＜0.05）， and negatively correlated with ACT scores （P＜0.01）. The DSSCM scores were significantly different between patients with different disease severity （H = 10.92， P = 0.01）， and the DSSCM scores of allergic patients were higher than those of non-allergic patients （Z = -4.19， P＜0.001）. ConclusionDSSCM has acceptable reliability and validity for patients with persistent asthma. The scores of DSSCM correlated with the disease duration， ACT score， GAD-7 score， PHQ-9 score， disease severity and allergic status of persistent asthmatics.

BACKGROUND:Studies have shown that there is a close association between spinal cord injury and ferroptosis,and that tetramethylpyrazine has the function of regulating redox reactions. OBJECTIVE:To investigate the regulatory effect of tetramethylpyrazine on ferroptosis in rats with spinal cord injury and its mechanism. METHODS:Thirty-six female specific pathogen-free Sprague-Dawley rats were randomly divided into sham-operated group,model group and tetramethylpyrazine group,with 12 rats in each group.Animal models of spinal cord injury were established using the modified Allen's method in the latter two groups.No treatment was given in the sham-operated group,while rats in the model and tetramethylpyrazine groups were given intraperitoneal injection of normal saline and tetramethylpyrazine solution,once a day,for 28 days. RESULTS AND CONCLUSION:The Basso,Beattie&Bresnahan Locomotor Rating Scale score in the tetramethylpyrazine group was lower than that in the sham-operated group but higher than that in the model group after 14,21,and 28 days of treatment(P＜0.05).After 28 days of treatment,hematoxylin-eosin staining showed that in the model group,the spinal cord tissue of rats showed cavity formation,necrotic tissue and inflammatory infiltration with fibrous tissue formation;in the tetramethylpyrazine group,the area of spinal cord tissue defects was smaller,and inflammatory infiltration and fibrous tissue formation were less than those in the model group.After 28 days of treatment,Prussian blue staining showed that a large amount of iron deposition was seen in the spinal cord tissue of rats in the model group,and less iron deposition was seen in the spinal cord tissue of rats in the tetramethylpyrazine group than in the model group.After 28 days of treatment,the levels of glutathione and superoxide dismutase in the rat spinal cord tissue were decreased(P＜0.05)and the level of malondialdehyde was increased in the model group compared with the sham-operated group(P＜0.05);the levels of glutathione and superoxide dismutase in the rat spinal cord tissue were increased(P＜0.05)and the level of malondialdehyde was decreased in the tetramethylpyrazine group compared with the model group(P＜0.05).After 28 days of treatment,qRT-PCR and western blot assay showed that the mRNA and protein levels of glutathione peroxidase 4,ferritin heavy chain,and ferroportin in the rat spinal cord tissue in the model group were decreased compared with those in the sham-operated group(P＜0.05),while the mRNA and protein levels of glutathione peroxidase 4,ferritin heavy chain,and ferroportin in the rat spinal cord tissue in the tetramethylpyrazine group were increased compared with those in the model group(P＜0.05).Immunofluorescence staining showed that after 28 days of treatment,the neuronal nuclei positive staining in the spinal cord of rats was the most in the sham-operated group and the least in the model group.To conclude,tetramethylpyrazine can improve motor function and play a neuroprotective role in rats with spinal cord injury by regulating ferroptosis.

BACKGROUND:Poor incision healing and infection often occur in elderly patients with lateral malleolar fractures after traditional lateral plate fixation.With the application of engineering software in medicine,a new type of plate placed posterolateral can be designed to solve the above-described problems. OBJECTIVE:To design a new type of posterior lateral low-profile steel plate with the aid of medical bioengineering software,based on the 3D CT data of the distance between the top of the lateral ankle fracture line to the anterior starting point(ACD),the distance between the top of the fracture line to the tip of the lateral ankle(CTD),the distance between the top of the fracture line to the posterior edge of the fracture line(PCD)and the angle between the anterior and posterior lateral sides of the distal fibula(CA). METHODS:Thirty cases of unstable lateral malleolar fracture and normal ankle were taken for CT scanning and three-dimensional reconstruction.The ACD,CTD,and PCD values in patients with lateral malleolar fracture were measured by 3-matic software,and the characteristics of lateral malleolar fracture line were plotted and described.The mimics software was used to measure the value of CA in the normal ankle joint.Based on the data measured above,3-matic software and solidworks software were used to design the low-profile steel plate and the thickness of the steel plate and the direction of the nail path were constructed.In Geomagic Studio software,fine surface,automatic surface,and fitting surface were used to generate the prototype of the low-profile steel plate,and then 3D printing was performed.After making a posterolateral incision of the lateral malleolus,the peroneus longus and brevis tendons were removed,and the prototype of the 3D-printed steel plate was placed behind the fibula to test its size and fit to the bone surface. RESULTS AND CONCLUSION:(1)The mean of ACD was(2.97±0.03)cm,and the variation was 5.23.The mean of PCD was(3.17±0.11)cm,and the variation was 17.60.The mean of CTD was(4.52±0.07)cm,and the variation was 8.60.(2)The fracture line of the lateral malleolus was drawn with an inverted"V"shape.The mean of CA between anterior and posterior lateral surfaces of the distal fibula was(103.20±1.94)°.At the midpoint section of the upper and lower vertices of the anterior edge of the distal fibula,the angle of the anterior and posterior lateral sides(CA)of the distal fibula was(78.50±1.78)°.(3)By using 3-matic,Solidworks,and Geomagic Studio software,a new type of posterior lateral low-profile steel could be successfully designed.Three to four holes were reserved for the screw holes at the proximal end of the plate with screw directions from back to front,and three screw holes were reserved on the inner and outer sides at the far end.The direction of the inner three holes could be from back to front,and the outer three screw holes needed to be biased towards the inner side,with an angle of 9.72°-13.28°.(4)It is indicated that the variability of the ACD position on the anterior lateral fracture line of the lateral malleolus is relatively small,while the variability of the posterior lateral PCD position is relatively large.The angle between the anterolateral and posterolateral sides of the lateral ankle fracture block shows a decreasing trend,with a smaller variation in the proximal angle and a larger variation in the distal angle.Based on three-dimensional CT reconstruction data of the external ankle,with the help of computer bioengineering software and the use of reverse design concept,a new type of low-profile lateral malleolus steel plate with a good fit can be quickly and conveniently designed to provide a valuable reference for the design of internal fixation devices.