OBJECTIVE: To elucidate the mechanism of Banxia Houpo Decoction (BHD) in treating gastroesophageal reflux disease (GERD) by integrating and utilizing the compound analysis, network pharmacology, and empirical verification. METHODS: Ultra-high performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) was utilized to identify the primary compounds in BHD. Network pharmacology was employed to retrieve target genes. A GERD rat model was developed and 32 SD rats were randomly divided into model, BHD-L (3 g/kg), BHD-H (6 g/kg), and mosapride (0.75 mg/kg) groups using a random number table, 8 rats in each group. Eight rats without the construction of a GERD model were selected as the blank group. Esophageal damage was evaluated through visualization and histopathology evaluation. 5-hydroxytryptamine (5-HT) levels in serum and lower esophageal sphincter (LES) were determined by ELISA. LES contractility was measured with a force transducer, and serotonin transporter (SERT) and 5-HT4R expressions in LES were assessed by RT-PCR, Western blot, and immunofluorescence staining, respectively. RESULTS: UPLC-HRMS analysis identified 37 absorption peaks and 157 compounds in BHD. Functional enrichment identified SERT as a significant target for LES contractility. Histopathological findings indicated less severe esophageal mucosal damage in the BHD-H group compared with the model group. Although serum 5-HT levels showed no significant difference, 5-HT concentration in LES tissue was notably higher in the BHD-H group (P<0.05). Within the range from 10^-10 to 10^-7 mmol/L, LES contractility in the BHD-H and mosapride groups was significantly increased (P<0.05). Within the range from 3 × 10^-7 to 3 × 10^-6 mmol/L 5-HT, LES contractility in the BHD-H group was increased (P<0.05). No significant difference was detected within the range from 10^-5 to 10^-4 mmol/L 5-HT. Notably, SERT expression in the BHD-H group assessed by RT-PCR, Western blot, and immunofluorescence staining were significantly lower than that in the model group (all P<0.01); while 5-HT4R expression remained unchanged. CONCLUSION BHD may increase LES contractility by inhibiting SERT expression in LES tissue.
Animals ; Gastroesophageal Reflux/physiopathology* ; Drugs, Chinese Herbal/chemistry* ; Rats, Sprague-Dawley ; Network Pharmacology ; Male ; Serotonin/metabolism* ; Rats ; Disease Models, Animal ; Serotonin Plasma Membrane Transport Proteins/metabolism* ; Esophagus/drug effects*

Objective To design and evaluate a dilation incision device capable of facilitating stable support and flexible adjustment during neurosurgical procedures.Methods The dilation incision device was composed of a support plate,an adjustment assembly,a brain support ring,a rotation assembly,an electric motor,an expansion assembly and a neck support ring.The support plate was made of high-strength stainless steel;the adjustment assembly was made up of a first screw,a lifting groove,a slide bar and a nut;the brain support ring was fixed to the adjustment assembly through a support rod,with an outer layer of medical-grade silicone and an inner layer of stainless steel skeleton;the rotation assembly connected the brain support ring with the expansion assembly and consisted of a rotating shaft,a connecting rod and a rotating lug;a high-precision direct current servo motor was selected for the device;the expansion assembly included a spring,an expansion plate and a moving plate,which realized auto expansion or contraction through spring pressure;the neck support ring had its outer layer made of flexible polyurethane foam and inner layer being a stainless steel skeleton.The device had its stability and safety evaluated by static and dynamic tests at different heights(50,100,150 mm)and angles(0°,30°,60°),which was compared with the traditional fixation device to verify its application effect.Results Static and dynamic tests indicated the device showed high stability and safety in different heights and angles,and gained advantages over the traditional device in stability,convenient operation and surgical field visualization.Conclusion The device developed meets the requirements of neurosurgical procedures,and enhances the safety and portability of neurosurgical procedures.[Chinese Medical Equipment Journal,2024,45(10):37-40]

Osteocytes are the most abundant and long-lived cells in bone,serving as primary regulators of bone remodeling.Besides playing critical roles in endocrine regulation and calcium-phosphate metabolism,osteocytes are primary responders to mechanical stimuli,perceiving and responding to these stimuli directly and indirectly.The process of mechanotransduction in osteocytes is a complex and finely tuned regulation involving interactions between the cell and its surrounding environment,neighboring cells,and various mechanosensors within the cells with distinct functions.The known major mechanosensors in osteocytes include primary cilia,Piezo ion channels,integrins,extracellular matrix,and connexin-based intercellular junctions.These mechanosensors play crucial roles in osteocytes,perceiving and transducing mechanical signals to regulate bone homeostasis.This review aims to provide a systematic introduction to these five mechanosensors,offering new perspectives and insights into understanding how osteocytes respond to mechanical stimuli and maintain bone tissue homeostasis.

Refractory depression is a drug-resistant subtype of major depressive disorder for which there is a lack of effective and durable treatments.Seroxibine,the active substance in the mushroom Capsicum annuum,is a natural 5-hydroxytryptamine hallucinogen that activates the 5-hydroxytryptamine 2A receptor to mediate multiple aspects of antidepressant effects.In recent years,it has received renewed attention for its outstanding therapeutic effects in the treatment of refractory depression or other psychiatric disorders.Therefore,this paper summarizes the studies on neuroplasticity,brain neural connectivity network,neurotransmitters,immune factors,microbiota-gut-brain axis,and clinical efficacy of seloxipine in domestic and international literature,and explores the possible mechanisms of seloxipine's effect on refractory depression,with a view to providing theoretical basis for the clinical application of this drug.

Objective To investigate the role of squalene epoxidase(SQLE)knockout in anti-tumor effect vial im-proving CD8+T cell infiltration in melanoma tumor microenvironment.Methods Both immunodeficient and immu-nocompetent mice were inoculated with SQLE knockout B16F10 cells to determine the cell-autonomous and non-au-tonomous regulation of malignancy.Antibody blockade,Luminex multiplex assays,and flow cytometry were em-ployed to explore the impact of SQLE gene knockout on the secretion of cytokines/chemokines and immune cell in-filtration.Bioinformatics analysis was conducted to validate the correlation between SQLE expression and immune infiltration as well as clinical prognosis in melanoma patients.Results Compared with immunodeficient mice,SQLE knockout significantly inhibited melanoma proliferation in immunocompetent mice and prolonged their surviv-al.SQLE knockout induced the secretion of cytokines and chemokines from tumor cells,improved CD8+T cell in-filtration in the tumor microenvironment,thereby potentiating anti-tumor immunity.Bioinformatics analysis sugges-ted a significant correlation between SQLE and its corresponding immune infiltration markers with the prognosis of melanoma patients.Conclusion SQLE regulates anti-tumor immunity by controlling cytokines and chemokines re-leasing in tumor microenvironment,thus holding promise as a novel tumor immunotherapy target and efficacy predic-tion molecular indicator.

Objective : To investigate the willingness to receive HIV testing in primary health service institutions (PHSIs) among young students in Wuhan City, so as to provide the evidence for improving the detection of HIV testing among young students. Methods: Fifteen PHSIs were sampled using a stratified random sampling method in 14 districts of Wuhan City, and school students at ages of 15 to 24 years were sampled from each district using a convenience sampling method. Participants' demographics, awareness of AIDS-related knowledge, HIV testing and willingness to receive HIV testing were collected using questionnaires, and factors affecting the willingness to receive HIV testing in PHSIs were identified among school students using a multivariable logistic regression model. Results : A total of 301 questionnaires were allocated, and 299 valid questionnaires were recovered, with an effective recovery rate of 99.34%. The respondents included 143 men (47.83%) and 156 women (52.17%), and had a mean age of (19.36±2.40) years; there were 223 respondents with an educational level of diploma and above (74.58%). The awareness of AIDS-related knowledge was 71.57% among the respondents, and 144 respondents had received AIDS-related health education in PHSIs (48.16%). There were 34 respondents that had received HIV testing (11.37%) and 203 respondents that were willing to receive HIV testing in PHSIs (67.89%). The respondents that were unwilling to receive HIV testing in PHSIs were mainly attributed to considering to be unlikely to get HIV infections (82.29%). Multivariable logistic regression analysis showed that school students who knew AIDS-related knowledge (OR=2.797, 95%CI: 1.583-4.941), knew free HIV counseling and testing services in PHSIs (OR=2.070, 95%CI: 1.123-3.814), and had received AIDS-related health education in PHSIs (OR=2.814, 95%CI: 1.573-5.032) were more willing to receive HIV testing in PHSIs. Conclusions There were 67.89% of school students that were willing to receive HIV testing in PHSIs in Wuhan City, and the willingness to receive HIV testing was correlated with the awareness of risk of HIV infections, and awareness and experience of AIDS control services in PHSIs.

ObjectiveTo observe the effects of Qingzao Jiufeitang on the expression of adenosine 5′-monophosphate （AMP）-activated protein kinase （AMPK）， mammalian target of rapamycin （mTOR）， and UNC-51-like kinase 1 （ULK1） in lung cancer cells after the application of AMPK inhibitor （compound C）. MethodMale C57BL/6J mice were randomly divided into a model group， a cyclophosphamide （CTX） group （50 mg·kg^-1）， a Qingzao Jiufeitang group （11 g·kg^-1）， an AMPK inhibitor group （10 mg·kg^-1）， and a Qingzao Jiufeitang combined with AMPK inhibitor group （combination group） （11 g·kg^-1+10 mg·kg^-1）. Lewis lung cancer cells were subcutaneously injected into the right axilla to induce a tumor-bearing model. 24 hours after modeling， the mice in the CTX group were intraperitoneally injected once every other day for seven times in total. The mice in the AMPK inhibitor group and the combination group received intraperitoneal injection of compound C， once a day for 14 days. The mice in the Qingzao Jiufeitang group and the combination group were administered orally at the set dose for 14 days before and after modeling. At the end of the experiment， the mice in each group were sacrificed. The tumor-bearing tissues were collected， and the tumor weight of each group was counted. Transmission electron microscopy （TEM） was used to observe the formation of autolysosomes in lung cancer tissues of each group. Western blot was used to detect the protein expression of AMPK， phosphorylated AMPK （p-AMPK）， mTOR， phosphorylated mTOR （p-mTOR）， ULK1， phosphorylated ULK1 （p-ULK1）， microtubule-associated protein 1 light chain 3B （LC3B）， and p62. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of lung cancer in each group. ResultCompared with the model group， the Qingzao Jiufeitang group showed decreased tumor weight （P<0.01）， the formation of autolysosomes under the electron microscope， increased protein expression of p-AMPK， p-ULK1， LC3B， LC3B-Ⅱ， and p-AMPK/AMPK， p-ULK1/ULK1， and LC3B-Ⅱ/LC3B-Ⅰratios （P<0.01， P<0.05）， and reduced protein expression of p-mTOR， p62， and p-mTOR/mTOR ratio （P<0.05）. Compared with the Qingzao Jiufeitang group， the combination group showed no autolysosomes formation under the electron microscope， decreased protein expression of p-AMPK， p-ULK1， LC3B， LC3B-Ⅱ， and p-AMPK/AMPK， p-ULK1/ULK1， LC3B-Ⅱ/LC3B-Ⅰ ratios （P<0.05， P<0.01）， and increased p62 protein expression （P<0.05）. HE staining results showed that the pathological changes of lung cancer tissues in the groups with drug intervention were improved compared with those in the model group. ConclusionQingzao Jiufeitang can promote the elevation of LC3B-Ⅱ and decrease the expression of p62 protein， thus inducing autophagy. The mechanism of autophagy initiation may be achieved by the AMPK/ULK1 pathway instead of the mediation by the AMPK/mTOR/ULK1 pathway.

Objective:To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for early hypopharyngeal carcinoma and precancerous lesions.Methods:Clinical data of 41 patients who received ESD for early hypopharyngeal carcinoma and precancerous lesions from August 2013 to August 2019 in the Department of Endoscopy of Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College were retrospectively analyzed. Main outcome measurements included operation completion rate, operation time, en bloc resection rate, R0 resection rate, complication rate and recurrence.Results:ESD was successfully completed in all 41 cases, with a success rate of 100.0% and a mean time of 49.1 min (ranged 10-110 min). Fifty-four lesions underwent en bloc resection, with an en bloc resection rate of 98.2% (54/55), of which 41 had negative horizontal and vertical margins, and the R0 resection rate was 74.5% (41/55). During the operation of 55 lesions, there was a small amount of blood oozing on the wound surface, and electrocoagulation with thermal biopsy forceps could successfully stop the bleeding. No perforation occurred, and 2 cases (4.3%) had delayed bleeding after ESD, and hemostasis was successful under emergency endoscopy. Postoperative endoscopy showed that 1 case (2.2%) had esophageal entrance stenosis, and the obstruction was relieved after repeated water balloon dilatation. The follow-up period ranged from 3 to 72 months, and the median time was 18 months. One case was found to have mucosal lesions in the same part of the hypopharynx and received ESD treatment again. Follow-up to October 2020, no residual lesions and recurrence were found.Conclusion:ESD is a safe and effective option for the treatment of early hypopharyngeal carcinoma and precancerous lesions, which is worthy of clinical application.

Objective:To determine the potential risk factors of delayed hemorrhage after endoscopic submucosal dissection (ESD) in patients with early gastric carcinomas or precancerous lesions.Methods:The clinical data of 637 patients with early gastric carcinomas (EGC) who treated with ESD in Department of Endoscopy at Cancer Hospital, Chinese Academy of Medical Sciences, from August 2013 to August 2019, were retrospectively analyzed. Univariate analysis and multivariate logistic analysis were conducted to evaluate the risk factors associated with delayed bleeding.Results:A total of 699 lesions in 637 patients, of which 696 lesions were resected enbloc, the curative resection rate was 92.1% (644/699). The pathological diagnosis after ESD showed that 46 cases were low-grade intraepithelial neoplasia, 71 were high-grade intraepithelial neoplasia, and 582 were cancer. Delayed bleeding occurred in 74 lesions, while other 625 lesions without postoperative bleeding. The incidence was 10.6%. Compared with the non-bleeding group, there were statistically significant differences in the maximum length of the lesion, the gross shape of the lesion, the control of intra operative bleeding, and the operation time in the delayed bleeding group ( P<0.05). Multivariate logistic regression analysis showed that the maximum length of the lesion and the gross shape of the lesion were independent factors of delayed bleeding after ESD. Delayed bleeding was inclined to occur in patients with lesion size ≥3.0 cm ( OR=1.958, 95% CI: 1.162-3.299) and the superficial and flat lesion ( OR=10.598, 95% CI: 1.313-85.532) after ESD. Conclusions:The maximum length of the lesion and the gross shape of the lesion are independent impact factors of delayed bleeding occurring in patients with EGC and precancerous lesions after ESD. Patients with lesion size≥3 cm, or superficial flat lesion should be paid attention after ESD operation. It needs to take timely measures to prevent the very likely bleeding in order to ensure postoperative recovery and improve the quality of life for postoperative patients.

The novel coronavirus disease (COVID-19) pandemic is emerging as a global health threat and shows a higher risk for men than women. Thus far, the studies on andrological consequences of COVID-19 are limited. To ascertain the consequences of COVID-19 on sperm parameters after recovery, we recruited 41 reproductive-aged male patients who had recovered from COVID-19, and analyzed their semen parameters and serum sex hormones at a median time of 56 days after hospital discharge. For longitudinal analysis, a second sampling was obtained from 22 of the 41 patients after a median time interval of 29 days from first sampling. Compared with controls who had not suffered from COVID-19, the total sperm count, sperm concentration, and percentages of motile and progressively motile spermatozoa in the patients were significantly lower at first sampling, while sperm vitality and morphology were not affected. The total sperm count, sperm concentration, and number of motile spermatozoa per ejaculate were significantly increased and the percentage of morphologically abnormal sperm was reduced at the second sampling compared with those at first in the 22 patients examined. Though there were higher prolactin and lower progesterone levels in patients at first sampling than those in controls, no significant alterations were detected for any sex hormones examined over time following COVID-19 recovery in the 22 patients. Although it should be interpreted carefully, these findings indicate an adverse but potentially reversible consequence of COVID-19 on sperm quality.
Adult ; Asthenozoospermia/virology* ; COVID-19/physiopathology* ; China ; Gonadal Steroid Hormones/blood* ; Humans ; Male ; Progesterone/blood* ; Prolactin/blood* ; SARS-CoV-2 ; Semen/physiology* ; Semen Analysis ; Sperm Count ; Sperm Motility ; Spermatozoa/physiology* ; Time Factors