ObjectiveTo investigate the mechanism by which Feixin decoction treats hypoxic pulmonary hypertension （HPH） by regulating the peroxisome proliferator-activated receptor gamma （PPARγ）/nuclear factor-kappa B （NF-κB）/NOD-like receptor pyrin domain containing 3 （NLRP3） signaling pathway. MethodsForty-eight male SD rats were randomly allocated into normal， hypoxia， and low-， medium- and high-dose （5.85， 11.7， 23.4 g·kg^-1， respectively） Feixin decoction groups， with 8 rats in each group. Except the normal group， the remaining five groups were placed in a hypoxia chamber with an oxygen concentration of （10.0±0.5）% for 8 h per day， 28 days， and administrated with corresponding drugs during the modeling process. After 4 weeks of treatment， echocardiographic parameters ［pulmonary artery acceleration time （PAT）， pulmonary artery ejection time （PET）， right ventricular anterior wall thickness （RVAWd）， and tricuspid annular plane systolic excursion （TAPSE）］ were measured for each group. The right ventricular systolic pressure （RVSP） was measured by the right heart catheterization method， and the right ventricular hypertrophy index （RVHI） was calculated by weighing the heart. The pathological changes in pulmonary arterioles were observed by hematoxylin-eosin staining. The co-localization of α-smooth muscle actin （α-SMA） with NLRP3， N-terminal gasdermin D （N-GSDMD）， and cysteinyl aspartate-specific proteinase-1 （Caspase-1） in pulmonary arteries was detected by immunofluorescence. The protein levels of PPARγ， NF-κB， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， N-GSDMD， interleukin-1β （IL-1β）， interleukin-18（IL-18）， and cleaved Caspase-1 in the lung tissue was determined by Western blot. The ultrastructural changes in pulmonary artery smooth muscle cells （PASMCs） were observed by transmission electron microscopy. ResultsCompared with the normal group， the hypoxia group showed increased RVSP and RVHI （P<0.01）， decreased right heart function （P<0.01）， increased pulmonary vascular remodeling （P<0.01）， increased co-localization of α-SMA with NLRP3， N-GSDMD， and Caspase-1 in pulmonary arterioles （P<0.01）， up-regulated protein levels of NF-κB， NLRP3， ASC， N-GSDMD， IL-1β， IL-18， and cleaved Caspase-1 in the lung tissue （P<0.05， P<0.01）， a down-regulated protein level of PPARγ （P<0.05， P<0.01）， and pyroptosis in PASMCs. Compared with the hypoxia group， Feixin decoction reduced RVSP and RVHI， improved the right heart function and ameliorated pulmonary vascular remodeling （P<0.05， P<0.01）， decreased the co-localization of α-SMA with NLRP3， N-GSDMD， and Caspase-1 （P<0.05， P<0.01）， down-regulated the protein levels of NF-κB， NLRP3， ASC， N-GSDMD， IL-1β， IL-18， and cleaved Caspase-1 in the lung tissue （P<0.05， P<0.01）， up-regulated the protein level of PPARγ （P<0.05， P<0.01）， and alleviated pyroptosis in PASMCs. ConclusionFeixin decoction can ameliorate pulmonary vascular remodeling and right heart dysfunction in chronically induced HPH rats by regulating pyroptosis in PASMCs through the PPARγ/NF-κB/NLRP3 pathway.

This paper reports a case of a patient with sleep-related painful erections treated by acupuncture combined with abdominal vibration therapy. The main symptom was repeated painful penile erections during nighttime sleep. The syndrome was differentiated as "water failing to nourish wood" and "liver qi stagnation". Acupuncture was applied at Baihui (GV20), Sishencong (EX-HN1), Guanyuan (CV4), and bilateral Neiguan (PC6), Hegu (LI4), Taichong (LR3), Taixi (KI3), Guilai (ST29), Yongquan (KI1), Yanglingquan (GB34), and Sanyinjiao (SP6). The treatment was combined with abdominal vibration therapy. Treatment was given once daily, five times per week. After the first treatment, the severity and duration of nocturnal erection pain were reduced, and sleep quality was improved. After two weeks of treatment, nocturnal erection pain persisted but became tolerable, with significantly shortened duration.
Humans ; Male ; Acupuncture Points ; Acupuncture Therapy ; Erectile Dysfunction/physiopathology* ; Penile Erection ; Sleep

BACKGROUND: To evaluate the efficacy and safety of the first cohort of people in China treated with a responsive neurostimulation system (Epilcure TM , GenLight MedTech, Hangzhou, China) for focal drug-resistant epilepsy in this study. METHODS: This multicenter, before-and-after self-controlled study was conducted across 8 centers from March 2022 to June 2023, involving patients with drug-resistant epilepsy who were undergoing responsive neurostimulation (RNS). The study was based on an ongoing multi-center, single-blind, randomized controlled study. Efficacy was assessed through metrics including median seizure count, seizure frequency reduction (SFR), and response rate. Multivariable linear regression analysis was conducted to explore the relationships of basic clinical factors and intracranial electrophysiological characteristics with SFR. The postoperative quality of life, cognitive function, depression, and anxiety were evaluated as well. RESULTS: The follow-up period for the 19 participants was 10.7 ± 3.4 months. Seizure counts decreased significantly 6 months after device activation, with median SFR of 48% at the 6th month (M6) and 58% at M12 ( P  <0.05). The average response rate after 13 months of treatment was 42%, with 21% ( n  = 4) of the participants achieving seizure freedom. Patients who have previously undergone resective surgery appear to achieve better therapeutic outcomes at M11, M12 and M13 ( β  <0, P  <0.05). No statistically significant differences were observed in patients' scores of quality of life, cognition, depression and anxiety following stimulation when compared to baseline measurements. No serious adverse events related to the devices were observed. CONCLUSIONS: The preliminary findings suggest that Epilcure TM exhibits promising therapeutic potential in reducing the frequency of epileptic seizures. However, to further validate its efficacy, larger-scale randomized controlled trials are required. REGISTRATION Chinese Clinical Trial Registry (No. ChiCTR2200055247).
Humans ; Female ; Male ; Drug Resistant Epilepsy/therapy* ; Adult ; Young Adult ; Middle Aged ; China ; Adolescent ; Treatment Outcome ; Quality of Life ; Single-Blind Method ; Seizures ; Electric Stimulation Therapy/methods*

Humans ; Nasal Polyps/epidemiology* ; Cross-Sectional Studies ; Rhinosinusitis ; Asthma/epidemiology* ; Sinusitis/epidemiology* ; Chronic Disease

Objective:To evaluate the clinical effect of orbital fat releasing and repositioning through supra-suborbicularis oculi fat (SOOF) in lower eyelid blepharoplasty.Methods:The authors retrospectively analyzed the clinical data of patients who received lower eyelid blepharoplasty in the Department of Plastic Surgery, Beijing Tsinghua Changgung Hospital from January 2017 to January 2023. Lower eyelid blepharoplasty with orbital fat releasing and repositioning through supra-SOOF was performed. The tear trough ligament and orbicularis retaining ligament were released between the orbicularis oculi muscle and SOOF via skin approach. Orbital septal fat was released to this space, lateral fat flap was fixed to the SOOF capsule, medial fat flap was fixed to the superficial fascia of the levator labii superioris muscle, orbital septum was repositioned, and lateral canthus was suspended. After the operation, lower eyelid morphology and complications were evaluated.Results:A total of 58 patients were enrolled, including 8 males and 50 females with the age of (49.8 ± 10.4) years (32 to 70 years). All patients had obvious lower eyelid bags on both sides, combining the tear trough deformity and (or) palabromalar groove. Fifty-seven patients were followed up for (29.1 ± 16.9) months (6-67 months). All patients were satisfied with the operation. The appearance of lower eyelid was greatly improved, with elimination of fat prominence and tear trough deformity. Mild lower eyelid ectropion was observed two cases 1 week after the operation, and were relieved by moderate massage 2 weeks postoperatively. In one case, mild lower eyelid retraction was observed 1 month postoperatively, with no complaint of discomfort or further treatments. Bulbar conjunctival hemorrhage occurred in 1 case and recovered without further interventions.Conclusion:Lower eyelid blepharoplasty with orbital fat releasing and reposting through supra-SOOF can effectively release the tear trough ligament and the orbicularis retaining ligament, with stronger fat fixation and less surgical difficulty. After the operation, eyelid contour was flat and tight with fewer complications and higher patient satisfaction.

Objective:To analyze the current adoption of palliative care by patients with unresectable metastatic colorectal cancer (mCRC) in China.Methods:From 1 March 2023 to 30 June 2023, a questionnaire survey was conducted by random sampling. An exclusive research platform for the Blue Book on Clinical Diagnosis and Treatment of Metastatic Colorectal Cancer. An online questionnaire was sent to medical oncologists (including chief physicians, associate chief physicians, attending physicians and residents) in general hospitals and oncology hospitals in four major regions of East, Central, South and Northeast China. The questionnaire contained 28 questions requesting basic information about doctors, the number of patients with mCRC, the status of treatment from first to fourth line and beyond, points concerning treatment of pain in patients with mCRC, and expectations for the future. A medical team was responsible for the quality control of data collected, whereas statisticians performed the data cleaning and sorting and statistical analysis.Results:A total of 300 clinical questionnaires were collected, including 217 (72%) from doctors in general hospitals and 83 (28%) from doctors in oncology hospitals. Senior physicians (including associate chief physicians and chief physicians) accounted for 65% of the respondents, attending physicians 30%, and residents 5%. Within 3 months (average for each month), 46.4±26.6% patients were diagnosed with recurrent or unresectable mCRC by each physician, 51.6±26.8% of the patients being in cancer hospitals and 44.4±26.3% in general hospitals. One hundred percent of patients receiving first-line treatment received palliative care, as did 80.3% of those receiving second-line treatment, 58.2% of those receiving third-line treatment, and 35.1% of those receiving ≥fourth-line treatment. The primary factor governing selection of first-line treatment was guideline recommendations, whereas comorbidities and the patients' physical status dictated second line to fourth line treatment. Standard first-line treatment was administered to 93.8% of eligible patients, standard second-line treatment to 94.3%; and standard third-line treatment to 73.5%. First-line therapy included targeted therapy in 63.6% of patients and immunotherapy in 2.8%; second-line therapy included targeted therapy in 63.0% of patients and immunotherapy in 2.0%; third-line therapy included targeted therapy in 59.2% of patients and immunotherapy in 2.2%; and fourth-line therapy included targeted therapy in 48.7% of patients and immunotherapy in 3.1%. First-line treatment lasted an average of 9.6 months, second-line treatment 6.7 months, third-line treatment 4.9 months, and fourth-line treatment 3.7 months. More than 70% of the patients maintained a good quality of life after receiving first and second-line treatment and more than 60% of them had ECOG performance scores of 0–1. After receiving third- and fourth-line treatment, 50%–60% of patients maintained a good quality of life and 40%–50% of them maintained ECOG performance scores of 0–1. The survey also revealed that the main deficiencies in treatment were limited effectiveness of third-line treatment, insufficient availability and opportunity for clinical research, popularity of new drugs or new drug combination strategies, and limited channels for participation in multidisciplinary diagnosis and treatment. Clinicians reported looking forward to participating in more clinical research on new drugs, hearing about the experience of experts in the field, and discovery of new targets and new drugs that increased the options for posterior line treatment of colorectal cancer.Conclusions:This report objectively summarizes the current situation, treatment difficulties, and expectations of frontline physicians concerning management of mCRC, thus providing a basis for decision-making and future direction for the diagnosis and research on treatment of mCRC.

Objective To construct chimeric antigen receptors modified γδT cells targeting at BCMA(BCMA CAR-γδT)and to evaluate its efficacy of anti-multiple myeloma in vitro.Methods Lentiviral vectors containing BCMA single-chain variable fragment were constructed and transiently transfected into 293T cells.The expression of foreign genes was verified by fluorescence microscopy and Western blot;the lentivirus was packaged and the virus titer was determined by flow cytometry.Human peripheral blood αβT cells were infected and γδT cells were examined for its infection efficiency;LDH release method was used to detect the cytotoxic activity of BCMA CAR-γδT cells against human multiple myeloma cell lines in vitro,and the difference of cytotoxic activity between CAR-γδT cells and CAR-αβT cells was compared by Incucyte S3 Live-Cell Analysis Instrument.Results Twenty-four hours after BCMA-CAR lentiviral vector was transferred into 293T cells,the expression of exogenous ZsGreen was microscopied by fluorescence microscope;CD3ζ was detected by Western blot,which showed that BCMA-CAR could be success-fully expressed.The lentivirus was packaged,collected and concentrated(virus titer of 2.23×108 Tu/mL).Infected αβT cells and γδT cells from human peripheral blood in MOI=5,and the results of flow cytometry showed that infection efficiency of αβT cells was 59.18%±2.56%,γδT cells was 48.15±9.86%.The cytotoxic activity of CAR-γδT cells against human myeloma cell lines MM1.S,H929 with high expression of BCMA and K562 cells with over-expression of BCMA was higher than that of empty vector control γδ T cells,which were signifi-cantly enhanced(P＜0.001),but there was no difference in cell lines negative for BCMA expression;Live-Cell Analysis Instrument results showed that the cytotoxic activity of BCMA CAR-γδT cells and BCMA CAR-αβT cells against H929 in vitro was significantly better than their vector control cells.There was no difference in the cytotoxic activities of BCMA CAR-γδT cells as compared with against BCMA negative cell lines,and so do BCMA CAR-T cells.Conclusions Cytotoxic activity of BCMA CAR-γδT targeting at BCMA in vitro was significantly enhanced,which is expected to serve as a novel allogeneic γδT cell product for cell a-doptive immunotherapy of multiple myeloma.

Objective To evaluate the efficacy and safety of ozone injection therapy for lumbar disc hemiation(LDH).Methods A computerized retrieval of academic papers concerning the randomized controlled trial(RCT)on ozone injection therapy for LDH from the databases of Embase,PubMed,Cochrane library and Web of science was conducted.The retrieval time period was from the establishment of the database to February 2023.The literature retrieval,screening,and data extraction were independently performed by two researchers.Cochrane bias risk assessment tool was used to assess the quality of the included literature.Stata 17.0 software was used to make meta-analysis.Results A total of 9 RCTs including 702 patients were finally included in this study.The results of meta-analysis showed that compared with radiofrequency thermocoagulation,percutaneous rotation and other treatments for LDH,the combination use of ozone injection could signifiicantly improve the effective rate based on Macnab efficacy evaluation criteria(RR=1.097,95％CI:1.038～1.159,P=0.001)and the excellent rate(RR=1.185～95％CI:1.074～1.309,P=0.001),and decrease the visual analog scale(VAS)pain score(WMD=-0.810～95％CI:-1.205～-0.414,P=0.000),and the differences in the above indexes were statistically significant.Conclusion Compared with the simple use of radiofrequency thermocoagulation,percutaneous rotation,and other treatment for LDH,the combination use of ozone injection therapy can significantly improve the effective rate and excellent rate based on Macnab efficacy evaluation criteria,decrease VAS score,with a high clinical safety.Limited by the quantity and quality of the original studies included in this study,the above conclusions need to be further verified by multi-center,large-sample and high-quality studies.

Objective To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma(ESCC).Methods We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients.GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog,and TIMER online tool was used to analyze the correlations among TβR1,MMP-2,and MMP-9 in esophageal cancer.Results Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated.Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age,gender,or tumor differentiation.The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time.Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-β signaling pathway,and the expressions of MMP-2/MMP-9 and TβR1 were positively correlated.In cultured ESCC cells,Nanog knockdown significantly decreased the expression of TβR1,p-Smad2/3,MMP-2,and MMP-9 and strongly inhibited cell migration.Conclusion The high expressions of Nanog,MMP-2,and MMP-9,which are positively correlated,are closely related with invasion depth,lymph node metastasis,and prognosis of ESCC.Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-β signaling pathway,and its high expression promotes migration of ESCC cells.