OBJECTIVE: To explore the preventive effect of transcutaneous phrenic nerve stimulation on ventilator-induced diaphragmatic dysfunction (VIDD) in patients requiring invasive mechanical ventilation. METHODS: A randomized controlled trial was conducted. The patients requiring invasive mechanical ventilation admitted to the intensive care unit (ICU) of Jiaxing First Hospital from November 2022 to December 2023 were enrolled. Participants were randomized into the control group and the observation group using a random number table. The control group was given ICU standardized nursing intervention, including turning over and slapping the back, raising the head of the bed, sputum aspiration on demand, aerosol inhalation, oral care, and monitoring of airbag pressure and gastric retention, the observation group was given additional transcutaneous phrenic nerve stimulation intervention on the basis of ICU standardized nursing intervention. The stimulation intensity was set to 10 U, the pulse frequency was set to 40 Hz, and the stimulation frequency was set to 12 times/min. Transcutaneous phrenic nerve stimulation was administered once a day for 30 minutes each time, for a total of 5 days. Diaphragm thickening fraction (DTF) and arterial blood gas parameters on days 1, 3, and 5 of intervention were compared between the two groups. After 5 days of intervention, other parameters including the incidence of VIDD, duration of mechanical ventilation, and length of ICU stay were compared. RESULTS: A total of 120 patients requiring invasive mechanical ventilation were enrolled, with 16 dropouts (dropout rate was 13.33%). Ultimately, 51 patients in the control group and 53 patients in the observation group were analyzed. Baseline characteristics, including gender, age, body mass index (BMI), acute physiology and chronic health evaluation II (APACHE II) score, albumin (Alb), hemoglobin (Hb), and disease type, showed no significant differences between the two groups. DTF in both groups gradually increased over duration of intervention [DTF on days 1, 3, and 5 in the control group was (20.83±2.33)%, (21.92±1.27)%, and (23.93±2.33)%, respectively, and that in the observation group was (20.89±1.96)%, (22.56±1.64)%, and (25.34±2.38)%, respectively], with more significant changes in DTF in the observation group, showing time effects (F_time = 105.975, P < 0.001), intervention effects (F_intervention = 7.378, P = 0.008), and interaction effects (F_interaction = 3.322, P = 0.038). Arterial blood gas parameters did not differ significantly before intervention between the groups, but after 5 days of intervention, arterial partial pressure of oxygen (PaO₂) in the observation group was significantly higher than that in the control group [mmHg (1 mmHg≈0.133 kPa): 100.72±15.75 vs. 93.62±15.54, P < 0.05], and arterial partial pressure of carbon dioxide (PaCO₂) was significantly lower than that in the control group (mmHg: 36.53±3.10 vs. 37.69±2.02, P < 0.05). At 5 days of intervention, the incidence of VIDD in the observation group was significantly lower than that in the control group [15.09% (8/53) vs. 37.25% (19/51), P < 0.05], and both duration of mechanical ventilation and length of ICU stay were significantly shorter than those in the control group [duration of mechanical ventilation (days): 7.93±2.06 vs. 8.77±1.76, length of ICU stay (days): 9.64±2.35 vs. 11.01±2.01, both P < 0.05]. CONCLUSIONS Transcutaneous phrenic nerve stimulation can improve diaphragmatic and respiratory function in patients receiving invasive mechanical ventilation, reduce the incidence of VIDD, and shorten the duration of mechanical ventilation and length of ICU stay.
Humans ; Transcutaneous Electric Nerve Stimulation ; Respiration, Artificial/adverse effects* ; Diaphragm/physiopathology* ; Phrenic Nerve ; Intensive Care Units ; Male ; Female ; Middle Aged

Objective To explore the clinical efficacy of high-frequency electric snare device under elec-tronic laryngoscope in the treatment of epiglottic cyst.Methods A total of 100 patients with definitely diag-nosed epiglottic cyst receiving outpatient operation treatment in the First Affiliated Hospital of Gannan Medi-cal University from April 2021 to March 2023 were selected as the research subjects and included into the ob-servation group and control group according to the visiting order,50 cases in each group.The observation group was treated with high-frequency electric snare for epiglottic cyst resection under electronic laryngo-scope,and the control group was treated with laryngeal tissue forceps under electronic laryngoscope for uncov-ering operation of epiglottic cyst.The operation time,intraoperative blood loss volume,pain degree within postoperative 24 h,pain duration,complete resection rate and recurrence rate in postoperative 3 months were compared between the two operation methods.Results The operation time,intraoperative blood loss volume,VAS score within postoperative 24 h and pain duration in the observation group were significantly less than those in the control group,the complete resection rate was significantly higher than that in the control group,and the differences were statistically significant (P<0.05).The two groups were followed up for 3 months. Only 2 cases in the control group relapsed,which were epiglottic multiple cyst,and the recurrence rate had no statistical difference between the two groups (P>0.05).No dyspnea,massive bleeding and epiglottic adhesion appeared.Conclusion The high-frequency electric snare device under electronic laryngoscope for treating epi-glottic cyst has the advantages of short operation time,less blood loss,postoperative light pain and high com-plete resection rate.

OBJECTIVE: To investigate the effectiveness of modified temporomandibular joint disc reduction and suture with tragus incision assisted by arthroscopy for temporomandibular joint anterior disc displacement (ADD). METHODS: A clinical data of 30 patients (45 sides) with temporomandibular joint ADD, who met selective criteria and were admitted between September 2022 and February 2024, was retrospectively analyzed. Among them, 15 patients (23 sides) were treated with temporomandibular joint disc reduction and suture via small incision (open operation group), and 15 patients (22 sides) with modified temporomandibular joint disc reduction and suture with tragus incision assisted by arthroscopy (arthroscopy group). There was no significant difference in gender, age, disease duration, affected side, Wilkes-Bronstein stage, preoperative visual analogue scale (VAS) score, maximal interincisal opening (MIO), and temporomandibular joint dysfunction index (DI), craniomandibular index (CMI), palpation index (PI), and other baseline data between groups ( P>0.05). VAS score, MIO, and temporomandibular joint function indicators (PI, DI, CMI) of patients were recorded at 3 months after operation, and the difference (change value) of the above indicators between pre- and post-operation was calculated. At 1 week after operation, MRI was performed to evaluate the reduction of the articular disc compared to the preoperative image. The results were classified as excellent, good, and poor, with excellent and good being considered effective reduction. The condition of condyle process repair was observed by cone beam CT (CBCT) at 3 months after operation. RESULTS: All incisions healed by first intention in the two groups. All patients were followed up 3-18 months (mean, 8.2 months). Facial nerve injury occurred in 3 cases in the open operation group and 1 case in the arthroscopy group, all of which returned to normal after physiotherapy and drug treatment. At 3 months after operation, MIO and VAS scores of both groups significantly improved when compared with those before operation ( P<0.05), and temporomandibular joint function indicators (PI, DI, CMI) significantly decreased ( P<0.05). The change values of MIO and temporomandibular joint function indicators in arthroscopy group were significantly higher than those in open operation group ( P<0.05). There was no significant difference in the change value of VAS score between groups ( P>0.05). There was no recurrence during follow-up. Postoperative MRI review showed that the effective reduction rate of joint disc was 95.65% (22/23) in the open operation group and 95.45% (21/22) in the arthroscopy group, with no significant difference between groups ( P>0.05). Postoperative CBCT found that early and timely effective reduction of joint disc was conducive to condyle process repair and reconstruction. CONCLUSION Modified temporomandibular joint disc reduction and suture with tragus incision assisted by arthroscopy has a clear effect in the treatment of ADD, with less trauma, fewer postoperative complications, and good early effectiveness.
Humans ; Arthroscopy/methods* ; Retrospective Studies ; Temporomandibular Joint Disorders/surgery* ; Temporomandibular Joint Disc/surgery* ; Male ; Treatment Outcome ; Female ; Suture Techniques ; Adult ; Joint Dislocations/surgery* ; Range of Motion, Articular ; Middle Aged ; Pain Measurement ; Young Adult ; Sutures

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
Animals ; Mice ; Methylation ; Chromatin ; Histones/metabolism* ; RNA, Messenger/genetics* ; Methyltransferases/metabolism* ; RNA/metabolism*

The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death (ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment (ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin (DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels (DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful anti-tumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.

Aberrant activation of oncogenic signaling pathways in tumors can promote resistance to the antitumor immune response. However, single blockade of these pathways is usually ineffective because of the complex crosstalk and feedback among oncogenic signaling pathways. The enhanced toxicity of free small molecule inhibitor combinations is considered an insurmountable barrier to their clinical applications. To circumvent this issue, we rationally designed an effective tumor microenvironment-activatable prodrug nanomicelle (PNM) for cancer therapy. PNM was engineered by integrating the PI3K/mTOR inhibitor PF-04691502 (PF) and the broad spectrum CDK inhibitor flavopiridol (Flav) into a single nanoplatform, which showed tumor-specific accumulation, activation and deep penetration in response to the high glutathione (GSH) tumoral microenvironment. The codelivery of PF and Flav could trigger gasdermin E (GSDME)-based immunogenic pyroptosis of tumor cells to elicit a robust antitumor immune response. Furthermore, the combination of PNM-induced immunogenic pyroptosis with anti-programmed cell death-1 (αPD-1) immunotherapy further boosted the antitumor effect and prolonged the survival time of mice. Collectively, these results indicated that the pyroptosis-induced nanoplatform codelivery of PI3K/mTOR and CDK inhibitors can reprogram the immunosuppressive tumor microenvironment and efficiently improve checkpoint blockade cancer immunotherapy.

The internal organs and meridians were associated with Yin and Yang, five elements, six qi, and time and space, based on the holistic view of heaven, earth and human, according to Huangdi Neijing. The syndrome differentiation system of six meridians and Zang Fu meridians were established by Shanghan Zabing Lun, on the basis of the three Yin, three Yang, six meridians, and five Zang system in Huangdi Neijing. We put forward the concept of the six meridians syndrome differentiation system of circular motion, considering that the six meridians syndrome differentiation system actually implies the theory of circular motion. The syndrome differentiation system was constructed with the circular model of one qi circulating around the road, rising left and falling right, corresponding up and down, and maintaining conservation in the middle as the core, integrating Yin and Yang, five elements, six qi, Zang Fu and meridians, qi, blood and body fluid, and the integration of heaven, earth and human, focusing on "disease location and disease nature", taking classical prescriptions as the main treatments, and cooperating with external treatments such as acupuncture and moxibustion. We organically combined the circular motion with the syndrome differentiation of the six meridians, systematically interpreted the physiological bases, pathological changes, progressive patterns, and the treatments, based on syndrome differentiation, by inheriting the classical thinking mode of Hetu, Luoshu,Zhouyi, Huangdi Neijing, ShennongHerbal Classic, and Shanghan Zabing Lun.

Objective To investigate the current situation of animal injury among children in Chongqing, and to provide a scientific basis for relevant departments to formulate and implement strategies and measures to prevent and control animal injury to children. Methods According to the method of multi-stage stratified cluster sampling, 14,056 children in grades 4-12 in four districts of Chongqing were selected as the investigation subjects, and the occurrence of animal injuries in the past 6 months was investigated. Results The incidence of animal injury among school children in Chongqing was 0.35% and the incidence of person-time was 0.36%. The incidence rate in males (0.48%) was higher than that in females (0.31%). The incidence rate in urban children (0.43%) was higher than that in rural children (0.30%). The incidence of animal injury was the lowest in nuclear families (0.25%), and the highest in single-parent families (0.82%). There were statistically significant differences in the incidence of animal injuries in children among different fathers' occupational types, family types and parents' parenting styles (P<0.05).  The main place of child animal injury was home (57.14%). Recreational activities were the main cause of animal injury (51.02%). The main injuries were lower limbs (42.86%), upper limbs (24.49%) and head (10.20%). Conclusion The prevention and control of children's animal injury in Chongqing should focus on boys and families. It is suggested to take targeted and comprehensive interventions to prevent animal injuries in children.

ObjectiveTo investigate the population with an advantage of clinical cure previously treated with nucleos(t)ide analogues (NAs), and to provide more methods for clinicians in pursuing the clinical cure of hepatitis B. MethodsA total of 42 chronic hepatitis B patients with low-level HBsAg who received NAs treatment in Hebi Third People’s Hospital from October 2017 to October 2019 were enrolled as subjects and divided into combination treatment group (group A) and NA monotherapy group (group B). The 22 subjects in group A were treated with NAs combined with PEG-IFN antiviral therapy for 48 weeks, and some patients withdrew from PEG-IFN after 24 weeks and continued to receive NA monotherapy, while the 20 subjects in group B received NA antiviral therapy alone. Both groups were observed till week 48, and the five makers for hepatitis B were measured to evaluate clinical outcome. The t-test was used for comparison of continuous data between two groups, and the Fisher’s exact test was used for comparison of categorical data between two groups; a multivariate logistic regression analysis was used to perform a multivariate analysis. ResultsCompared with group B at the 48-week treatment endpoint, group A had significantly higher HBsAg clearance rate (45.5% vs 0, P＜0.01) and HBsAg seroconversion rate (31.8% vs 0, P＜0.01). The population with HBsAg ＜1000 IU/ml, ＜500 IU/ml, ＜100 IU/ml, and ＜10 IU/ml had an HBsAg clearance rate of 52.6%, 61.5%, 66.7%, and 100%, respectively, and the population with an HBsAg level of 500-1000 IU/ml, 100-500 IU/ml, 10-100 IU/ml, and ＜10 IU/ml had an HBsAg clearance rate of 33.3%, 50%, 40%, and 100%, respectively. The 4 patients with baseline HBsAg ＜10 IU/ml (accounting for 18.2% in group A) achieved clinical cure at week 12 of combined treatment, and after observation to week 48, 2 patients had an anti-HBs level of ＞100 IU/ml and 2 had an anti-HBs level of ＞1000 IU/ml. The multivariate logistic regression analysis of HBsAg clearance showed that age at the initiation of combined treatment affected HBsAg clearance (odds ratio ［OR］=0.877, 95% confidence interval ［CI］: 0.781-0.985, P=0.026), and most of the patients with HBsAg clearance had an age of 36-49 (44.20±4.49) years; baseline HBsAg level also had an impact on HBsAg clearance (OR=0.996, 95% CI: 0.992-1.000, P=0.050). ConclusionThe addition of interferon therapy in chronic hepatitis B patients with low-level HBsAg previously treated with NAs can significantly improve the clinical cure rate. The younger the age and the lower the HBsAg level, the shorter the duration of combined treatment. Age and baseline HBsAg level are more important than the duration and type of NA medication.

BACKGROUND: We aim to explore the association between self-reported snoring and hypertension among adults aged 30-79 in Chongqing, China. METHODS: A total of 23,342 individuals aged 30-79 were included at baseline from August 2018 to January 2019, and the final sample size for the analysis was 22,423. Face-to-face interviews and physical examinations were conducted by trained investigators. Logistic regression was performed to study age-specific and gender-specific associations between snoring and hypertension. RESULTS: Frequent snoring was associated with the risk of hypertension for each age and gender group, and the frequency of snoring was positively correlated with the risk for hypertension. For the three age groups (< 45, 45-59, ≥ 60), compared with the non-snoring group, those who snore often had a 64.5%, 53.3%, and 24.5% increased risk of hypertension (< 45: OR = 1.65, 95%CI 1.34-2.02; 45-59: OR = 1.53, 95%CI 1.37-1.72; ≥ 60: OR = 1.25, 95%CI 1.09-1.42), respectively. For men and women, those who snore often had a 46.8% and 97.2% increased risk of hypertension, respectively, than the non-snoring group (men: OR = 1.47, 95%CI 1.33-1.63; women: OR = 1.97, 95%CI 1.75-2.23). CONCLUSIONS People who snore frequently should pay close attention to their blood pressure levels in order to achieve early prevention of hypertension, particularly for snorers who are female and aged under 45; importance should be attached to their blood pressure control.
Adult ; Aged ; China/epidemiology* ; Cross-Sectional Studies ; Female ; Humans ; Hypertension/etiology* ; Male ; Middle Aged ; Self Report ; Snoring/complications*