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

ObjectiveTo observe the effect of neural mobilization based on shoulder control training on shoulder pain and upper limb function in stroke patients with hemiplegia. MethodsFrom January, 2020 to November, 2021, 43 patients with hemiplegia after stroke in the Second People's Hospital of Nantong were randomly divided into control group (n = 21) and treatment group (n = 22). The control group received shoulder control training, while the treatment group received neural mobilization in addition. Before and after four weeks of treatment, they were evaluated with the Numeric Rating Scale (NRS) of pain and Fugl-Meyer Assessment-Upper Extremities (FMA-UE). ResultsOne case dropped off in the control group and two cases dropped off in the treatment group. After treatment, the NRS score and FMA-UE score improved in both groups (|t| >7.898, P < 0.001), and they were better in the treatment group than in the control group (|t| >2.337, P < 0.05). ConclusionNeural mobilization based on shoulder control training can significantly alleviate shoulder pain and improve upper limb motor function in stroke patients with hemiplegia.

Early identification and intervention of high-risk factors during pregnancy is important for the prevention of maternal mortality. A certain hospital has established a management system for pregnant women undergoing first visit in non-obstetric departments and started applying it in three campus of the hospital in July 2023. Through the information management module for pregnant women undergoing first visit in non-obstetric departments that embedded in the hospital information system, abnormal pregnancy situations could be screened in a timely, comprehensive, and standardized manner, and quality control management could be carried out. At the same time, the hospital established a graded management path based on the severity of the condition of pregnant women, and provided early intervention for critically ill pregnant women reported through standardized management and multidisciplinary collaboration. From July to December 2023, a total of 5 766 pregnant women were first diagnosed and reported in 41 non-obstetric departments. Telephone follow-up showed a true reporting rate of 93.0%, and a total of 11 critical illness case were reported, including 2 cases of misoperation, with an accuracy rate of 81.8%. There were no adverse outcomes caused by failure to detect critical illness cases in a timely manner. In contrast, the relevant statistical data from January to June 2023 showed that there were 257 cases of pregnant women reported by non-obstetric departments, including 0 cases of critical illness and 1 case of missed critical illness. In addition, the time for non-obstetricians to screen for critically illness pregnant women of childbearing age has been reduced from 5-10 min per person before the system application to 15 s-1 min per person. The application of this system has reduced the missed reporting of critical illnesses, effectively ensured the safety of pregnant women, and improved work efficiency. It can provide reference for safety management of pregnant women in other medical institutions.

Concurrent chemoradiotherapy (CCRT) refers to the simultaneous treatment of chemotherapy and radiotherapy, and the effect of radiotherapy is enhanced with low-dose chemotherapy, which can reduce tumor recurrence and metastasis and improve clinical prognosis of patients. At present, the main factors for the increase of radiosensitivity of concurrent chemotherapy is that concurrent chemotherapy prevents the repair of tumor cells, and chemotherapy and radiotherapy act on different cell cycles and have synergistic effects. However, even for patients with locally advanced cervical cancer (LACC) who have undergone CCRT, the 5-year survival rate is only 60%, which is still not ideal. In order to improve the efficacy, researchers have conducted a series of exploratory studies, which consist of the combination of targeted drugs and immunodrugs, and neoadjuvant regimens before CCRT, etc. Although targeted or immunologic drugs are effective treatment of LACC, in view of the lack of large-scale evidence-based medical evidence, multi-center prospective and randomized phase III clinical trials and high-level articles are needed to improve the level of evidence-based medicine. This consensus summarizes several key evidence-based medical studies published recently, especially the clinical research progress in targeted and immunological therapies, providing reference for domestic peers.

Objective To explore the establishment of a new model of informational drug treatment pathway management.Methods The orthopedic drug treatment pathways was developed through multidisciplinary diagnosis and treatment(MDT),and the pathway management was implemented with the help of an information systems to implement refined control rules.Cases before the implementation of the management pathway(January to May 2022)were selected as the control group,and cases after the implementation of the management pathway(June to December 2022)were selected as the improvement group to evaluate the management effectiveness.Results After establishing drug treatment pathways for 8 major types of surgeries,maintaining 990 medical prescriptions for recommended drugs in the HIS system,and 176 control rules in the MINDS system.There was a significant improvement in the orthopaedic department's indexes of antimicrobial drug use rate,antibacterial drug use intensity,average inpatient medication cost,and percentage of the amount of basic medication after applying a new model of drug treatment pathway management.According to the case analysis before and after the implementation of the pathway,the rational rate of using orthopedic antibiotics,analgesics,fluid replacement and volume expansion drugs,acid inhibiting and stomach protecting drugs,blood activating and swelling-reducing proprietary Chinese medicines were increased by 21.6%,12.7%,23.3%,32.1% and 27.1%,respectively.The average drug costs was reduced by 111.51 yuan,15.33 yuan,49.84 yuan,42.29 yuan and 14.23 yuan,respectively.Conclusion The management mode of drug treatment pathway based on MDT established by our hospital is practical and effective,and the relevant experience may provide valuable insights for pharmaceutical peers.

OBJECTIVE To establish the path-based management mode of 5-hydroxytryptamine-3 receptor antagonist （5- HT3RA） in chemotherapy patients， and to improve the rationality of medication in chemotherapy patients. METHODS 5-HT3RA standardized drug use control rules were formulated， with the help of medical intelligence and decision support （MINDS） system， path-based management was carried out for chemotherapy patients using 5-HT3RA in the form of whole-process information capture and prescription pre-review， and whole-process intervention was implemented on medication indications， usage and dosage， course of treatment， etc. The intervention effect was analyzed by comparing the changes in the use of 5-HT3RA without indication， unreasonable usage and dosage， repeated medication， unreasonable course of treatment， and per capita drug cost before and after the implementation of path-based management. RESULTS A total of 9 181 patients were included. After the implementation of path- based management， the proportion of unindicated drugs decreased by 0.48%， and the rate of unreasonable single dosage， unreasonable frequency， repeated medication， unreasonable treatment course （5-HT3RA still used 3 days after chemotherapy） decreased by 10.48%， 0.65%， 1.33% and 0.34%； per capita cost of 5-HT3RA decreased by 13.72 yuan； there were statistical significance （P＜0.05）. CONCLUSIONS 5-HT3RA path-based management mode effectively improves the rationality of medication and provides a new idea for rational clinical drug use.

Objective:To investigate the prevalence of pretreatment drug resistance and the genetic polymorphism of CRF08_BC strains among HIV-1 patients in China.Methods:This cross-sectional survey involved the plasma samples of HIV patients in a national pretreatment HIV drug resistance survey conducted in 2018. RNA was extracted from the samples. The fragments containing protease and partial reverse transcriptase (PR/RT) regions were obtained and sequenced. Drug resistance was analyzed using Stanford HIVdb Program. Differences in polymorphic mutations between drug-resistant and non-drug-resistant HIV-1 strains were analyzed by Chi-square test or Fisher′s exact test. The association between drug-resistant and polymorphic mutations was evaluated using CorMut R package. Molecular transmission networks were constructed using HIV-TRACE software. Results:Totally 465 partial pol sequences were obtained from individuals with CRF08_BC infection in 25 provinces and cities. The total pretreatment drug resistance rate was 17.8% (83/465). The pretreatment drug resistance rates to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs) were 16.6% (77/465), 1.1% (5/465) and 0.9% (4/465), respectively. The resistance rate to rilpivirine (RPV) was the highest (15.7%, 73/465). The most common mutation was E138A (11.6%, 54/465). There were six polymorphic mutations (S162C, K102Q, T200A, V179E, I202V, T200M) that co-variated with E138A. The molecular transmission network showed that patients infected with CRF08_BC strains carrying the resistant mutations at position E138 mainly gathered in clusters in Yunnan and Sichuan, and the highest degree of connection was in Lincang, Yunnan. Conclusions:In China, HIV-1 CRF08_BC-infected patients showed a high rate of pretreatment resistance to one of the second-generation NNRTIs, namely RPV. Further researches were warranted to evaluate the impacts of co-mutations of the E138A mutation and polymorphic sites on HIV resistance and replicative capacity.

OBJECTIVE: To explore the characteristics of copy number variation (CNV) within the Y chromosome azoospermia factor (AZF) region in patients with spermatogenesis disorders in the Shenzhen area. METHODS: A total of 123 patients with spermatogenesis disorders who had visited Shenzhen People's Hospital from January 2016 to October 2022 (including 73 patients with azoospermia and 50 patients with oligozoospermia) and 100 normal semen males were selected as the study subjects. The AZF region was detected with multiplex ligation-dependent probe amplification (MLPA), and the correlation between the CNV in the AZF region and spermatogenesis disorders was analyzed using the chi-square test or Fisher's exact test. RESULTS: 19 CNV were detected among 53 patients from the 223 samples, including 20 cases (27.40%, 20/73) from the azoospermia group, 19 cases (38%, 19/50) from the oligozoospermia group, and 14 cases (14%, 14/100) from the normal control group. In the azoospermia, oligozoospermia, and normal control groups, the detection rates for CNV related to the AZFa region (including AZFab and AZFabc) were 5.48% (4/73), 2.00% (1/50), and 0 (0/100), respectively. The detection rates for the AZFb region (including the AZFbc region) were 6.85% (5/73), 0 (0/50), and 0 (0/100), respectively. The detection rates for gr/gr deletions in the AZFc region were 2.74% (2/73), 6.00% (3/50), and 9.00% (9/100), respectively, and those for b2/b4 deletions in the AZFc region were 2.74% (2/73), 10.00% (5/50), and 0 (0/100), respectively. The detection rates for complex rearrangements in the AZFc region were 6.85% (5/73), 18.00% (9/50), and 3.00% (3/100), respectively. Statistical analysis showed no significant difference in the detection rate of gr/gr deletions between the three groups (Fisher's Exact Test value = 2.712, P = 0.249); the differences in the detection rate of b2/b4 deletions between the three groups were statistically significant (Fisher's Exact Test value = 9.489, P = 0.002); the differences in the detection rate of complex rearrangements in the AZFc region between the three groups were statistically significant (Fisher's Exact Test value = 9.493, P = 0.006). In this study, a rare AZFa region ARSLP1 gene deletion (involving SY86 deletion) was detected in a patient with oligozoospermia. CONCLUSION CNV in the AZFa and AZFb regions have a severe impact on spermatogenesis, but partial deletion in the AZFa region (ARSLP1 gene deletion) has a minor impact on spermatogenesis. The b2/b4 deletion and complex rearrangement in the AZFc region may be risk factors for male infertility. The gr/gr deletion may not serve as a risk factor for male infertility in the Shenzhen area.
Humans ; Male ; Azoospermia/genetics* ; DNA Copy Number Variations ; Oligospermia/genetics* ; Infertility, Male/genetics* ; Y Chromosome

The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC₅₀ = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC₅₀ = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 ( 5) and AZD5099 ( 6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 ( 6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.

Objective: To evaluate the dietary risk of neonicotinoid insecticides in market-sold vegetables in Guangzhou City, so as to provide insights into ensuring food safety for residents. Methods: Forty-five samples of 21 kinds of vegetables were collected from supermarkets and farmer's markets in Guangzhou City from June to September in 2022, and 10 kinds of neonicotinoid insecticides were determined using liquid chromatography-mass spectrometry (LC-MS). The vegetable consumption was obtained through the survey of food consumption and nutrients intake of residents in Guangzhou City. The dietary risk was evaluated by calculating daily exposure and non-carcinogenic risk quotients of neonicotinoid insecticides. Results: A total of 27 samples of vegetables were detected with neonicotinoid insecticides, and the detection rate was 60.00%. Among 10 kinds of neonicotinoid insecticides, 6 kinds were identified, including clothianidin, thiamethoxam, imidacloprid, acetamiprid, dinotefuranand and nitenpyram. The detection rates of clothianidin, thiamethoxam and imidacloprid were relatively high (26.67%, 11.11% and 6.67%), and some samples exceeded the standard, with the rate of 4.44%, 2.22% and 2.22%, respectively. The total exposure of neonicotinoid pesticides (IMIRPF) was 3 053.00 ng/g, and the contents and IMIRPF of imidacloprid were the highest in roots and tubers. The daily exposure of imidacloprid, acetamiprid, dinotefuran, clothianidin, thiamethoxam and nitenpyram was 34.58, 3.85, 1.20, 6.87, 7.19 and 0.86 ng/(kg·d). Non-carcinogenic risk quotients of imidacloprid, acetamiprid, dinotefuran, clothianidin, thiamethoxam and nitenpyram was 5.76×10-4, 0.55×10-4, 0.06×10-4, 0.69×10-4, 0.90×10-4 and 0.02×10-4, respectively, which was lower than 1; and the sum of non-carcinogenic risk quotients was 7.98×10-4, which was lower than 1. Conclusions The dietary risk of neonicotinoid pesticides is low in 21 kinds of market-sold vegetables in Guangzhou City; however, the contents of neonicotinoid insecticides in some vegetable samples exceed the standard. The supervision of vegetable markets should be strengthened.