The department of critical care medicine has a high prevalence of hospital acquired infections, which are closely associated with prognosis of critically ill patients. With hospital acquired infections as the axis, the treatment of critically ill patients can be divided into three phases: management of the primary disease and support of organ function, treatment of various complications resulting from the primary disease, and control of further damage and new complications. The cycle of the last two phases may put the patient in a state of Persistent inflammation, Immunosuppression, and Catabolism Syndrome (PICS), which ultimately leads to a poor prognosis. Fine control of the above three stages to reduce the risk of hospital acquired infections is a non-negligible component of the critical care process. Therefore, how to understand, prevent and treat hospital acquired infections is a top priority in the current development of critical care medicine. This review provides a comprehensive overview of strategies for the prevention and management of hospital acquired infections in critical care, covering five areas: changing the perception of hospital acquired infections, standardizing specific prevention interventions, consolidating the theoretical basis, recognizing that hospital acquired infection prevention are treatments, and integrating treatment to quality assurance. The aim is to develop the concept of severe treatment based on the prevention and control of severe patients, reduce the risk of hospital acquired infections of severe patients and improve the quality of critical care.

Catheter related blood stream infection (CRBSI), a common complication in the department of critical care medicine, may result in longer stay in the department of critical care medicine, increased hospitalization costs, even sepsis that leads to increased mortality in severe patients. The infection control of CRBSI has become the focus of the department of critical care medicine and even hospital management as well as the core of quality control. At present, the prevention program of CRBSI in the department of critical care medicine has been basically in place, and the national standards for infection prevention during central venous catheter placement and maintenance have been established. The establishment and implementation of these norms can effectively reduce the incidence of CRBSI, but CRBSI in the department of critical care medicine is still common and serious, indicating that there are defects in the aseptic operation during central vein catheterization and use. The corre- sponding operation process should be investigated and improved, and efforts should be made from the aspects of theory, management, education, norms, and supervision to avoid or reduce the occurrence of CRBSI and even achieve zero infection by improving and implementing various sensory control requirements in clinical operation.

Critically ill patients are at high risk for hospital acquired infections, which can significantly increase the mortality rate and treatment costs for these patients. Therefore, in the process of treating the primary disease, strict prevention and control of new hospital infections is an essential component of the treatment for critically ill patients. The treatment of critically ill patients involves multiple steps and requires a concerted effort from various aspects such as theory, management, education, standards, and supervision to achieve effective prevention and control of hospital infections. However, there is currently a lack of unified understanding and standards for hospital infection prevention and control. To address this, in March 2024, a group of experts in critical care medicine, infectious diseases, and hospital infection from China discussed the current situation and issues of hospital infection control in the intensive care unit together. Based on a review of the latest evidence-based medical evidence from both domestic and international sources, 2024 Expert Consensus on Hospital Acquired Infection Control Principles in the Department of Critical Care Medicine was formed, aiming to provide a basis for the development of hospital infection prevention and control strategies in the field of critical care medicine.

ObjectiveTo investigate the effect and mechanism of Nongsuo Dangguiwan in improving ovarian oxidative stress in rats with ovarian dysfunction. MethodThirty-six adult female SD rats were randomly divided into normal group， model group， positive drug group （Femoston， 0.3 mg·kg^-1）， and high-， medium-， and low-dose groups of concentrated Nongsuo Dangguiwan （2.08， 4.16， 8.32 g·kg^-1）， with six rats in each group. Rats， except for those in the normal group， were injected with 80 mg·kg^-1 vinyl cyclohexene dioxide （VCD） per day for 14 consecutive days to induce ovarian dysfunction. From the 15th day， rats were treated with corresponding drugs by gavage， while those in the model group received 2 mL·kg^-1 saline， once daily for 28 consecutive days. The ovarian index， levels of related hormones including estradiol （E₂）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and anti-mullerian hormone （AMH） in serum， as well as superoxide dismutase （SOD） activity and glutathione （GSH） content in serum were measured by enzyme-linked immunosorbent assay （ELISA）. The malondialdehyde （MDA） content in serum was detected by the thiobarbituric acid （TAB） method. Ovarian morphology was observed by hematoxylin-eosin （HE） staining. The expression of nuclear factor E₂-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， SOD2， and SOD1 in ovarian tissues was detected by immunohistochemistry （IHC） and Western blot. ResultCompared with the normal group， the model group showed a significant reduction in growing follicles in the ovary， loose arrangement of granulosa cells in the follicle， decreased body weight， ovarian index， and serum AMH and E₂ levels， increased LH and FSH levels （P<0.01）， reduced levels of SOD and GSH in serum （P<0.01）， and increased MDA level （P<0.01）. Compared with the model group， the groups with drug intervention showed increased ovarian index （P<0.05， P<0.01）， increased serum E₂ level （P<0.05， P<0.01）， decreased FSH， AMH， and LH levels （P<0.05， P<0.01）， increased number of growing follicles in the ovary， potentiated SOD activity in serum， increased GSH content， decreased MDA content （P<0.05， P<0.01）， and up-regulated expression levels of Nrf2， HO-1， SOD2， and SOD1 proteins in ovarian tissues （P<0.05， P<0.01）. ConclusionNongsuo Dangguiwan can regulate serum hormone levels， increase the expression of Nrf2， HO-1， SOD2， and SOD1 in ovarian tissues， and improve ovarian antioxidant capacity to resist oxidative stress injury， thereby improving ovarian reserve function.

Objective:To compare the clinical efficacy and safety of Shuo Tong ureteroscopy(ST-URS) and flexible ureteroscope(FURS)combined with holmium laser lithotripsy in the treatment of upper ureteral calculi with CT numerical value ≥ 1000 HU.Methods:A retrospective analysis of the clinical data of patients of upper ureteral calculi with CT numberical value≥1000 HU in the First Affiliated Hospital of Xiamen University was made from January 2018 to November 2020.There were 61 cases treated with ShuoTong ureteroscopy holmium laser lithotripsy (ST-URS group), including 45 males and 16 females, with 40 on the left and 21 on the right, age of(48.3±12.7) years, body mass index of(24.7±2.7)kg/m 2, the diameter of stone of(1.50±0.45)cm, and the CT numberical value of(1 288.8±179.0)(1 017-1 738)HU. There were 87 cases were treated with flexible ureteroscopy holmium laser lithotripsy (FURS group), including 58 males and 29 females, with 56 on the left and 31 on the right, age of(48.5±13.0) years, body mass index of(24.1±3.8)kg/m 2, the stone diameter of(1.45±0.40)cm, and the CT numberical value of(1 311.3±188.9)(1 009-1 817)HU. There were no significant differences in gender, age, body mass index, the location of stone, the diameter of stone and the CT numberical value of stone( P>0.05)between the two groups. For ST-URS group, a rigid ureteral channel sheath and standard mirror(F7.5/11.5)were placed under direct vision, exiting the standard mirror, leaving the channel sheath, inserting a lithotripsy mirror(F4.5/6.5)and a holmium laser[Power: 8-30 W(0.4-1.0 J/20-30 Hz)], and withdrawing the stone fragments after crushing the stone by "nibbling method" . For FURS group, a hard ureteroscope(F8/9.8)was used to explore the lesion side of the ureter, inserting a guide wire and placing a soft ureteral sheath, then inserting a flexible ureteroscope(F8)for holmium laser lithotripsy, and useing a stone basket to remove larger stone fragments. Ureteral stent was routinely indwelled after the operation. On the day 1 and 1 month after the operation, imaging examinations were performed to evaluate the stone-free rate. No residual stones or the diameter of stone was ≤0.4 cm and no urinary tract infection or any symptoms were defined as stone free. The operation time, blood loss, success rate of stage Ⅰ ureteral access sheath placement, incidence of postoperative complications, stone-free rate(SFR) at 1 day after operation, SFR at 1 month after operation, postoperative hospital stay and hospitalization costs were compared between the two groups. According to the size of calculi, the 2 groups were divided into 2 subgroups(≥1.5 cm and <1.5 cm)in order to make further analysis. The operation time, stone-free rate(SFR) at day 1 after operation and SFR at 1 month after operation were compared between the two groups. Results:The operation time of the ST-URS group was shorter than the FURS group(40.10 min vs. 49.43 min, P=0.020), and the incidence of postoperative complications was lower than the FURS group[3.28%(2/61)vs. 13.79%(12/87), P=0.031]. The SFR at day 1 after operation was significantly higher than the FURS group[60.7%(37/61)vs. 25.3%(22/87), P<0.01], and the hospitalization cost was lower than that of the FURS group(27 686 yuan vs. 32 281 yuan, P<0.010). There were no significant differences in the blood loss[(4.92±9.51)ml vs.(3.95±6.04)ml, P=0.452], success rate of stageⅠureteral access sheath placement[ 96.7%(59/61)vs. 96.6%(84/87), P=1.000], SFR at 1 month after operation[81.97%(50/61) vs. 75.86%(66/87), P=0.375] and postoperative hospital stay[(2.5±1.4)d vs.(2.4±0.8)d, P=0.543] between the two groups. When the size of calculi was ≥1.5cm, the operation time of the ST-URS group was shorter than the FURS group (43.67 min vs 55.00 min), the SFR at 1 day after operation was higher than the FURS group[40.00%(12/30)vs. 9.38%(3/32)], and the above differences are all statistically significant ( P<0.05). Conclusions:Compared with the FURS, for the treatment of upper ureteral calculi with CT numerical value ≥1000 HU, the ST-URS has shorter in operative time, lower in hospitalization cost and incidence of postoperative complications and higher SFR at day 1 after operation. The ST-URS is a safe and effective surgical technique, which is superior in the treatment of larger(≥1.5 cm) stones.

Objective:To analyze the local recurrence patterns after concurrent chemoradiotherapy (CCRT) for thoracic esophageal squamous cell carcinoma (ESCC) through image fusion, and to explore the risk factors of local recurrence and its relationships with dosimetric indices.Methods:A retrospective analysis was conducted for 209 thoracic ESCC patients who received radical CCRT in Fourth Hospital of Hebei Medical University during 2016-2019. For the patients diagnosed as the local recurrence of esophageal lesions, their CT images were fused with the original planning CT images using image registration software to identify the recurrence sites. Through 1∶1 propensity score matching (PSM) of the clinal data of patients with local recurrence (the recurrence group, nbefore = 81, nafter = 62) and those without local recurrence (the recurrence-free group, nbefore = 128, nafter=62), the dose and volume parameters of the treatment plans for the two groups were compared. Univariate and multivariate analyses were conducted using the Kaplan-Meier method and the Cox regression model to analyze the factors affecting the overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS). Results:All patients had 1-, 3-, and 5-year OS rates of 80.9%, 42.6%, and 33.0%, respectively, 1-, 3-, and 5-year PFS rates of 67.9%, 34.0%, and 27.9%, respectively, and 1-, 3-, and 5-year RFS rates of 71.3%, 39.2%, and 30.5%, respectively. T stage, N stage, and radiation dose were independent prognostic factors for the OS, PFS, and RFS ( HR = 1.42-1.87, P < 0.05) of the patients, respectively. Among 68 patients with local recurrence, 62 cases (91.2%) suffered recurrence within the gross tumor volume (GTV). The dose and volume parameters of patients with local recurrence, such as GTV- D95%, clinical target volume (CTV)- D95%, GTV- D50%, CTV- D50%, and planning target volume (PTV)- D50%, GTV- V60, CTV- V60, and PTV- V60, were significantly lower than those of patients free from the local recurrence ( t=1.90-2.15, P < 0.05). Conclusions:Local recurrence of patients with thoracic ESCC after radical CCRT occurs mainly within the GTV. Increasing radiation doses may contribute to their survival benefits. The D50% for each target volume in the radiotherapy plan may be related to local recurrence, and it is necessary to conduct further research.

Objective:To analyze whether involved-field irradiation (IFI) was associated with improved survival and reduced treatment-related adverse events compared with elective nodal irradiation (ENI) in Chinese patients with esophageal squamous cell carcinoma receiving radiotherapy.Methods:Literature review was conducted from CNKI, Wanfang Data, PubMed, Embase, Web of Science and Cochrane Central databases (until July 31, 2022). Relevant data were collected according to the inclusion and exclusion criteria. Primary outcomes included overall survival (OS) rate and treatment-related adverse events. Secondary outcomes included progression-free survival (PFS) rate and local control rate (LCR). Risk of bias was assessed using the Cochrane Risk of Bias tool. The quality of the results was assessed by using the meta analysis of Evidence Evaluation and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methods.Results:A total of 7 articles with 918 patients were included of which 465 received IFI and 453 received ENI. The 1-, 2-, 3-and 5-year OS rates in the IFI group were not significantly different from those in the ENI group (1-year OS rate: RR=1.00, 95% CI=0.94-1.07, P=0.97, high certainty; 2-year OS rate: RR=1.01, 95% CI=0.90-1.13, P=0.90, high certainty; 3-year OS rate: RR=0.86, 95% CI=0.71-1.05, P=0.14, high certainty; 5-year OS rate: RR=0.76, 95% CI=0.42-1.37, P=0.36, low certainty). In the IFI group, patients with ≥grade 2 acute radiation esophagitis ( RR=0.71, 95% CI=0.58-0.87, P=0.001, high certainty), ≥grade 3 acute radiation esophagitis ( RR=0.39, 95% CI=0.24-0.64, P<0.001, high certainty) and ≥grade 2 acute radiation pneumonitis ( RR=0.72, 95% CI=0.52-0.99, P=0.04, high certainty) were significantly lower compared with those in the ENI group. However, no significant differences were observed in the incidence of ≥grade 3 late radiation esophagitis, ≥grade 3 acute radiation pneumonitis and ≥grade 3 late radiation pneumonitis between two groups. No significant differences were noted in the 1-, 2-, 3-PFS rates and LCR between two groups. Conclusions:For Chinese patients with esophageal squamous cell carcinoma, IFI and ENI yield similar efficacy in terms of OS, PFS and LCR. However, IFI has a lower incidence of ≥grade 2 acute radiation esophagitis, ≥grade 3 acute radiation esophagitis and ≥grade 2 acute radiation pneumonitis than ENI.

Objective:To investigate the prognostic value of Onodera's prognostic nutrition index (PNI) before treatment in patients with cervical and upper thoracic esophageal squamous cell carcinoma (CUTESCC) undergoing definitive chemoradiotherapy (dCRT) and its predictive value in the occurrence of ≥ grade 2 radiation esophagitis (RE).Methods:The data of 163 CUTESCC patients eligible for inclusion criteria admitted to the Fourth Hospital of Hebei Medical University from January 2012 to December 2017 were retrospectively analyzed. The receiver operating characteristic (ROC) curve was used to calculate the best cut-off value of PNI for predicting the prognosis of patients. The prognosis of patients was analyzed by univariate and Cox multivariate analyses. Logistics binary regression model was adopted to analyze the risk factors of ≥ grade 2 RE in univariate and multivariate analyses. The significant factors in logistic multivariate analysis were used to construct nomogram for predicting ≥ grade 2 RE.Results:The optimal cut-off value of PNI was 48.57 [area under the curve (AUC): 0.653, P<0.001]. The median overall survival (OS) and progression-free survival (PFS) were 26.1 and 19.4 months, respectively. The OS ( χ2=6.900, P=0.009) and PFS ( χ2=9.902, P=0.003) of patients in the PNI ≥ 48.57 group ( n=47) were significantly better than those in the PNI < 48.57 group ( n=116). Cox multivariate analysis showed that cTNM stage and PNI were the independent predictors of OS ( HR=1.513, 95% CI: 1.193-1.920, P=0.001; HR=1.807, 95% CI: 1.164-2.807, P=0.008) and PFS ( HR=1.595, 95% CI: 1.247-2.039, P<0.001; HR=2.260, 95% CI: 1.439-3.550, P<0.001). Short-term efficacy was another independent index affecting PFS ( HR=2.072, 95% CI: 1.072-4.003, P=0.030). Logistic multivariate analysis showed that the maximum transverse diameter of the lesion ( OR=3.026, 95% CI: 1.266-7.229, P=0.013), gross tumor volume (GTV) ( OR=3.456, 95% CI: 1.373-8.699, P=0.008), prescription dose ( OR=3.124, 95% CI: 1.346-7.246, P=0.009) and PNI ( OR=2.072, 95% CI: 1.072-4.003, P=0.030) were the independent factors affecting the occurrence of ≥ grade 2 RE. These four indicators were included in the nomogram model, and ROC curve analysis showed that the model could properly predict the occurrence of ≥ grade 2 RE (AUC=0.686, 95% CI: 0.585-0.787). The calibration curve indicated that the actually observed values were in good agreement with the predicted RE. Decision curve analysis (DCA) demonstrated satisfactory nomogram positive net returns in most threshold probabilities. Conclusions:PNI before treatment is an independent prognostic factor for patients with CUTESCC who received definitive chemoradiotherapy. The maximum transverse diameter of the lesion, GTV, prescription dose and PNI are the risk factors for ≥ grade 2 RE in this cohort. Establishing a prediction model including these factors has greater predictive value.

Natural cyclohexapeptide AFN A₁ fromStreptomyces alboflavus 313 has moderate antibacterial and antitumor activities. An artificial designed AFN A₁ homodimer, di-AFN A₁, is an antibiotic exhibiting 10 to 150 fold higher biological activities, compared with the monomer. Unfortunately, the yield of di-AFN A₁ is very low (0.09 ± 0.03 mg·L^-1) in the engineered strain Streptomyces alboflavus 313_hmtS (S. albo/313_hmtS), which is not friendly to be genetically engineered for titer improvement of di-AFN A₁ production. In this study, we constructed a biosynthetic gene cluster for di-AFN A₁ and increased its production through heterologous expression. During the collection of di-AFN A₁ biosynthetic genes, the afn genes were located at three sites of S. alboflavus 313 genome. The di-AFN A₁ biosynthetic gene cluster (BGC) was first assembled on one plasmid and introduced into the model strain Streptomyces lividans TK24, which produced di-AFN A₁ at a titer of 0.43 ± 0.01 mg·L^-1. To further increase the yield of di-AFN A₁, the di-AFN A₁ BGC was multiplied and split to mimic the natural afn biosynthetic genes, and the production of di-AFN A₁ increased to 0.62 ± 0.11 mg·L^-1 in S. lividans TK24 by the later strategy. Finally, different Streptomyces hosts were tested and the titer of di-AFN A₁ increased to 0.81 ± 0.17 mg·L^-1, about 8.0-fold higher than that in S. albo/313_hmtS. Successful heterologous expression of di-AFN A₁ with a remarkable increased titer will greatly facilitate the following synthetic biological study and drug development of this dimeric cyclohexapeptide.
Cloning, Molecular ; Streptomyces/metabolism* ; Multigene Family ; Anti-Bacterial Agents/metabolism* ; Plasmids/genetics*

ObjectiveTo explore the mechanism of Jianpi Yishen Huazhuo prescription in the improvement of ovarian function in polycystic ovary syndrome （PCOS）. MethodSeventy female SD rats in SPF grade were randomly divided into 6 groups， 15 in the blank group and 15 in the model group， 10 in the metformin group （0.1 g·kg^-1·d^-1）， and 10 in the low （1.275 g·kg^-1·d^-1）， medium （2.55 g·kg^-1·d^-1）， and high-dose （5.10 g·kg^-1·d^-1） Jianpi Yishen Huazhuo prescription groups. The blank group was given normal saline （10 mL·kg^-1·d^-1） by gavage and ordinary feed， and the other groups were given letrozole （1 mg·kg^-1·d^-1） by gavage combined with high-fat feed for 21 days to induce the model of PCOS. After modeling， the blank group and model group were given equal volume normal saline by gavage， and each drug group was given the corresponding dose of the drug by gavage for 30 days. The changes in body mass and fasting blood glucose （FPG） of rats before and after modeling were compared. Hematoxylin eosin （HE） staining was used to observe the morphological change in the ovaries of rats in each group. The serum levels of follicle stimulating hormone （FSH）， luteinizing hormone （LH）， testosterone （T）， anti-Mullerian hormone （AMH）， and estradiol （E₂） were measured by enzyme-linked immunosorbent assay （ELISA）， and the LH/FSH ratio was calculated. Immunohistochemical staining （IHC） and Western blot were used to detect the protein expression levels of nucleoside binding oligomerization domain protein like receptor 3 （NALP3）， apoptosis-associated speck-like protein （ASC）， cysteine protease-1 （Caspase-1）， nuclear transcription factor-κB （NF-κB）， interleukin-1β （IL-1β）， interleukin-18 （IL-18）， and interleukin-6 （IL-6） in the rat ovaries. ResultAs compared with the blank group， large follicles with polycystic expansion were found in the ovaries of the model group， no dominant follicles were found， the granular layer of follicles decreased and arranged loosely， and the number of corpus luteum decreased significantly. Serum T， LH， AMH and LH/FSH increased in the model group （P<0.05， P<0.01）， while FSH and E₂ decreased （P<0.05， P<0.01）. The relative protein expression levels of NALP3， ASC， Caspase-1， NF-κB， IL-1β， IL-18， and IL-6 increased （P<0.05， P<0.01） in the ovaries of the model group. Compared with the model group， the low， medium， and high-dose Jianpi Yishen Huazhuo prescription groups and the metformin group showed growing follicles and corpus luteum at all levels， the number of cystic expanding follicles decreased， the thickness of follicular granular layer increased， the number of follicular fluid increased， mature follicles were visible， and the local morphology of oocytes was complete. Serum T， LH， AMH， and LH/FSH in these groups decreased （P<0.05， P<0.01）， while E₂ and FSH increased （P<0.05）. The relative protein expressions of NALP3， ASC， Caspase-1， NF-κB， IL-1β， IL-18， and IL-6 in the ovaries of these groups decreased （P<0.05， P<0.01）. There was no significant difference among the treatment groups. ConclusionBy inhibiting the activation of NLRP3 inflammasome， Jianpi Yishen Huazhuo prescription reduces the release of NALP3， ASC， Caspase-1， NF-κB， IL-18， IL-1β， and IL-6 inflammatory factors in ovarian tissues， regulates endocrine level， and effectively reduces PCOS inflammatory statu， so as to play a role in improving ovarian function.