: Bacteroides, as one of the most abundant and diverse genera in the human gut, is regarded as a window into the study of gut microbiota-host interactions. Currently, CRISPR/Cas-based gene editing systems targeting Bacteroides have been widely applied, while the large size of Cas nucleases limits their potential application scenarios (such as in situ gut Bacteroides editing based on phage delivery). Therefore, this study aims to develop a compact and highly efficient genetic editing tool in Bacteroides., We developed a miniaturized CRISPR/Cas gene editing system for human gut Bacteroides. First, the editing capabilities of different miniaturized CRISPR/Cas systems, including AsCas12f, CasΦ2, and ISDge10, were evaluated in Bacteroides fragilis. Subsequently, the editing capability of AsCas12f was assessed across various Bacteroides species, and the size of this system was further optimized. The results demonstrated that the CRISPR/AsCas12f genome editing system exhibited the highest editing efficiency in B. fragilis. The CRISPR/AsCas12f system achieved efficient genome editing in B. fragilis, Bacteroides thetaiotaomicron, and Phocaeicola vulgatus. Furthermore, with a repair template of 500 bp homologous arms, the editing efficiency remained as high as 94.7%. In conclusion, CRISPR/AsCas12f can serve as a chassis tool enzyme for the development of Bacteroides-based miniature gene editors and derivative technologies, laying a foundation for the further development of gene editing technology for Bacteroides.
CRISPR-Cas Systems/genetics* ; Gene Editing/methods* ; Bacteroides/genetics* ; Humans ; Gastrointestinal Microbiome/genetics* ; Bacteroides fragilis/genetics*

Objective To analyze the current status and emerging technology trends in domestic medical drainage tube patents,so as to explore possible factors for low patent conversion rates.Methods Patents associated with"drainage tube","medical drainage tube","surgical drainage tube"and related terms were retrieved from the National Intellectual Property Administration Database and the Innojoy Patent Search Engine,covering the period from 2010 to 2020.Screening and visual analysis were conducted using Excel and SPSS 27.0.Results A total of 2 895 relevant patents were identified,comprising 2 489 utility model patents,367 invention patents and 39 design patents.The number of patent applications demonstrated a year-on-year growth trend,with a higher concentration in eastern coastal regions and provinces housing numerous top-tier hospitals and medical institutions.Approximately 49.26％of the patents filed by individuals were affiliated with hospitals,universities,or enterprises.Innovation hotspots included the design,functionality,performance,and safety aspects of drainage tubes and probes.Of the patents,72.61％were invalid,and 61.73％had a survival period of three years or less.Only 5.15％were commercially utilized through transfers,pledges,or licensing.Conclusion Domestic patent applications for medical drainage tubes have seen rapid growth,with a focus on enhancing tube structures such as sleeves,balloons,drainage holes,and threaded designs.However,the unsatisfactory situation of patent conversion and operation have been mainly limited by factors such as weak core technology of patents,insufficient awareness of achievements conversion,poor operation of patent conversion mechanism,insufficient market promotion,and insufficient integration of industry,academia,and research.To address this issue,enhancing intellectual property protection,revitalizing valid patents,and expanding transformation channels would benefit patients and facilitate hospitals'high-quality development,injecting new vitality into the health industry.

Objective To investigate the relationships of serum procalcitonin(PCT),α1-acid glycoprotein(α1-AGP)and cluster of differentiation 64(CD64)index with the severity of illness and prognosis in patients with pulmonary Candida infection after lung cancer surgery.Methods A pro-spective study was conducted in 120 patients with pulmonary Candida infection after lung cancer sur-gery as infection group,and 60 patients without infection after lung cancer surgery in the same period were selected as control group.Baseline characteristics and laboratory indicators were compared be-tween the two groups.Differences in serum PCT,α1-AGP,CD64 index in peripheral blood,and plasma 1,3-β-D glucan test(BG)were compared among patients with different severities of illness and prognoses in the infection group.The relationship between serum indicators and prognosis as well as their predictive efficiencies were analyzed,and external validation was performed.Results The levels of serum PCT,α1-AGP,CD64 index in peripheral blood,and plasma BG in the infection group were significantly higher than those in the control group(P＜0.05).In the infection group,the levels of serum PCT,α1-AGP,and CD64 gradually decreased significantly in patients with severe,moderate,and mild illness,and the levels of these indicators in dead patients were significantly higher than those in surviving patients(P＜0.05).Survival curve analysis showed that patients with low levels of serum PCT,α1-AGP,and CD64 index before treatment had higher survival rates than those with high levels of these indicators.Receiver operating characteristic(ROC)curve analysis revealed that the combined prediction of PCT,α1-AGP,and CD64 index for mortality was superior to individual indicators or their pairwise combinations,and external validation confirmed the good predictive efficacy of the combined prediction.Conclusion PCT,α1-AGP,and CD64 index are closely related to pulmonary Candida infection after lung cancer surgery,and the combined detection of these indicators has certain predictive value for 28-day prognosis.

Objective To analyze the current status and emerging technology trends in domestic medical drainage tube patents,so as to explore possible factors for low patent conversion rates.Methods Patents associated with"drainage tube","medical drainage tube","surgical drainage tube"and related terms were retrieved from the National Intellectual Property Administration Database and the Innojoy Patent Search Engine,covering the period from 2010 to 2020.Screening and visual analysis were conducted using Excel and SPSS 27.0.Results A total of 2 895 relevant patents were identified,comprising 2 489 utility model patents,367 invention patents and 39 design patents.The number of patent applications demonstrated a year-on-year growth trend,with a higher concentration in eastern coastal regions and provinces housing numerous top-tier hospitals and medical institutions.Approximately 49.26％of the patents filed by individuals were affiliated with hospitals,universities,or enterprises.Innovation hotspots included the design,functionality,performance,and safety aspects of drainage tubes and probes.Of the patents,72.61％were invalid,and 61.73％had a survival period of three years or less.Only 5.15％were commercially utilized through transfers,pledges,or licensing.Conclusion Domestic patent applications for medical drainage tubes have seen rapid growth,with a focus on enhancing tube structures such as sleeves,balloons,drainage holes,and threaded designs.However,the unsatisfactory situation of patent conversion and operation have been mainly limited by factors such as weak core technology of patents,insufficient awareness of achievements conversion,poor operation of patent conversion mechanism,insufficient market promotion,and insufficient integration of industry,academia,and research.To address this issue,enhancing intellectual property protection,revitalizing valid patents,and expanding transformation channels would benefit patients and facilitate hospitals'high-quality development,injecting new vitality into the health industry.

Objective To investigate the clinical advantages and safety of an acupoint auto-positioning moxibustion robot combined with massage techniques in the treatment of lumbar disc herniation.Methods Totally 114 patients with lumbar disc herniation treated between June 2021 and December 2023 at Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,the Outpatient Department of Rehabilitation Medicine,Changhai Hospital and Shanghai Third Rehabilitation Hospital were divided into control group and experimental group with random number table method,with 57 cases in each group.The control group received conventional moxibustion combined with massage techniques,while the experimental group was treated using an acupoint auto-positioning moxibustion robot combined with massage techniques.Both groups underwent treatment once every three days,totaling 10 sessions over one month.Clinical efficacy was observed between the two groups by comparing pre-treatment and post-treatment(after 3,6 and 10 sessions)scores on the visual analogue scale(VAS)for pain,the Japanese Orthopaedic Association(JOA)lower back pain score,and lumbar range of motion(LROM).Adverse reactions during the intervention were recorded.Satisfaction with the moxibustion robot in the experimental group was assessed using a Likert scale.Additionally,20 healthy subjects were recruited to evaluate the accuracy of the robot's acupoint auto-positioning function.Results The overall effective rate was 91.23%(52/57)in the experimental group and 94.74%(54/57)in the control group,without statistical significance between the two groups(P>0.05).Compared to pre-treatment,both groups showed significant improvements in VAS scores,JOA scores and LROM across all measured directions after 3,6,and 10 treatment sessions(P<0.001).In the Likert scale assessment,86.96%of subjects agreed that the device was convenient to use,87.72%agreed that the device was safer than conventional moxibustion therapy,and 94.74%were willing to recommend the device to other patients.The accuracy evaluation of the acupoint auto-positioning moxibustion robot demonstrated that the average deviation between robot-positioned acupoints and standard acupoints was(1.68±0.46)mm,achieving a positioning accuracy rate exceeding 95%.No adverse reactions were reported during the intervention.Conclusion The combination of an acupoint auto-positioning moxibustion robot with massage techniques is as effective as conventional moxibustion combined with massage techniques in improving clinical symptoms,alleviating pains,enhancing lumbar function and increasing lumbar mobility in patients with lumbar disc herniation.Participants have exhibited a high willingness to use the device,and the robot achieved a high accuracy rate in acupoint positioning.

Objective To investigate the clinical advantages and safety of an acupoint auto-positioning moxibustion robot combined with massage techniques in the treatment of lumbar disc herniation.Methods Totally 114 patients with lumbar disc herniation treated between June 2021 and December 2023 at Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,the Outpatient Department of Rehabilitation Medicine,Changhai Hospital and Shanghai Third Rehabilitation Hospital were divided into control group and experimental group with random number table method,with 57 cases in each group.The control group received conventional moxibustion combined with massage techniques,while the experimental group was treated using an acupoint auto-positioning moxibustion robot combined with massage techniques.Both groups underwent treatment once every three days,totaling 10 sessions over one month.Clinical efficacy was observed between the two groups by comparing pre-treatment and post-treatment(after 3,6 and 10 sessions)scores on the visual analogue scale(VAS)for pain,the Japanese Orthopaedic Association(JOA)lower back pain score,and lumbar range of motion(LROM).Adverse reactions during the intervention were recorded.Satisfaction with the moxibustion robot in the experimental group was assessed using a Likert scale.Additionally,20 healthy subjects were recruited to evaluate the accuracy of the robot's acupoint auto-positioning function.Results The overall effective rate was 91.23%(52/57)in the experimental group and 94.74%(54/57)in the control group,without statistical significance between the two groups(P>0.05).Compared to pre-treatment,both groups showed significant improvements in VAS scores,JOA scores and LROM across all measured directions after 3,6,and 10 treatment sessions(P<0.001).In the Likert scale assessment,86.96%of subjects agreed that the device was convenient to use,87.72%agreed that the device was safer than conventional moxibustion therapy,and 94.74%were willing to recommend the device to other patients.The accuracy evaluation of the acupoint auto-positioning moxibustion robot demonstrated that the average deviation between robot-positioned acupoints and standard acupoints was(1.68±0.46)mm,achieving a positioning accuracy rate exceeding 95%.No adverse reactions were reported during the intervention.Conclusion The combination of an acupoint auto-positioning moxibustion robot with massage techniques is as effective as conventional moxibustion combined with massage techniques in improving clinical symptoms,alleviating pains,enhancing lumbar function and increasing lumbar mobility in patients with lumbar disc herniation.Participants have exhibited a high willingness to use the device,and the robot achieved a high accuracy rate in acupoint positioning.

Calcium-activated chloride channels(CaCCs)are a class of channel proteins that trans-port chloride ions activated by intracellular calcium,which play a crucial role in regulating membrane potential,intracellular calcium balance,and cell excitability,particularly in neurons and muscle cells.In the Anoctamin(Ano)family,Ano1 is the most classic CaCC.Targeted modulators of Ano1 have poten-tial therapeutic effects against such diseases as cancer,cystic fibrosis,hypertension,diarrhea,and asthma.Since the discovery of Ano1 in 2008,several methods for screening CaCC-specific modulators have emerged including high-throughput primary screening of fluorescent proteins,electrophysiological patch clamp technique and virtual screening,and identification of small molecule modulators with diverse pharmacological effects.This paper summarizes the principles,advantages and disadvantages of the mainstream screening methods,and reviews the chemical structures and potential applications of Ano1-specific modulators discovered to date.

Objective:To investigate the clinical effects of Meek skin grafting combined with platelet-rich plasma (PRP) in repairing of extensive deep burn wounds.Methods:This study was a retrospective observational study. From August 2018 to August 2023, 44 patients who met the inclusion criteria were admitted to the First Affiliated Hospital of Air Force Medical University, including 23 males and 21 females. Their age ranged from 22 to 62 years and the total burn area was 30%-80% total body surface area, the burns on limbs or torso were deep partial-thickness to full-thickness. According to the treatment process of deep burns on the limbs or torso, the patients were divided into observation group (21 cases) and control group (23 cases). patients in observation group were treated with Meek skin grafting combined with PRP at the same time, while patients in control group were treated with Meek skin grafting alone. The survival of Meek skin grafts was observed on the 10 th day after operation. The wound healing rate in the operation area of patients was observed on the 14 th day after operation. The postoperative wound healing time and positive rate of bacterial culture of wound secretion specimens were recorded. Results:On the 10 th day after operation, the skin grafting area of patients in observation group were dry, and the skin grafts adhered closely to the wound base with ruddy color, with a survival rate of (89±4)%; whereas in control group, some of Meek skin grafts fell off in the skin graft area, and the residual wounds were scattered in irregular map shape, accompanied by purulent secretions. The survival rate of skin grafts was (79±6)%, which was significantly lower than that in observation group ( t=6.72, P<0.05). On the 14 th day after operation, 19 patients in observation group had complete wound healing in the operation area, and the other 2 patients had small residual wounds, which healed after 1 week delay through dressing changes; in control group, the wounds in 12 patients healed completely, the wounds in 6 patients healed after supplementary stamp skin grafting, and the wounds in 5 patients healed with delay after routine dressing changes. The wound healing rate was significantly lower than that in observation group ( P<0.05). After operation, the wound healing time of the operation area of patients in observation group was (13.3±1.6) days, which was significantly shorter than (16.4±3.5) days in control group ( t=3.72, P<0.05); there was no statistically significant difference in the positive rate of bacterial culture of wound secretion specimens between observation group and control group after operation ( P>0.05). Conclusions:Compared with Meek skin grafting alone, Meek skin grafting combined with autologous PRP can promote the survival of skin grafts, accelerate the expansion and fusion of skin grafts, and shorten the wound healing time, thereby improving the therapeutic effect in the repairing of extensive deep burn wounds.

Objective:To investigate the clinical effects of Meek skin grafting combined with platelet-rich plasma (PRP) in repairing of extensive deep burn wounds.Methods:This study was a retrospective observational study. From August 2018 to August 2023, 44 patients who met the inclusion criteria were admitted to the First Affiliated Hospital of Air Force Medical University, including 23 males and 21 females. Their age ranged from 22 to 62 years and the total burn area was 30%-80% total body surface area, the burns on limbs or torso were deep partial-thickness to full-thickness. According to the treatment process of deep burns on the limbs or torso, the patients were divided into observation group (21 cases) and control group (23 cases). patients in observation group were treated with Meek skin grafting combined with PRP at the same time, while patients in control group were treated with Meek skin grafting alone. The survival of Meek skin grafts was observed on the 10 th day after operation. The wound healing rate in the operation area of patients was observed on the 14 th day after operation. The postoperative wound healing time and positive rate of bacterial culture of wound secretion specimens were recorded. Results:On the 10 th day after operation, the skin grafting area of patients in observation group were dry, and the skin grafts adhered closely to the wound base with ruddy color, with a survival rate of (89±4)%; whereas in control group, some of Meek skin grafts fell off in the skin graft area, and the residual wounds were scattered in irregular map shape, accompanied by purulent secretions. The survival rate of skin grafts was (79±6)%, which was significantly lower than that in observation group ( t=6.72, P<0.05). On the 14 th day after operation, 19 patients in observation group had complete wound healing in the operation area, and the other 2 patients had small residual wounds, which healed after 1 week delay through dressing changes; in control group, the wounds in 12 patients healed completely, the wounds in 6 patients healed after supplementary stamp skin grafting, and the wounds in 5 patients healed with delay after routine dressing changes. The wound healing rate was significantly lower than that in observation group ( P<0.05). After operation, the wound healing time of the operation area of patients in observation group was (13.3±1.6) days, which was significantly shorter than (16.4±3.5) days in control group ( t=3.72, P<0.05); there was no statistically significant difference in the positive rate of bacterial culture of wound secretion specimens between observation group and control group after operation ( P>0.05). Conclusions:Compared with Meek skin grafting alone, Meek skin grafting combined with autologous PRP can promote the survival of skin grafts, accelerate the expansion and fusion of skin grafts, and shorten the wound healing time, thereby improving the therapeutic effect in the repairing of extensive deep burn wounds.

Objective:To investigate the prognosis and influencing factors in critically ill surgical patients of different feeding intolerance trajectories.Methods:The retrospective cohort study was conducted. The clinical data of 354 critically ill surgical patients who were admitted to 69 medical centers in the Chinese Critical Care Nutrition Trials Group -NEED database from March 2018 to July 2019 were selected. There were 247 males and 107 females, aged 58(46,68)years. According to the trajectory model of feeding intolerance change, 354 patients were divided into 3 categories as feeding intolerance, decreased feeding intolerance, continuous feeding intolerance, including 164, 49, 141 cases respectively. Observation indicators: (1) general situations of patients of different feeding intolerance trajectories; (2) treatment of patients of different feeding intolerance trajectories; (3) survival of patients of different feeding intolerance trajectories; (4) analysis of pro-gnostic factors in critically ill surgical patients. Measurement data of normal distribution were expressed as Mean± SD, and one-way analysis of variance was used for comparison between groups. Measurement data of skewed distribution were expressed as M( Q1, Q3), and Kruskal-Wallis rank sum test was used for comparison between groups. Count data were expressed as absolute numbers or percentages, and chi-square test was used for comparison between groups. Ordinal data were compared using the Kruskal-Wallis rank sum test. Bonferroni correction was used for pairwise comparison. Group-based trajectory model was constructed according to Traj plug-in in Stata17.0 statistical software, and the optimal trajectory model was evaluated by Bayesian information criterion and average posterior probability parameter. The Kaplan-Meier method was used to draw the survival curve and calculate the survival rate, and Log-Rank test was used for survival analyses. Univariate and multivariate analyses were conducted using the COX proportional hazard regression model. Results:(1) General situations of patients of different feeding intolerance trajectories. Of 354 critically ill surgical patients, 257 cases underwent enteral nutrition and 97 cases underwent enteral plus parenteral nutrition. The acute physiological and chronic health score (APACHEII) was 17(13,21), and the sequential organ failure score (SOFA) was 6(5,8). The modified Critical Illness Nutritional risk score (mNUTRIC) was 4 (2,5), the number of complications was 2(1,3). There were 293, 55 and 6 patients with grade Ⅰ, grade Ⅱ and grade Ⅲ acute gastrointestinal injury (AGI), and there were 224, 17 and 61 patients who were treated with mechanical ventilation, continuous renal replacement therapy and vasoactive drugs, respectively. The incidence of feeding intolerance in 354 patients increased first and then decreased, reaching a peak of 25.42%(90/354) on the third day and 53.67%(190/354) within 7 days. Of 354 critically ill surgical patients, cases with no feeding intolerance, decreased feeding intolerance, continuous feeding intolerance had the APACHE Ⅱ as 16(12,20), 17(14,25), 18(13,22), mNUTRIC as 3(2,5), 4(3,6), 4(3,5), the number of complications as 2(1,2), 2(2,3), 2(2,3). There were 152, 27, 114 cases with grade Ⅰ AGI, 12, 22, 27 cases with grade Ⅱ-Ⅲ AGI, 95, 39, 90 cases with mechanical ventilation. There were significant differences in the above indicators among the three groups ( H=6.14, 13.11, 28.05, χ2=37.96, 7.65, P< 0.05). Further analysis showed that compared with patients with no feeding intolerance, patients with decreased feeding intolerance and continuous feeding intolerance had the higher number of complications and grade of AGI ( Z=60.32, 54.69, χ2=39.72, 9.52, P<0.05), patients with decreased feeding intolerance had the higher mNUTRIC scores and ratio of mechanical ventilation ( Z=53.41, χ2=7.59, P<0.05). (2) Treatment of patients of different feeding intolerance trajectories. Cases with prokinetic drugs use and post-pyloric feeding were 36, 13 of patients with no feeding intolerance, 25 and 10 of patients with decreased feeding intolerance, 46 and 19 of patients with continuous feeding intolerance, respectively, showing significant differences in the above indicators among the three groups ( χ2=15.76, 6.20, P<0.05). Further analysis showed that compared with patients with no feeding intolerance, patients with decreased feeding intolerance had higher ratio of prokinetic drugs use and ratio of post-pyloric feeding ( χ2=15.60, 6.10, P<0.05). (3) Survival of patients of different feeding intolerance trajectories. The 28-day overall survival rates of patients with no feeding intolerance, decreased feeding intolerance, and continued feeding intolerance were 96.96%, 95.92%, and 87.94%, respectively, showing a significant difference ( χ2=10.39, P<0.05). Further analysis showed a significant difference between patents with no feeding intolerance and patients with continuous feeding intolerance ( χ2=9.19, P<0.05). (4) Analysis of prognostic factors in critically ill surgical patients. Multivariate analysis showed that continuous feeding intolerance was an independent risk factor for 28-day death in critically ill surgical patients ( hazard ratio=3.92, 95% confidence interval as 1.43-10.79, P<0.05). Conclusion:For surgical critically ill patients, patients with continuous feeding intolerance have a higher 28-day mortality than patients with no feeding intolerance, and the continuous feeding intolerance is an independent risk factor for 28-day death in critically ill surgical patients.