Currently， there are many difficulties in formulating recommendations of traditional Chinese medicine （TCM） clinical practice guidelines. This paper analyzed and summarized the unique or prominent difficult issues in the formulation of recommendations faced by TCM guidelines， such as experts' professional background and experience bringing about the preferance from the academic emotion， inconsistency between different academic schools making it difficult to reach consensus， lack of guiding principles of the decision weight of different dimensions for recommendations. Therefore， methodological suggestions have been put forward， including organizing parallel TCM and western medicine consensus group， improving the method of combining TCM and western medicine paradigm， attaching great importance to the evidence-based governance of academic schools， and promoting the research on different dimensions for recommendation formulation， which may provide a methodological reference for the guideline development.

Objective To evaluate the effectiveness and safety of moxibustion for knee osteoarthritis and the methodological quality of systematic reviews(SRs).Methods SRs of moxibustion for knee osteoarthritis were retrieved from CNKI,VIP,Wanfang Data,SinoMed,PubMed,Cochrane Library,Embase and Web of Science was conducted from the establishment of the databases to February 10,2022.AMSTAR 2 was used to assess the methodological quality of SRs.The randomized controlled trials(RCTs)included in these SRs were screened and summarized according to inclusion standard.RevMan 5.4 software was used for Meta-analysis,and GRADE approach was used to assess the certainty of evidence.Results A total of 15 SRs were included.The evaluation results of the AMSTAR 2 showed that the methodological quality was very low for 14 SRs,and low for other 1 SR.A total of 36 RCTs were included.Meta-analysis results showed that compared with the non-steroidal anti-inflammatory drugs(NSAIDs),the moxibustion group had better effects on improvement of WOMAC scores[mean difference(MD)=-5.95;95%confidence interval(CI):-9.25 to-2.65;low quality],relieving pain[MD=-1.26;95%CI:-2.19 to-0.32;very low quality],and improving effective rate[risk ratio(RR)=1.16;95%CI:1.11 to 1.22;low quality].In the moxibustion group,some patients experienced blisters,and most healed in 3 days.Conclusion Moxibustion has advantages in pain reduction and improving effective rate compared with routine Western therapy for knee osteoarthritis.However,well-designed high-quality RCTs are needed for further verification.

Currently, there are practical and technical difficulties in the construction of clinical questions in the development of clinical practice guidelines. Clinicians or guideline developers seldom construct clinical questions based the actual case scenario, leading to some information loss between structured and actual clinical connotation. To overcome this challenge, we proposed a case-guided questions construction approach, and carried out case research and verification in the formulation of the guideline. We found that this method could more efficiently and scientifically assist the formulation of clinical questions, and provide reference for clinicians or guideline developers.

Objective:To explore the properties of gelatin-polyethylene glycol hydrogel loaded with silver nanoparticle (AgNP) Chlorella (hereinafter referred to as the composite hydrogel) and its effects on healing of infected full-thickness skin defect wounds in mice. Methods:The research was an experimental research. The simple gelatin-polyethylene glycol hydrogel (hereinafter referred to as the simple hydrogel) and the composite hydrogel were prepared, and the appearance and injectability of the two hydrogels were observed at 55 and 37 ℃, and under the irradiation of 808 nm near-infrared light, respectively. An electronic universal testing machine was employed to assess the tensile and compressive stress-strain properties of both types of hydrogels at room temperature. Additionally, the cyclic compressive stress-strain properties of the composite hydrogel were examined at 80% of the maximum compressive stress. Staphylococcus aureus or Escherichia coli solution was added to phosphate buffer solution (PBS), simple hydrogel, and composite hydrogel, respectively. The part of composite hydrogel containing Staphylococcus aureus or Escherichia coli solution was irradiated with near-infrared light for 5 minutes. After each sample was incubated for 6 h, the dilution plating method was used to detect and calculate the mortality rates of the two bacteria at 24 h of culture ( n=5). The discarded foreskin tissue was taken from a 6-year-old healthy boy admitted to the Department of Urology of the First Affiliated Hospital of Naval Medical University for circumcision. Primary human fibroblasts (HFbs) were isolated using the enzyme extraction method, routinely cultured to the 3 rd to 6 th passages for subsequent cellular experiments. Composite hydrogel extracts with final mass concentrations of 100.0, 50.0, 25.0, 12.5, and 0 mg/mL were respectively prepared and used to culture HFbs, and the cell proliferation after 24 h of culture was detected using a cell counting kit 8 ( n=3). A total of twenty 6-8 weeks old C57BL/6J female mice were utilized, and a full-thickness skin defect was surgically created on the back of each mouse. The wounds were infected with Staphylococcus aureus solution. The infected mice were divided into blank control group, simple hydrogel group, composite hydrogel group, and combined treatment group according to the random number table, and the wounds were treated with PBS, simple hydrogel, composite hydrogel, and composite hydrogel+light irradiation (under the irradiation of 808 nm near-infrared light for 5 min), respectively, with 5 mice in each group. On post injury day (PID) 0 (immediately after the first wound treatment), 3, 7, and 14, an overall assessment of wound exudation and healing were conducted, and the wound healing rates on PID 7 and 14 were calculated ( n=5). On PID 14, hematoxylin-eosin staining was performed to observe histopathological changes in the mouse wound. Results:Both simple hydrogel and composite hydrogel were in a solution state at 55 ℃ and transition to a gel state when cooling to 37 ℃. After the two hydrogels were irradiated by near-infrared light, only the composite hydrogel reheated up and returned to the solution state again with injectability. The maximum tensile stress of the composite hydrogel was up to 301.42 kPa, with a corresponding strain of 87.19%; the maximum compressive stress was up to 413.79 kPa, with a corresponding strain of 91.67%, which was similar to the tensile and compressive properties of the simple hydrogel. After 10 compression cycles, the maximum compressive stress of the composite hydrogel still reached 84.1% of the first compressive stress. After 24 h of culture, the mortality rate of Staphylococcus aureus treated with simple hydrogel was significantly higher than that treated with PBS ( P<0.05); the mortality rates of Escherichia coli and Staphylococcus aureus treated with composite hydrogel alone were significantly higher than those treated with simple hydrogel ( P<0.05); the mortality rates of Escherichia coli and Staphylococcus aureus treated with composite hydrogel+light irradiation were significantly higher than those treated with composite hydrogel alone ( P<0.05). After 24 h of culture, compared with that cultured in composite hydrogel immersion solution with final mass concentration of 0 mg/mL, the proliferation activity of HFbs cultured in composite hydrogel immersion solution with final mass concentrations of 25.0 and 50.0 mg/mL was significantly enhanced ( P<0.05), while the proliferation activity of HFbs cultured in composite hydrogel immersion solution with final mass concentration of 100 mg/mL was significantly decreased ( P<0.05). On PID 0 and 3, more purulent secretions were seen in the wounds of mice in blank control group and simple hydrogel group, while only a small amount of exudate was observed in the wounds of mice in composite hydrogel group, and no obvious infection was observed in the wounds of mice in combined treatment group. On PID 7 and 14, the wound healing rates of mice in simple hydrogel group were significantly higher than those in blank control group ( P<0.05); the wound healing rates of mice in composite hydrogel group were significantly higher than those in simple hydrogel group ( P<0.05); the wound healing rates in combined treatment group were significantly higher than those in composite hydrogel group ( P<0.05). On PID 14, the wounds of mice in blank control group exhibited a high infiltration of inflammatory cells with no new epithelial layer observed; the wounds of mice in simple hydrogel group displayed a short length of newly formed epithelium with a small amount of inflammatory cells; the wounds of mice in composite hydrogel group exhibited continuous formation of new epithelium and a large amount of immature granulation tissue; the wounds of mice in combined treatment group showed continuous epithelialization with less immature granulation tissue. Conclusions:The prepared composite hydrogel exhibits excellent thermosensitivity, photothermal properties, and injectability, as well as excellent mechanical properties, antibacterial properties, and biocompatibility, and can promote the healing of infected full-thickness skin defect wounds in mice.

Syndrome differentiation and treatment is a unique mode of diagnosis in traditional Chinese medicine （TCM）. The establishment of scientific and standardized syndrome diagnosis standards is an important link to evaluate the clinical efficacy of TCM objectively and systematically， and also a prerequisite for the promotion and development of TCM to obtain international recognition. This article reviewed the basic modes and existed problems of the current syndrome diagnosis criteria， and proposed to construct a multidimensional core information set integrating the minimized core symptoms， the artificial intelligence signs， the multi-modal laboratory indicators， and multi-omics specific markers， so as to present syndrome characteristics from multiple perspectives systematically. This paper also described the basic mode， constructure， as well as the process and methodology to be adopted in the establishment of the standardized diagnostic research method. The core information set of diagnostic symptoms not only took into account the specificity of the disease， but also improved the inconsistency due to the complexity and subjectivity of the syndrome differentiation， thereby providing a methodological basis for the standardization of TCM syndrome differentiation in clinical research.

Enzyme-driven micro/nanomotors consuming in situ chemical fuels have attracted lots of attention for biomedical applications. However, motor systems composed by organism-derived organics that maximize the therapeutic efficacy of enzymatic products remain challenging. Herein, swimming proteomotors based on biocompatible urease and human serum albumin are constructed for enhanced antitumor therapy via active motion and ammonia amplification. By decomposing urea into carbon dioxide and ammonia, the designed proteomotors are endowed with self-propulsive capability, which leads to improved internalization and enhanced penetration in vitro. As a glutamine synthetase inhibitor, the loaded l-methionine sulfoximine further prevents the conversion of toxic ammonia into non-toxic glutamine in both tumor and stromal cells, resulting in local ammonia amplification. After intravesical instillation, the proteomotors achieve longer bladder retention and thus significantly inhibit the growth of orthotopic bladder tumor in vivo without adverse effects. We envision that the as-developed swimming proteomotors with amplification of the product toxicity may be a potential platform for active cancer treatment.

Objective To study the constituents of urinary stones in patients in Zhejiang,and analyze the composition difference between patients from northern Zhejiang province and southern Zhejiang province.Methods From October 2012 to October 2018,clinical data of 4 423 urinary stone patients treated in Sir Run Run Shaw Hospital,the Second Affiliated Hospital of Wenzhou Medical University,and Huzhou First People's Hospital was retrospectively analyzed.Infrared spectrum was used to analyze urinary calculi constituents.Among 4 423 patients,there were 3 041 males and 1 382 females,male to female ratio was 2.2∶ 1,and the mean age was (51.2 ±16.5) years.There were 2 974 northern Zhejiang patients and 1 449 southern Zhejiang patients.High incidence age group was 41-60 years [48.2％ (2 136/4 423)].The distribution characteristics of urinary calculi constituents in different groups of sex,age,and region were analyzed.Results Among the 4 423 cases,the mixed urinary stones were dominant in the urinary calculus [73.1％ (3 235/4 423)],in which,the most component was the calcium oxalate monohydrate + calcium oxalate dehydrate + carbonated apatite [36.2％ (1 604/4 423)];among the pure stones,the most component was the calcium oxalate monohydrate [16.3 ％ (719/4 423)].Carbonated apatite stones [70.1％ (970/1 382) vs.61.0％ (1 856/3 041),P ＜0.05] and magnesium ammonium phosphate stones [12.7％ (176/1 382) vs.4.9％ (150/3 041),P ＜ 0.05] were both more prevalent in females than males,but uric acid stones[10.6％ (325/3 041) vs.5.8％ (81/1 382),P ＜0.05] were more common in males than females.The proportions of calcium oxalate stones[90.6％ (961/1 060) vs.76.2％ (935/1 227),P ＜0.05],carbonated apatite stones [77.6％ (823/1 060) vs.50.7％ (623/1 227),P ＜ 0.05],and magnesium ammonium phosphate stones[9.1％ (97/1 060) vs.6.5％ (80/1 227),P ＜0.05] of 0-40 years group were all higher than ＞ 60 years group,however,uric acid stones were more frequent in ＞ 60 years group [3.5％ (38/1 060) vs.17.0％ (209/1 227),P ＜ 0.05].The proportion of calcium oxalate stones in southern Zhejiang was lower than northern Zhejiang [79.0％ (1 145/1 449) vs.89.4％ (2 661/ 2 974),P ＜ 0.05].However,carbonated apatite stones [71.5％ (1 037/1 449) vs.60.1％ (1 789/2 974),P ＜ 0.05],magnesium ammonium phosphate stones [15.1％ (220/1 449) vs.3.5％ (106/ 2 974),P ＜ 0.05],and uric acid stones [10.7％ (156/1 449) vs.8.4％ (250/2 974),P ＜ 0.05] were more prevalent in southern Zhejiang than northern Zhejiang.Conclusions The distribution of constituents of urinary stones in Zhejiang was different in genders,age,and regions.Carbonated apatite stones and magnesium ammonium phosphate stones were more prevalent in females and young people,and uric acid stones were more common in males and old people.Calcium oxalate stones were more common in youths.Moreover,calcium oxalate stones were more frequent in northern Zhejiang,and carbonated apatite stones,magnesium ammonium phosphate stones and uric acid stones were common in southern Zhejiang.

Cell death plays important roles in living organisms and is a hallmark of numerous disorders such as cardiovascular diseases, sepsis and acute pancreatitis. Moreover, cell death also plays a pivotal role in the treatment of certain diseases, for example, cancer. Noninvasive visualization of cell death contributes to gained insight into diseases, development of individualized treatment plans, evaluation of treatment responses, and prediction of patient prognosis. On the other hand, cell death can also be targeted for the treatment of diseases. Although there are many ways for a cell to die, only apoptosis and necrosis have been extensively studied in terms of cell death related theranostics. This review mainly focuses on molecular imaging and therapeutic strategies directed against necrosis. Necrosis shares common morphological characteristics including the rupture of cell membrane integrity and release of cellular contents, which provide potential biomarkers for visualization of necrosis and necrosis targeted therapy. In the present review, we summarize the updated joint efforts to develop molecular imaging probes and therapeutic strategies targeting the biomarkers exposed by necrotic cells. Moreover, we also discuss the challenges in developing necrosis imaging probes and propose several biomarkers of necrosis that deserve to be explored in future imaging and therapy research.

Objective To study the risk of bloodstream infection in relation with peripherally inserted central venous catheter (PICC) in hospitalized non-cancer patients.Methods Clinical data of 172 non-cancer patients admitted to our hospital for PICC were collected.The risk of PICC-related bloodstream infection (CRBSI) in domestic hospitalized non-cancer patients was analyzed and systematically assessed.Results Of the 183 PICCs placed in 172 patients included in this study,61.7％ were placed in general wards,38.3％ were placed in ICU,87.8％ were placed in combination with indwelling urinary catheter,29.7％ were placed in combination with mechanical ventilation.The median PICC indwelling time was 35 days.CRBSI occurred in 6 patients with an incidence of 0.6/1000 PICCs/day.The risk of CRBSI was centralized in domestic tumor patients after PICC.The reported CRBSI was significantly different in hospitalized non-cancer patients (0.26-33.10/100 PICC).Conclusion The risk of CRBSI is lower in hospitalized patients after PICC placement than after traditional central venous catheter placement.Further studies are needed to assess its value in ICU.

Objective To study the current situation of migrant children' s social adaptation and ex?plore its influencing factors. Methods The study population was 1547 children aged 10?16 years recruited from Shijiazhuang city. Social adaptation was collected through social adaptation questionnaire,whereas self?control was measured by children' s self?control investigating questionnaire. The data were statistically ana?lyzed with the ANOVA and stepwise regression analysis. Results ①There was no significant difference on social adaptation scores between migrant children and urban children (3.71±0.65,3.70±0.69, P>0.05). ②Among migrant children,girls scored significantly higher than boys(3.80±0.59,3.63±0.69, P<0.01). And as the grade of the migrant children increased,the social adaptation scores decreased (3.82±0.68,3.72±0.64, 3.58±0.60, P<0.01). ③The poor control system had a significantly negative prediction on migrant children' s social adaptation ( β=-0.299, P<0.01),whereas the good self?control system had a significantly positive prediction on migrant children' s social adaptation ( β=0.243, P<0.01) . Both parent?child relationship and peer relationship significantly positively predicted migrant children ' s social adaptation ( β=0. 179, β=0.092, P<0.01) . There was no significant correlation between the proportion of the migrant children in the classes and migrant children's social adaptation (P>0.05). Conclusion There is no significant difference on social adaptation between migrant children and urban children. Children' s self?control,parent?child rela?tionship and peer relationship have significant influence on social adaptation of migrant children .