Based on the traditional Chinese medicine （TCM） theories of body fluid metabolism and turbid phlegm obstructing the orifices， and drawing on recent advances in cerebrospinal fluid-interstitial fluid （CSF-ISF） exchange， glymphatic clearance， and extracellular matrix （ECM） regulation， this article discusses the possible scientific connotation of "invisible phlegm" from the perspectives of pathogenesis， clinical manifestations， and therapeutic implications. Impaired brain fluid exchange may lead to reduced clearance， the retention of metabolic wastes and pathological proteins. Abnormal ECM remodeling may further disrupt molecular diffusion and local microenvironmental homeostasis， resulting in a pathological process characterized by slowed fluid movement， reduced clearance， and abnormal retention. This process bears a certain functional resemblance to the TCM pathogenesis of impaired distribution of body fluids， endogenous formation of turbid phlegm and obstruction of the brain orifices， and may also be associated with manifestations such as a clouded sensation in the head， cognitive abnormalities， and emotional disturbances. On this basis， the potential effects of certain phlegm-dissolving Chinese medicines in improving brain clearance function and extracellular microenvironmental homeostasis warrant further investigation. We therefore propose that， the "invisible phlegm" of TCM in brain tissue may manifest as a pathological retention state characterized by restricted fluid exchange， impaired clearance function， and extracellular microenvironmental imbalance. This perspective may provide a new avenue for investigating TCM treatment of neurological and psychiatric disorders from the perspective of phlegm.

Based on the traditional Chinese medicine （TCM） theories of body fluid metabolism and turbid phlegm obstructing the orifices， and drawing on recent advances in cerebrospinal fluid-interstitial fluid （CSF-ISF） exchange， glymphatic clearance， and extracellular matrix （ECM） regulation， this article discusses the possible scientific connotation of "invisible phlegm" from the perspectives of pathogenesis， clinical manifestations， and therapeutic implications. Impaired brain fluid exchange may lead to reduced clearance， the retention of metabolic wastes and pathological proteins. Abnormal ECM remodeling may further disrupt molecular diffusion and local microenvironmental homeostasis， resulting in a pathological process characterized by slowed fluid movement， reduced clearance， and abnormal retention. This process bears a certain functional resemblance to the TCM pathogenesis of impaired distribution of body fluids， endogenous formation of turbid phlegm and obstruction of the brain orifices， and may also be associated with manifestations such as a clouded sensation in the head， cognitive abnormalities， and emotional disturbances. On this basis， the potential effects of certain phlegm-dissolving Chinese medicines in improving brain clearance function and extracellular microenvironmental homeostasis warrant further investigation. We therefore propose that， the "invisible phlegm" of TCM in brain tissue may manifest as a pathological retention state characterized by restricted fluid exchange， impaired clearance function， and extracellular microenvironmental imbalance. This perspective may provide a new avenue for investigating TCM treatment of neurological and psychiatric disorders from the perspective of phlegm.

Specification for Quality Control in Traditional Chinese Medicine Clinical Trials（GB/T 47336-2026） is the first national standard in the field of clinical research on traditional Chinese medicine （TCM）， aims to address the core issue that the quality shortcomings of current TCM clinical research restrict the transformation of achievements and international recognition. Through the interpretation of the core contents of this standard， including its scope of application， graded quality control system， TCM-specific quality control requirements， implementation and responsible entities， responsibilities of quality control personnel， formulation of quality control plans， critical nodes of quality control， and quality control archive management， it is believed that the promotion and implementation of this standard are of great significance for improving the standard system of TCM clinical research， enhancing research quality， optimizing the quality management model， and promoting the internationalization process of TCM. Meanwhile， the implementation paths for the standard are discussed， including carrying out pilot applications in institutions， establishing publicity， implementation， and training mechanisms， encouraging multi-party collaborative supervision， and setting up implementation feedback mechanisms. On this basis， the challenges that may be encountered during implementation， such as resource input pressure， difficulties in implementing TCM-specific quality control， and a relative shortage of interdisciplinary composite talents， are sorted out， and corresponding strategies are proposed， which can provide references for relevant researchers and practitioners.

Objective:To compare the mid- to long-term clinical outcomes of arthrolysis versus revision arthroplasty for arthrofibrosis-related stiffness following total knee arthroplasty (TKA).Methods:A retrospective analysis was conducted of the 20 patients (26 knees) with post-TKA arthrofibrosis who had been treated at Department of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital between January 2004 and January 2020. The patients were divided into 2 groups based on their treatment: an arthrolysis group of 8 cases (10 knees) [1 male (2 knees)and 7 females (8 knees); median age: 44.0 (21.0, 62.0) years] and a revision arthroplasty group of 13 cases (16 knees) [4 males (6 knees)and 9 females (10 knees); median age: 41.5 (30.0, 56.0) years]. The knee range of motion (ROM) and the American Hospital for Special Surgery (HSS) knee score as well as their improvements were compared between preoperation and the last follow-up, as well as between the 2 groups; the satisfaction of the patients at the last follow-up was compared between the 2 groups.Results:No significant differences in the baseline characteristics were observed between the 2 groups, indicating comparability ( P>0.05). The preoperative knee ROM [55.0° (48.8°, 61.3°)] and HSS knee score [54.0 (47.0, 61.8) points] in the arthrolysis group were significantly higher than those in the revision group [27.5° (6.3°, 50.0°), 33.0 (27.3, 47.8) points] ( P<0.05). In the arthrolysis and revision arthroplasty groups, the knee ROMs [90.0° (65.0°, 100.0°), 90.0° (63.5°, 98.8°)] and HSS knee scores [(69.8±19.9) points, (77.6±11.3) points] at the last follow-up were significantly improved compared with those before operation ( P<0.05). In the revision arthroplasty group, the improvement in knee ROM (48.9°±21.7°) was insignificantly larger than that in the arthrolysis group (34.5°±13.2°) ( P>0.05), but the improvement in HSS knee score [39.5 (25.3, 57.0) points] was significantly larger than that in the arthrolysis group [16.0 (10.5, 25.3) points] ( P<0.05). Respectively, 14 and 3 knees in the revision arthroplasty group and the arthrolysis group resulted in patient satisfaction, showing a significant difference between the 2 groups ( P<0.05). Conclusions:Both arthrolysis and revision arthroplasty can significantly improve knee ROM and HSS knee score in post-TKA arthrofibrosis. However, since revision arthroplasty demonstrates superior improvements in HSS knee score and patient satisfaction, it is preferable for patients with lower preoperative knee ROM.

Objective:To compare the mid- to long-term clinical outcomes of arthrolysis versus revision arthroplasty for arthrofibrosis-related stiffness following total knee arthroplasty (TKA).Methods:A retrospective analysis was conducted of the 20 patients (26 knees) with post-TKA arthrofibrosis who had been treated at Department of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital between January 2004 and January 2020. The patients were divided into 2 groups based on their treatment: an arthrolysis group of 8 cases (10 knees) [1 male (2 knees)and 7 females (8 knees); median age: 44.0 (21.0, 62.0) years] and a revision arthroplasty group of 13 cases (16 knees) [4 males (6 knees)and 9 females (10 knees); median age: 41.5 (30.0, 56.0) years]. The knee range of motion (ROM) and the American Hospital for Special Surgery (HSS) knee score as well as their improvements were compared between preoperation and the last follow-up, as well as between the 2 groups; the satisfaction of the patients at the last follow-up was compared between the 2 groups.Results:No significant differences in the baseline characteristics were observed between the 2 groups, indicating comparability ( P>0.05). The preoperative knee ROM [55.0° (48.8°, 61.3°)] and HSS knee score [54.0 (47.0, 61.8) points] in the arthrolysis group were significantly higher than those in the revision group [27.5° (6.3°, 50.0°), 33.0 (27.3, 47.8) points] ( P<0.05). In the arthrolysis and revision arthroplasty groups, the knee ROMs [90.0° (65.0°, 100.0°), 90.0° (63.5°, 98.8°)] and HSS knee scores [(69.8±19.9) points, (77.6±11.3) points] at the last follow-up were significantly improved compared with those before operation ( P<0.05). In the revision arthroplasty group, the improvement in knee ROM (48.9°±21.7°) was insignificantly larger than that in the arthrolysis group (34.5°±13.2°) ( P>0.05), but the improvement in HSS knee score [39.5 (25.3, 57.0) points] was significantly larger than that in the arthrolysis group [16.0 (10.5, 25.3) points] ( P<0.05). Respectively, 14 and 3 knees in the revision arthroplasty group and the arthrolysis group resulted in patient satisfaction, showing a significant difference between the 2 groups ( P<0.05). Conclusions:Both arthrolysis and revision arthroplasty can significantly improve knee ROM and HSS knee score in post-TKA arthrofibrosis. However, since revision arthroplasty demonstrates superior improvements in HSS knee score and patient satisfaction, it is preferable for patients with lower preoperative knee ROM.

The activation of the P2X7 receptor as an ATP-gated ion channel,triggers the release of pro-inflammato-ry cytokines in tumor carring individuals and stimulate excitation of injury-causing neurons,thereby exacerbating the transmission of pain.In preclinical cancer pain models,it has the potential to serve as a new therapeutic target for cancer pain management.

Objective:To monitor and investigate the long-term growth trend and nutritional status of very preterm infants (VPIs, born at gestational age between [28~31 +] weeks) with extrauterine growth restriction (EUGR) from birth to preschool period. Methods:VPIs who met with the following criteria were enrolled: infants born in Huai'an Maternity and Child Heath Care Hospital from January 1 to December 31, 2015; infants admitted to the Neonatal Medical Center and discharged alive; infants who received multi-disciplinary treatment in Child Care Division from discharge to preschool period. All of the VPIs were divided into the EUGR group and the non-EUGR group according to whether the weight at hospital discharge was below the 10 th percentile for corrected age in body weight. The weight for age Z score (WAZ), height for age Z score (HAZ), and head circumference for age Z score (HCZ) were calculated at each specified time point (at 40 weeks of age; at 1, 2, 3, 4, 5, 6 and 24 months of corrected age; and at 48 months of age). The growth trend and the nutritional status at 48 months of age were compared between the two groups. Results:1. A total of 53 VPIs were enrolled, among whom 35 cases were boys and 20 cases were with EUGR. The differences in the gestational age, birth weight, incidence of very low birth weight infants, neonatal respiratory distress syndrome (NRDS) and bronchopulmonary dysplasia (BPD) were all statistically significant between the EUGR group and the control group ( x 2= 2.306, 3.543, 10.852, 9.515, 0.001, respectively; all P<0.05). 2. The WAZ and HAZ of the EUGR group were lower at each time point. The WAZ at 40 weeks of age and the HAZ at 3 months of corrected age were significantly different between the two groups. From 40 weeks of age to 2 months of corrected age and from 6 months to 24 months of corrected age, the WAZ, HAZ and HCZ in both groups showed an increasing trend. However, the WAZ in the EUGR group and the WAZ, HAZ and HCZ in the non-EUGR group showed a declining trend from 24 months of corrected age to 48 months of age. 3. There was no significant differences in growth restriction incidence at each time point between the EUGR group and the control group. 4. The nutritional status showed no significant difference between the two groups, either ( P>0.05). Conclusions:Low gestational age, low birth weight, NRDS and BPD are the risk factors of EUGR. The growth trend of the EUGR VPIs shows an overall upward trend from hospital discharge to 24 months of corrected age but declined thereafter, while the nutritional status is good at 48 months of age. Thus, in addition to the integrated management, continuous monitoring of long-term growth and nutrient input after 24 months of age is required for VPIs.

OBJECTIVE:To provide reference for formulating related provisions,guidelines and regulations for off-label drug use,standardizing medical behavior in medical health institutions. METHODS:According to the connotation of off-label drug use,Questionnaire for off-label drug use was developed for medical institutions,in which drug name,treatment disease,the type and use evidence ofoff-label drug usewere included. The questionnaires were delivered to pharmacists who participatedClinical phar-macist practice skills training in Sichuan province to collect the related information of off-label drug use for statistical analysis, and suggestions were put forward. RESULTS:Totally 150 questionnaires were sent out,124 were effectively received with effec-tively recovery of 82.7%;the surveyed pharmacists came from 22 medical institutions,including 18 tertiary hospitals and 4 second-ary hospitals;there were 128 information about off-label drug use,including 14 (10.9%) with incomplete reporting information. The another 114 information were major in“super indication”(61) and“super administration”(43),accounting for 53.5% and 37.7%,respectively,and there are 8 other drug overdose(7.0%),2 super object(1.8%). The relevant off-label drug use mainly included anti-infection drugs (34 information,29.8%),anti-tumor drugs (16 information,14.0%),TCM injections (8 informa-tion,7.0%),and etc.;the relative concentration of varieties were metronidazole,dexamethasone,gentamicin,methotrexate, azithromycin,irinotecan,vancomycin,nystatin,etc.. Some medical institutions were absence of effective regulatory measures. CONCLUSIONS:Off-label drug use is quite common in medical institutions of Sichuan province,some of them exist obvious med-ication risk. It is suggested that the state should be as soon as possible to develop related provisions,guidelines and regulations for off-label drug use,endowing legal force for off-label drug use;medical staff should avoid no evidence-based drug use,unreason-able or even unnecessary off-label drug use;pharmaceutical production enterprises should strengthen communication with medical institutions and pay attention to collect information related to the clinical medication,timely update the drug instructions to ensure the legitimate rights for patients and the interests for medical staff.

OBJECTIVE:To systematically review the efficacy and safety of nedaplatin or cisplatin combined with paclitaxel in the treatment of advanced non-small cell lung cancer(NSCLC)and esophageal cancer. METHOD:Retrieved from PubMed,CJFD and Wanfang Database,randomized controlled trials(RCT)about nedaplatin combined with paclitaxel(TN)or cisplatin combined with paclitaxel (TP) in the treatment of advanced NSCLC and esophageal cancer were collected. Meta-analysis was performed by using Rev Man 5.3 software after data extract and quality evaluation. RESULTS:Totally 7 RCTs were included,involving 505 pa-tients. Results of Meta-analysis showed,there were no significant differences in the short-term efficacy [NSCLC:OR=1.08,95%CI (0.66,1.75),P=0.76;esophageal cancer:OR=1.44,95%CI(0.68,3.06),P=0.34],1-year survival rate [NSCLC:OR=1.21, 95%CI(0.60,2.44),P=0.59],2-year survival rate [NSCLC:OR=1.01,95%CI(0.38,2.68),P=0.99],the incidence ofⅢ/Ⅳleuko-penia [esophageal cancer:OR=1.36,95%CI(0.62,2.96),P=0.44],incidence ofⅢ/Ⅳthrombocytopenia [NSCLC:OR=1.37,95%CI(0.64,2.92),P=0.42;esophageal cancer:OR=0.97,95%CI(0.30,3.18),P=0.96] and incidence of Ⅲ/Ⅳ neutropenia [NSCLC:OR=1.38,95%CI(0.70,2.74),P=0.35]. Compared with TP,TN can significantly reduce the incidences of nausea and vomiting [NSCLC:OR=0.34,95%CI(0.20,0.60),P<0.001;esophageal cancer:OR=0.16,95%CI(0.07,0.35),P<0.001] and nephrotox-icity [esophageal cancer:OR=0.10,95%CI(0.02,0.55),P=0.009]. CONCLUSIONS:Both TN and TP show good efficacy in the treatment of NSCLC,but TN has lower incidences of astrointestinal reactions and nephrotoxicity.

Objective To evaluate the role of interleukin-12 (IL-12) in the spinal cord in the maintenance of arthritic pain (AP) in rats.Methods Adult male Sprague-Dawley rats, aged 6-8 weeks,weighing 200-300 g, were randomly divided into 4 groups using a random number table: control group (group C, n=6);AP group (n=9);phosphate buffer solution (PBS) group (n=6);IL-12 antibody group (n =6).AP was induced by injecting 50 μl of complete Freund' s adjuvant into the ankle joint cavity of the left hindpaw of rats anesthetized with isoflurane.Goat anti-rat IL-12 antibody 1.50 μg (20 μl) was intrathecally injected on 9 days after establishment of the model in group IL-12 antibody, while 0.01 mol/L PBS (20 μl) was administered in group PBS.The mechanical paw withdrawal threshold to yon Frey filament stimulation (MWT) was measured before establishment of the model (baseline) and on 9 and 10 days after establishment of the model.The rats were sacrificed after the last measurement of pain threshold, and the L4 6 segments of the spinal cord were obtained for detection of IL-12 expression in the spinal dorsal horn (by immunofluorescence) , and the co-expression of IL-12 and glial fibrillary acidic protein (an astrocyte marker) was examined simultaneously in group AP.Results Compared with group C, the MWT was significantly decreased, and the expression of IL-12 was up-regulated on 9 and 10 days after establishment of the model in AP, PBS and IL-12 antibody groups.Compared with group AP, the MWT was significantly increased at 10 days after establishment of the model, and the expression of IL-12 was down-regulated in group IL-12 antibody, and no significant change was found in the MWT at 10 days after establishment of the model and expression of IL-12 in group PBS.IL-12 was co-expressed with glial fibrillary acidic protein in group AP.Conclusion IL-12 in the spinal cord is involved in the maintenance of AP in rats.