Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

OBJECTIVE: Previous studies have shown that insomnia is closely related to erectile dysfunction（ED）. However, the causal relationship between them is still unclear. Mendelian randomization (MR) provides a new method for studying the relationship between the two, and the theory of heart-kidney interaction in TCM provides a new idea for exploring the causal relationship between them. METHODS: Based on the statistical data collected by genome-wide association studies (GWAS), the causal relationship between insomnia and ED was discussed by MR. Inverse variance weighted (IVW) is the main analysis method, and weighted median (WME), simple mode (SM), weighted mode (WM) and MR Egger method were the supplementary analysis to evaluate the causal effect. MR-Egger intercept test, Cochran Q test and leave-one-out method were used in sensitivity analysis to verify the reliability of MR results. RESULTS: Thirty-nine SNPs significantly related to insomnia were finally included for MR analysis. The results of IVW method in MR analysis showed that insomnia had a significant causal relationship with the increased risk of ED (OR = 3.111，95% CI= 1.566－6.181，P=1.193×10－3). The results obtained by MR-Egger method, WME method, WM method and SM method were consistent with IVW method in the direction of effect. The sensitivity results suggested that the results of this study were robust. CONCLUSION Our study reveals the causal relationship between insomnia and ED, which provides a new basis for future clinical practice and prevention and treatment of ED.
Causality ; Sleep Initiation and Maintenance Disorders/genetics* ; Erectile Dysfunction/genetics* ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; Humans ; Male ; Heart/physiology* ; Kidney/physiology* ; Polymorphism, Single Nucleotide ; Data Interpretation, Statistical

OBJECTIVE: To explore the effectiveness of manipulation treatment for lumbar disc herniation (LDH) based on the model of muscle and bone assessment. METHODS: From May 2022 to August 2023, using the methods single-center randomized controlled in Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 72 patients were treated with LDH and divided into muscle and bone assessment model manipulation group and the two step seven gimmick group according to the random number table method, the muscle and bone assessment model manipulation group fall off in 1 case, the two step seven gimmick group falls off in 2 cases. There were 35 cases in the muscle and bone assessment model manipulation group, including 12 males and 23 females;The age was 27 to 48 years old with an average of (37.77±7.63) years old. The course of disease was 35 to 180 days with an average of (83.68±69.01) days. The patients were treated with manual therapy under the guidance of muscle and bone assessment model, twice a week for 4 weeks. There were 34 cases in the two step seven gimmick group including 12 males and 22 females;The age was 26 to 49 years old with an average of (37.59±7.43) years old;The course of disease was 40 to 175 days with an average of (82.15±68.87) days. The patients were treated with two step seven gimmick method, 2 times a week, for 4 weeks. The visual analogue scale (VAS) and Oswestry disability index (Oswestry disability index, ODI) questionnaire, muscle tension and lumbar spine angle and the straight leg-raising activities were compared between two groups before and 4 weeks after treatment. RESULTS: The VAS of the muscle and bone assessment model manipulation group and the two step seven gimmick group(6.51±0.61) and (6.62±0.56) before treatment decreased to 2.40±0.81 and 3.18±0.78 after 4 weeks of treatment, respectively, and the muscle and bone assessment model manipulation group was significantly lower than the two step seven gimmick group (P<0.01). The ODI of the muscle and bone assessment model manipulation group and the two step seven gimmick group were (64.57±5.11) and (65.02±5.18) before treatment, decreased to (18.60±2.27) and (24.70±2.14) after 4 weeks of treatment, and the ODI of the muscle and bone assessment model manipulation group was significantly lower than that of the two step seven gimmick group (P<0.01). Before the treatment, side erector spinae, gluteus medius, and gastrocnemius muscle tension were (59.95±2.60), (62.59±2.51), (49.97±2.01) in the muscle and bone assessment model manipulation group and (60.39±3.84), (62.47±3.27), (49.55±1.27) in the two step seven gimmick group;After 4 weeks of treatment, the muscle tension of erector spinae, gluteus medius and gastrocnemius on the affected side were (56.58±2.71), (60.44±2.31) and (49.19±1.57) in the muscle and bone assessment model manipulation group, (58.28±3.79), (60.11±2.87), (48.55±0.90) in the two step seven gimmick group, the differences had statistical significance before and after treatment of two groups(P<0.01). The muscle and bone assessment model manipulation group was better than the two step seven gimmick group in improving the erector spinae muscle tension on the affected side (P<0.05), and there was no significant difference in the rest (P>0.05). Before the treatment, lumbar proneness, stretch, subject to lateral flexion and lateral angle of the straight leg-raising on the affected side were (46.00±8.89)°, (13.57±3.75)°, (12.29±3.50) °, (43.71±7.98) ° in the muscle and bone assessment model manipulation group, (45.14±6.24) °, (12.23±3.75) °, (12.66±2.98) ° and (44.18±3.50) ° in the two step seven gimmick group. After 4 weeks of treatment, the angles of lumbar flexion, extension, flexion on the affected side and straight leg raising on the affected side were (76.29±4.43) °, (20.00±1.71) °, (22.43±2.81) °, (70.41±7.59) ° in the muscle and bone assessment model manipulation group, and (75.75±6.38) °, (16.43±3.36) °, (20.19±3.52) °, (65.42±6.15) ° in the two step seven gimmick group. The difference had statistical significance before and after treatment in two groups(P<0.01), a comparison between groups, after 4 weeks of treatment, the angles of lumbar flexion and extension, affected side flexion, and lower limb straight leg elevation in the muscle and bone assessment model manipulation group were better than those in the two step seven gimmick group (P<0.05). Before the treatment, pelvic tilt, lumbar lordosis angle were (2.71±1.01) mm, (37.63±3.35) ° in the muscle and bone assessment model manipulation group, and (2.69±0.97) mm, (36.98±3.73) ° in the two step seven gimmick group;After 4 weeks of treatment, the pelvic tilt and lumbar lordosis angle were (0.84±0.36) mm and (41.64±2.96) ° in the muscle and bone assessment model manipulation group, and those in the method of two step seven gimmick group were (1.18±0.75) mm and (41.70±3.14) °. There were significant differences before and after treatment in both groups (P<0.01), and the improvement of pelvic tilt in the muscle and bone assessment model manipulation group was better than that in the method of two step seven gimmick group after 4 weeks of treatment (P<0.05). CONCLUSION The manipulation under the guidance of the muscle and bone assessment model can effectively improve the pain and dysfunction of LDH patients, and has a better effect than the two-step seven-method manipulation group in improving the muscle tension, lumbar motion function and posture.
Humans ; Male ; Female ; Intervertebral Disc Displacement/physiopathology* ; Middle Aged ; Adult ; Lumbar Vertebrae

An automatic ash-removal heat-sensitive moxibustion device was developed, which could keep relatively constant temperature of heat-sensitive moxibustion, and realize the automatic ignition and automatic ash removal of moxa sticks during heat-sensitive moxibustion. The automatic ash-removal heat-sensitive moxibustion device comprises a bracket and a moxibustion box fixed on the top of the bracket; the bracket is composed of a base and a movable telescopic arm. This device can solve the problems of temperature instability, moxa ash blocking heat transfer and moxa ash falling during heat-sensitive moxibustion, avoiding the scalding caused by moxa ash falling, and reduce the workload of medical staff.
Humans ; Hot Temperature ; Moxibustion ; Temperature

OBJECTIVE: To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine. METHODS: Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients. RESULTS: Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD. CONCLUSIONS Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).
Humans ; Male ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Hyperuricemia ; Kidney ; Proteinuria ; Renal Insufficiency, Chronic/complications*

A moxibustion device with the functions of auricular fumigation moxibustion and heat-sensitive moxibustion is designed. The smoke of the ignited moxa stick is used for the fumigation moxibustion at the external auditory canal, while the heat generated works on Dazhui (GV 14) for heat-sensitive moxibustion. The device consists of five parts, i.e. combustion chamber, smoke pipe, smoke processing chamber, power module and connector. It solves the limitations such as unpleasant experience in treatment, unfavorable temperature control, easy scalding and excessive manual dependence induced by usual fumigation moxibustion and during heat-sensitive moxibustion. This moxibustion device may improve the safety and convenience when delivering the treatment with fumigation moxibustion and heat-sensitive moxibustion, as well as the work efficiency of medical staff.
Humans ; Moxibustion ; Hot Temperature ; Fumigation ; Smoke ; Temperature

Objective: Currently, the Overlap anastomosis is one of the most favored reconstruction methods of intracorporeal esophagojejunostomy (EJS). Despite many advantages of the method, it remains some shortcomings to be improved when it comes to the retraction of the esophagus stump, the insertion of the anvil fork of the linear stapler into a "pseudo" lumen, and the closure of the common entry hole. This study aims to investigate the safety and feasibility of a multi-mode modified Overlap anastomosis. Methods: A descriptive case series study was conducted. Medical records of 152 consecutive patients who underwent totally laparoscopic total gastrectomy (TLTG) with our multi-mode modified Overlap EJS method by the same surgical team at our department from February 2017 to June 2020 were retrospectively analyzed. The multi-mode modified Overlap method mainly included (1) After ensuring the safety of tumor resection margin (proximal margin was at least 3 cm from the tumor), the esophagus was partially transected from left to right (with 5-8 mm width esophagus continuation). The specimen was then placed in a plastic bag which was tied up at the mouth using strings with a part of the esophageal wall poking through. Then the plastic bag containing the specimen was transferred to the right lumbar region, while the patient's body position was adjusted so that the abdominal esophagus could be pulled by the gravity of the specimen. (2) Using the "three-direction traction" method. The esophageal lumen was properly exposed, then guided by the gastric tube, the anvil fork was accurately placed into the esophageal lumen for completing the side-to-side EJS. (3) The 3-0 barbed suture was used in the closure of the common entry hole of the stapler from dorsally to ventrally with simple one-layer continuous suture (the stitch going from inside to inside) followed by continuous Lembert's suture (the stitch going from outside to outside). Combined with clinicopathological characteristics, the perioperative outcomes and postoperative complications of the whole group were analyzed and evaluated. Results: The study cohort included 129 men and 23 women, with a mean age of (60.2±9.1) years and a mean body mass index (BMI) of (23.2±3.1) kg/m(2). Of the 152 patients, 23 patients (15.1%) had a history of previous abdominal surgery; dentate line was invaded by tumor in 21 patients (13.8%). The mean length of the proximal resection margin was (3.3±0.3) cm and the postoperative pathological examination indicated negative resection margin tumor. The mean operative time and anastomotic time were (302.1±39.9) minutes and (29.8±5.4) minutes, respectively. The mean estimated blood loss was (87.9±46.4) ml. The mean length of postoperative hospital stay was (12.3±7.3) days. The overall severe postoperative complications (Clavien-Dindo ≥ II) occurred in 22 patients (14.5%). Six cases of pancreatic leakage were successfully recovered by adequate drainage, inhibition of pancreatic exocrine secretion and nutritional support. Ten cases of pneumonia and three cases of abdominal infection were cured with anti-infection and physical therapy. Two patients developed anastomotic leakage postoperatively. One case was caused by excessive tension of the Roux loop of the jejunum and excessive opening on the side of the jejunum after side-to-side anastomosis, and the other case was caused by an accidental intraoperative occurrence of "nasogastric tube stapled to the side-to-side anastomosis". Both of them recovered after conservative treatment including adequate drainage, anti-infection, and adequate nutritional support. One patient underwent immediate open surgery because of Peterson's hernia 7 days after TLTG, and the patient died due to extensive small bowel necrosis. Conclusions: Multi-mode modified overlap method simplifies the operation and reduces the difficulty of EJS. It is a safe and feasible method for EJS.
Aged ; Anastomosis, Surgical/methods* ; Feasibility Studies ; Female ; Gastrectomy/methods* ; Humans ; Laparoscopy/methods* ; Male ; Margins of Excision ; Middle Aged ; Plastics ; Postoperative Complications/etiology* ; Retrospective Studies ; Stomach Neoplasms/pathology*

Humans ; Computed Tomography Angiography ; Deep Learning ; Coronary Angiography ; Coronary Artery Disease ; Tomography, X-Ray Computed ; Coronary Stenosis/diagnosis* ; Retrospective Studies ; Fractional Flow Reserve, Myocardial ; Predictive Value of Tests

OBJECTIVES: To study the role and mechanism of autophagy in lipopolysaccharide (LPS)-induced inflammatory response of human alveolar epithelial A549 cells. METHODS: A549 cells were stimulated with LPS to establish a cell model of inflammatory response, and were then grouped (n=3 each) by concentration (0, 1, 5, and 10 μg/mL) and time (0, 4, 8, 12, and 24 hours). The A549 cells were treated with autophagy inhibitor 3-methyladenine (3-MA) to be divided into four groups (n=3 each): control, LPS, 3-MA, and 3-MA+LPS. The A549 cells were treated with autophagy agonist rapamycin (RAPA) to be divided into four groups (n=3 each): control, LPS, RAPA, and RAPA+LPS. The A549 cells were transfected with the Toll-like receptor 4 (TLR4) overexpression plasmid to be divided into four groups (n=3 each): TLR4 overexpression control, TLR4 overexpression, TLR4 overexpression control+LPS, and TLR4 overexpression+LPS. The A549 cells were transfected with TLR4 siRNA to be divided into four groups (n=3 each): TLR4 silencing control,TLR4 silencing, TLR4 silencing control+LPS, and TLR4 silencing+LPS. CCK-8 assay was used to measure cell viability. Western blot was used to measure the protein expression levels of inflammatory indicators (NLRP3, Caspase-1, and ASC), autophagic indicators (LC3B, Beclin-1, and P62), and TLR4. RESULTS: After stimulation with 1 μg/mL LPS for 12 hours, the levels of inflammatory indicators (NLRP3, Caspase-1, and ASC), autophagic indicators (LC3B, Beclin-1, and P62), and TLR4 increased and reached the peak (P<0.05). Compared with the LPS group, the 3-MA+LPS group had reduced expression of autophagy-related proteins and increased expression of inflammation-related proteins and TLR4, while the RAPA+LPS group had increased expression of autophagy-related proteins and reduced inflammation-related proteins and TLR4 (P<0.05). The TLR4 overexpression+LPS group had reduced autophagy-related proteins and increased inflammation-related proteins compared with the TLR4 overexpression control+LPS group, and the TLR4 silencing+LPS group had increased autophagy-related proteins and reduced inflammation-related proteins compared with the TLR4 silencing control+LPS group (P<0.05). CONCLUSIONS In the LPS-induced inflammatory response of human alveolar epithelial A549 cells, autophagic flux has a certain protective effect on A549 cells. TLR4-mediated autophagic flux negatively regulates the LPS-induced inflammatory response of A549 cells.
Humans ; A549 Cells ; Autophagy ; Beclin-1/metabolism* ; Caspase 1/metabolism* ; Inflammation ; Lipopolysaccharides/pharmacology* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Toll-Like Receptor 4/metabolism*