With the rapid development of artificial intelligence technology,small molecule generation models have emerged as a significant research direction in the field of drug discovery.These models,including Generative Adversarial Networks(GANs),Variational Autoencoders(VAEs),and diffusion models,have proven to possess remarkable capabilities in optimizing drug properties and generating complex molecular structures.This article comprehensively analyzes the application of the aforementioned advanced technologies in the drug discovery process,demonstrating how they supplement and enhance traditional drug design methods.At the same time,it addresses the challenges facing current methods in terms of data quality,model complexity,computational cost,and generalization ability,with a prospect of future research directions.

This paper reports a case of reparing the tissue defect after resection of a malignant tumor in the glabellar nasion with bilateral modified horizontal advancement flaps. The patient, a 20-year-old female, was admitted to the hospital because of a mass on the nasion between the eyebrows for more than 5 years, with enlargement and ulceration for 5 months. Surgical resection of the tumor was performed. Intraoperative rapid frozen sections showed that the tumor was basal cell carcinoma, and there were no cancer cells at the margins. Bilateral modified horizontal advancement flap repair was performed. At three months after the operation, the incision area healed well, the appearance and eyelid function were normal, and there was no sign of recurrence of basal cell carcinoma. Bilateral modified horizontal advancement flap was effective in repairing the tissue defect after resection of glabellar nasal root basal cell carcinoma.

Objective:To explore the surgical effects of continuous trapezoidal suture method between subcutaneous and subconjunctival tissue in buried-suture double-eyelid blepharoplasty.Methods:A retrospective study was conducted on patients who underwent the operation of continuous trapezoidal suture method between subcutaneous and subconjunctival tissue in buried-suture double-eyelid blepharoplasty at the Department of Plastic and Aesthetic Surgery of Qingdao Municipal Hospital from September 2021 to September 2023. Six points were marked on the skin surface of the designed double eyelid line on patient' s upper eyelid, 8 points were marked on the corresponding conjunctival surface of the designed double eyelid line. A 6-0 nylon thread attached with one needle on each end was used for suturing, with two ends running through and between the subcutaneous and subconjunctival layers alternatively, forming a " trapezoidal" shape of path. Finally, two ends exited at the same point on the most lateral side of the designed double eyelid line on skin surface and were tied together with the knot hidden within the orbicularis oculi muscle. The morphology of the double eyelids and postoperative complications were observed and evaluated after surgery, the follow-up period was at least 6 months. At the last time of follow-up, the satisfaction rates were evaluated by patients themselves. Four aspects of the surgical effects of the double eyelids were put into the evaluation system, which were radian, width, smoothness and symmetry, with score from 0-5 points for each. The total score was 0-20 points, of which 17-20 points indicated high satisfaction, score of 13-16 points indicated relative satisfaction, ≤ 12 points indicated dissatisfaction.Results:A total of 52 female patients were included, aged 18 to 29 years old, with an average age of 22.5 years. Among all patients, 33 cases had shallow double eyelid lines while 19 cases had single eyelids. All patients’ upper eyelids were relatively thin and without obvious looseness. The surgical procedures were all done smoothly and successfully, with an average operation time of (0.72±0.13) h. Immediately after surgery, the radian of the double eyelid lines on both sides looked smooth, the widths of the double eyelids were also basically symmetrical. During the follow-up period of 6-12 months postoperatively, the morphologies of the double eyelids were relatively natural and realistic, the double eyelid lines and widths remained deep and stable, and the incision scars were left unobvious for all patients. Besides, no complications such as ptosis, incomplete upper eyelid closure and ectropion were observed. Among the 52 patients, 45 cases were highly satisfied with the surgical result (17-20 points) , 7 were relatively satisfied (13-16 points) , while none of them required reoperation.Conclusions:The continuous trapezoidal suture method between subcutaneous and subconjunctival tissue in buried-suture double-eyelid blepharoplasty has advantages of short operation time, good and stable surgical effects such as natural and realistic morphology of double eyelids, few complications, and high patients' satisfaction rate.

Objective:To explore the surgical effects of continuous trapezoidal suture method between subcutaneous and subconjunctival tissue in buried-suture double-eyelid blepharoplasty.Methods:A retrospective study was conducted on patients who underwent the operation of continuous trapezoidal suture method between subcutaneous and subconjunctival tissue in buried-suture double-eyelid blepharoplasty at the Department of Plastic and Aesthetic Surgery of Qingdao Municipal Hospital from September 2021 to September 2023. Six points were marked on the skin surface along the designed double eyelid line on patient’s upper eyelid, 8 points were marked on the corresponding conjunctival surface along the designed double eyelid line. A 6-0 nylon thread attached with one needle on each end was used for suturing, with two ends running through and between the subcutaneous and subconjunctival layers alternatively, forming a "trapezoidal" shape of path. Finally, two ends exited at the same point on the most lateral side of the designed double eyelid line on skin surface and were tied together with the knot hidden within the orbicularis oculi muscle. The morphology of the double eyelids and postoperative complications were observed and evaluated after surgery, the follow-up period was at least 6 months. At the last time of follow-up, the satisfaction rates were evaluated by patients themselves. Four aspects of the surgical effects of the double eyelids were put into the evaluation system, which were radian, width, smoothness and symmetry, with score from 0-5 points for each. The total score was 0-20 points, of which 17-20 points indicated high satisfaction, 13-16 points indicated relative satisfaction, ≤12 points indicated dissatisfaction.Results:A total of 52 female patients were included, aged 18 to 29 years old, with an average age of 22.5 years. Among all patients, 33 cases had shallow double eyelid lines while 19 cases had single eyelids. All patients’ upper eyelids were relatively thin and without obvious looseness. The surgical procedures were all done smoothly and successfully, with an average operation time of (0.72±0.13) h. Immediately after surgery, the radian of the double eyelid lines on both sides looked smooth, the widths of the double eyelids were also basically symmetrical. During the follow-up period of 6-12 months postoperatively, the morphologies of the double eyelids were relatively natural and realistic, the double eyelid lines and widths remained deep and stable, and the incision scars were unobvious for all patients. Besides, no complications such as ptosis, incomplete upper eyelid closure and ectropion were observed. Among the 52 patients, 45 cases were highly satisfied with the surgical result, 7 cases were relatively satisfied, while none of them required reoperation.Conclusion:The continuous trapezoidal suture method between subcutaneous and subconjunctival tissue in buried-suture double-eyelid blepharoplasty has advantages of short operation time, good and stable surgical effects such as natural and realistic morphology of double eyelids, few complications, and high patients’ satisfaction rate.

Objective:To explore the surgical effects of continuous trapezoidal suture method between subcutaneous and subconjunctival tissue in buried-suture double-eyelid blepharoplasty.Methods:A retrospective study was conducted on patients who underwent the operation of continuous trapezoidal suture method between subcutaneous and subconjunctival tissue in buried-suture double-eyelid blepharoplasty at the Department of Plastic and Aesthetic Surgery of Qingdao Municipal Hospital from September 2021 to September 2023. Six points were marked on the skin surface of the designed double eyelid line on patient' s upper eyelid, 8 points were marked on the corresponding conjunctival surface of the designed double eyelid line. A 6-0 nylon thread attached with one needle on each end was used for suturing, with two ends running through and between the subcutaneous and subconjunctival layers alternatively, forming a " trapezoidal" shape of path. Finally, two ends exited at the same point on the most lateral side of the designed double eyelid line on skin surface and were tied together with the knot hidden within the orbicularis oculi muscle. The morphology of the double eyelids and postoperative complications were observed and evaluated after surgery, the follow-up period was at least 6 months. At the last time of follow-up, the satisfaction rates were evaluated by patients themselves. Four aspects of the surgical effects of the double eyelids were put into the evaluation system, which were radian, width, smoothness and symmetry, with score from 0-5 points for each. The total score was 0-20 points, of which 17-20 points indicated high satisfaction, score of 13-16 points indicated relative satisfaction, ≤ 12 points indicated dissatisfaction.Results:A total of 52 female patients were included, aged 18 to 29 years old, with an average age of 22.5 years. Among all patients, 33 cases had shallow double eyelid lines while 19 cases had single eyelids. All patients’ upper eyelids were relatively thin and without obvious looseness. The surgical procedures were all done smoothly and successfully, with an average operation time of (0.72±0.13) h. Immediately after surgery, the radian of the double eyelid lines on both sides looked smooth, the widths of the double eyelids were also basically symmetrical. During the follow-up period of 6-12 months postoperatively, the morphologies of the double eyelids were relatively natural and realistic, the double eyelid lines and widths remained deep and stable, and the incision scars were left unobvious for all patients. Besides, no complications such as ptosis, incomplete upper eyelid closure and ectropion were observed. Among the 52 patients, 45 cases were highly satisfied with the surgical result (17-20 points) , 7 were relatively satisfied (13-16 points) , while none of them required reoperation.Conclusions:The continuous trapezoidal suture method between subcutaneous and subconjunctival tissue in buried-suture double-eyelid blepharoplasty has advantages of short operation time, good and stable surgical effects such as natural and realistic morphology of double eyelids, few complications, and high patients' satisfaction rate.

Objective:To explore the surgical effects of continuous trapezoidal suture method between subcutaneous and subconjunctival tissue in buried-suture double-eyelid blepharoplasty.Methods:A retrospective study was conducted on patients who underwent the operation of continuous trapezoidal suture method between subcutaneous and subconjunctival tissue in buried-suture double-eyelid blepharoplasty at the Department of Plastic and Aesthetic Surgery of Qingdao Municipal Hospital from September 2021 to September 2023. Six points were marked on the skin surface along the designed double eyelid line on patient’s upper eyelid, 8 points were marked on the corresponding conjunctival surface along the designed double eyelid line. A 6-0 nylon thread attached with one needle on each end was used for suturing, with two ends running through and between the subcutaneous and subconjunctival layers alternatively, forming a "trapezoidal" shape of path. Finally, two ends exited at the same point on the most lateral side of the designed double eyelid line on skin surface and were tied together with the knot hidden within the orbicularis oculi muscle. The morphology of the double eyelids and postoperative complications were observed and evaluated after surgery, the follow-up period was at least 6 months. At the last time of follow-up, the satisfaction rates were evaluated by patients themselves. Four aspects of the surgical effects of the double eyelids were put into the evaluation system, which were radian, width, smoothness and symmetry, with score from 0-5 points for each. The total score was 0-20 points, of which 17-20 points indicated high satisfaction, 13-16 points indicated relative satisfaction, ≤12 points indicated dissatisfaction.Results:A total of 52 female patients were included, aged 18 to 29 years old, with an average age of 22.5 years. Among all patients, 33 cases had shallow double eyelid lines while 19 cases had single eyelids. All patients’ upper eyelids were relatively thin and without obvious looseness. The surgical procedures were all done smoothly and successfully, with an average operation time of (0.72±0.13) h. Immediately after surgery, the radian of the double eyelid lines on both sides looked smooth, the widths of the double eyelids were also basically symmetrical. During the follow-up period of 6-12 months postoperatively, the morphologies of the double eyelids were relatively natural and realistic, the double eyelid lines and widths remained deep and stable, and the incision scars were unobvious for all patients. Besides, no complications such as ptosis, incomplete upper eyelid closure and ectropion were observed. Among the 52 patients, 45 cases were highly satisfied with the surgical result, 7 cases were relatively satisfied, while none of them required reoperation.Conclusion:The continuous trapezoidal suture method between subcutaneous and subconjunctival tissue in buried-suture double-eyelid blepharoplasty has advantages of short operation time, good and stable surgical effects such as natural and realistic morphology of double eyelids, few complications, and high patients’ satisfaction rate.

This paper reports a case of reparing the tissue defect after resection of a malignant tumor in the glabellar nasion with bilateral modified horizontal advancement flaps. The patient, a 20-year-old female, was admitted to the hospital because of a mass on the nasion between the eyebrows for more than 5 years, with enlargement and ulceration for 5 months. Surgical resection of the tumor was performed. Intraoperative rapid frozen sections showed that the tumor was basal cell carcinoma, and there were no cancer cells at the margins. Bilateral modified horizontal advancement flap repair was performed. At three months after the operation, the incision area healed well, the appearance and eyelid function were normal, and there was no sign of recurrence of basal cell carcinoma. Bilateral modified horizontal advancement flap was effective in repairing the tissue defect after resection of glabellar nasal root basal cell carcinoma.

Biapenem is a carbapenem antibiotic， and can be used for the treatment of sepsis， pneumonia， lung abscess， chronic respiratory lesions secondary infection， complex urinary tract infection and pyelonephritis， etc. This article reviewed the studies on the pharmacokinetics， pharmacodynamics and therapeutic drug monitoring （TDM） of biapenem. The pharmacokinetic parameters of biapenem are not significantly different in healthy subjects， and there is no accumulation after multiple doses of biapenem. However， there are large differences in pharmacokinetic parameters in patients with severe disease and patients with abnormal renal function compared with healthy subjects， which leads to conventional treatment regimens not achieving the desired outcome. In terms of pharmacodynamics， biapenem can improve the rate of reaching the target value by increasing the frequency of administration and prolonging the infusion time. For patients with anuria in end-stage renal disease， dosing intervals can be extended to avoid drug accumulation. However, for patients with severe infection, a daily dose of 1.2 g still can not control infections caused by Acinetobacter baumannii or Pseudomonas aeruginosa, which limits its use in patients with severe disease. It is recommended to implement TDM in severe patients and patients with abnormal renal function， and explore the best dosing regimen for biapenem in combination with pharmacokinetic models to ensure that the time that the free blood concentration of biapenem remains above minimum inhibitory concentration as a percentage of the time between doses （%fT＞MIC） is within the effective range，so that biapenem can exert a greater efficacy in severe patients and patients with abnormal renal function. For medical institutions that cannot carry out TDM， the efficacy of biapenem can be maximized by increasing the frequency of administration and prolonging the infusion time. For infections caused by P. aeruginosa， A. baumannii and Serratia marcescens with high drug resistance rates， it is recommended to combine or replace other antibiotics.

Molecular knowledge of human gastric corpus epithelium remains incomplete. Here, by integrated analyses using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) techniques, we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium. Specifically, we identified a stem/progenitor cell population in the isthmus of human gastric corpus, where EGF and WNT signaling pathways were activated. Meanwhile, LGR4, but not LGR5, was responsible for the activation of WNT signaling pathway. Importantly, FABP5 and NME1 were identified and validated as crucial for both normal gastric stem/progenitor cells and gastric cancer cells. Finally, we explored the epigenetic regulation of critical genes for gastric corpus epithelium at chromatin state level, and identified several important cell-type-specific transcription factors. In summary, our work provides novel insights to systematically understand the cellular diversity and homeostasis of human gastric corpus epithelium in vivo.
Humans ; Epigenesis, Genetic ; Gastric Mucosa/metabolism* ; Chromatin/metabolism* ; Stem Cells ; Epithelium/metabolism* ; Fatty Acid-Binding Proteins/metabolism*

OBJECTIVE:To observe the efficacy and safety of neoadjuvant chemotherapy in advanced gastric carcinoma patients before laparoscopic minimally invasive resction.METHODS:In retrospective analysis,93 patients with advanced gastric carcinoma were divided into single group (55 cases) and combined group (38 cases).Single group received laparoscopic minimally invasive operation.Combination group was given Tetrahydrofolate injection 400 mg/m2+Oxaliplatin injection 85 mg/m2,i.v.,2 h,d1+ Fluorouracil injection 2 400 mg/m2,i.v.,46 h,d2.A treatment course lasted for 2 weeks,both received 2-4 courses of treatment and 4 weeks later received laparoscopic minimally invasive resection.Both groups received routine treatment as parenteral nutrition and preventive anti-inflammation.They were given oxaliplatin+capecitabine or gimeracil oteracil potassium capsule+oxaliplatin chemotherapy for 6 courses.Clinical efficacies and ADR of combination group were observed.Operation time,intraoperative blood loss,intraoperative blood transfusion,resection range,conversions to laparotomy,the number of lymph node dissection,complete resection and postoperative first exhaust time,the time of fluid feeding recovery,the length of hospital stay and complications were observed in 2 groups.RESULTS:The objective remission rate and disease control rate of combination group were 44.8％ and 92.2％;there were 23 case time of grade Ⅰ ADR,13 case time of grade Ⅱ ADR and 3 case time of grade Ⅲ ADR.Complete resection rate of combination group was significantly higher than that of single group,with statistical significance (P＜0.05).There was no statistical significance in operation time,intraoperative blood loss,intraoperative blood transfusion,resection range,conversions to laparotomy,the number of lymph node dissection,postoperative first exhaust time,the time of fluid feeding recovery,the length of hospital stay or the incidence of complications between 2 groups (P＞0.05).CONCLUSIONS:For advanced gastric carcinoma patients before laparosapic minimally invasive resection,tetrahydrofolate,oxaliplatin and fluorouracil neoadjuvant chemotherapy show therapeutic efficacy and can improve the rate of complete resection without increasing the incidence of ADR.