Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

BACKGROUND:Plastic as a durable,inexpensive,easy to manufacture organic synthetic polymer materials are widely used.At the same time,plastic resistance to high temperatures,acid and alkali resistance,corrosion-resistant properties make it difficult to degrade in nature,and ultimately forming a huge number of microplastic pollution threatening human health. OBJECTIVE:To investigate the effects of microplastic exposure on growth and development and hepatic lipid metabolism in mice. METHODS:Twenty C57BL/6J male mice were adaptively fed for one week,and then randomly divided into normal and microplastic groups(n=10 per group).Mice in the normal group were given a normal diet and water,for 4 weeks.Mice in the microplastic group were given a normal diet and free drinking of microplastic(polystyrene)water with a concentration of 1 000 μg/L,for 4 weeks.At 2 and 4 weeks of drinking,body mass and grip strength,blood lipids and liver and kidney function,ultrasonic morphology and pathological morphology of liver and lipid deposition were detected. RESULTS AND CONCLUSION:(1)With the extension of time,the body mass of mice in the two groups gradually increased,and the body mass of mice in the microplastic group was greater than that in the normal group after 2,4 weeks of drinking water(P<0.05).With the extension of time,the grip strength of mice in the normal group gradually increased,and the grip strength of mice in the microplastic group first decreased and then increased,and the grip strength of mice in the microplastic group was lower than that in the normal group after drinking water for 4 weeks(P<0.05).(2)Liver ultrasound examination showed that compared with the normal group,the ultrasonic echo signal of the liver in the microplastic group was enhanced after 2 and 4 weeks of drinking water.(3)Hematoxylin-eosin staining showed that the morphology of liver cells in the microplastic group did not change significantly after 2 and 4 weeks of drinking water,but inflammatory cell infiltration could be seen.Oil red O staining showed that obvious lipid deposition was observed in the liver of microplastic group after 2 and 4 weeks of drinking water.(4)Compared with the normal group,the levels of serum high density lipoprotein cholesterol,triacylglycerol,and aspartate aminotransferase in the microplastic group were decreased after 2 weeks of drinking water(P<0.05),and the serum triacylglycerol concentration was decreased after 4 weeks of drinking water(P<0.05).(5)These findings confirm that microplastics may cause weight gain,loss of physical strength,and abnormal hepatic lipid metabolism in mice.

BACKGROUND:Laser therapy is a non-invasive and painless treatment that is considered to be an effective method suitable for the treatment of osteoarthritis due to its simplicity and non-invasive nature.Currently,the mechanism of action of laser therapy is unclear and the results of studies on its clinical application are controversial. OBJECTIVE:To review and summarize the latest research progress of laser therapy on chondrocytes,animal experiments and clinical efficacy,and to explore the possible mechanism of laser-mediated multi-pathway biological effects,so as to provide a theoretical basis for further research on the laser treatment of osteoarthritis of the knee joint. METHODS:A literature search was performed in CNKI,WanFang Data,VIP and PubMed databases for relevant literature published from 2018 to 2023,with"laser therapy,low level laser therapy,high level laser therapy,photobiomodulation,knee osteoarthritis,chondrocytes"as the search terms in Chinese and English,respectively.Together with 14 articles searched manually,70 articles were finally included for review. RESULTS AND CONCLUSION:Laser therapy in the treatment of knee osteoarthritis is mainly categorized into two types:low-level laser therapy and high-level laser therapy.Differences in laser parameters and treatment protocols have a direct impact on laser efficacy.When appropriate parameters are used,low-level lasers show positive effects in cellular experiments,animal models,and clinical efficacy.High-level lasers have been less studied in the treatment of knee osteoarthritis,but some preliminary clinical studies have shown positive results.Cell experiments have shown that low-level laser promotes chondrocyte proliferation and cartilage matrix synthesis,thereby reducing inflammatory response.Animal experiments have shown that low-level laser can reduce the release of pro-inflammatory factors,promote cartilage matrix synthesis,inhibit matrix degradation,and effectively improve the repair process of cartilage tissue.Low-level laser is also able to reduce oxidative stress damage and relieve pain in knee osteoarthritis.In clinical trials,both low-and high-level laser can reduce patients'pain and improve functional activities.The combination of laser therapy and exercise therapy modalities may improve the therapeutic effect.Lasers may affect intracellular signaling and cellular functions through photobiological or thermodynamic effects.This provides direct evidence that laser promotes articular cartilage regeneration.

Objective To investigate the clinical efficacy of arthroscopic simple repair technique and en-hanced repair technique in the treatment of chronic lateral ankle instability(CLAI).Methods Forty-one cases of CLAI treated in the General Hospital of Northern Theater Command of PLA from January 2018 to January 2019 were selected and conducted arthroscopic lateral ankle ligament repair or enhanced repair treatment.The follow up data in 39 cases were complete.Among them,18 cases conducted the anterior talofibular ligament repair with wire anchor under arthroscopy and were included in the repair group,while 21 cases conducted the arthroscopic enhanced repair with linear anchors and knots free anchors and were included in the enhanced re-pair group.The postoperative follow up lasted for 12 months.The VAS score and AOFAS ankle-hind foot score before operation and in postoperative,3,6,12 months were compared between the two groups.The effi-cacies of treating CLAI by the two operation modes were evaluated.Results The preoperative VAS score and AOFAS ankle-hind foot score had no statistical differences between the two groups(P＞0.05).The VAS score at postoperative time points had no statistical difference between the enhanced repair group and repair group(P＞0.05).The AOFAS ankle-hind foot score in the enhanced repair group was higher than that in the repair group,and the difference was statistically significant(P＜0.05).No serious complications occurred in the grouped patients during the follow up period.Conclusion In terms of pain and ankle function,the effect of arthroscopic enhanced repair in treating CLAI is better than that of simple repair.

Objective To investigate the effects of different deflation methods of endotracheal tube cuff on coughing response and hemodynamics during extubation. Methods Ninety patients undergoing elective surgery for endotracheal intubation under general anesthesia were selected as study subjects and randomly divided into study group and control group, with 45 patients in each group. In the study group, the cuff end of the endotracheal tube cuff was connected to a syringe and a non-liquid pressure gauge through a three-way stopcock. Before extubation, the cuff was aspirated to decrease the cuff pressure at a rate of 3 cmH₂O/s. In the control group, the gas in cuff was rapidly deflated by aspirating all the gas inside with a syringe during extubation. The incidence and severity of coughing response during extubation were recorded in both groups. Mean arterial pressure (MAP) and heart rate (HR) were recorded before induction of general anesthesia (T₀), before cuff deflation (T₁), immediately after cuff deflation (T₂), 1 minute after extubation (T₃), 3 minutes after extubation (T₄), and 5 minutes after extubation (T₅). Adverse events were also recorded in both groups. Results The coughing response during extubation started immediately after cuff deflation in both groups. The incidence and severity of coughing response were lower in the study group than in the control group (P < 0.05). Compared with the control group, values of MAP were lower at T₂ to T₄ and values of HR were lower at T₂ to T₅ in the study group (P < 0.05). The incidence of post-extubation pharyngeal discomfort was 6.67 % in the study group, which was lower than 26.67 % in the control group (P < 0.05). There was no significant difference in the incidence of post-extubation hypoventilation between the two groups (P>0.05). Conclusion The method of slowly reducing the pressure of the endotracheal tube cuff at a constant rate can reduce the incidence and severity of coughing, decrease postoperative extubation complications, and stabilize hemodynamics, with better effects than the method of rapidly aspirating all the gas inside the cuff at once.

OBJECTIVE To investigate the effect of ropivacaine combined with dexmedetomidine on postoperative analgesia in women undergoing cesarean section， and to explore the feasibility of the opioid-free analgesia mode after cesarean section under spinal-epidural anesthesia. METHODS Totally 80 women undergoing cesarean section were randomly divided into observation group （ropivacaine combined with dexmedetomidine for analgesia） and control group （ropivacaine combined with opioid drug sufentanil for analgesia） ， with 40 cases in each group. The exercise and rest score in visual analogue scale （VAS） within 48 hours after operation， the use of analgesia pump （the time of first analgesia pump pressing， the times of analgesia pump pressing within 24 hours and 48 hours after operation）， the time of block （the onset time of spinal anesthesia sensory block， the time to the highest level of spinal anesthesia sensory block， the time of sensory recovery and the time of movement recovery） ， the time of prognosis （the time of gastrointestinal ventilation recovery， the time of getting out of bed and the hospitalization time）， and the incidence of adverse events were compared in 2 groups. RESULTS Finally， 64 parturients （32 in the observation group and 32 in the control group） were involved in the analysis. Compared with the control group， the recovery time of sensation and movement were significantly prolonged， the ventilation time was significantly shortened， and the incidence of nausea， vomiting and abdominal distension was significantly decreased in the observation group （P＜0.05） . There was no significant difference in the other indexes between the two groups （P＞0.05）. CONCLUSIONS Ropivacaine combined with dexmedetomidine under spinal-epidural anesthesia could provide similar analgesic effect as combined with opioids drug sufentanil， shorten the time of gastrointestinal ventilation recovery， and reduce the incidence of nausea，vomiting and abdominal distension， with no increased risk of low blood pressure or urinary retention.